Sample records for regulatory network architecture

  1. Computational architecture of the yeast regulatory network

    NASA Astrophysics Data System (ADS)

    Maslov, Sergei; Sneppen, Kim

    2005-12-01

    The topology of regulatory networks contains clues to their overall design principles and evolutionary history. We find that while in- and out-degrees of a given protein in the regulatory network are not correlated with each other, there exists a strong negative correlation between the out-degree of a regulatory protein and in-degrees of its targets. Such correlation positions large regulatory modules on the periphery of the network and makes them rather well separated from each other. We also address the question of relative importance of different classes of proteins quantified by the lethality of null-mutants lacking one of them as well as by the level of their evolutionary conservation. It was found that in the yeast regulatory network highly connected proteins are in fact less important than their low-connected counterparts.

  2. Developmental gene regulatory network architecture across 500 million years of echinoderm evolution

    NASA Technical Reports Server (NTRS)

    Hinman, Veronica F.; Nguyen, Albert T.; Cameron, R. Andrew; Davidson, Eric H.

    2003-01-01

    Evolutionary change in morphological features must depend on architectural reorganization of developmental gene regulatory networks (GRNs), just as true conservation of morphological features must imply retention of ancestral developmental GRN features. Key elements of the provisional GRN for embryonic endomesoderm development in the sea urchin are here compared with those operating in embryos of a distantly related echinoderm, a starfish. These animals diverged from their common ancestor 520-480 million years ago. Their endomesodermal fate maps are similar, except that sea urchins generate a skeletogenic cell lineage that produces a prominent skeleton lacking entirely in starfish larvae. A relevant set of regulatory genes was isolated from the starfish Asterina miniata, their expression patterns determined, and effects on the other genes of perturbing the expression of each were demonstrated. A three-gene feedback loop that is a fundamental feature of the sea urchin GRN for endoderm specification is found in almost identical form in the starfish: a detailed element of GRN architecture has been retained since the Cambrian Period in both echinoderm lineages. The significance of this retention is highlighted by the observation of numerous specific differences in the GRN connections as well. A regulatory gene used to drive skeletogenesis in the sea urchin is used entirely differently in the starfish, where it responds to endomesodermal inputs that do not affect it in the sea urchin embryo. Evolutionary changes in the GRNs since divergence are limited sharply to certain cis-regulatory elements, whereas others have persisted unaltered.

  3. A genomic regulatory network for development

    NASA Technical Reports Server (NTRS)

    Davidson, Eric H.; Rast, Jonathan P.; Oliveri, Paola; Ransick, Andrew; Calestani, Cristina; Yuh, Chiou-Hwa; Minokawa, Takuya; Amore, Gabriele; Hinman, Veronica; Arenas-Mena, Cesar; hide

    2002-01-01

    Development of the body plan is controlled by large networks of regulatory genes. A gene regulatory network that controls the specification of endoderm and mesoderm in the sea urchin embryo is summarized here. The network was derived from large-scale perturbation analyses, in combination with computational methodologies, genomic data, cis-regulatory analysis, and molecular embryology. The network contains over 40 genes at present, and each node can be directly verified at the DNA sequence level by cis-regulatory analysis. Its architecture reveals specific and general aspects of development, such as how given cells generate their ordained fates in the embryo and why the process moves inexorably forward in developmental time.

  4. A service-oriented architecture for integrating the modeling and formal verification of genetic regulatory networks

    PubMed Central

    2009-01-01

    Background The study of biological networks has led to the development of increasingly large and detailed models. Computer tools are essential for the simulation of the dynamical behavior of the networks from the model. However, as the size of the models grows, it becomes infeasible to manually verify the predictions against experimental data or identify interesting features in a large number of simulation traces. Formal verification based on temporal logic and model checking provides promising methods to automate and scale the analysis of the models. However, a framework that tightly integrates modeling and simulation tools with model checkers is currently missing, on both the conceptual and the implementational level. Results We have developed a generic and modular web service, based on a service-oriented architecture, for integrating the modeling and formal verification of genetic regulatory networks. The architecture has been implemented in the context of the qualitative modeling and simulation tool GNA and the model checkers NUSMV and CADP. GNA has been extended with a verification module for the specification and checking of biological properties. The verification module also allows the display and visual inspection of the verification results. Conclusions The practical use of the proposed web service is illustrated by means of a scenario involving the analysis of a qualitative model of the carbon starvation response in E. coli. The service-oriented architecture allows modelers to define the model and proceed with the specification and formal verification of the biological properties by means of a unified graphical user interface. This guarantees a transparent access to formal verification technology for modelers of genetic regulatory networks. PMID:20042075

  5. Architecture and dynamics of overlapped RNA regulatory networks.

    PubMed

    Lapointe, Christopher P; Preston, Melanie A; Wilinski, Daniel; Saunders, Harriet A J; Campbell, Zachary T; Wickens, Marvin

    2017-11-01

    A single protein can bind and regulate many mRNAs. Multiple proteins with similar specificities often bind and control overlapping sets of mRNAs. Yet little is known about the architecture or dynamics of overlapped networks. We focused on three proteins with similar structures and related RNA-binding specificities-Puf3p, Puf4p, and Puf5p of S. cerevisiae Using RNA Tagging, we identified a "super-network" comprised of four subnetworks: Puf3p, Puf4p, and Puf5p subnetworks, and one controlled by both Puf4p and Puf5p. The architecture of individual subnetworks, and thus the super-network, is determined by competition among particular PUF proteins to bind mRNAs, their affinities for binding elements, and the abundances of the proteins. The super-network responds dramatically: The remaining network can either expand or contract. These strikingly opposite outcomes are determined by an interplay between the relative abundance of the RNAs and proteins, and their affinities for one another. The diverse interplay between overlapping RNA-protein networks provides versatile opportunities for regulation and evolution. © 2017 Lapointe et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  6. Dynamics of Bacterial Gene Regulatory Networks.

    PubMed

    Shis, David L; Bennett, Matthew R; Igoshin, Oleg A

    2018-05-20

    The ability of bacterial cells to adjust their gene expression program in response to environmental perturbation is often critical for their survival. Recent experimental advances allowing us to quantitatively record gene expression dynamics in single cells and in populations coupled with mathematical modeling enable mechanistic understanding on how these responses are shaped by the underlying regulatory networks. Here, we review how the combination of local and global factors affect dynamical responses of gene regulatory networks. Our goal is to discuss the general principles that allow extrapolation from a few model bacteria to less understood microbes. We emphasize that, in addition to well-studied effects of network architecture, network dynamics are shaped by global pleiotropic effects and cell physiology.

  7. Regulatory gene networks and the properties of the developmental process

    NASA Technical Reports Server (NTRS)

    Davidson, Eric H.; McClay, David R.; Hood, Leroy

    2003-01-01

    Genomic instructions for development are encoded in arrays of regulatory DNA. These specify large networks of interactions among genes producing transcription factors and signaling components. The architecture of such networks both explains and predicts developmental phenomenology. Although network analysis is yet in its early stages, some fundamental commonalities are already emerging. Two such are the use of multigenic feedback loops to ensure the progressivity of developmental regulatory states and the prevalence of repressive regulatory interactions in spatial control processes. Gene regulatory networks make it possible to explain the process of development in causal terms and eventually will enable the redesign of developmental regulatory circuitry to achieve different outcomes.

  8. Functional architecture and global properties of the Corynebacterium glutamicum regulatory network: Novel insights from a dataset with a high genomic coverage.

    PubMed

    Freyre-González, Julio A; Tauch, Andreas

    2017-09-10

    Corynebacterium glutamicum is a Gram-positive, anaerobic, rod-shaped soil bacterium able to grow on a diversity of carbon sources like sugars and organic acids. It is a biotechnological relevant organism because of its highly efficient ability to biosynthesize amino acids, such as l-glutamic acid and l-lysine. Here, we reconstructed the most complete C. glutamicum regulatory network to date and comprehensively analyzed its global organizational properties, systems-level features and functional architecture. Our analyses show the tremendous power of Abasy Atlas to study the functional organization of regulatory networks. We created two models of the C. glutamicum regulatory network: all-evidences (containing both weak and strong supported interactions, genomic coverage=73%) and strongly-supported (only accounting for strongly supported evidences, genomic coverage=71%). Using state-of-the-art methodologies, we prove that power-law behaviors truly govern the connectivity and clustering coefficient distributions. We found a non-previously reported circuit motif that we named complex feed-forward motif. We highlighted the importance of feedback loops for the functional architecture, beyond whether they are statistically over-represented or not in the network. We show that the previously reported top-down approach is inadequate to infer the hierarchy governing a regulatory network because feedback bridges different hierarchical layers, and the top-down approach disregards the presence of intermodular genes shaping the integration layer. Our findings all together further support a diamond-shaped, three-layered hierarchy exhibiting some feedback between processing and coordination layers, which is shaped by four classes of systems-level elements: global regulators, locally autonomous modules, basal machinery and intermodular genes. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Architecture of the human regulatory network derived from ENCODE data.

    PubMed

    Gerstein, Mark B; Kundaje, Anshul; Hariharan, Manoj; Landt, Stephen G; Yan, Koon-Kiu; Cheng, Chao; Mu, Xinmeng Jasmine; Khurana, Ekta; Rozowsky, Joel; Alexander, Roger; Min, Renqiang; Alves, Pedro; Abyzov, Alexej; Addleman, Nick; Bhardwaj, Nitin; Boyle, Alan P; Cayting, Philip; Charos, Alexandra; Chen, David Z; Cheng, Yong; Clarke, Declan; Eastman, Catharine; Euskirchen, Ghia; Frietze, Seth; Fu, Yao; Gertz, Jason; Grubert, Fabian; Harmanci, Arif; Jain, Preti; Kasowski, Maya; Lacroute, Phil; Leng, Jing Jane; Lian, Jin; Monahan, Hannah; O'Geen, Henriette; Ouyang, Zhengqing; Partridge, E Christopher; Patacsil, Dorrelyn; Pauli, Florencia; Raha, Debasish; Ramirez, Lucia; Reddy, Timothy E; Reed, Brian; Shi, Minyi; Slifer, Teri; Wang, Jing; Wu, Linfeng; Yang, Xinqiong; Yip, Kevin Y; Zilberman-Schapira, Gili; Batzoglou, Serafim; Sidow, Arend; Farnham, Peggy J; Myers, Richard M; Weissman, Sherman M; Snyder, Michael

    2012-09-06

    Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.

  10. Transcriptional Regulatory Networks in Saccharomyces cerevisiae

    NASA Astrophysics Data System (ADS)

    Lee, Tong Ihn; Rinaldi, Nicola J.; Robert, François; Odom, Duncan T.; Bar-Joseph, Ziv; Gerber, Georg K.; Hannett, Nancy M.; Harbison, Christopher T.; Thompson, Craig M.; Simon, Itamar; Zeitlinger, Julia; Jennings, Ezra G.; Murray, Heather L.; Gordon, D. Benjamin; Ren, Bing; Wyrick, John J.; Tagne, Jean-Bosco; Volkert, Thomas L.; Fraenkel, Ernest; Gifford, David K.; Young, Richard A.

    2002-10-01

    We have determined how most of the transcriptional regulators encoded in the eukaryote Saccharomyces cerevisiae associate with genes across the genome in living cells. Just as maps of metabolic networks describe the potential pathways that may be used by a cell to accomplish metabolic processes, this network of regulator-gene interactions describes potential pathways yeast cells can use to regulate global gene expression programs. We use this information to identify network motifs, the simplest units of network architecture, and demonstrate that an automated process can use motifs to assemble a transcriptional regulatory network structure. Our results reveal that eukaryotic cellular functions are highly connected through networks of transcriptional regulators that regulate other transcriptional regulators.

  11. A prior-based integrative framework for functional transcriptional regulatory network inference

    PubMed Central

    Siahpirani, Alireza F.

    2017-01-01

    Abstract Transcriptional regulatory networks specify regulatory proteins controlling the context-specific expression levels of genes. Inference of genome-wide regulatory networks is central to understanding gene regulation, but remains an open challenge. Expression-based network inference is among the most popular methods to infer regulatory networks, however, networks inferred from such methods have low overlap with experimentally derived (e.g. ChIP-chip and transcription factor (TF) knockouts) networks. Currently we have a limited understanding of this discrepancy. To address this gap, we first develop a regulatory network inference algorithm, based on probabilistic graphical models, to integrate expression with auxiliary datasets supporting a regulatory edge. Second, we comprehensively analyze our and other state-of-the-art methods on different expression perturbation datasets. Networks inferred by integrating sequence-specific motifs with expression have substantially greater agreement with experimentally derived networks, while remaining more predictive of expression than motif-based networks. Our analysis suggests natural genetic variation as the most informative perturbation for network inference, and, identifies core TFs whose targets are predictable from expression. Multiple reasons make the identification of targets of other TFs difficult, including network architecture and insufficient variation of TF mRNA level. Finally, we demonstrate the utility of our inference algorithm to infer stress-specific regulatory networks and for regulator prioritization. PMID:27794550

  12. A swarm intelligence framework for reconstructing gene networks: searching for biologically plausible architectures.

    PubMed

    Kentzoglanakis, Kyriakos; Poole, Matthew

    2012-01-01

    In this paper, we investigate the problem of reverse engineering the topology of gene regulatory networks from temporal gene expression data. We adopt a computational intelligence approach comprising swarm intelligence techniques, namely particle swarm optimization (PSO) and ant colony optimization (ACO). In addition, the recurrent neural network (RNN) formalism is employed for modeling the dynamical behavior of gene regulatory systems. More specifically, ACO is used for searching the discrete space of network architectures and PSO for searching the corresponding continuous space of RNN model parameters. We propose a novel solution construction process in the context of ACO for generating biologically plausible candidate architectures. The objective is to concentrate the search effort into areas of the structure space that contain architectures which are feasible in terms of their topological resemblance to real-world networks. The proposed framework is initially applied to the reconstruction of a small artificial network that has previously been studied in the context of gene network reverse engineering. Subsequently, we consider an artificial data set with added noise for reconstructing a subnetwork of the genetic interaction network of S. cerevisiae (yeast). Finally, the framework is applied to a real-world data set for reverse engineering the SOS response system of the bacterium Escherichia coli. Results demonstrate the relative advantage of utilizing problem-specific knowledge regarding biologically plausible structural properties of gene networks over conducting a problem-agnostic search in the vast space of network architectures.

  13. Modularity and design principles in the sea urchin embryo gene regulatory network

    PubMed Central

    Peter, Isabelle S.; Davidson, Eric H.

    2010-01-01

    The gene regulatory network (GRN) established experimentally for the pre-gastrular sea urchin embryo provides causal explanations of the biological functions required for spatial specification of embryonic regulatory states. Here we focus on the structure of the GRN which controls the progressive increase in complexity of territorial regulatory states during embryogenesis; and on the types of modular subcircuits of which the GRN is composed. Each of these subcircuit topologies executes a particular operation of spatial information processing. The GRN architecture reflects the particular mode of embryogenesis represented by sea urchin development. Network structure not only specifies the linkages constituting the genomic regulatory code for development, but also indicates the various regulatory requirements of regional developmental processes. PMID:19932099

  14. Integrating non-coding RNAs in JAK-STAT regulatory networks

    PubMed Central

    Witte, Steven; Muljo, Stefan A

    2014-01-01

    Being a well-characterized pathway, JAK-STAT signaling serves as a valuable paradigm for studying the architecture of gene regulatory networks. The discovery of untranslated or non-coding RNAs, namely microRNAs and long non-coding RNAs, provides an opportunity to elucidate their roles in such networks. In principle, these regulatory RNAs can act as downstream effectors of the JAK-STAT pathway and/or affect signaling by regulating the expression of JAK-STAT components. Examples of interactions between signaling pathways and non-coding RNAs have already emerged in basic cell biology and human diseases such as cancer, and can potentially guide the identification of novel biomarkers or drug targets for medicine. PMID:24778925

  15. A provisional regulatory gene network for specification of endomesoderm in the sea urchin embryo

    NASA Technical Reports Server (NTRS)

    Davidson, Eric H.; Rast, Jonathan P.; Oliveri, Paola; Ransick, Andrew; Calestani, Cristina; Yuh, Chiou-Hwa; Minokawa, Takuya; Amore, Gabriele; Hinman, Veronica; Arenas-Mena, Cesar; hide

    2002-01-01

    We present the current form of a provisional DNA sequence-based regulatory gene network that explains in outline how endomesodermal specification in the sea urchin embryo is controlled. The model of the network is in a continuous process of revision and growth as new genes are added and new experimental results become available; see http://www.its.caltech.edu/mirsky/endomeso.htm (End-mes Gene Network Update) for the latest version. The network contains over 40 genes at present, many newly uncovered in the course of this work, and most encoding DNA-binding transcriptional regulatory factors. The architecture of the network was approached initially by construction of a logic model that integrated the extensive experimental evidence now available on endomesoderm specification. The internal linkages between genes in the network have been determined functionally, by measurement of the effects of regulatory perturbations on the expression of all relevant genes in the network. Five kinds of perturbation have been applied: (1) use of morpholino antisense oligonucleotides targeted to many of the key regulatory genes in the network; (2) transformation of other regulatory factors into dominant repressors by construction of Engrailed repressor domain fusions; (3) ectopic expression of given regulatory factors, from genetic expression constructs and from injected mRNAs; (4) blockade of the beta-catenin/Tcf pathway by introduction of mRNA encoding the intracellular domain of cadherin; and (5) blockade of the Notch signaling pathway by introduction of mRNA encoding the extracellular domain of the Notch receptor. The network model predicts the cis-regulatory inputs that link each gene into the network. Therefore, its architecture is testable by cis-regulatory analysis. Strongylocentrotus purpuratus and Lytechinus variegatus genomic BAC recombinants that include a large number of the genes in the network have been sequenced and annotated. Tests of the cis-regulatory predictions of

  16. Design Principles of Regulatory Networks: Searching for the Molecular Algorithms of the Cell

    PubMed Central

    Lim, Wendell A.; Lee, Connie M.; Tang, Chao

    2013-01-01

    A challenge in biology is to understand how complex molecular networks in the cell execute sophisticated regulatory functions. Here we explore the idea that there are common and general principles that link network structures to biological functions, principles that constrain the design solutions that evolution can converge upon for accomplishing a given cellular task. We describe approaches for classifying networks based on abstract architectures and functions, rather than on the specific molecular components of the networks. For any common regulatory task, can we define the space of all possible molecular solutions? Such inverse approaches might ultimately allow the assembly of a design table of core molecular algorithms that could serve as a guide for building synthetic networks and modulating disease networks. PMID:23352241

  17. Airport Surface Network Architecture Definition

    NASA Technical Reports Server (NTRS)

    Nguyen, Thanh C.; Eddy, Wesley M.; Bretmersky, Steven C.; Lawas-Grodek, Fran; Ellis, Brenda L.

    2006-01-01

    Currently, airport surface communications are fragmented across multiple types of systems. These communication systems for airport operations at most airports today are based dedicated and separate architectures that cannot support system-wide interoperability and information sharing. The requirements placed upon the Communications, Navigation, and Surveillance (CNS) systems in airports are rapidly growing and integration is urgently needed if the future vision of the National Airspace System (NAS) and the Next Generation Air Transportation System (NGATS) 2025 concept are to be realized. To address this and other problems such as airport surface congestion, the Space Based Technologies Project s Surface ICNS Network Architecture team at NASA Glenn Research Center has assessed airport surface communications requirements, analyzed existing and future surface applications, and defined a set of architecture functions that will help design a scalable, reliable and flexible surface network architecture to meet the current and future needs of airport operations. This paper describes the systems approach or methodology to networking that was employed to assess airport surface communications requirements, analyze applications, and to define the surface network architecture functions as the building blocks or components of the network. The systems approach used for defining these functions is relatively new to networking. It is viewing the surface network, along with its environment (everything that the surface network interacts with or impacts), as a system. Associated with this system are sets of services that are offered by the network to the rest of the system. Therefore, the surface network is considered as part of the larger system (such as the NAS), with interactions and dependencies between the surface network and its users, applications, and devices. The surface network architecture includes components such as addressing/routing, network management, network

  18. Information network architectures

    NASA Technical Reports Server (NTRS)

    Murray, N. D.

    1985-01-01

    Graphs, charts, diagrams and outlines of information relative to information network architectures for advanced aerospace missions, such as the Space Station, are presented. Local area information networks are considered a likely technology solution. The principle needs for the network are listed.

  19. Tracking of time-varying genomic regulatory networks with a LASSO-Kalman smoother

    PubMed Central

    2014-01-01

    It is widely accepted that cellular requirements and environmental conditions dictate the architecture of genetic regulatory networks. Nonetheless, the status quo in regulatory network modeling and analysis assumes an invariant network topology over time. In this paper, we refocus on a dynamic perspective of genetic networks, one that can uncover substantial topological changes in network structure during biological processes such as developmental growth. We propose a novel outlook on the inference of time-varying genetic networks, from a limited number of noisy observations, by formulating the network estimation as a target tracking problem. We overcome the limited number of observations (small n large p problem) by performing tracking in a compressed domain. Assuming linear dynamics, we derive the LASSO-Kalman smoother, which recursively computes the minimum mean-square sparse estimate of the network connectivity at each time point. The LASSO operator, motivated by the sparsity of the genetic regulatory networks, allows simultaneous signal recovery and compression, thereby reducing the amount of required observations. The smoothing improves the estimation by incorporating all observations. We track the time-varying networks during the life cycle of the Drosophila melanogaster. The recovered networks show that few genes are permanent, whereas most are transient, acting only during specific developmental phases of the organism. PMID:24517200

  20. Genome-wide inference of regulatory networks in Streptomyces coelicolor.

    PubMed

    Castro-Melchor, Marlene; Charaniya, Salim; Karypis, George; Takano, Eriko; Hu, Wei-Shou

    2010-10-18

    The onset of antibiotics production in Streptomyces species is co-ordinated with differentiation events. An understanding of the genetic circuits that regulate these coupled biological phenomena is essential to discover and engineer the pharmacologically important natural products made by these species. The availability of genomic tools and access to a large warehouse of transcriptome data for the model organism, Streptomyces coelicolor, provides incentive to decipher the intricacies of the regulatory cascades and develop biologically meaningful hypotheses. In this study, more than 500 samples of genome-wide temporal transcriptome data, comprising wild-type and more than 25 regulatory gene mutants of Streptomyces coelicolor probed across multiple stress and medium conditions, were investigated. Information based on transcript and functional similarity was used to update a previously-predicted whole-genome operon map and further applied to predict transcriptional networks constituting modules enriched in diverse functions such as secondary metabolism, and sigma factor. The predicted network displays a scale-free architecture with a small-world property observed in many biological networks. The networks were further investigated to identify functionally-relevant modules that exhibit functional coherence and a consensus motif in the promoter elements indicative of DNA-binding elements. Despite the enormous experimental as well as computational challenges, a systems approach for integrating diverse genome-scale datasets to elucidate complex regulatory networks is beginning to emerge. We present an integrated analysis of transcriptome data and genomic features to refine a whole-genome operon map and to construct regulatory networks at the cistron level in Streptomyces coelicolor. The functionally-relevant modules identified in this study pose as potential targets for further studies and verification.

  1. Genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architecture.

    PubMed

    Jothi, Raja; Balaji, S; Wuster, Arthur; Grochow, Joshua A; Gsponer, Jörg; Przytycka, Teresa M; Aravind, L; Babu, M Madan

    2009-01-01

    Although several studies have provided important insights into the general principles of biological networks, the link between network organization and the genome-scale dynamics of the underlying entities (genes, mRNAs, and proteins) and its role in systems behavior remain unclear. Here we show that transcription factor (TF) dynamics and regulatory network organization are tightly linked. By classifying TFs in the yeast regulatory network into three hierarchical layers (top, core, and bottom) and integrating diverse genome-scale datasets, we find that the TFs have static and dynamic properties that are similar within a layer and different across layers. At the protein level, the top-layer TFs are relatively abundant, long-lived, and noisy compared with the core- and bottom-layer TFs. Although variability in expression of top-layer TFs might confer a selective advantage, as this permits at least some members in a clonal cell population to initiate a response to changing conditions, tight regulation of the core- and bottom-layer TFs may minimize noise propagation and ensure fidelity in regulation. We propose that the interplay between network organization and TF dynamics could permit differential utilization of the same underlying network by distinct members of a clonal cell population.

  2. UMA/GAN network architecture analysis

    NASA Astrophysics Data System (ADS)

    Yang, Liang; Li, Wensheng; Deng, Chunjian; Lv, Yi

    2009-07-01

    This paper is to critically analyze the architecture of UMA which is one of Fix Mobile Convergence (FMC) solutions, and also included by the third generation partnership project(3GPP). In UMA/GAN network architecture, UMA Network Controller (UNC) is the key equipment which connects with cellular core network and mobile station (MS). UMA network could be easily integrated into the existing cellular networks without influencing mobile core network, and could provides high-quality mobile services with preferentially priced indoor voice and data usage. This helps to improve subscriber's experience. On the other hand, UMA/GAN architecture helps to integrate other radio technique into cellular network which includes WiFi, Bluetooth, and WiMax and so on. This offers the traditional mobile operators an opportunity to integrate WiMax technique into cellular network. In the end of this article, we also give an analysis of potential influence on the cellular core networks ,which is pulled by UMA network.

  3. Initial deployment of the cardiogenic gene regulatory network in the basal chordate, Ciona intestinalis.

    PubMed

    Woznica, Arielle; Haeussler, Maximilian; Starobinska, Ella; Jemmett, Jessica; Li, Younan; Mount, David; Davidson, Brad

    2012-08-01

    The complex, partially redundant gene regulatory architecture underlying vertebrate heart formation has been difficult to characterize. Here, we dissect the primary cardiac gene regulatory network in the invertebrate chordate, Ciona intestinalis. The Ciona heart progenitor lineage is first specified by Fibroblast Growth Factor/Map Kinase (FGF/MapK) activation of the transcription factor Ets1/2 (Ets). Through microarray analysis of sorted heart progenitor cells, we identified the complete set of primary genes upregulated by FGF/Ets shortly after heart progenitor emergence. Combinatorial sequence analysis of these co-regulated genes generated a hypothetical regulatory code consisting of Ets binding sites associated with a specific co-motif, ATTA. Through extensive reporter analysis, we confirmed the functional importance of the ATTA co-motif in primary heart progenitor gene regulation. We then used the Ets/ATTA combination motif to successfully predict a number of additional heart progenitor gene regulatory elements, including an intronic element driving expression of the core conserved cardiac transcription factor, GATAa. This work significantly advances our understanding of the Ciona heart gene network. Furthermore, this work has begun to elucidate the precise regulatory architecture underlying the conserved, primary role of FGF/Ets in chordate heart lineage specification. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Sensor Network Architectures for Monitoring Underwater Pipelines

    PubMed Central

    Mohamed, Nader; Jawhar, Imad; Al-Jaroodi, Jameela; Zhang, Liren

    2011-01-01

    This paper develops and compares different sensor network architecture designs that can be used for monitoring underwater pipeline infrastructures. These architectures are underwater wired sensor networks, underwater acoustic wireless sensor networks, RF (Radio Frequency) wireless sensor networks, integrated wired/acoustic wireless sensor networks, and integrated wired/RF wireless sensor networks. The paper also discusses the reliability challenges and enhancement approaches for these network architectures. The reliability evaluation, characteristics, advantages, and disadvantages among these architectures are discussed and compared. Three reliability factors are used for the discussion and comparison: the network connectivity, the continuity of power supply for the network, and the physical network security. In addition, the paper also develops and evaluates a hierarchical sensor network framework for underwater pipeline monitoring. PMID:22346669

  5. Sensor network architectures for monitoring underwater pipelines.

    PubMed

    Mohamed, Nader; Jawhar, Imad; Al-Jaroodi, Jameela; Zhang, Liren

    2011-01-01

    This paper develops and compares different sensor network architecture designs that can be used for monitoring underwater pipeline infrastructures. These architectures are underwater wired sensor networks, underwater acoustic wireless sensor networks, RF (radio frequency) wireless sensor networks, integrated wired/acoustic wireless sensor networks, and integrated wired/RF wireless sensor networks. The paper also discusses the reliability challenges and enhancement approaches for these network architectures. The reliability evaluation, characteristics, advantages, and disadvantages among these architectures are discussed and compared. Three reliability factors are used for the discussion and comparison: the network connectivity, the continuity of power supply for the network, and the physical network security. In addition, the paper also develops and evaluates a hierarchical sensor network framework for underwater pipeline monitoring.

  6. Topological and statistical analyses of gene regulatory networks reveal unifying yet quantitatively different emergent properties.

    PubMed

    Ouma, Wilberforce Zachary; Pogacar, Katja; Grotewold, Erich

    2018-04-01

    Understanding complexity in physical, biological, social and information systems is predicated on describing interactions amongst different components. Advances in genomics are facilitating the high-throughput identification of molecular interactions, and graphs are emerging as indispensable tools in explaining how the connections in the network drive organismal phenotypic plasticity. Here, we describe the architectural organization and associated emergent topological properties of gene regulatory networks (GRNs) that describe protein-DNA interactions (PDIs) in several model eukaryotes. By analyzing GRN connectivity, our results show that the anticipated scale-free network architectures are characterized by organism-specific power law scaling exponents. These exponents are independent of the fraction of the GRN experimentally sampled, enabling prediction of properties of the complete GRN for an organism. We further demonstrate that the exponents describe inequalities in transcription factor (TF)-target gene recognition across GRNs. These observations have the important biological implication that they predict the existence of an intrinsic organism-specific trans and/or cis regulatory landscape that constrains GRN topologies. Consequently, architectural GRN organization drives not only phenotypic plasticity within a species, but is also likely implicated in species-specific phenotype.

  7. Hubs of Anticorrelation in High-Resolution Resting-State Functional Connectivity Network Architecture.

    PubMed

    Gopinath, Kaundinya; Krishnamurthy, Venkatagiri; Cabanban, Romeo; Crosson, Bruce A

    2015-06-01

    A major focus of brain research recently has been to map the resting-state functional connectivity (rsFC) network architecture of the normal brain and pathology through functional magnetic resonance imaging. However, the phenomenon of anticorrelations in resting-state signals between different brain regions has not been adequately examined. The preponderance of studies on resting-state fMRI (rsFMRI) have either ignored anticorrelations in rsFC networks or adopted methods in data analysis, which have rendered anticorrelations in rsFC networks uninterpretable. The few studies that have examined anticorrelations in rsFC networks using conventional methods have found anticorrelations to be weak in strength and not very reproducible across subjects. Anticorrelations in rsFC network architecture could reflect mechanisms that subserve a number of important brain processes. In this preliminary study, we examined the properties of anticorrelated rsFC networks by systematically focusing on negative cross-correlation coefficients (CCs) among rsFMRI voxel time series across the brain with graph theory-based network analysis. A number of methods were implemented to enhance the neuronal specificity of resting-state functional connections that yield negative CCs, although at the cost of decreased sensitivity. Hubs of anticorrelation were seen in a number of cortical and subcortical brain regions. Examination of the anticorrelation maps of these hubs indicated that negative CCs in rsFC network architecture highlight a number of regulatory interactions between brain networks and regions, including reciprocal modulations, suppression, inhibition, and neurofeedback.

  8. Sensing and Measurement Architecture for Grid Modernization

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Taft, Jeffrey D.; De Martini, Paul

    2016-02-01

    This paper addresses architecture for grid sensor networks, with primary emphasis on distribution grids. It describes a forward-looking view of sensor network architecture for advanced distribution grids, and discusses key regulatory, financial, and planning issues.

  9. Modular architectures for quantum networks

    NASA Astrophysics Data System (ADS)

    Pirker, A.; Wallnöfer, J.; Dür, W.

    2018-05-01

    We consider the problem of generating multipartite entangled states in a quantum network upon request. We follow a top-down approach, where the required entanglement is initially present in the network in form of network states shared between network devices, and then manipulated in such a way that the desired target state is generated. This minimizes generation times, and allows for network structures that are in principle independent of physical links. We present a modular and flexible architecture, where a multi-layer network consists of devices of varying complexity, including quantum network routers, switches and clients, that share certain resource states. We concentrate on the generation of graph states among clients, which are resources for numerous distributed quantum tasks. We assume minimal functionality for clients, i.e. they do not participate in the complex and distributed generation process of the target state. We present architectures based on shared multipartite entangled Greenberger–Horne–Zeilinger states of different size, and fully connected decorated graph states, respectively. We compare the features of these architectures to an approach that is based on bipartite entanglement, and identify advantages of the multipartite approach in terms of memory requirements and complexity of state manipulation. The architectures can handle parallel requests, and are designed in such a way that the network state can be dynamically extended if new clients or devices join the network. For generation or dynamical extension of the network states, we propose a quantum network configuration protocol, where entanglement purification is used to establish high fidelity states. The latter also allows one to show that the entanglement generated among clients is private, i.e. the network is secure.

  10. Dynamics and design principles of a basic regulatory architecture controlling metabolic pathways.

    PubMed

    Chin, Chen-Shan; Chubukov, Victor; Jolly, Emmitt R; DeRisi, Joe; Li, Hao

    2008-06-17

    The dynamic features of a genetic network's response to environmental fluctuations represent essential functional specifications and thus may constrain the possible choices of network architecture and kinetic parameters. To explore the connection between dynamics and network design, we have analyzed a general regulatory architecture that is commonly found in many metabolic pathways. Such architecture is characterized by a dual control mechanism, with end product feedback inhibition and transcriptional regulation mediated by an intermediate metabolite. As a case study, we measured with high temporal resolution the induction profiles of the enzymes in the leucine biosynthetic pathway in response to leucine depletion, using an automated system for monitoring protein expression levels in single cells. All the genes in the pathway are known to be coregulated by the same transcription factors, but we observed drastically different dynamic responses for enzymes upstream and immediately downstream of the key control point-the intermediate metabolite alpha-isopropylmalate (alphaIPM), which couples metabolic activity to transcriptional regulation. Analysis based on genetic perturbations suggests that the observed dynamics are due to differential regulation by the leucine branch-specific transcription factor Leu3, and that the downstream enzymes are strictly controlled and highly expressed only when alphaIPM is available. These observations allow us to build a simplified mathematical model that accounts for the observed dynamics and can correctly predict the pathway's response to new perturbations. Our model also suggests that transient dynamics and steady state can be separately tuned and that the high induction levels of the downstream enzymes are necessary for fast leucine recovery. It is likely that principles emerging from this work can reveal how gene regulation has evolved to optimize performance in other metabolic pathways with similar architecture.

  11. Quantifying loopy network architectures.

    PubMed

    Katifori, Eleni; Magnasco, Marcelo O

    2012-01-01

    Biology presents many examples of planar distribution and structural networks having dense sets of closed loops. An archetype of this form of network organization is the vasculature of dicotyledonous leaves, which showcases a hierarchically-nested architecture containing closed loops at many different levels. Although a number of approaches have been proposed to measure aspects of the structure of such networks, a robust metric to quantify their hierarchical organization is still lacking. We present an algorithmic framework, the hierarchical loop decomposition, that allows mapping loopy networks to binary trees, preserving in the connectivity of the trees the architecture of the original graph. We apply this framework to investigate computer generated graphs, such as artificial models and optimal distribution networks, as well as natural graphs extracted from digitized images of dicotyledonous leaves and vasculature of rat cerebral neocortex. We calculate various metrics based on the asymmetry, the cumulative size distribution and the Strahler bifurcation ratios of the corresponding trees and discuss the relationship of these quantities to the architectural organization of the original graphs. This algorithmic framework decouples the geometric information (exact location of edges and nodes) from the metric topology (connectivity and edge weight) and it ultimately allows us to perform a quantitative statistical comparison between predictions of theoretical models and naturally occurring loopy graphs.

  12. The Role of Network Architecture in Collagen Mechanics.

    PubMed

    Jansen, Karin A; Licup, Albert J; Sharma, Abhinav; Rens, Robbie; MacKintosh, Fred C; Koenderink, Gijsje H

    2018-06-05

    Collagen forms fibrous networks that reinforce tissues and provide an extracellular matrix for cells. These networks exhibit remarkable strain-stiffening properties that tailor the mechanical functions of tissues and regulate cell behavior. Recent models explain this nonlinear behavior as an intrinsic feature of disordered networks of stiff fibers. Here, we experimentally validate this theoretical framework by measuring the elastic properties of collagen networks over a wide range of self-assembly conditions. We show that the model allows us to quantitatively relate both the linear and nonlinear elastic behavior of collagen networks to their underlying architecture. Specifically, we identify the local coordination number (or connectivity) 〈z〉 as a key architectural parameter that governs the elastic response of collagen. The network elastic response reveals that 〈z〉 decreases from 3.5 to 3 as the polymerization temperature is raised from 26 to 37°C while being weakly dependent on concentration. We furthermore infer a Young's modulus of 1.1 MPa for the collagen fibrils from the linear modulus. Scanning electron microscopy confirms that 〈z〉 is between three and four but is unable to detect the subtle changes in 〈z〉 with polymerization conditions that rheology is sensitive to. Finally, we show that, consistent with the model, the initial stress-stiffening response of collagen networks is controlled by the negative normal stress that builds up under shear. Our work provides a predictive framework to facilitate future studies of the regulatory effect of extracellular matrix molecules on collagen mechanics. Moreover, our findings can aid mechanobiological studies of wound healing, fibrosis, and cancer metastasis, which require collagen matrices with tunable mechanical properties. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  13. The Architectural Organization of Human Stem Cell Cycle Regulatory Machinery

    PubMed Central

    Stein, Gary S.; Stein, Janet L.; Wijnen, Andre van J; Lian, Jane B.; Montecino, Martin; Medina, Ricardo; Kapinas, Kristie; Ghule, Prachi; Grandy, Rodrigo; Zaidi, Sayyed K.; Becker, Klaus A.

    2013-01-01

    Two striking features of human embryonic stem cells that support biological activity are an abbreviated cell cycle and reduced complexity to nuclear organization. The potential implications for rapid proliferation of human embryonic stem cells within the context of sustaining pluripotency, suppressing phenotypic gene expression and linkage to simplicity in the architectural compartmentalization of regulatory machinery in nuclear microenvironments is explored. Characterization of the molecular and architectural commitment steps that license human embryonic stem cells to initiate histone gene expression is providing understanding of the principal regulatory mechanisms that control the G1/S phase transition in primitive pluripotent cells. From both fundamental regulatory and clinical perspectives, further understanding of the pluripotent cell cycle in relation to compartmentalization of regulatory machinery in nuclear microenvironments is relevant to applications of stem cells for regenerative medicine and new dimensions to therapy where traditional drug discovery strategies have been minimally effective. PMID:22394165

  14. Data center networks and network architecture

    NASA Astrophysics Data System (ADS)

    Esaki, Hiroshi

    2014-02-01

    This paper discusses and proposes the architectural framework, which is for data center networks. The data center networks require new technical challenges, and it would be good opportunity to change the functions, which are not need in current and future networks. Based on the observation and consideration on data center networks, this paper proposes; (i) Broadcast-free layer 2 network (i.e., emulation of broadcast at the end-node), (ii) Full-mesh point-to-point pipes, and (iii) IRIDES (Invitation Routing aDvertisement for path Engineering System).

  15. Genomic analysis of regulatory network dynamics reveals large topological changes

    NASA Astrophysics Data System (ADS)

    Luscombe, Nicholas M.; Madan Babu, M.; Yu, Haiyuan; Snyder, Michael; Teichmann, Sarah A.; Gerstein, Mark

    2004-09-01

    Network analysis has been applied widely, providing a unifying language to describe disparate systems ranging from social interactions to power grids. It has recently been used in molecular biology, but so far the resulting networks have only been analysed statically. Here we present the dynamics of a biological network on a genomic scale, by integrating transcriptional regulatory information and gene-expression data for multiple conditions in Saccharomyces cerevisiae. We develop an approach for the statistical analysis of network dynamics, called SANDY, combining well-known global topological measures, local motifs and newly derived statistics. We uncover large changes in underlying network architecture that are unexpected given current viewpoints and random simulations. In response to diverse stimuli, transcription factors alter their interactions to varying degrees, thereby rewiring the network. A few transcription factors serve as permanent hubs, but most act transiently only during certain conditions. By studying sub-network structures, we show that environmental responses facilitate fast signal propagation (for example, with short regulatory cascades), whereas the cell cycle and sporulation direct temporal progression through multiple stages (for example, with highly inter-connected transcription factors). Indeed, to drive the latter processes forward, phase-specific transcription factors inter-regulate serially, and ubiquitously active transcription factors layer above them in a two-tiered hierarchy. We anticipate that many of the concepts presented here-particularly the large-scale topological changes and hub transience-will apply to other biological networks, including complex sub-systems in higher eukaryotes.

  16. A research on the application of software defined networking in satellite network architecture

    NASA Astrophysics Data System (ADS)

    Song, Huan; Chen, Jinqiang; Cao, Suzhi; Cui, Dandan; Li, Tong; Su, Yuxing

    2017-10-01

    Software defined network is a new type of network architecture, which decouples control plane and data plane of traditional network, has the feature of flexible configurations and is a direction of the next generation terrestrial Internet development. Satellite network is an important part of the space-ground integrated information network, while the traditional satellite network has the disadvantages of difficult network topology maintenance and slow configuration. The application of SDN technology in satellite network can solve these problems that traditional satellite network faces. At present, the research on the application of SDN technology in satellite network is still in the stage of preliminary study. In this paper, we start with introducing the SDN technology and satellite network architecture. Then we mainly introduce software defined satellite network architecture, as well as the comparison of different software defined satellite network architecture and satellite network virtualization. Finally, the present research status and development trend of SDN technology in satellite network are analyzed.

  17. Stable architectures for deep neural networks

    NASA Astrophysics Data System (ADS)

    Haber, Eldad; Ruthotto, Lars

    2018-01-01

    Deep neural networks have become invaluable tools for supervised machine learning, e.g. classification of text or images. While often offering superior results over traditional techniques and successfully expressing complicated patterns in data, deep architectures are known to be challenging to design and train such that they generalize well to new data. Critical issues with deep architectures are numerical instabilities in derivative-based learning algorithms commonly called exploding or vanishing gradients. In this paper, we propose new forward propagation techniques inspired by systems of ordinary differential equations (ODE) that overcome this challenge and lead to well-posed learning problems for arbitrarily deep networks. The backbone of our approach is our interpretation of deep learning as a parameter estimation problem of nonlinear dynamical systems. Given this formulation, we analyze stability and well-posedness of deep learning and use this new understanding to develop new network architectures. We relate the exploding and vanishing gradient phenomenon to the stability of the discrete ODE and present several strategies for stabilizing deep learning for very deep networks. While our new architectures restrict the solution space, several numerical experiments show their competitiveness with state-of-the-art networks.

  18. Hybrid architecture for building secure sensor networks

    NASA Astrophysics Data System (ADS)

    Owens, Ken R., Jr.; Watkins, Steve E.

    2012-04-01

    Sensor networks have various communication and security architectural concerns. Three approaches are defined to address these concerns for sensor networks. The first area is the utilization of new computing architectures that leverage embedded virtualization software on the sensor. Deploying a small, embedded virtualization operating system on the sensor nodes that is designed to communicate to low-cost cloud computing infrastructure in the network is the foundation to delivering low-cost, secure sensor networks. The second area focuses on securing the sensor. Sensor security components include developing an identification scheme, and leveraging authentication algorithms and protocols that address security assurance within the physical, communication network, and application layers. This function will primarily be accomplished through encrypting the communication channel and integrating sensor network firewall and intrusion detection/prevention components to the sensor network architecture. Hence, sensor networks will be able to maintain high levels of security. The third area addresses the real-time and high priority nature of the data that sensor networks collect. This function requires that a quality-of-service (QoS) definition and algorithm be developed for delivering the right data at the right time. A hybrid architecture is proposed that combines software and hardware features to handle network traffic with diverse QoS requirements.

  19. An Architecture for SCADA Network Forensics

    NASA Astrophysics Data System (ADS)

    Kilpatrick, Tim; Gonzalez, Jesus; Chandia, Rodrigo; Papa, Mauricio; Shenoi, Sujeet

    Supervisory control and data acquisition (SCADA) systems are widely used in industrial control and automation. Modern SCADA protocols often employ TCP/IP to transport sensor data and control signals. Meanwhile, corporate IT infrastructures are interconnecting with previously isolated SCADA networks. The use of TCP/IP as a carrier protocol and the interconnection of IT and SCADA networks raise serious security issues. This paper describes an architecture for SCADA network forensics. In addition to supporting forensic investigations of SCADA network incidents, the architecture incorporates mechanisms for monitoring process behavior, analyzing trends and optimizing plant performance.

  20. Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks

    PubMed Central

    Yan, Koon-Kiu; Fang, Gang; Bhardwaj, Nitin; Alexander, Roger P.; Gerstein, Mark

    2010-01-01

    The genome has often been called the operating system (OS) for a living organism. A computer OS is described by a regulatory control network termed the call graph, which is analogous to the transcriptional regulatory network in a cell. To apply our firsthand knowledge of the architecture of software systems to understand cellular design principles, we present a comparison between the transcriptional regulatory network of a well-studied bacterium (Escherichia coli) and the call graph of a canonical OS (Linux) in terms of topology and evolution. We show that both networks have a fundamentally hierarchical layout, but there is a key difference: The transcriptional regulatory network possesses a few global regulators at the top and many targets at the bottom; conversely, the call graph has many regulators controlling a small set of generic functions. This top-heavy organization leads to highly overlapping functional modules in the call graph, in contrast to the relatively independent modules in the regulatory network. We further develop a way to measure evolutionary rates comparably between the two networks and explain this difference in terms of network evolution. The process of biological evolution via random mutation and subsequent selection tightly constrains the evolution of regulatory network hubs. The call graph, however, exhibits rapid evolution of its highly connected generic components, made possible by designers’ continual fine-tuning. These findings stem from the design principles of the two systems: robustness for biological systems and cost effectiveness (reuse) for software systems. PMID:20439753

  1. Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks.

    PubMed

    Yan, Koon-Kiu; Fang, Gang; Bhardwaj, Nitin; Alexander, Roger P; Gerstein, Mark

    2010-05-18

    The genome has often been called the operating system (OS) for a living organism. A computer OS is described by a regulatory control network termed the call graph, which is analogous to the transcriptional regulatory network in a cell. To apply our firsthand knowledge of the architecture of software systems to understand cellular design principles, we present a comparison between the transcriptional regulatory network of a well-studied bacterium (Escherichia coli) and the call graph of a canonical OS (Linux) in terms of topology and evolution. We show that both networks have a fundamentally hierarchical layout, but there is a key difference: The transcriptional regulatory network possesses a few global regulators at the top and many targets at the bottom; conversely, the call graph has many regulators controlling a small set of generic functions. This top-heavy organization leads to highly overlapping functional modules in the call graph, in contrast to the relatively independent modules in the regulatory network. We further develop a way to measure evolutionary rates comparably between the two networks and explain this difference in terms of network evolution. The process of biological evolution via random mutation and subsequent selection tightly constrains the evolution of regulatory network hubs. The call graph, however, exhibits rapid evolution of its highly connected generic components, made possible by designers' continual fine-tuning. These findings stem from the design principles of the two systems: robustness for biological systems and cost effectiveness (reuse) for software systems.

  2. Satellite ATM Networks: Architectures and Guidelines Developed

    NASA Technical Reports Server (NTRS)

    vonDeak, Thomas C.; Yegendu, Ferit

    1999-01-01

    An important element of satellite-supported asynchronous transfer mode (ATM) networking will involve support for the routing and rerouting of active connections. Work published under the auspices of the Telecommunications Industry Association (http://www.tiaonline.org), describes basic architectures and routing protocol issues for satellite ATM (SATATM) networks. The architectures and issues identified will serve as a basis for further development of technical specifications for these SATATM networks. Three ATM network architectures for bent pipe satellites and three ATM network architectures for satellites with onboard ATM switches were developed. The architectures differ from one another in terms of required level of mobility, supported data rates, supported terrestrial interfaces, and onboard processing and switching requirements. The documentation addresses low-, middle-, and geosynchronous-Earth-orbit satellite configurations. The satellite environment may require real-time routing to support the mobility of end devices and nodes of the ATM network itself. This requires the network to be able to reroute active circuits in real time. In addition to supporting mobility, rerouting can also be used to (1) optimize network routing, (2) respond to changing quality-of-service requirements, and (3) provide a fault tolerance mechanism. Traffic management and control functions are necessary in ATM to ensure that the quality-of-service requirements associated with each connection are not violated and also to provide flow and congestion control functions. Functions related to traffic management were identified and described. Most of these traffic management functions will be supported by on-ground ATM switches, but in a hybrid terrestrial-satellite ATM network, some of the traffic management functions may have to be supported by the onboard satellite ATM switch. Future work is planned to examine the tradeoffs of placing traffic management functions onboard a satellite as

  3. The NASA Space Communications Data Networking Architecture

    NASA Technical Reports Server (NTRS)

    Israel, David J.; Hooke, Adrian J.; Freeman, Kenneth; Rush, John J.

    2006-01-01

    The NASA Space Communications Architecture Working Group (SCAWG) has recently been developing an integrated agency-wide space communications architecture in order to provide the necessary communication and navigation capabilities to support NASA's new Exploration and Science Programs. A critical element of the space communications architecture is the end-to-end Data Networking Architecture, which must provide a wide range of services required for missions ranging from planetary rovers to human spaceflight, and from sub-orbital space to deep space. Requirements for a higher degree of user autonomy and interoperability between a variety of elements must be accommodated within an architecture that necessarily features minimum operational complexity. The architecture must also be scalable and evolvable to meet mission needs for the next 25 years. This paper will describe the recommended NASA Data Networking Architecture, present some of the rationale for the recommendations, and will illustrate an application of the architecture to example NASA missions.

  4. Intrinsic and task-evoked network architectures of the human brain

    PubMed Central

    Cole, Michael W.; Bassett, Danielle S.; Power, Jonathan D.; Braver, Todd S.; Petersen, Steven E.

    2014-01-01

    Summary Many functional network properties of the human brain have been identified during rest and task states, yet it remains unclear how the two relate. We identified a whole-brain network architecture present across dozens of task states that was highly similar to the resting-state network architecture. The most frequent functional connectivity strengths across tasks closely matched the strengths observed at rest, suggesting this is an “intrinsic”, standard architecture of functional brain organization. Further, a set of small but consistent changes common across tasks suggests the existence of a task-general network architecture distinguishing task states from rest. These results indicate the brain’s functional network architecture during task performance is shaped primarily by an intrinsic network architecture that is also present during rest, and secondarily by evoked task-general and task-specific network changes. This establishes a strong relationship between resting-state functional connectivity and task-evoked functional connectivity – areas of neuroscientific inquiry typically considered separately. PMID:24991964

  5. Scalable Architecture for Multihop Wireless ad Hoc Networks

    NASA Technical Reports Server (NTRS)

    Arabshahi, Payman; Gray, Andrew; Okino, Clayton; Yan, Tsun-Yee

    2004-01-01

    A scalable architecture for wireless digital data and voice communications via ad hoc networks has been proposed. Although the details of the architecture and of its implementation in hardware and software have yet to be developed, the broad outlines of the architecture are fairly clear: This architecture departs from current commercial wireless communication architectures, which are characterized by low effective bandwidth per user and are not well suited to low-cost, rapid scaling in large metropolitan areas. This architecture is inspired by a vision more akin to that of more than two dozen noncommercial community wireless networking organizations established by volunteers in North America and several European countries.

  6. An Evolutionary Optimization Framework for Neural Networks and Neuromorphic Architectures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schuman, Catherine D; Plank, James; Disney, Adam

    2016-01-01

    As new neural network and neuromorphic architectures are being developed, new training methods that operate within the constraints of the new architectures are required. Evolutionary optimization (EO) is a convenient training method for new architectures. In this work, we review a spiking neural network architecture and a neuromorphic architecture, and we describe an EO training framework for these architectures. We present the results of this training framework on four classification data sets and compare those results to other neural network and neuromorphic implementations. We also discuss how this EO framework may be extended to other architectures.

  7. On the contributions of topological features to transcriptional regulatory network robustness

    PubMed Central

    2012-01-01

    Background Because biological networks exhibit a high-degree of robustness, a systemic understanding of their architecture and function requires an appraisal of the network design principles that confer robustness. In this project, we conduct a computational study of the contribution of three degree-based topological properties (transcription factor-target ratio, degree distribution, cross-talk suppression) and their combinations on the robustness of transcriptional regulatory networks. We seek to quantify the relative degree of robustness conferred by each property (and combination) and also to determine the extent to which these properties alone can explain the robustness observed in transcriptional networks. Results To study individual properties and their combinations, we generated synthetic, random networks that retained one or more of the three properties with values derived from either the yeast or E. coli gene regulatory networks. Robustness of these networks were estimated through simulation. Our results indicate that the combination of the three properties we considered explains the majority of the structural robustness observed in the real transcriptional networks. Surprisingly, scale-free degree distribution is, overall, a minor contributor to robustness. Instead, most robustness is gained through topological features that limit the complexity of the overall network and increase the transcription factor subnetwork sparsity. Conclusions Our work demonstrates that (i) different types of robustness are implemented by different topological aspects of the network and (ii) size and sparsity of the transcription factor subnetwork play an important role for robustness induction. Our results are conserved across yeast and E Coli, which suggests that the design principles examined are present within an array of living systems. PMID:23194062

  8. ARACNe-based inference, using curated microarray data, of Arabidopsis thaliana root transcriptional regulatory networks

    PubMed Central

    2014-01-01

    Background Uncovering the complex transcriptional regulatory networks (TRNs) that underlie plant and animal development remains a challenge. However, a vast amount of data from public microarray experiments is available, which can be subject to inference algorithms in order to recover reliable TRN architectures. Results In this study we present a simple bioinformatics methodology that uses public, carefully curated microarray data and the mutual information algorithm ARACNe in order to obtain a database of transcriptional interactions. We used data from Arabidopsis thaliana root samples to show that the transcriptional regulatory networks derived from this database successfully recover previously identified root transcriptional modules and to propose new transcription factors for the SHORT ROOT/SCARECROW and PLETHORA pathways. We further show that these networks are a powerful tool to integrate and analyze high-throughput expression data, as exemplified by our analysis of a SHORT ROOT induction time-course microarray dataset, and are a reliable source for the prediction of novel root gene functions. In particular, we used our database to predict novel genes involved in root secondary cell-wall synthesis and identified the MADS-box TF XAL1/AGL12 as an unexpected participant in this process. Conclusions This study demonstrates that network inference using carefully curated microarray data yields reliable TRN architectures. In contrast to previous efforts to obtain root TRNs, that have focused on particular functional modules or tissues, our root transcriptional interactions provide an overview of the transcriptional pathways present in Arabidopsis thaliana roots and will likely yield a plethora of novel hypotheses to be tested experimentally. PMID:24739361

  9. GREAT: a web portal for Genome Regulatory Architecture Tools

    PubMed Central

    Bouyioukos, Costas; Bucchini, François; Elati, Mohamed; Képès, François

    2016-01-01

    GREAT (Genome REgulatory Architecture Tools) is a novel web portal for tools designed to generate user-friendly and biologically useful analysis of genome architecture and regulation. The online tools of GREAT are freely accessible and compatible with essentially any operating system which runs a modern browser. GREAT is based on the analysis of genome layout -defined as the respective positioning of co-functional genes- and its relation with chromosome architecture and gene expression. GREAT tools allow users to systematically detect regular patterns along co-functional genomic features in an automatic way consisting of three individual steps and respective interactive visualizations. In addition to the complete analysis of regularities, GREAT tools enable the use of periodicity and position information for improving the prediction of transcription factor binding sites using a multi-view machine learning approach. The outcome of this integrative approach features a multivariate analysis of the interplay between the location of a gene and its regulatory sequence. GREAT results are plotted in web interactive graphs and are available for download either as individual plots, self-contained interactive pages or as machine readable tables for downstream analysis. The GREAT portal can be reached at the following URL https://absynth.issb.genopole.fr/GREAT and each individual GREAT tool is available for downloading. PMID:27151196

  10. Integrated Network Architecture for NASA's Orion Missions

    NASA Technical Reports Server (NTRS)

    Bhasin, Kul B.; Hayden, Jeffrey L.; Sartwell, Thomas; Miller, Ronald A.; Hudiburg, John J.

    2008-01-01

    NASA is planning a series of short and long duration human and robotic missions to explore the Moon and then Mars. The series of missions will begin with a new crew exploration vehicle (called Orion) that will initially provide crew exchange and cargo supply support to the International Space Station (ISS) and then become a human conveyance for travel to the Moon. The Orion vehicle will be mounted atop the Ares I launch vehicle for a series of pre-launch tests and then launched and inserted into low Earth orbit (LEO) for crew exchange missions to the ISS. The Orion and Ares I comprise the initial vehicles in the Constellation system of systems that later includes Ares V, Earth departure stage, lunar lander, and other lunar surface systems for the lunar exploration missions. These key systems will enable the lunar surface exploration missions to be initiated in 2018. The complexity of the Constellation system of systems and missions will require a communication and navigation infrastructure to provide low and high rate forward and return communication services, tracking services, and ground network services. The infrastructure must provide robust, reliable, safe, sustainable, and autonomous operations at minimum cost while maximizing the exploration capabilities and science return. The infrastructure will be based on a network of networks architecture that will integrate NASA legacy communication, modified elements, and navigation systems. New networks will be added to extend communication, navigation, and timing services for the Moon missions. Internet protocol (IP) and network management systems within the networks will enable interoperability throughout the Constellation system of systems. An integrated network architecture has developed based on the emerging Constellation requirements for Orion missions. The architecture, as presented in this paper, addresses the early Orion missions to the ISS with communication, navigation, and network services over five

  11. Evolutionary rewiring of bacterial regulatory networks

    PubMed Central

    Taylor, Tiffany B.; Mulley, Geraldine; McGuffin, Liam J.; Johnson, Louise J.; Brockhurst, Michael A.; Arseneault, Tanya; Silby, Mark W.; Jackson, Robert W.

    2015-01-01

    Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks - homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. In our recent study [Taylor, et al. Science (2015), 347(6225)] we find that mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but that such mutations come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs. PMID:28357301

  12. Predicate calculus for an architecture of multiple neural networks

    NASA Astrophysics Data System (ADS)

    Consoli, Robert H.

    1990-08-01

    Future projects with neural networks will require multiple individual network components. Current efforts along these lines are ad hoc. This paper relates the neural network to a classical device and derives a multi-part architecture from that model. Further it provides a Predicate Calculus variant for describing the location and nature of the trainings and suggests Resolution Refutation as a method for determining the performance of the system as well as the location of needed trainings for specific proofs. 2. THE NEURAL NETWORK AND A CLASSICAL DEVICE Recently investigators have been making reports about architectures of multiple neural networksL234. These efforts are appearing at an early stage in neural network investigations they are characterized by architectures suggested directly by the problem space. Touretzky and Hinton suggest an architecture for processing logical statements1 the design of this architecture arises from the syntax of a restricted class of logical expressions and exhibits syntactic limitations. In similar fashion a multiple neural netword arises out of a control problem2 from the sequence learning problem3 and from the domain of machine learning. 4 But a general theory of multiple neural devices is missing. More general attempts to relate single or multiple neural networks to classical computing devices are not common although an attempt is made to relate single neural devices to a Turing machines and Sun et a!. develop a multiple neural architecture that performs pattern classification.

  13. NASA Integrated Network Monitor and Control Software Architecture

    NASA Technical Reports Server (NTRS)

    Shames, Peter; Anderson, Michael; Kowal, Steve; Levesque, Michael; Sindiy, Oleg; Donahue, Kenneth; Barnes, Patrick

    2012-01-01

    The National Aeronautics and Space Administration (NASA) Space Communications and Navigation office (SCaN) has commissioned a series of trade studies to define a new architecture intended to integrate the three existing networks that it operates, the Deep Space Network (DSN), Space Network (SN), and Near Earth Network (NEN), into one integrated network that offers users a set of common, standardized, services and interfaces. The integrated monitor and control architecture utilizes common software and common operator interfaces that can be deployed at all three network elements. This software uses state-of-the-art concepts such as a pool of re-programmable equipment that acts like a configurable software radio, distributed hierarchical control, and centralized management of the whole SCaN integrated network. For this trade space study a model-based approach using SysML was adopted to describe and analyze several possible options for the integrated network monitor and control architecture. This model was used to refine the design and to drive the costing of the four different software options. This trade study modeled the three existing self standing network elements at point of departure, and then described how to integrate them using variations of new and existing monitor and control system components for the different proposed deployments under consideration. This paper will describe the trade space explored, the selected system architecture, the modeling and trade study methods, and some observations on useful approaches to implementing such model based trade space representation and analysis.

  14. Security Shift in Future Network Architectures

    DTIC Science & Technology

    2010-11-01

    RTO-MP-IST-091 2 - 1 Security Shift in Future Network Architectures Tim Hartog, M.Sc Information Security Dept. TNO Information and...current practice military communication infrastructures are deployed as stand-alone networked information systems. Network -Enabled Capabilities (NEC) and...information architects and security specialists about the separation of network and information security, the consequences of this shift and our view

  15. Modeling gene regulatory network motifs using statecharts

    PubMed Central

    2012-01-01

    Background Gene regulatory networks are widely used by biologists to describe the interactions among genes, proteins and other components at the intra-cellular level. Recently, a great effort has been devoted to give gene regulatory networks a formal semantics based on existing computational frameworks. For this purpose, we consider Statecharts, which are a modular, hierarchical and executable formal model widely used to represent software systems. We use Statecharts for modeling small and recurring patterns of interactions in gene regulatory networks, called motifs. Results We present an improved method for modeling gene regulatory network motifs using Statecharts and we describe the successful modeling of several motifs, including those which could not be modeled or whose models could not be distinguished using the method of a previous proposal. We model motifs in an easy and intuitive way by taking advantage of the visual features of Statecharts. Our modeling approach is able to simulate some interesting temporal properties of gene regulatory network motifs: the delay in the activation and the deactivation of the "output" gene in the coherent type-1 feedforward loop, the pulse in the incoherent type-1 feedforward loop, the bistability nature of double positive and double negative feedback loops, the oscillatory behavior of the negative feedback loop, and the "lock-in" effect of positive autoregulation. Conclusions We present a Statecharts-based approach for the modeling of gene regulatory network motifs in biological systems. The basic motifs used to build more complex networks (that is, simple regulation, reciprocal regulation, feedback loop, feedforward loop, and autoregulation) can be faithfully described and their temporal dynamics can be analyzed. PMID:22536967

  16. The Caenorhabditis elegans vulva: A post-embryonic gene regulatory network controlling organogenesis

    PubMed Central

    Ririe, Ted O.; Fernandes, Jolene S.; Sternberg, Paul W.

    2008-01-01

    The Caenorhabditis elegans vulva is an elegant model for dissecting a gene regulatory network (GRN) that directs postembryonic organogenesis. The mature vulva comprises seven cell types (vulA, vulB1, vulB2, vulC, vulD, vulE, and vulF), each with its own unique pattern of spatial and temporal gene expression. The mechanisms that specify these cell types in a precise spatial pattern are not well understood. Using reverse genetic screens, we identified novel components of the vulval GRN, including nhr-113 in vulA. Several transcription factors (lin-11, lin-29, cog-1, egl-38, and nhr-67) interact with each other and act in concert to regulate target gene expression in the diverse vulval cell types. For example, egl-38 (Pax2/5/8) stabilizes the vulF fate by positively regulating vulF characteristics and by inhibiting characteristics associated with the neighboring vulE cells. nhr-67 and egl-38 regulate cog-1, helping restrict its expression to vulE. Computational approaches have been successfully used to identify functional cis-regulatory motifs in the zmp-1 (zinc metalloproteinase) promoter. These results provide an overview of the regulatory network architecture for each vulval cell type. PMID:19104047

  17. Determining Regulatory Networks Governing the Differentiation of Embryonic Stem Cells to Pancreatic Lineage

    NASA Astrophysics Data System (ADS)

    Banerjee, Ipsita

    2009-03-01

    Knowledge of pathways governing cellular differentiation to specific phenotype will enable generation of desired cell fates by careful alteration of the governing network by adequate manipulation of the cellular environment. With this aim, we have developed a novel method to reconstruct the underlying regulatory architecture of a differentiating cell population from discrete temporal gene expression data. We utilize an inherent feature of biological networks, that of sparsity, in formulating the network reconstruction problem as a bi-level mixed-integer programming problem. The formulation optimizes the network topology at the upper level and the network connectivity strength at the lower level. The method is first validated by in-silico data, before applying it to the complex system of embryonic stem (ES) cell differentiation. This formulation enables efficient identification of the underlying network topology which could accurately predict steps necessary for directing differentiation to subsequent stages. Concurrent experimental verification demonstrated excellent agreement with model prediction.

  18. GREAT: a web portal for Genome Regulatory Architecture Tools.

    PubMed

    Bouyioukos, Costas; Bucchini, François; Elati, Mohamed; Képès, François

    2016-07-08

    GREAT (Genome REgulatory Architecture Tools) is a novel web portal for tools designed to generate user-friendly and biologically useful analysis of genome architecture and regulation. The online tools of GREAT are freely accessible and compatible with essentially any operating system which runs a modern browser. GREAT is based on the analysis of genome layout -defined as the respective positioning of co-functional genes- and its relation with chromosome architecture and gene expression. GREAT tools allow users to systematically detect regular patterns along co-functional genomic features in an automatic way consisting of three individual steps and respective interactive visualizations. In addition to the complete analysis of regularities, GREAT tools enable the use of periodicity and position information for improving the prediction of transcription factor binding sites using a multi-view machine learning approach. The outcome of this integrative approach features a multivariate analysis of the interplay between the location of a gene and its regulatory sequence. GREAT results are plotted in web interactive graphs and are available for download either as individual plots, self-contained interactive pages or as machine readable tables for downstream analysis. The GREAT portal can be reached at the following URL https://absynth.issb.genopole.fr/GREAT and each individual GREAT tool is available for downloading. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. On-board processing satellite network architecture and control study

    NASA Technical Reports Server (NTRS)

    Campanella, S. Joseph; Pontano, Benjamin A.; Chalmers, Harvey

    1987-01-01

    The market for telecommunications services needs to be segmented into user classes having similar transmission requirements and hence similar network architectures. Use of the following transmission architecture was considered: satellite switched TDMA; TDMA up, TDM down; scanning (hopping) beam TDMA; FDMA up, TDM down; satellite switched MF/TDMA; and switching Hub earth stations with double hop transmission. A candidate network architecture will be selected that: comprises multiple access subnetworks optimized for each user; interconnects the subnetworks by means of a baseband processor; and optimizes the marriage of interconnection and access techniques. An overall network control architecture will be provided that will serve the needs of the baseband and satellite switched RF interconnected subnetworks. The results of the studies shall be used to identify elements of network architecture and control that require the greatest degree of technology development to realize an operational system. This will be specified in terms of: requirements of the enabling technology; difference from the current available technology; and estimate of the development requirements needed to achieve an operational system. The results obtained for each of these tasks are presented.

  20. Software Defined Networking (SDN) controlled all optical switching networks with multi-dimensional switching architecture

    NASA Astrophysics Data System (ADS)

    Zhao, Yongli; Ji, Yuefeng; Zhang, Jie; Li, Hui; Xiong, Qianjin; Qiu, Shaofeng

    2014-08-01

    Ultrahigh throughout capacity requirement is challenging the current optical switching nodes with the fast development of data center networks. Pbit/s level all optical switching networks need to be deployed soon, which will cause the high complexity of node architecture. How to control the future network and node equipment together will become a new problem. An enhanced Software Defined Networking (eSDN) control architecture is proposed in the paper, which consists of Provider NOX (P-NOX) and Node NOX (N-NOX). With the cooperation of P-NOX and N-NOX, the flexible control of the entire network can be achieved. All optical switching network testbed has been experimentally demonstrated with efficient control of enhanced Software Defined Networking (eSDN). Pbit/s level all optical switching nodes in the testbed are implemented based on multi-dimensional switching architecture, i.e. multi-level and multi-planar. Due to the space and cost limitation, each optical switching node is only equipped with four input line boxes and four output line boxes respectively. Experimental results are given to verify the performance of our proposed control and switching architecture.

  1. Recurrent rewiring and emergence of RNA regulatory networks.

    PubMed

    Wilinski, Daniel; Buter, Natascha; Klocko, Andrew D; Lapointe, Christopher P; Selker, Eric U; Gasch, Audrey P; Wickens, Marvin

    2017-04-04

    Alterations in regulatory networks contribute to evolutionary change. Transcriptional networks are reconfigured by changes in the binding specificity of transcription factors and their cognate sites. The evolution of RNA-protein regulatory networks is far less understood. The PUF (Pumilio and FBF) family of RNA regulatory proteins controls the translation, stability, and movements of hundreds of mRNAs in a single species. We probe the evolution of PUF-RNA networks by direct identification of the mRNAs bound to PUF proteins in budding and filamentous fungi and by computational analyses of orthologous RNAs from 62 fungal species. Our findings reveal that PUF proteins gain and lose mRNAs with related and emergent biological functions during evolution. We demonstrate at least two independent rewiring events for PUF3 orthologs, independent but convergent evolution of PUF4/5 binding specificity and the rewiring of the PUF4/5 regulons in different fungal lineages. These findings demonstrate plasticity in RNA regulatory networks and suggest ways in which their rewiring occurs.

  2. RegNetwork: an integrated database of transcriptional and post-transcriptional regulatory networks in human and mouse

    PubMed Central

    Liu, Zhi-Ping; Wu, Canglin; Miao, Hongyu; Wu, Hulin

    2015-01-01

    Transcriptional and post-transcriptional regulation of gene expression is of fundamental importance to numerous biological processes. Nowadays, an increasing amount of gene regulatory relationships have been documented in various databases and literature. However, to more efficiently exploit such knowledge for biomedical research and applications, it is necessary to construct a genome-wide regulatory network database to integrate the information on gene regulatory relationships that are widely scattered in many different places. Therefore, in this work, we build a knowledge-based database, named ‘RegNetwork’, of gene regulatory networks for human and mouse by collecting and integrating the documented regulatory interactions among transcription factors (TFs), microRNAs (miRNAs) and target genes from 25 selected databases. Moreover, we also inferred and incorporated potential regulatory relationships based on transcription factor binding site (TFBS) motifs into RegNetwork. As a result, RegNetwork contains a comprehensive set of experimentally observed or predicted transcriptional and post-transcriptional regulatory relationships, and the database framework is flexibly designed for potential extensions to include gene regulatory networks for other organisms in the future. Based on RegNetwork, we characterized the statistical and topological properties of genome-wide regulatory networks for human and mouse, we also extracted and interpreted simple yet important network motifs that involve the interplays between TF-miRNA and their targets. In summary, RegNetwork provides an integrated resource on the prior information for gene regulatory relationships, and it enables us to further investigate context-specific transcriptional and post-transcriptional regulatory interactions based on domain-specific experimental data. Database URL: http://www.regnetworkweb.org PMID:26424082

  3. ReNE: A Cytoscape Plugin for Regulatory Network Enhancement

    PubMed Central

    Politano, Gianfranco; Benso, Alfredo; Savino, Alessandro; Di Carlo, Stefano

    2014-01-01

    One of the biggest challenges in the study of biological regulatory mechanisms is the integration, americanmodeling, and analysis of the complex interactions which take place in biological networks. Despite post transcriptional regulatory elements (i.e., miRNAs) are widely investigated in current research, their usage and visualization in biological networks is very limited. Regulatory networks are commonly limited to gene entities. To integrate networks with post transcriptional regulatory data, researchers are therefore forced to manually resort to specific third party databases. In this context, we introduce ReNE, a Cytoscape 3.x plugin designed to automatically enrich a standard gene-based regulatory network with more detailed transcriptional, post transcriptional, and translational data, resulting in an enhanced network that more precisely models the actual biological regulatory mechanisms. ReNE can automatically import a network layout from the Reactome or KEGG repositories, or work with custom pathways described using a standard OWL/XML data format that the Cytoscape import procedure accepts. Moreover, ReNE allows researchers to merge multiple pathways coming from different sources. The merged network structure is normalized to guarantee a consistent and uniform description of the network nodes and edges and to enrich all integrated data with additional annotations retrieved from genome-wide databases like NCBI, thus producing a pathway fully manageable through the Cytoscape environment. The normalized network is then analyzed to include missing transcription factors, miRNAs, and proteins. The resulting enhanced network is still a fully functional Cytoscape network where each regulatory element (transcription factor, miRNA, gene, protein) and regulatory mechanism (up-regulation/down-regulation) is clearly visually identifiable, thus enabling a better visual understanding of its role and the effect in the network behavior. The enhanced network produced by Re

  4. Stochasticity versus determinism: consequences for realistic gene regulatory network modelling and evolution.

    PubMed

    Jenkins, Dafyd J; Stekel, Dov J

    2010-02-01

    Gene regulation is one important mechanism in producing observed phenotypes and heterogeneity. Consequently, the study of gene regulatory network (GRN) architecture, function and evolution now forms a major part of modern biology. However, it is impossible to experimentally observe the evolution of GRNs on the timescales on which living species evolve. In silico evolution provides an approach to studying the long-term evolution of GRNs, but many models have either considered network architecture from non-adaptive evolution, or evolution to non-biological objectives. Here, we address a number of important modelling and biological questions about the evolution of GRNs to the realistic goal of biomass production. Can different commonly used simulation paradigms, in particular deterministic and stochastic Boolean networks, with and without basal gene expression, be used to compare adaptive with non-adaptive evolution of GRNs? Are these paradigms together with this goal sufficient to generate a range of solutions? Will the interaction between a biological goal and evolutionary dynamics produce trade-offs between growth and mutational robustness? We show that stochastic basal gene expression forces shrinkage of genomes due to energetic constraints and is a prerequisite for some solutions. In systems that are able to evolve rates of basal expression, two optima, one with and one without basal expression, are observed. Simulation paradigms without basal expression generate bloated networks with non-functional elements. Further, a range of functional solutions was observed under identical conditions only in stochastic networks. Moreover, there are trade-offs between efficiency and yield, indicating an inherent intertwining of fitness and evolutionary dynamics.

  5. Enhancing gene regulatory network inference through data integration with markov random fields

    DOE PAGES

    Banf, Michael; Rhee, Seung Y.

    2017-02-01

    Here, a gene regulatory network links transcription factors to their target genes and represents a map of transcriptional regulation. Much progress has been made in deciphering gene regulatory networks computationally. However, gene regulatory network inference for most eukaryotic organisms remain challenging. To improve the accuracy of gene regulatory network inference and facilitate candidate selection for experimentation, we developed an algorithm called GRACE (Gene Regulatory network inference ACcuracy Enhancement). GRACE exploits biological a priori and heterogeneous data integration to generate high- confidence network predictions for eukaryotic organisms using Markov Random Fields in a semi-supervised fashion. GRACE uses a novel optimization schememore » to integrate regulatory evidence and biological relevance. It is particularly suited for model learning with sparse regulatory gold standard data. We show GRACE’s potential to produce high confidence regulatory networks compared to state of the art approaches using Drosophila melanogaster and Arabidopsis thaliana data. In an A. thaliana developmental gene regulatory network, GRACE recovers cell cycle related regulatory mechanisms and further hypothesizes several novel regulatory links, including a putative control mechanism of vascular structure formation due to modifications in cell proliferation.« less

  6. Enhancing gene regulatory network inference through data integration with markov random fields

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Banf, Michael; Rhee, Seung Y.

    Here, a gene regulatory network links transcription factors to their target genes and represents a map of transcriptional regulation. Much progress has been made in deciphering gene regulatory networks computationally. However, gene regulatory network inference for most eukaryotic organisms remain challenging. To improve the accuracy of gene regulatory network inference and facilitate candidate selection for experimentation, we developed an algorithm called GRACE (Gene Regulatory network inference ACcuracy Enhancement). GRACE exploits biological a priori and heterogeneous data integration to generate high- confidence network predictions for eukaryotic organisms using Markov Random Fields in a semi-supervised fashion. GRACE uses a novel optimization schememore » to integrate regulatory evidence and biological relevance. It is particularly suited for model learning with sparse regulatory gold standard data. We show GRACE’s potential to produce high confidence regulatory networks compared to state of the art approaches using Drosophila melanogaster and Arabidopsis thaliana data. In an A. thaliana developmental gene regulatory network, GRACE recovers cell cycle related regulatory mechanisms and further hypothesizes several novel regulatory links, including a putative control mechanism of vascular structure formation due to modifications in cell proliferation.« less

  7. Space Mobile Network: A Near Earth Communication and Navigation Architecture

    NASA Technical Reports Server (NTRS)

    Israel, Dave J.; Heckler, Greg; Menrad, Robert J.

    2016-01-01

    This paper describes a Space Mobile Network architecture, the result of a recently completed NASA study exploring architectural concepts to produce a vision for the future Near Earth communications and navigation systems. The Space Mobile Network (SMN) incorporates technologies, such as Disruption Tolerant Networking (DTN) and optical communications, and new operations concepts, such as User Initiated Services, to provide user services analogous to a terrestrial smartphone user. The paper will describe the SMN Architecture, envisioned future operations concepts, opportunities for industry and international collaboration and interoperability, and technology development areas and goals.

  8. Regulatory Architecture of Gene Expression Variation in the Threespine Stickleback Gasterosteus aculeatus

    PubMed Central

    Pritchard, Victoria L.; Viitaniemi, Heidi M.; McCairns, R. J. Scott; Merilä, Juha; Nikinmaa, Mikko; Primmer, Craig R.; Leder, Erica H.

    2016-01-01

    Much adaptive evolutionary change is underlain by mutational variation in regions of the genome that regulate gene expression rather than in the coding regions of the genes themselves. An understanding of the role of gene expression variation in facilitating local adaptation will be aided by an understanding of underlying regulatory networks. Here, we characterize the genetic architecture of gene expression variation in the threespine stickleback (Gasterosteus aculeatus), an important model in the study of adaptive evolution. We collected transcriptomic and genomic data from 60 half-sib families using an expression microarray and genotyping-by-sequencing, and located expression quantitative trait loci (eQTL) underlying the variation in gene expression in liver tissue using an interval mapping approach. We identified eQTL for several thousand expression traits. Expression was influenced by polymorphism in both cis- and trans-regulatory regions. Trans-eQTL clustered into hotspots. We did not identify master transcriptional regulators in hotspot locations: rather, the presence of hotspots may be driven by complex interactions between multiple transcription factors. One observed hotspot colocated with a QTL recently found to underlie salinity tolerance in the threespine stickleback. However, most other observed hotspots did not colocate with regions of the genome known to be involved in adaptive divergence between marine and freshwater habitats. PMID:27836907

  9. Network perturbation by recurrent regulatory variants in cancer

    PubMed Central

    Cho, Ara; Lee, Insuk; Choi, Jung Kyoon

    2017-01-01

    Cancer driving genes have been identified as recurrently affected by variants that alter protein-coding sequences. However, a majority of cancer variants arise in noncoding regions, and some of them are thought to play a critical role through transcriptional perturbation. Here we identified putative transcriptional driver genes based on combinatorial variant recurrence in cis-regulatory regions. The identified genes showed high connectivity in the cancer type-specific transcription regulatory network, with high outdegree and many downstream genes, highlighting their causative role during tumorigenesis. In the protein interactome, the identified transcriptional drivers were not as highly connected as coding driver genes but appeared to form a network module centered on the coding drivers. The coding and regulatory variants associated via these interactions between the coding and transcriptional drivers showed exclusive and complementary occurrence patterns across tumor samples. Transcriptional cancer drivers may act through an extensive perturbation of the regulatory network and by altering protein network modules through interactions with coding driver genes. PMID:28333928

  10. Architecture for networked electronic patient record systems.

    PubMed

    Takeda, H; Matsumura, Y; Kuwata, S; Nakano, H; Sakamoto, N; Yamamoto, R

    2000-11-01

    There have been two major approaches to the development of networked electronic patient record (EPR) architecture. One uses object-oriented methodologies for constructing the model, which include the GEHR project, Synapses, HL7 RIM and so on. The second approach uses document-oriented methodologies, as applied in examples of HL7 PRA. It is practically beneficial to take the advantages of both approaches and to add solution technologies for network security such as PKI. In recognition of the similarity with electronic commerce, a certificate authority as a trusted third party will be organised for establishing networked EPR system. This paper describes a Japanese functional model that has been developed, and proposes a document-object-oriented architecture, which is-compared with other existing models.

  11. Architectures of fiber optic network in telecommunications

    NASA Astrophysics Data System (ADS)

    Vasile, Irina B.; Vasile, Alexandru; Filip, Luminita E.

    2005-08-01

    The operators of telecommunications have targeted their efforts towards realizing applications using broad band fiber optics systems in the access network. Thus, a new concept related to the implementation of fiber optic transmission systems, named FITL (Fiber In The Loop) has appeared. The fiber optic transmission systems have been extensively used for realizing the transport and intercommunication of the public telecommunication network, as well as for assuring the access to the telecommunication systems of the great corporations. Still, the segment of the residential users and small corporations did not benefit on large scale of this technology implementation. For the purpose of defining fiber optic applications, more types of architectures were conceived, like: bus, ring, star, tree. In the case of tree-like networks passive splitters (that"s where the name of PON comes from - Passive Optical Network-), which reduce significantly the costs of the fiber optic access, by separating the costs of the optical electronic components. That's why the passive fiber optics architectures (PON represent a viable solution for realizing the access at the user's loop. The main types of fiber optics architectures included in this work are: FTTC (Fiber To The Curb); FTTB (Fiber To The Building); FTTH (Fiber To The Home).

  12. On-board processing satellite network architectures for broadband ISDN

    NASA Technical Reports Server (NTRS)

    Inukai, Thomas; Faris, Faris; Shyy, Dong-Jye

    1992-01-01

    Onboard baseband processing architectures for future satellite broadband integrated services digital networks (B-ISDN's) are addressed. To assess the feasibility of implementing satellite B-ISDN services, critical design issues, such as B-ISDN traffic characteristics, transmission link design, and a trade-off between onboard circuit and fast packet switching, are analyzed. Examples of the two types of switching mechanisms and potential onboard network control functions are presented. A sample network architecture is also included to illustrate a potential onboard processing system.

  13. Networks: A Review of Their Technology, Architecture, and Implementation.

    ERIC Educational Resources Information Center

    Learn, Larry L.

    1988-01-01

    This overview of network-related technologies covers network elements, analog and digital signals, transmission media and their characteristics, equipment certification, multiplexing, network types, access technologies, network architectures local-area network technologies and attributes, protocols, internetworking, fiber optics versus satellites,…

  14. Integrated Module and Gene-Specific Regulatory Inference Implicates Upstream Signaling Networks

    PubMed Central

    Roy, Sushmita; Lagree, Stephen; Hou, Zhonggang; Thomson, James A.; Stewart, Ron; Gasch, Audrey P.

    2013-01-01

    Regulatory networks that control gene expression are important in diverse biological contexts including stress response and development. Each gene's regulatory program is determined by module-level regulation (e.g. co-regulation via the same signaling system), as well as gene-specific determinants that can fine-tune expression. We present a novel approach, Modular regulatory network learning with per gene information (MERLIN), that infers regulatory programs for individual genes while probabilistically constraining these programs to reveal module-level organization of regulatory networks. Using edge-, regulator- and module-based comparisons of simulated networks of known ground truth, we find MERLIN reconstructs regulatory programs of individual genes as well or better than existing approaches of network reconstruction, while additionally identifying modular organization of the regulatory networks. We use MERLIN to dissect global transcriptional behavior in two biological contexts: yeast stress response and human embryonic stem cell differentiation. Regulatory modules inferred by MERLIN capture co-regulatory relationships between signaling proteins and downstream transcription factors thereby revealing the upstream signaling systems controlling transcriptional responses. The inferred networks are enriched for regulators with genetic or physical interactions, supporting the inference, and identify modules of functionally related genes bound by the same transcriptional regulators. Our method combines the strengths of per-gene and per-module methods to reveal new insights into transcriptional regulation in stress and development. PMID:24146602

  15. Comparative analysis of gene regulatory networks: from network reconstruction to evolution.

    PubMed

    Thompson, Dawn; Regev, Aviv; Roy, Sushmita

    2015-01-01

    Regulation of gene expression is central to many biological processes. Although reconstruction of regulatory circuits from genomic data alone is therefore desirable, this remains a major computational challenge. Comparative approaches that examine the conservation and divergence of circuits and their components across strains and species can help reconstruct circuits as well as provide insights into the evolution of gene regulatory processes and their adaptive contribution. In recent years, advances in genomic and computational tools have led to a wealth of methods for such analysis at the sequence, expression, pathway, module, and entire network level. Here, we review computational methods developed to study transcriptional regulatory networks using comparative genomics, from sequence to functional data. We highlight how these methods use evolutionary conservation and divergence to reliably detect regulatory components as well as estimate the extent and rate of divergence. Finally, we discuss the promise and open challenges in linking regulatory divergence to phenotypic divergence and adaptation.

  16. Reconstructing directed gene regulatory network by only gene expression data.

    PubMed

    Zhang, Lu; Feng, Xi Kang; Ng, Yen Kaow; Li, Shuai Cheng

    2016-08-18

    Accurately identifying gene regulatory network is an important task in understanding in vivo biological activities. The inference of such networks is often accomplished through the use of gene expression data. Many methods have been developed to evaluate gene expression dependencies between transcription factor and its target genes, and some methods also eliminate transitive interactions. The regulatory (or edge) direction is undetermined if the target gene is also a transcription factor. Some methods predict the regulatory directions in the gene regulatory networks by locating the eQTL single nucleotide polymorphism, or by observing the gene expression changes when knocking out/down the candidate transcript factors; regrettably, these additional data are usually unavailable, especially for the samples deriving from human tissues. In this study, we propose the Context Based Dependency Network (CBDN), a method that is able to infer gene regulatory networks with the regulatory directions from gene expression data only. To determine the regulatory direction, CBDN computes the influence of source to target by evaluating the magnitude changes of expression dependencies between the target gene and the others with conditioning on the source gene. CBDN extends the data processing inequality by involving the dependency direction to distinguish between direct and transitive relationship between genes. We also define two types of important regulators which can influence a majority of the genes in the network directly or indirectly. CBDN can detect both of these two types of important regulators by averaging the influence functions of candidate regulator to the other genes. In our experiments with simulated and real data, even with the regulatory direction taken into account, CBDN outperforms the state-of-the-art approaches for inferring gene regulatory network. CBDN identifies the important regulators in the predicted network: 1. TYROBP influences a batch of genes that are

  17. Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

    PubMed

    Gonçalves, Joana P; Aires, Ricardo S; Francisco, Alexandre P; Madeira, Sara C

    2012-01-01

    Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched

  18. Regulatory Snapshots: Integrative Mining of Regulatory Modules from Expression Time Series and Regulatory Networks

    PubMed Central

    Gonçalves, Joana P.; Aires, Ricardo S.; Francisco, Alexandre P.; Madeira, Sara C.

    2012-01-01

    Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched

  19. Inference of developmental gene regulatory networks beyond classical model systems: new approaches in the post-genomic era.

    PubMed

    Fernandez-Valverde, Selene L; Aguilera, Felipe; Ramos-Díaz, René Alexander

    2018-06-18

    The advent of high-throughput sequencing technologies has revolutionized the way we understand the transformation of genetic information into morphological traits. Elucidating the network of interactions between genes that govern cell differentiation through development is one of the core challenges in genome research. These networks are known as developmental gene regulatory networks (dGRNs) and consist largely of the functional linkage between developmental control genes, cis-regulatory modules and differentiation genes, which generate spatially and temporally refined patterns of gene expression. Over the last 20 years, great advances have been made in determining these gene interactions mainly in classical model systems, including human, mouse, sea urchin, fruit fly, and worm. This has brought about a radical transformation in the fields of developmental biology and evolutionary biology, allowing the generation of high-resolution gene regulatory maps to analyse cell differentiation during animal development. Such maps have enabled the identification of gene regulatory circuits and have led to the development of network inference methods that can recapitulate the differentiation of specific cell-types or developmental stages. In contrast, dGRN research in non-classical model systems has been limited to the identification of developmental control genes via the candidate gene approach and the characterization of their spatiotemporal expression patterns, as well as to the discovery of cis-regulatory modules via patterns of sequence conservation and/or predicted transcription-factor binding sites. However, thanks to the continuous advances in high-throughput sequencing technologies, this scenario is rapidly changing. Here, we give a historical overview on the architecture and elucidation of the dGRNs. Subsequently, we summarize the approaches available to unravel these regulatory networks, highlighting the vast range of possibilities of integrating multiple technical

  20. Changes in cis-regulatory elements of a key floral regulator are associated with divergence of inflorescence architectures.

    PubMed

    Kusters, Elske; Della Pina, Serena; Castel, Rob; Souer, Erik; Koes, Ronald

    2015-08-15

    Higher plant species diverged extensively with regard to the moment (flowering time) and position (inflorescence architecture) at which flowers are formed. This seems largely caused by variation in the expression patterns of conserved genes that specify floral meristem identity (FMI), rather than changes in the encoded proteins. Here, we report a functional comparison of the promoters of homologous FMI genes from Arabidopsis, petunia, tomato and Antirrhinum. Analysis of promoter-reporter constructs in petunia and Arabidopsis, as well as complementation experiments, showed that the divergent expression of leafy (LFY) and the petunia homolog aberrant leaf and flower (ALF) results from alterations in the upstream regulatory network rather than cis-regulatory changes. The divergent expression of unusual floral organs (UFO) from Arabidopsis, and the petunia homolog double top (DOT), however, is caused by the loss or gain of cis-regulatory promoter elements, which respond to trans-acting factors that are expressed in similar patterns in both species. Introduction of pUFO:UFO causes no obvious defects in Arabidopsis, but in petunia it causes the precocious and ectopic formation of flowers. This provides an example of how a change in a cis-regulatory region can account for a change in the plant body plan. © 2015. Published by The Company of Biologists Ltd.

  1. Security Aspects of an Enterprise-Wide Network Architecture.

    ERIC Educational Resources Information Center

    Loew, Robert; Stengel, Ingo; Bleimann, Udo; McDonald, Aidan

    1999-01-01

    Presents an overview of two projects that concern local area networks and the common point between networks as they relate to network security. Discusses security architectures based on firewall components, packet filters, application gateways, security-management components, an intranet solution, user registration by Web form, and requests for…

  2. Robust Networking Architecture and Secure Communication Scheme for Heterogeneous Wireless Sensor Networks

    ERIC Educational Resources Information Center

    McNeal, McKenzie, III.

    2012-01-01

    Current networking architectures and communication protocols used for Wireless Sensor Networks (WSNs) have been designed to be energy efficient, low latency, and long network lifetime. One major issue that must be addressed is the security in data communication. Due to the limited capabilities of low cost and small sized sensor nodes, designing…

  3. Architecture for Cognitive Networking within NASAs Future Space Communications Infrastructure

    NASA Technical Reports Server (NTRS)

    Clark, Gilbert J., III; Eddy, Wesley M.; Johnson, Sandra K.; Barnes, James; Brooks, David

    2016-01-01

    Future space mission concepts and designs pose many networking challenges for command, telemetry, and science data applications with diverse end-to-end data delivery needs. For future end-to-end architecture designs, a key challenge is meeting expected application quality of service requirements for multiple simultaneous mission data flows with options to use diverse onboard local data buses, commercial ground networks, and multiple satellite relay constellations in LEO, MEO, GEO, or even deep space relay links. Effectively utilizing a complex network topology requires orchestration and direction that spans the many discrete, individually addressable computer systems, which cause them to act in concert to achieve the overall network goals. The system must be intelligent enough to not only function under nominal conditions, but also adapt to unexpected situations, and reorganize or adapt to perform roles not originally intended for the system or explicitly programmed. This paper describes architecture features of cognitive networking within the future NASA space communications infrastructure, and interacting with the legacy systems and infrastructure in the meantime. The paper begins by discussing the need for increased automation, including inter-system collaboration. This discussion motivates the features of an architecture including cognitive networking for future missions and relays, interoperating with both existing endpoint-based networking models and emerging information-centric models. From this basis, we discuss progress on a proof-of-concept implementation of this architecture as a cognitive networking on-orbit application on the SCaN Testbed attached to the International Space Station.

  4. Network-centric decision architecture for financial or 1/f data models

    NASA Astrophysics Data System (ADS)

    Jaenisch, Holger M.; Handley, James W.; Massey, Stoney; Case, Carl T.; Songy, Claude G.

    2002-12-01

    This paper presents a decision architecture algorithm for training neural equation based networks to make autonomous multi-goal oriented, multi-class decisions. These architectures make decisions based on their individual goals and draw from the same network centric feature set. Traditionally, these architectures are comprised of neural networks that offer marginal performance due to lack of convergence of the training set. We present an approach for autonomously extracting sample points as I/O exemplars for generation of multi-branch, multi-node decision architectures populated by adaptively derived neural equations. To test the robustness of this architecture, open source data sets in the form of financial time series were used, requiring a three-class decision space analogous to the lethal, non-lethal, and clutter discrimination problem. This algorithm and the results of its application are presented here.

  5. Convolutional neural network architectures for predicting DNA–protein binding

    PubMed Central

    Zeng, Haoyang; Edwards, Matthew D.; Liu, Ge; Gifford, David K.

    2016-01-01

    Motivation: Convolutional neural networks (CNN) have outperformed conventional methods in modeling the sequence specificity of DNA–protein binding. Yet inappropriate CNN architectures can yield poorer performance than simpler models. Thus an in-depth understanding of how to match CNN architecture to a given task is needed to fully harness the power of CNNs for computational biology applications. Results: We present a systematic exploration of CNN architectures for predicting DNA sequence binding using a large compendium of transcription factor datasets. We identify the best-performing architectures by varying CNN width, depth and pooling designs. We find that adding convolutional kernels to a network is important for motif-based tasks. We show the benefits of CNNs in learning rich higher-order sequence features, such as secondary motifs and local sequence context, by comparing network performance on multiple modeling tasks ranging in difficulty. We also demonstrate how careful construction of sequence benchmark datasets, using approaches that control potentially confounding effects like positional or motif strength bias, is critical in making fair comparisons between competing methods. We explore how to establish the sufficiency of training data for these learning tasks, and we have created a flexible cloud-based framework that permits the rapid exploration of alternative neural network architectures for problems in computational biology. Availability and Implementation: All the models analyzed are available at http://cnn.csail.mit.edu. Contact: gifford@mit.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307608

  6. Regulatory network rewiring for secondary metabolism in Arabidopsis thaliana under various conditions

    PubMed Central

    2014-01-01

    Background Plant secondary metabolites are critical to various biological processes. However, the regulations of these metabolites are complex because of regulatory rewiring or crosstalk. To unveil how regulatory behaviors on secondary metabolism reshape biological processes, we constructed and analyzed a dynamic regulatory network of secondary metabolic pathways in Arabidopsis. Results The dynamic regulatory network was constructed through integrating co-expressed gene pairs and regulatory interactions. Regulatory interactions were either predicted by conserved transcription factor binding sites (TFBSs) or proved by experiments. We found that integrating two data (co-expression and predicted regulatory interactions) enhanced the number of highly confident regulatory interactions by over 10% compared with using single data. The dynamic changes of regulatory network systematically manifested regulatory rewiring to explain the mechanism of regulation, such as in terpenoids metabolism, the regulatory crosstalk of RAV1 (AT1G13260) and ATHB1 (AT3G01470) on HMG1 (hydroxymethylglutaryl-CoA reductase, AT1G76490); and regulation of RAV1 on epoxysqualene biosynthesis and sterol biosynthesis. Besides, we investigated regulatory rewiring with expression, network topology and upstream signaling pathways. Regulatory rewiring was revealed by the variability of genes’ expression: pathway genes and transcription factors (TFs) were significantly differentially expressed under different conditions (such as terpenoids biosynthetic genes in tissue experiments and E2F/DP family members in genotype experiments). Both network topology and signaling pathways supported regulatory rewiring. For example, we discovered correlation among the numbers of pathway genes, TFs and network topology: one-gene pathways (such as δ-carotene biosynthesis) were regulated by a fewer TFs, and were not critical to metabolic network because of their low degrees in topology. Upstream signaling pathways of 50

  7. Regulatory Architecture of Gene Expression Variation in the Threespine Stickleback Gasterosteus aculeatus.

    PubMed

    Pritchard, Victoria L; Viitaniemi, Heidi M; McCairns, R J Scott; Merilä, Juha; Nikinmaa, Mikko; Primmer, Craig R; Leder, Erica H

    2017-01-05

    Much adaptive evolutionary change is underlain by mutational variation in regions of the genome that regulate gene expression rather than in the coding regions of the genes themselves. An understanding of the role of gene expression variation in facilitating local adaptation will be aided by an understanding of underlying regulatory networks. Here, we characterize the genetic architecture of gene expression variation in the threespine stickleback (Gasterosteus aculeatus), an important model in the study of adaptive evolution. We collected transcriptomic and genomic data from 60 half-sib families using an expression microarray and genotyping-by-sequencing, and located expression quantitative trait loci (eQTL) underlying the variation in gene expression in liver tissue using an interval mapping approach. We identified eQTL for several thousand expression traits. Expression was influenced by polymorphism in both cis- and trans-regulatory regions. Trans-eQTL clustered into hotspots. We did not identify master transcriptional regulators in hotspot locations: rather, the presence of hotspots may be driven by complex interactions between multiple transcription factors. One observed hotspot colocated with a QTL recently found to underlie salinity tolerance in the threespine stickleback. However, most other observed hotspots did not colocate with regions of the genome known to be involved in adaptive divergence between marine and freshwater habitats. Copyright © 2017 Pritchard et al.

  8. Harnessing Diversity towards the Reconstructing of Large Scale Gene Regulatory Networks

    PubMed Central

    Yamanaka, Ryota; Kitano, Hiroaki

    2013-01-01

    Elucidating gene regulatory network (GRN) from large scale experimental data remains a central challenge in systems biology. Recently, numerous techniques, particularly consensus driven approaches combining different algorithms, have become a potentially promising strategy to infer accurate GRNs. Here, we develop a novel consensus inference algorithm, TopkNet that can integrate multiple algorithms to infer GRNs. Comprehensive performance benchmarking on a cloud computing framework demonstrated that (i) a simple strategy to combine many algorithms does not always lead to performance improvement compared to the cost of consensus and (ii) TopkNet integrating only high-performance algorithms provide significant performance improvement compared to the best individual algorithms and community prediction. These results suggest that a priori determination of high-performance algorithms is a key to reconstruct an unknown regulatory network. Similarity among gene-expression datasets can be useful to determine potential optimal algorithms for reconstruction of unknown regulatory networks, i.e., if expression-data associated with known regulatory network is similar to that with unknown regulatory network, optimal algorithms determined for the known regulatory network can be repurposed to infer the unknown regulatory network. Based on this observation, we developed a quantitative measure of similarity among gene-expression datasets and demonstrated that, if similarity between the two expression datasets is high, TopkNet integrating algorithms that are optimal for known dataset perform well on the unknown dataset. The consensus framework, TopkNet, together with the similarity measure proposed in this study provides a powerful strategy towards harnessing the wisdom of the crowds in reconstruction of unknown regulatory networks. PMID:24278007

  9. Learning, memory, and the role of neural network architecture.

    PubMed

    Hermundstad, Ann M; Brown, Kevin S; Bassett, Danielle S; Carlson, Jean M

    2011-06-01

    The performance of information processing systems, from artificial neural networks to natural neuronal ensembles, depends heavily on the underlying system architecture. In this study, we compare the performance of parallel and layered network architectures during sequential tasks that require both acquisition and retention of information, thereby identifying tradeoffs between learning and memory processes. During the task of supervised, sequential function approximation, networks produce and adapt representations of external information. Performance is evaluated by statistically analyzing the error in these representations while varying the initial network state, the structure of the external information, and the time given to learn the information. We link performance to complexity in network architecture by characterizing local error landscape curvature. We find that variations in error landscape structure give rise to tradeoffs in performance; these include the ability of the network to maximize accuracy versus minimize inaccuracy and produce specific versus generalizable representations of information. Parallel networks generate smooth error landscapes with deep, narrow minima, enabling them to find highly specific representations given sufficient time. While accurate, however, these representations are difficult to generalize. In contrast, layered networks generate rough error landscapes with a variety of local minima, allowing them to quickly find coarse representations. Although less accurate, these representations are easily adaptable. The presence of measurable performance tradeoffs in both layered and parallel networks has implications for understanding the behavior of a wide variety of natural and artificial learning systems.

  10. Reverse engineering highlights potential principles of large gene regulatory network design and learning.

    PubMed

    Carré, Clément; Mas, André; Krouk, Gabriel

    2017-01-01

    Inferring transcriptional gene regulatory networks from transcriptomic datasets is a key challenge of systems biology, with potential impacts ranging from medicine to agronomy. There are several techniques used presently to experimentally assay transcription factors to target relationships, defining important information about real gene regulatory networks connections. These techniques include classical ChIP-seq, yeast one-hybrid, or more recently, DAP-seq or target technologies. These techniques are usually used to validate algorithm predictions. Here, we developed a reverse engineering approach based on mathematical and computer simulation to evaluate the impact that this prior knowledge on gene regulatory networks may have on training machine learning algorithms. First, we developed a gene regulatory networks-simulating engine called FRANK (Fast Randomizing Algorithm for Network Knowledge) that is able to simulate large gene regulatory networks (containing 10 4 genes) with characteristics of gene regulatory networks observed in vivo. FRANK also generates stable or oscillatory gene expression directly produced by the simulated gene regulatory networks. The development of FRANK leads to important general conclusions concerning the design of large and stable gene regulatory networks harboring scale free properties (built ex nihilo). In combination with supervised (accepting prior knowledge) support vector machine algorithm we (i) address biologically oriented questions concerning our capacity to accurately reconstruct gene regulatory networks and in particular we demonstrate that prior-knowledge structure is crucial for accurate learning, and (ii) draw conclusions to inform experimental design to performed learning able to solve gene regulatory networks in the future. By demonstrating that our predictions concerning the influence of the prior-knowledge structure on support vector machine learning capacity holds true on real data ( Escherichia coli K14 network

  11. Satellite Networks: Architectures, Applications, and Technologies

    NASA Technical Reports Server (NTRS)

    Bhasin, Kul (Compiler)

    1998-01-01

    Since global satellite networks are moving to the forefront in enhancing the national and global information infrastructures due to communication satellites' unique networking characteristics, a workshop was organized to assess the progress made to date and chart the future. This workshop provided the forum to assess the current state-of-the-art, identify key issues, and highlight the emerging trends in the next-generation architectures, data protocol development, communication interoperability, and applications. Presentations on overview, state-of-the-art in research, development, deployment and applications and future trends on satellite networks are assembled.

  12. SATRAT: Staphylococcus aureus transcript regulatory network analysis tool.

    PubMed

    Gopal, Tamilselvi; Nagarajan, Vijayaraj; Elasri, Mohamed O

    2015-01-01

    Staphylococcus aureus is a commensal organism that primarily colonizes the nose of healthy individuals. S. aureus causes a spectrum of infections that range from skin and soft-tissue infections to fatal invasive diseases. S. aureus uses a large number of virulence factors that are regulated in a coordinated fashion. The complex regulatory mechanisms have been investigated in numerous high-throughput experiments. Access to this data is critical to studying this pathogen. Previously, we developed a compilation of microarray experimental data to enable researchers to search, browse, compare, and contrast transcript profiles. We have substantially updated this database and have built a novel exploratory tool-SATRAT-the S. aureus transcript regulatory network analysis tool, based on the updated database. This tool is capable of performing deep searches using a query and generating an interactive regulatory network based on associations among the regulators of any query gene. We believe this integrated regulatory network analysis tool would help researchers explore the missing links and identify novel pathways that regulate virulence in S. aureus. Also, the data model and the network generation code used to build this resource is open sourced, enabling researchers to build similar resources for other bacterial systems.

  13. A Developmental Systems Perspective on Epistasis: Computational Exploration of Mutational Interactions in Model Developmental Regulatory Networks

    PubMed Central

    Gutiérrez, Jayson

    2009-01-01

    perturbations are strongly conditioned by both the regulatory architecture (i.e. pattern of coupled feedback structures) and the dynamic nature of the spatio-temporal expression trajectories displayed by the simulated networks. PMID:19738908

  14. Nitrogen modulation of legume root architecture signaling pathways involves phytohormones and small regulatory molecules.

    PubMed

    Mohd-Radzman, Nadiatul A; Djordjevic, Michael A; Imin, Nijat

    2013-10-01

    Nitrogen, particularly nitrate is an important yield determinant for crops. However, current agricultural practice with excessive fertilizer usage has detrimental effects on the environment. Therefore, legumes have been suggested as a sustainable alternative for replenishing soil nitrogen. Legumes can uniquely form nitrogen-fixing nodules through symbiotic interaction with specialized soil bacteria. Legumes possess a highly plastic root system which modulates its architecture according to the nitrogen availability in the soil. Understanding how legumes regulate root development in response to nitrogen availability is an important step to improving root architecture. The nitrogen-mediated root development pathway starts with sensing soil nitrogen level followed by subsequent signal transduction pathways involving phytohormones, microRNAs and regulatory peptides that collectively modulate the growth and shape of the root system. This review focuses on the current understanding of nitrogen-mediated legume root architecture including local and systemic regulations by different N-sources and the modulations by phytohormones and small regulatory molecules.

  15. Modeling gene regulatory networks: A network simplification algorithm

    NASA Astrophysics Data System (ADS)

    Ferreira, Luiz Henrique O.; de Castro, Maria Clicia S.; da Silva, Fabricio A. B.

    2016-12-01

    Boolean networks have been used for some time to model Gene Regulatory Networks (GRNs), which describe cell functions. Those models can help biologists to make predictions, prognosis and even specialized treatment when some disturb on the GRN lead to a sick condition. However, the amount of information related to a GRN can be huge, making the task of inferring its boolean network representation quite a challenge. The method shown here takes into account information about the interactome to build a network, where each node represents a protein, and uses the entropy of each node as a key to reduce the size of the network, allowing the further inferring process to focus only on the main protein hubs, the ones with most potential to interfere in overall network behavior.

  16. Architecture for Cognitive Networking within NASA's Future Space Communications Infrastructure

    NASA Technical Reports Server (NTRS)

    Clark, Gilbert; Eddy, Wesley M.; Johnson, Sandra K.; Barnes, James; Brooks, David

    2016-01-01

    Future space mission concepts and designs pose many networking challenges for command, telemetry, and science data applications with diverse end-to-end data delivery needs. For future end-to-end architecture designs, a key challenge is meeting expected application quality of service requirements for multiple simultaneous mission data flows with options to use diverse onboard local data buses, commercial ground networks, and multiple satellite relay constellations in LEO, GEO, MEO, or even deep space relay links. Effectively utilizing a complex network topology requires orchestration and direction that spans the many discrete, individually addressable computer systems, which cause them to act in concert to achieve the overall network goals. The system must be intelligent enough to not only function under nominal conditions, but also adapt to unexpected situations, and reorganize or adapt to perform roles not originally intended for the system or explicitly programmed. This paper describes an architecture enabling the development and deployment of cognitive networking capabilities into the envisioned future NASA space communications infrastructure. We begin by discussing the need for increased automation, including inter-system discovery and collaboration. This discussion frames the requirements for an architecture supporting cognitive networking for future missions and relays, including both existing endpoint-based networking models and emerging information-centric models. From this basis, we discuss progress on a proof-of-concept implementation of this architecture, and results of implementation and initial testing of a cognitive networking on-orbit application on the SCaN Testbed attached to the International Space Station.

  17. An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling

    PubMed Central

    Sciammas, Roger; Li, Ying; Warmflash, Aryeh; Song, Yiqiang; Dinner, Aaron R; Singh, Harinder

    2011-01-01

    The B-lymphocyte lineage is a leading system for analyzing gene regulatory networks (GRNs) that orchestrate distinct cell fate transitions. Upon antigen recognition, B cells can diversify their immunoglobulin (Ig) repertoire via somatic hypermutation (SHM) and/or class switch DNA recombination (CSR) before differentiating into antibody-secreting plasma cells. We construct a mathematical model for a GRN underlying this developmental dynamic. The intensity of signaling through the Ig receptor is shown to control the bimodal expression of a pivotal transcription factor, IRF-4, which dictates B cell fate outcomes. Computational modeling coupled with experimental analysis supports a model of ‘kinetic control', in which B cell developmental trajectories pass through an obligate transient state of variable duration that promotes diversification of the antibody repertoire by SHM/CSR in direct response to antigens. More generally, this network motif could be used to translate a morphogen gradient into developmental inductive events of varying time, thereby enabling the specification of distinct cell fates. PMID:21613984

  18. Integration of multi-omics data for integrative gene regulatory network inference.

    PubMed

    Zarayeneh, Neda; Ko, Euiseong; Oh, Jung Hun; Suh, Sang; Liu, Chunyu; Gao, Jean; Kim, Donghyun; Kang, Mingon

    2017-01-01

    Gene regulatory networks provide comprehensive insights and indepth understanding of complex biological processes. The molecular interactions of gene regulatory networks are inferred from a single type of genomic data, e.g., gene expression data in most research. However, gene expression is a product of sequential interactions of multiple biological processes, such as DNA sequence variations, copy number variations, histone modifications, transcription factors, and DNA methylations. The recent rapid advances of high-throughput omics technologies enable one to measure multiple types of omics data, called 'multi-omics data', that represent the various biological processes. In this paper, we propose an Integrative Gene Regulatory Network inference method (iGRN) that incorporates multi-omics data and their interactions in gene regulatory networks. In addition to gene expressions, copy number variations and DNA methylations were considered for multi-omics data in this paper. The intensive experiments were carried out with simulation data, where iGRN's capability that infers the integrative gene regulatory network is assessed. Through the experiments, iGRN shows its better performance on model representation and interpretation than other integrative methods in gene regulatory network inference. iGRN was also applied to a human brain dataset of psychiatric disorders, and the biological network of psychiatric disorders was analysed.

  19. Integration of multi-omics data for integrative gene regulatory network inference

    PubMed Central

    Zarayeneh, Neda; Ko, Euiseong; Oh, Jung Hun; Suh, Sang; Liu, Chunyu; Gao, Jean; Kim, Donghyun

    2017-01-01

    Gene regulatory networks provide comprehensive insights and indepth understanding of complex biological processes. The molecular interactions of gene regulatory networks are inferred from a single type of genomic data, e.g., gene expression data in most research. However, gene expression is a product of sequential interactions of multiple biological processes, such as DNA sequence variations, copy number variations, histone modifications, transcription factors, and DNA methylations. The recent rapid advances of high-throughput omics technologies enable one to measure multiple types of omics data, called ‘multi-omics data’, that represent the various biological processes. In this paper, we propose an Integrative Gene Regulatory Network inference method (iGRN) that incorporates multi-omics data and their interactions in gene regulatory networks. In addition to gene expressions, copy number variations and DNA methylations were considered for multi-omics data in this paper. The intensive experiments were carried out with simulation data, where iGRN’s capability that infers the integrative gene regulatory network is assessed. Through the experiments, iGRN shows its better performance on model representation and interpretation than other integrative methods in gene regulatory network inference. iGRN was also applied to a human brain dataset of psychiatric disorders, and the biological network of psychiatric disorders was analysed. PMID:29354189

  20. Re-engineering Nascom's network management architecture

    NASA Technical Reports Server (NTRS)

    Drake, Brian C.; Messent, David

    1994-01-01

    The development of Nascom systems for ground communications began in 1958 with Project Vanguard. The low-speed systems (rates less than 9.6 Kbs) were developed following existing standards; but, there were no comparable standards for high-speed systems. As a result, these systems were developed using custom protocols and custom hardware. Technology has made enormous strides since the ground support systems were implemented. Standards for computer equipment, software, and high-speed communications exist and the performance of current workstations exceeds that of the mainframes used in the development of the ground systems. Nascom is in the process of upgrading its ground support systems and providing additional services. The Message Switching System (MSS), Communications Address Processor (CAP), and Multiplexer/Demultiplexer (MDM) Automated Control System (MACS) are all examples of Nascom systems developed using standards such as, X-windows, Motif, and Simple Network Management Protocol (SNMP). Also, the Earth Observing System (EOS) Communications (Ecom) project is stressing standards as an integral part of its network. The move towards standards has produced a reduction in development, maintenance, and interoperability costs, while providing operational quality improvement. The Facility and Resource Manager (FARM) project has been established to integrate the Nascom networks and systems into a common network management architecture. The maximization of standards and implementation of computer automation in the architecture will lead to continued cost reductions and increased operational efficiency. The first step has been to derive overall Nascom requirements and identify the functionality common to all the current management systems. The identification of these common functions will enable the reuse of processes in the management architecture and promote increased use of automation throughout the Nascom network. The MSS, CAP, MACS, and Ecom projects have indicated

  1. Gene regulatory networks and the underlying biology of developmental toxicity

    EPA Science Inventory

    Embryonic cells are specified by large-scale networks of functionally linked regulatory genes. Knowledge of the relevant gene regulatory networks is essential for understanding phenotypic heterogeneity that emerges from disruption of molecular functions, cellular processes or sig...

  2. Genome-Scale Architecture of Small Molecule Regulatory Networks and the Fundamental Trade-Off between Regulation and Enzymatic Activity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Reznik, Ed; Christodoulou, Dimitris; Goldford, Joshua E.

    Metabolic flux is in part regulated by endogenous small molecules that modulate the catalytic activity of an enzyme, e.g., allosteric inhibition. In contrast to transcriptional regulation of enzymes, technical limitations have hindered the production of a genome-scale atlas of small molecule-enzyme regulatory interactions. Here, we develop a framework leveraging the vast, but fragmented, biochemical literature to reconstruct and analyze the small molecule regulatory network (SMRN) of the model organism Escherichia coli, including the primary metabolite regulators and enzyme targets. Using metabolic control analysis, we prove a fundamental trade-off between regulation and enzymatic activity, and we combine it with metabolomic measurementsmore » and the SMRN to make inferences on the sensitivity of enzymes to their regulators. By generalizing the analysis to other organisms, we identify highly conserved regulatory interactions across evolutionarily divergent species, further emphasizing a critical role for small molecule interactions in the maintenance of metabolic homeostasis.« less

  3. Genome-Scale Architecture of Small Molecule Regulatory Networks and the Fundamental Trade-Off between Regulation and Enzymatic Activity

    DOE PAGES

    Reznik, Ed; Christodoulou, Dimitris; Goldford, Joshua E.; ...

    2017-09-12

    Metabolic flux is in part regulated by endogenous small molecules that modulate the catalytic activity of an enzyme, e.g., allosteric inhibition. In contrast to transcriptional regulation of enzymes, technical limitations have hindered the production of a genome-scale atlas of small molecule-enzyme regulatory interactions. Here, we develop a framework leveraging the vast, but fragmented, biochemical literature to reconstruct and analyze the small molecule regulatory network (SMRN) of the model organism Escherichia coli, including the primary metabolite regulators and enzyme targets. Using metabolic control analysis, we prove a fundamental trade-off between regulation and enzymatic activity, and we combine it with metabolomic measurementsmore » and the SMRN to make inferences on the sensitivity of enzymes to their regulators. By generalizing the analysis to other organisms, we identify highly conserved regulatory interactions across evolutionarily divergent species, further emphasizing a critical role for small molecule interactions in the maintenance of metabolic homeostasis.« less

  4. High-performance, scalable optical network-on-chip architectures

    NASA Astrophysics Data System (ADS)

    Tan, Xianfang

    The rapid advance of technology enables a large number of processing cores to be integrated into a single chip which is called a Chip Multiprocessor (CMP) or a Multiprocessor System-on-Chip (MPSoC) design. The on-chip interconnection network, which is the communication infrastructure for these processing cores, plays a central role in a many-core system. With the continuously increasing complexity of many-core systems, traditional metallic wired electronic networks-on-chip (NoC) became a bottleneck because of the unbearable latency in data transmission and extremely high energy consumption on chip. Optical networks-on-chip (ONoC) has been proposed as a promising alternative paradigm for electronic NoC with the benefits of optical signaling communication such as extremely high bandwidth, negligible latency, and low power consumption. This dissertation focus on the design of high-performance and scalable ONoC architectures and the contributions are highlighted as follow: 1. A micro-ring resonator (MRR)-based Generic Wavelength-routed Optical Router (GWOR) is proposed. A method for developing any sized GWOR is introduced. GWOR is a scalable non-blocking ONoC architecture with simple structure, low cost and high power efficiency compared to existing ONoC designs. 2. To expand the bandwidth and improve the fault tolerance of the GWOR, a redundant GWOR architecture is designed by cascading different type of GWORs into one network. 3. The redundant GWOR built with MRR-based comb switches is proposed. Comb switches can expand the bandwidth while keep the topology of GWOR unchanged by replacing the general MRRs with comb switches. 4. A butterfly fat tree (BFT)-based hybrid optoelectronic NoC (HONoC) architecture is developed in which GWORs are used for global communication and electronic routers are used for local communication. The proposed HONoC uses less numbers of electronic routers and links than its counterpart of electronic BFT-based NoC. It takes the advantages of

  5. Fast notification architecture for wireless sensor networks

    NASA Astrophysics Data System (ADS)

    Lee, Dong-Hahk

    2013-03-01

    In an emergency, since it is vital to transmit the message to the users immediately after analysing the data to prevent disaster, this article presents the deployment of a fast notification architecture for a wireless sensor network. The sensor nodes of the proposed architecture can monitor an emergency situation periodically and transmit the sensing data, immediately to the sink node. We decide on the grade of fire situation according to the decision rule using the sensing values of temperature, CO, smoke density and temperature increasing rate. On the other hand, to estimate the grade of air pollution, the sensing data, such as dust, formaldehyde, NO2, CO2, is applied to the given knowledge model. Since the sink node in the architecture has a ZigBee interface, it can transmit the alert messages in real time according to analysed results received from the host server to the terminals equipped with a SIM card-type ZigBee module. Also, the host server notifies the situation to the registered users who have cellular phone through short message service server of the cellular network. Thus, the proposed architecture can adapt an emergency situation dynamically compared to the conventional architecture using video processing. In the testbed, after generating air pollution and fire data, the terminal receives the message in less than 3 s. In the test results, this system can also be applied to buildings and public areas where many people gather together, to prevent unexpected disasters in urban settings.

  6. Network architecture for global biomedical monitoring service.

    PubMed

    Lopez-Casado, Carmen; Tejero-Calado, Juan; Bernal-Martin, Antonio; Lopez-Gomez, Miguel; Romero-Romero, Marco; Quesada, Guillermo; Lorca, Julio; Garcia, Eugenia

    2005-01-01

    Most of the patients who are in hospitals and, increasingly, patients controlled remotely from their homes, at-home monitoring, are continuously monitored in order to control their evolution. The medical devices used up to now, force the sanitary staff to go to the patients' room to control the biosignals that are being monitored, although in many cases, patients are in perfect conditions. If patient is at home, it is he or she who has to go to the hospital to take the record of the monitored signal. New wireless technologies, such as BlueTooth and WLAN, make possible the deployment of systems that allow the display and storage of those signals in any place where the hospital intranet is accessible. In that way, unnecessary displacements are avoided. This paper presents a network architecture that allows the identification of the biosignal acquisition device as IP network nodes. The system is based on a TCP/IP architecture which is scalable and avoids the deployment of a specific purpose network.

  7. Probabilistic representation of gene regulatory networks.

    PubMed

    Mao, Linyong; Resat, Haluk

    2004-09-22

    Recent experiments have established unambiguously that biological systems can have significant cell-to-cell variations in gene expression levels even in isogenic populations. Computational approaches to studying gene expression in cellular systems should capture such biological variations for a more realistic representation. In this paper, we present a new fully probabilistic approach to the modeling of gene regulatory networks that allows for fluctuations in the gene expression levels. The new algorithm uses a very simple representation for the genes, and accounts for the repression or induction of the genes and for the biological variations among isogenic populations simultaneously. Because of its simplicity, introduced algorithm is a very promising approach to model large-scale gene regulatory networks. We have tested the new algorithm on the synthetic gene network library bioengineered recently. The good agreement between the computed and the experimental results for this library of networks, and additional tests, demonstrate that the new algorithm is robust and very successful in explaining the experimental data. The simulation software is available upon request. Supplementary material will be made available on the OUP server.

  8. Enabling Tussle-Agile Inter-networking Architectures by Underlay Virtualisation

    NASA Astrophysics Data System (ADS)

    Dianati, Mehrdad; Tafazolli, Rahim; Moessner, Klaus

    In this paper, we propose an underlay inter-network virtualisation framework in order to enable tussle-agile flexible networking over the existing inter-network infrastructures. The functionalities that inter-networking elements (transit nodes, access networks, etc.) need to support in order to enable virtualisation are discussed. We propose the base architectures of each the abstract elements to support the required inter-network virtualisation functionalities.

  9. Comparison of different artificial neural network architectures in modeling of Chlorella sp. flocculation.

    PubMed

    Zenooz, Alireza Moosavi; Ashtiani, Farzin Zokaee; Ranjbar, Reza; Nikbakht, Fatemeh; Bolouri, Oberon

    2017-07-03

    Biodiesel production from microalgae feedstock should be performed after growth and harvesting of the cells, and the most feasible method for harvesting and dewatering of microalgae is flocculation. Flocculation modeling can be used for evaluation and prediction of its performance under different affective parameters. However, the modeling of flocculation in microalgae is not simple and has not performed yet, under all experimental conditions, mostly due to different behaviors of microalgae cells during the process under different flocculation conditions. In the current study, the modeling of microalgae flocculation is studied with different neural network architectures. Microalgae species, Chlorella sp., was flocculated with ferric chloride under different conditions and then the experimental data modeled using artificial neural network. Neural network architectures of multilayer perceptron (MLP) and radial basis function architectures, failed to predict the targets successfully, though, modeling was effective with ensemble architecture of MLP networks. Comparison between the performances of the ensemble and each individual network explains the ability of the ensemble architecture in microalgae flocculation modeling.

  10. Markov State Models of gene regulatory networks.

    PubMed

    Chu, Brian K; Tse, Margaret J; Sato, Royce R; Read, Elizabeth L

    2017-02-06

    Gene regulatory networks with dynamics characterized by multiple stable states underlie cell fate-decisions. Quantitative models that can link molecular-level knowledge of gene regulation to a global understanding of network dynamics have the potential to guide cell-reprogramming strategies. Networks are often modeled by the stochastic Chemical Master Equation, but methods for systematic identification of key properties of the global dynamics are currently lacking. The method identifies the number, phenotypes, and lifetimes of long-lived states for a set of common gene regulatory network models. Application of transition path theory to the constructed Markov State Model decomposes global dynamics into a set of dominant transition paths and associated relative probabilities for stochastic state-switching. In this proof-of-concept study, we found that the Markov State Model provides a general framework for analyzing and visualizing stochastic multistability and state-transitions in gene networks. Our results suggest that this framework-adopted from the field of atomistic Molecular Dynamics-can be a useful tool for quantitative Systems Biology at the network scale.

  11. Inference of cancer-specific gene regulatory networks using soft computing rules.

    PubMed

    Wang, Xiaosheng; Gotoh, Osamu

    2010-03-24

    Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.

  12. Efficient Reverse-Engineering of a Developmental Gene Regulatory Network

    PubMed Central

    Cicin-Sain, Damjan; Ashyraliyev, Maksat; Jaeger, Johannes

    2012-01-01

    Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to

  13. Deep Space Network information system architecture study

    NASA Technical Reports Server (NTRS)

    Beswick, C. A.; Markley, R. W. (Editor); Atkinson, D. J.; Cooper, L. P.; Tausworthe, R. C.; Masline, R. C.; Jenkins, J. S.; Crowe, R. A.; Thomas, J. L.; Stoloff, M. J.

    1992-01-01

    The purpose of this article is to describe an architecture for the Deep Space Network (DSN) information system in the years 2000-2010 and to provide guidelines for its evolution during the 1990s. The study scope is defined to be from the front-end areas at the antennas to the end users (spacecraft teams, principal investigators, archival storage systems, and non-NASA partners). The architectural vision provides guidance for major DSN implementation efforts during the next decade. A strong motivation for the study is an expected dramatic improvement in information-systems technologies, such as the following: computer processing, automation technology (including knowledge-based systems), networking and data transport, software and hardware engineering, and human-interface technology. The proposed Ground Information System has the following major features: unified architecture from the front-end area to the end user; open-systems standards to achieve interoperability; DSN production of level 0 data; delivery of level 0 data from the Deep Space Communications Complex, if desired; dedicated telemetry processors for each receiver; security against unauthorized access and errors; and highly automated monitor and control.

  14. The regulatory network analysis of long noncoding RNAs in human colorectal cancer.

    PubMed

    Zhang, Yuwei; Tao, Yang; Li, Yang; Zhao, Jinshun; Zhang, Lina; Zhang, Xiaohong; Dong, Changzheng; Xie, Yangyang; Dai, Xiaoyu; Zhang, Xinjun; Liao, Qi

    2018-05-01

    Colorectal cancer (CRC) is among one of the most prevalent and lethiferous diseases worldwide. Long noncoding RNAs (lncRNAs) are commonly accepted to function as a key regulatory factor in human cancer, but the potential regulatory mechanisms of CRC-associated lncRNA are largely obscure. Here, we integrated several expression profiles to obtain 55 differentially expressed (DE) lncRNAs. We first detected lncRNA interactions with transcription factors, microRNAs, mRNAs, and RNA-binding proteins to construct a regulatory network and then create functional enrichment analyses for them using bioinformatics approaches. We found the upregulated genes in the regulatory network are enriched in cell cycle and DNA damage response, while the downregulated genes are enriched in cell differentiation, cellular response, and cell signaling. We then employed module-based methods to mine several intriguing modules from the overall network, which helps to classify the functions of genes more specifically. Next, we confirmed the validity of our network by comparisons with a randomized network using computational method. Finally, we attempted to annotate lncRNA functions based on the regulatory network, which indicated its potential application. Our study of the lncRNA regulatory network provided significant clues to unveil lncRNAs potential regulatory mechanisms in CRC and laid a foundation for further experimental investigation.

  15. Sequence-based model of gap gene regulatory network.

    PubMed

    Kozlov, Konstantin; Gursky, Vitaly; Kulakovskiy, Ivan; Samsonova, Maria

    2014-01-01

    The detailed analysis of transcriptional regulation is crucially important for understanding biological processes. The gap gene network in Drosophila attracts large interest among researches studying mechanisms of transcriptional regulation. It implements the most upstream regulatory layer of the segmentation gene network. The knowledge of molecular mechanisms involved in gap gene regulation is far less complete than that of genetics of the system. Mathematical modeling goes beyond insights gained by genetics and molecular approaches. It allows us to reconstruct wild-type gene expression patterns in silico, infer underlying regulatory mechanism and prove its sufficiency. We developed a new model that provides a dynamical description of gap gene regulatory systems, using detailed DNA-based information, as well as spatial transcription factor concentration data at varying time points. We showed that this model correctly reproduces gap gene expression patterns in wild type embryos and is able to predict gap expression patterns in Kr mutants and four reporter constructs. We used four-fold cross validation test and fitting to random dataset to validate the model and proof its sufficiency in data description. The identifiability analysis showed that most model parameters are well identifiable. We reconstructed the gap gene network topology and studied the impact of individual transcription factor binding sites on the model output. We measured this impact by calculating the site regulatory weight as a normalized difference between the residual sum of squares error for the set of all annotated sites and for the set with the site of interest excluded. The reconstructed topology of the gap gene network is in agreement with previous modeling results and data from literature. We showed that 1) the regulatory weights of transcription factor binding sites show very weak correlation with their PWM score; 2) sites with low regulatory weight are important for the model output; 3

  16. Mining Gene Regulatory Networks by Neural Modeling of Expression Time-Series.

    PubMed

    Rubiolo, Mariano; Milone, Diego H; Stegmayer, Georgina

    2015-01-01

    Discovering gene regulatory networks from data is one of the most studied topics in recent years. Neural networks can be successfully used to infer an underlying gene network by modeling expression profiles as times series. This work proposes a novel method based on a pool of neural networks for obtaining a gene regulatory network from a gene expression dataset. They are used for modeling each possible interaction between pairs of genes in the dataset, and a set of mining rules is applied to accurately detect the subjacent relations among genes. The results obtained on artificial and real datasets confirm the method effectiveness for discovering regulatory networks from a proper modeling of the temporal dynamics of gene expression profiles.

  17. Robustness in Regulatory Interaction Networks. A Generic Approach with Applications at Different Levels: Physiologic, Metabolic and Genetic

    PubMed Central

    Demongeot, Jacques; Ben Amor, Hedi; Elena, Adrien; Gillois, Pierre; Noual, Mathilde; Sené, Sylvain

    2009-01-01

    Regulatory interaction networks are often studied on their dynamical side (existence of attractors, study of their stability). We focus here also on their robustness, that is their ability to offer the same spatiotemporal patterns and to resist to external perturbations such as losses of nodes or edges in the networks interactions architecture, changes in their environmental boundary conditions as well as changes in the update schedule (or updating mode) of the states of their elements (e.g., if these elements are genes, their synchronous coexpression mode versus their sequential expression). We define the generic notions of boundary, core, and critical vertex or edge of the underlying interaction graph of the regulatory network, whose disappearance causes dramatic changes in the number and nature of attractors (e.g., passage from a bistable behaviour to a unique periodic regime) or in the range of their basins of stability. The dynamic transition of states will be presented in the framework of threshold Boolean automata rules. A panorama of applications at different levels will be given: brain and plant morphogenesis, bulbar cardio-respiratory regulation, glycolytic/oxidative metabolic coupling, and eventually cell cycle and feather morphogenesis genetic control. PMID:20057955

  18. A security architecture for health information networks.

    PubMed

    Kailar, Rajashekar; Muralidhar, Vinod

    2007-10-11

    Health information network security needs to balance exacting security controls with practicality, and ease of implementation in today's healthcare enterprise. Recent work on 'nationwide health information network' architectures has sought to share highly confidential data over insecure networks such as the Internet. Using basic patterns of health network data flow and trust models to support secure communication between network nodes, we abstract network security requirements to a core set to enable secure inter-network data sharing. We propose a minimum set of security controls that can be implemented without needing major new technologies, but yet realize network security and privacy goals of confidentiality, integrity and availability. This framework combines a set of technology mechanisms with environmental controls, and is shown to be sufficient to counter commonly encountered network security threats adequately.

  19. Geometric control of capillary architecture via cell-matrix mechanical interactions.

    PubMed

    Sun, Jian; Jamilpour, Nima; Wang, Fei-Yue; Wong, Pak Kin

    2014-03-01

    Capillary morphogenesis is a multistage, multicellular activity that plays a pivotal role in various developmental and pathological situations. In-depth understanding of the regulatory mechanism along with the capability of controlling the morphogenic process will have direct implications on tissue engineering and therapeutic angiogenesis. Extensive research has been devoted to elucidate the biochemical factors that regulate capillary morphogenesis. The roles of geometric confinement and cell-matrix mechanical interactions on the capillary architecture, nevertheless, remain largely unknown. Here, we show geometric control of endothelial network topology by creating physical confinements with microfabricated fences and wells. Decreasing the thickness of the matrix also results in comparable modulation of the network architecture, supporting the boundary effect is mediated mechanically. The regulatory role of cell-matrix mechanical interaction on the network topology is further supported by alternating the matrix stiffness by a cell-inert PEG-dextran hydrogel. Furthermore, reducing the cell traction force with a Rho-associated protein kinase inhibitor diminishes the boundary effect. Computational biomechanical analysis delineates the relationship between geometric confinement and cell-matrix mechanical interaction. Collectively, these results reveal a mechanoregulation scheme of endothelial cells to regulate the capillary network architecture via cell-matrix mechanical interactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. A Security Architecture for Health Information Networks

    PubMed Central

    Kailar, Rajashekar

    2007-01-01

    Health information network security needs to balance exacting security controls with practicality, and ease of implementation in today’s healthcare enterprise. Recent work on ‘nationwide health information network’ architectures has sought to share highly confidential data over insecure networks such as the Internet. Using basic patterns of health network data flow and trust models to support secure communication between network nodes, we abstract network security requirements to a core set to enable secure inter-network data sharing. We propose a minimum set of security controls that can be implemented without needing major new technologies, but yet realize network security and privacy goals of confidentiality, integrity and availability. This framework combines a set of technology mechanisms with environmental controls, and is shown to be sufficient to counter commonly encountered network security threats adequately. PMID:18693862

  1. The middleware architecture supports heterogeneous network systems for module-based personal robot system

    NASA Astrophysics Data System (ADS)

    Choo, Seongho; Li, Vitaly; Choi, Dong Hee; Jung, Gi Deck; Park, Hong Seong; Ryuh, Youngsun

    2005-12-01

    On developing the personal robot system presently, the internal architecture is every module those occupy separated functions are connected through heterogeneous network system. This module-based architecture supports specialization and division of labor at not only designing but also implementation, as an effect of this architecture, it can reduce developing times and costs for modules. Furthermore, because every module is connected among other modules through network systems, we can get easy integrations and synergy effect to apply advanced mutual functions by co-working some modules. In this architecture, one of the most important technologies is the network middleware that takes charge communications among each modules connected through heterogeneous networks systems. The network middleware acts as the human nerve system inside of personal robot system; it relays, transmits, and translates information appropriately between modules that are similar to human organizations. The network middleware supports various hardware platform, heterogeneous network systems (Ethernet, Wireless LAN, USB, IEEE 1394, CAN, CDMA-SMS, RS-232C). This paper discussed some mechanisms about our network middleware to intercommunication and routing among modules, methods for real-time data communication and fault-tolerant network service. There have designed and implemented a layered network middleware scheme, distributed routing management, network monitoring/notification technology on heterogeneous networks for these goals. The main theme is how to make routing information in our network middleware. Additionally, with this routing information table, we appended some features. Now we are designing, making a new version network middleware (we call 'OO M/W') that can support object-oriented operation, also are updating program sources itself for object-oriented architecture. It is lighter, faster, and can support more operation systems and heterogeneous network systems, but other general

  2. Gene Regulatory Networks, Homology, and the Early Panarthropod Fossil Record.

    PubMed

    Tweedt, Sarah M

    2017-09-01

    The arthropod body plan is widely believed to have derived from an ancestral form resembling Cambrian-aged fossil lobopodians, and interpretations of morphological and molecular data have long favored this hypothesis. It is possible, however, that appendages and other morphologies observed in extinct and living panarthropods evolved independently. The key to distinguishing between morphological homology and homoplasy lies in the study of developmental gene regulatory networks (GRNs), and specifically, in determining the unique genetic circuits that construct characters. In this study, I discuss character identity and panarthropod appendage evolution within a developmental GRN framework, with a specific focus on potential limb character identity networks ("ChINs"). I summarize recent molecular studies, and argue that current data do not rule out the possibility of independent panarthropod limb evolution. The link between character identity and GRN architecture has broad implications for homology assessment, and this genetic framework offers alternative approaches to fossil character coding, phylogenetic analyses, and future research into the origin of the arthropod body plan. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  3. Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma

    PubMed Central

    Sun, Jingchun; Gong, Xue; Purow, Benjamin; Zhao, Zhongming

    2012-01-01

    Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in humans. Recent studies revealed that patterns of microRNA (miRNA) expression in GBM tissue samples are different from those in normal brain tissues, suggesting that a number of miRNAs play critical roles in the pathogenesis of GBM. However, little is yet known about which miRNAs play central roles in the pathology of GBM and their regulatory mechanisms of action. To address this issue, in this study, we systematically explored the main regulation format (feed-forward loops, FFLs) consisting of miRNAs, transcription factors (TFs) and their impacting GBM-related genes, and developed a computational approach to construct a miRNA-TF regulatory network. First, we compiled GBM-related miRNAs, GBM-related genes, and known human TFs. We then identified 1,128 3-node FFLs and 805 4-node FFLs with statistical significance. By merging these FFLs together, we constructed a comprehensive GBM-specific miRNA-TF mediated regulatory network. Then, from the network, we extracted a composite GBM-specific regulatory network. To illustrate the GBM-specific regulatory network is promising for identification of critical miRNA components, we specifically examined a Notch signaling pathway subnetwork. Our follow up topological and functional analyses of the subnetwork revealed that six miRNAs (miR-124, miR-137, miR-219-5p, miR-34a, miR-9, and miR-92b) might play important roles in GBM, including some results that are supported by previous studies. In this study, we have developed a computational framework to construct a miRNA-TF regulatory network and generated the first miRNA-TF regulatory network for GBM, providing a valuable resource for further understanding the complex regulatory mechanisms in GBM. The observation of critical miRNAs in the Notch signaling pathway, with partial verification from previous studies, demonstrates that our network-based approach is promising for the identification of new and important

  4. Population Dynamics of Genetic Regulatory Networks

    NASA Astrophysics Data System (ADS)

    Braun, Erez

    2005-03-01

    Unlike common objects in physics, a biological cell processes information. The cell interprets its genome and transforms the genomic information content, through the action of genetic regulatory networks, into proteins which in turn dictate its metabolism, functionality and morphology. Understanding the dynamics of a population of biological cells presents a unique challenge. It requires to link the intracellular dynamics of gene regulation, through the mechanism of cell division, to the level of the population. We present experiments studying adaptive dynamics of populations of genetically homogeneous microorganisms (yeast), grown for long durations under steady conditions. We focus on population dynamics that do not involve random genetic mutations. Our experiments follow the long-term dynamics of the population distributions and allow to quantify the correlations among generations. We focus on three interconnected issues: adaptation of genetically homogeneous populations following environmental changes, selection processes on the population and population variability and expression distributions. We show that while the population exhibits specific short-term responses to environmental inputs, it eventually adapts to a robust steady-state, largely independent of external conditions. Cycles of medium-switch show that the adapted state is imprinted in the population and that this memory is maintained for many generations. To further study population adaptation, we utilize the process of gene recruitment whereby a gene naturally regulated by a specific promoter is placed under a different regulatory system. This naturally occurring process has been recognized as a major driving force in evolution. We have recruited an essential gene to a foreign regulatory network and followed the population long-term dynamics. Rewiring of the regulatory network allows us to expose their complex dynamics and phase space structure.

  5. Efficient experimental design for uncertainty reduction in gene regulatory networks.

    PubMed

    Dehghannasiri, Roozbeh; Yoon, Byung-Jun; Dougherty, Edward R

    2015-01-01

    An accurate understanding of interactions among genes plays a major role in developing therapeutic intervention methods. Gene regulatory networks often contain a significant amount of uncertainty. The process of prioritizing biological experiments to reduce the uncertainty of gene regulatory networks is called experimental design. Under such a strategy, the experiments with high priority are suggested to be conducted first. The authors have already proposed an optimal experimental design method based upon the objective for modeling gene regulatory networks, such as deriving therapeutic interventions. The experimental design method utilizes the concept of mean objective cost of uncertainty (MOCU). MOCU quantifies the expected increase of cost resulting from uncertainty. The optimal experiment to be conducted first is the one which leads to the minimum expected remaining MOCU subsequent to the experiment. In the process, one must find the optimal intervention for every gene regulatory network compatible with the prior knowledge, which can be prohibitively expensive when the size of the network is large. In this paper, we propose a computationally efficient experimental design method. This method incorporates a network reduction scheme by introducing a novel cost function that takes into account the disruption in the ranking of potential experiments. We then estimate the approximate expected remaining MOCU at a lower computational cost using the reduced networks. Simulation results based on synthetic and real gene regulatory networks show that the proposed approximate method has close performance to that of the optimal method but at lower computational cost. The proposed approximate method also outperforms the random selection policy significantly. A MATLAB software implementing the proposed experimental design method is available at http://gsp.tamu.edu/Publications/supplementary/roozbeh15a/.

  6. Genomic analysis of the hierarchical structure of regulatory networks

    PubMed Central

    Yu, Haiyuan; Gerstein, Mark

    2006-01-01

    A fundamental question in biology is how the cell uses transcription factors (TFs) to coordinate the expression of thousands of genes in response to various stimuli. The relationships between TFs and their target genes can be modeled in terms of directed regulatory networks. These relationships, in turn, can be readily compared with commonplace “chain-of-command” structures in social networks, which have characteristic hierarchical layouts. Here, we develop algorithms for identifying generalized hierarchies (allowing for various loop structures) and use these approaches to illuminate extensive pyramid-shaped hierarchical structures existing in the regulatory networks of representative prokaryotes (Escherichia coli) and eukaryotes (Saccharomyces cerevisiae), with most TFs at the bottom levels and only a few master TFs on top. These masters are situated near the center of the protein–protein interaction network, a different type of network from the regulatory one, and they receive most of the input for the whole regulatory hierarchy through protein interactions. Moreover, they have maximal influence over other genes, in terms of affecting expression-level changes. Surprisingly, however, TFs at the bottom of the regulatory hierarchy are more essential to the viability of the cell. Finally, one might think master TFs achieve their wide influence through directly regulating many targets, but TFs with most direct targets are in the middle of the hierarchy. We find, in fact, that these midlevel TFs are “control bottlenecks” in the hierarchy, and this great degree of control for “middle managers” has parallels in efficient social structures in various corporate and governmental settings. PMID:17003135

  7. Empirical Bayes conditional independence graphs for regulatory network recovery.

    PubMed

    Mahdi, Rami; Madduri, Abishek S; Wang, Guoqing; Strulovici-Barel, Yael; Salit, Jacqueline; Hackett, Neil R; Crystal, Ronald G; Mezey, Jason G

    2012-08-01

    Computational inference methods that make use of graphical models to extract regulatory networks from gene expression data can have difficulty reconstructing dense regions of a network, a consequence of both computational complexity and unreliable parameter estimation when sample size is small. As a result, identification of hub genes is of special difficulty for these methods. We present a new algorithm, Empirical Light Mutual Min (ELMM), for large network reconstruction that has properties well suited for recovery of graphs with high-degree nodes. ELMM reconstructs the undirected graph of a regulatory network using empirical Bayes conditional independence testing with a heuristic relaxation of independence constraints in dense areas of the graph. This relaxation allows only one gene of a pair with a putative relation to be aware of the network connection, an approach that is aimed at easing multiple testing problems associated with recovering densely connected structures. Using in silico data, we show that ELMM has better performance than commonly used network inference algorithms including GeneNet, ARACNE, FOCI, GENIE3 and GLASSO. We also apply ELMM to reconstruct a network among 5492 genes expressed in human lung airway epithelium of healthy non-smokers, healthy smokers and individuals with chronic obstructive pulmonary disease assayed using microarrays. The analysis identifies dense sub-networks that are consistent with known regulatory relationships in the lung airway and also suggests novel hub regulatory relationships among a number of genes that play roles in oxidative stress and secretion. Software for running ELMM is made available at http://mezeylab.cb.bscb.cornell.edu/Software.aspx. ramimahdi@yahoo.com or jgm45@cornell.edu Supplementary data are available at Bioinformatics online.

  8. Gene regulatory network inference using fused LASSO on multiple data sets

    PubMed Central

    Omranian, Nooshin; Eloundou-Mbebi, Jeanne M. O.; Mueller-Roeber, Bernd; Nikoloski, Zoran

    2016-01-01

    Devising computational methods to accurately reconstruct gene regulatory networks given gene expression data is key to systems biology applications. Here we propose a method for reconstructing gene regulatory networks by simultaneous consideration of data sets from different perturbation experiments and corresponding controls. The method imposes three biologically meaningful constraints: (1) expression levels of each gene should be explained by the expression levels of a small number of transcription factor coding genes, (2) networks inferred from different data sets should be similar with respect to the type and number of regulatory interactions, and (3) relationships between genes which exhibit similar differential behavior over the considered perturbations should be favored. We demonstrate that these constraints can be transformed in a fused LASSO formulation for the proposed method. The comparative analysis on transcriptomics time-series data from prokaryotic species, Escherichia coli and Mycobacterium tuberculosis, as well as a eukaryotic species, mouse, demonstrated that the proposed method has the advantages of the most recent approaches for regulatory network inference, while obtaining better performance and assigning higher scores to the true regulatory links. The study indicates that the combination of sparse regression techniques with other biologically meaningful constraints is a promising framework for gene regulatory network reconstructions. PMID:26864687

  9. Network architecture test-beds as platforms for ubiquitous computing.

    PubMed

    Roscoe, Timothy

    2008-10-28

    Distributed systems research, and in particular ubiquitous computing, has traditionally assumed the Internet as a basic underlying communications substrate. Recently, however, the networking research community has come to question the fundamental design or 'architecture' of the Internet. This has been led by two observations: first, that the Internet as it stands is now almost impossible to evolve to support new functionality; and second, that modern applications of all kinds now use the Internet rather differently, and frequently implement their own 'overlay' networks above it to work around its perceived deficiencies. In this paper, I discuss recent academic projects to allow disruptive change to the Internet architecture, and also outline a radically different view of networking for ubiquitous computing that such proposals might facilitate.

  10. A multi-agent system architecture for sensor networks.

    PubMed

    Fuentes-Fernández, Rubén; Guijarro, María; Pajares, Gonzalo

    2009-01-01

    The design of the control systems for sensor networks presents important challenges. Besides the traditional problems about how to process the sensor data to obtain the target information, engineers need to consider additional aspects such as the heterogeneity and high number of sensors, and the flexibility of these networks regarding topologies and the sensors in them. Although there are partial approaches for resolving these issues, their integration relies on ad hoc solutions requiring important development efforts. In order to provide an effective approach for this integration, this paper proposes an architecture based on the multi-agent system paradigm with a clear separation of concerns. The architecture considers sensors as devices used by an upper layer of manager agents. These agents are able to communicate and negotiate services to achieve the required functionality. Activities are organized according to roles related with the different aspects to integrate, mainly sensor management, data processing, communication and adaptation to changes in the available devices and their capabilities. This organization largely isolates and decouples the data management from the changing network, while encouraging reuse of solutions. The use of the architecture is facilitated by a specific modelling language developed through metamodelling. A case study concerning a generic distributed system for fire fighting illustrates the approach and the comparison with related work.

  11. rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks

    PubMed Central

    2018-01-01

    Abstract Here, we present the updated rSNPBase 3.0 database (http://rsnp3.psych.ac.cn), which provides human SNP-related regulatory elements, element-gene pairs and SNP-based regulatory networks. This database is the updated version of the SNP regulatory annotation database rSNPBase and rVarBase. In comparison to the last two versions, there are both structural and data adjustments in rSNPBase 3.0: (i) The most significant new feature is the expansion of analysis scope from SNP-related regulatory elements to include regulatory element–target gene pairs (E–G pairs), therefore it can provide SNP-based gene regulatory networks. (ii) Web function was modified according to data content and a new network search module is provided in the rSNPBase 3.0 in addition to the previous regulatory SNP (rSNP) search module. The two search modules support data query for detailed information (related-elements, element-gene pairs, and other extended annotations) on specific SNPs and SNP-related graphic networks constructed by interacting transcription factors (TFs), miRNAs and genes. (3) The type of regulatory elements was modified and enriched. To our best knowledge, the updated rSNPBase 3.0 is the first data tool supports SNP functional analysis from a regulatory network prospective, it will provide both a comprehensive understanding and concrete guidance for SNP-related regulatory studies. PMID:29140525

  12. Efficient experimental design for uncertainty reduction in gene regulatory networks

    PubMed Central

    2015-01-01

    Background An accurate understanding of interactions among genes plays a major role in developing therapeutic intervention methods. Gene regulatory networks often contain a significant amount of uncertainty. The process of prioritizing biological experiments to reduce the uncertainty of gene regulatory networks is called experimental design. Under such a strategy, the experiments with high priority are suggested to be conducted first. Results The authors have already proposed an optimal experimental design method based upon the objective for modeling gene regulatory networks, such as deriving therapeutic interventions. The experimental design method utilizes the concept of mean objective cost of uncertainty (MOCU). MOCU quantifies the expected increase of cost resulting from uncertainty. The optimal experiment to be conducted first is the one which leads to the minimum expected remaining MOCU subsequent to the experiment. In the process, one must find the optimal intervention for every gene regulatory network compatible with the prior knowledge, which can be prohibitively expensive when the size of the network is large. In this paper, we propose a computationally efficient experimental design method. This method incorporates a network reduction scheme by introducing a novel cost function that takes into account the disruption in the ranking of potential experiments. We then estimate the approximate expected remaining MOCU at a lower computational cost using the reduced networks. Conclusions Simulation results based on synthetic and real gene regulatory networks show that the proposed approximate method has close performance to that of the optimal method but at lower computational cost. The proposed approximate method also outperforms the random selection policy significantly. A MATLAB software implementing the proposed experimental design method is available at http://gsp.tamu.edu/Publications/supplementary/roozbeh15a/. PMID:26423515

  13. Routing architecture and security for airborne networks

    NASA Astrophysics Data System (ADS)

    Deng, Hongmei; Xie, Peng; Li, Jason; Xu, Roger; Levy, Renato

    2009-05-01

    Airborne networks are envisioned to provide interconnectivity for terrestial and space networks by interconnecting highly mobile airborne platforms. A number of military applications are expected to be used by the operator, and all these applications require proper routing security support to establish correct route between communicating platforms in a timely manner. As airborne networks somewhat different from traditional wired and wireless networks (e.g., Internet, LAN, WLAN, MANET, etc), security aspects valid in these networks are not fully applicable to airborne networks. Designing an efficient security scheme to protect airborne networks is confronted with new requirements. In this paper, we first identify a candidate routing architecture, which works as an underlying structure for our proposed security scheme. And then we investigate the vulnerabilities and attack models against routing protocols in airborne networks. Based on these studies, we propose an integrated security solution to address routing security issues in airborne networks.

  14. Variable neighborhood search for reverse engineering of gene regulatory networks.

    PubMed

    Nicholson, Charles; Goodwin, Leslie; Clark, Corey

    2017-01-01

    A new search heuristic, Divided Neighborhood Exploration Search, designed to be used with inference algorithms such as Bayesian networks to improve on the reverse engineering of gene regulatory networks is presented. The approach systematically moves through the search space to find topologies representative of gene regulatory networks that are more likely to explain microarray data. In empirical testing it is demonstrated that the novel method is superior to the widely employed greedy search techniques in both the quality of the inferred networks and computational time. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Reveal, A General Reverse Engineering Algorithm for Inference of Genetic Network Architectures

    NASA Technical Reports Server (NTRS)

    Liang, Shoudan; Fuhrman, Stefanie; Somogyi, Roland

    1998-01-01

    Given the immanent gene expression mapping covering whole genomes during development, health and disease, we seek computational methods to maximize functional inference from such large data sets. Is it possible, in principle, to completely infer a complex regulatory network architecture from input/output patterns of its variables? We investigated this possibility using binary models of genetic networks. Trajectories, or state transition tables of Boolean nets, resemble time series of gene expression. By systematically analyzing the mutual information between input states and output states, one is able to infer the sets of input elements controlling each element or gene in the network. This process is unequivocal and exact for complete state transition tables. We implemented this REVerse Engineering ALgorithm (REVEAL) in a C program, and found the problem to be tractable within the conditions tested so far. For n = 50 (elements) and k = 3 (inputs per element), the analysis of incomplete state transition tables (100 state transition pairs out of a possible 10(exp 15)) reliably produced the original rule and wiring sets. While this study is limited to synchronous Boolean networks, the algorithm is generalizable to include multi-state models, essentially allowing direct application to realistic biological data sets. The ability to adequately solve the inverse problem may enable in-depth analysis of complex dynamic systems in biology and other fields.

  16. Portrait of Candida Species Biofilm Regulatory Network Genes.

    PubMed

    Araújo, Daniela; Henriques, Mariana; Silva, Sónia

    2017-01-01

    Most cases of candidiasis have been attributed to Candida albicans, but Candida glabrata, Candida parapsilosis and Candida tropicalis, designated as non-C. albicans Candida (NCAC), have been identified as frequent human pathogens. Moreover, Candida biofilms are an escalating clinical problem associated with significant rates of mortality. Biofilms have distinct developmental phases, including adhesion/colonisation, maturation and dispersal, controlled by complex regulatory networks. This review discusses recent advances regarding Candida species biofilm regulatory network genes, which are key components for candidiasis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Understanding genetic regulatory networks

    NASA Astrophysics Data System (ADS)

    Kauffman, Stuart

    2003-04-01

    Random Boolean networks (RBM) were introduced about 35 years ago as first crude models of genetic regulatory networks. RBNs are comprised of N on-off genes, connected by a randomly assigned regulatory wiring diagram where each gene has K inputs, and each gene is controlled by a randomly assigned Boolean function. This procedure samples at random from the ensemble of all possible NK Boolean networks. The central ideas are to study the typical, or generic properties of this ensemble, and see 1) whether characteristic differences appear as K and biases in Boolean functions are introducted, and 2) whether a subclass of this ensemble has properties matching real cells. Such networks behave in an ordered or a chaotic regime, with a phase transition, "the edge of chaos" between the two regimes. Networks with continuous variables exhibit the same two regimes. Substantial evidence suggests that real cells are in the ordered regime. A key concept is that of an attractor. This is a reentrant trajectory of states of the network, called a state cycle. The central biological interpretation is that cell types are attractors. A number of properties differentiate the ordered and chaotic regimes. These include the size and number of attractors, the existence in the ordered regime of a percolating "sea" of genes frozen in the on or off state, with a remainder of isolated twinkling islands of genes, a power law distribution of avalanches of gene activity changes following perturbation to a single gene in the ordered regime versus a similar power law distribution plus a spike of enormous avalanches of gene changes in the chaotic regime, and the existence of branching pathway of "differentiation" between attractors induced by perturbations in the ordered regime. Noise is serious issue, since noise disrupts attractors. But numerical evidence suggests that attractors can be made very stable to noise, and meanwhile, metaplasias may be a biological manifestation of noise. As we learn more

  18. Automatic inference of multicellular regulatory networks using informative priors.

    PubMed

    Sun, Xiaoyun; Hong, Pengyu

    2009-01-01

    To fully understand the mechanisms governing animal development, computational models and algorithms are needed to enable quantitative studies of the underlying regulatory networks. We developed a mathematical model based on dynamic Bayesian networks to model multicellular regulatory networks that govern cell differentiation processes. A machine-learning method was developed to automatically infer such a model from heterogeneous data. We show that the model inference procedure can be greatly improved by incorporating interaction data across species. The proposed approach was applied to C. elegans vulval induction to reconstruct a model capable of simulating C. elegans vulval induction under 73 different genetic conditions.

  19. Robust quantum network architectures and topologies for entanglement distribution

    NASA Astrophysics Data System (ADS)

    Das, Siddhartha; Khatri, Sumeet; Dowling, Jonathan P.

    2018-01-01

    Entanglement distribution is a prerequisite for several important quantum information processing and computing tasks, such as quantum teleportation, quantum key distribution, and distributed quantum computing. In this work, we focus on two-dimensional quantum networks based on optical quantum technologies using dual-rail photonic qubits for the building of a fail-safe quantum internet. We lay out a quantum network architecture for entanglement distribution between distant parties using a Bravais lattice topology, with the technological constraint that quantum repeaters equipped with quantum memories are not easily accessible. We provide a robust protocol for simultaneous entanglement distribution between two distant groups of parties on this network. We also discuss a memory-based quantum network architecture that can be implemented on networks with an arbitrary topology. We examine networks with bow-tie lattice and Archimedean lattice topologies and use percolation theory to quantify the robustness of the networks. In particular, we provide figures of merit on the loss parameter of the optical medium that depend only on the topology of the network and quantify the robustness of the network against intermittent photon loss and intermittent failure of nodes. These figures of merit can be used to compare the robustness of different network topologies in order to determine the best topology in a given real-world scenario, which is critical in the realization of the quantum internet.

  20. The Reconstruction and Analysis of Gene Regulatory Networks.

    PubMed

    Zheng, Guangyong; Huang, Tao

    2018-01-01

    In post-genomic era, an important task is to explore the function of individual biological molecules (i.e., gene, noncoding RNA, protein, metabolite) and their organization in living cells. For this end, gene regulatory networks (GRNs) are constructed to show relationship between biological molecules, in which the vertices of network denote biological molecules and the edges of network present connection between nodes (Strogatz, Nature 410:268-276, 2001; Bray, Science 301:1864-1865, 2003). Biologists can understand not only the function of biological molecules but also the organization of components of living cells through interpreting the GRNs, since a gene regulatory network is a comprehensively physiological map of living cells and reflects influence of genetic and epigenetic factors (Strogatz, Nature 410:268-276, 2001; Bray, Science 301:1864-1865, 2003). In this paper, we will review the inference methods of GRN reconstruction and analysis approaches of network structure. As a powerful tool for studying complex diseases and biological processes, the applications of the network method in pathway analysis and disease gene identification will be introduced.

  1. Criteria for Evaluating Alternative Network and Link Layer Protocols for the NASA Constellation Program Communication Architecture

    NASA Technical Reports Server (NTRS)

    Benbenek, Daniel; Soloff, Jason; Lieb, Erica

    2010-01-01

    Selecting a communications and network architecture for future manned space flight requires an evaluation of the varying goals and objectives of the program, development of communications and network architecture evaluation criteria, and assessment of critical architecture trades. This paper uses Cx Program proposed exploration activities as a guideline; lunar sortie, outpost, Mars, and flexible path options are described. A set of proposed communications network architecture criteria are proposed and described. They include: interoperability, security, reliability, and ease of automating topology changes. Finally a key set of architecture options are traded including (1) multiplexing data at a common network layer vs. at the data link layer, (2) implementing multiple network layers vs. a single network layer, and (3) the use of a particular network layer protocol, primarily IPv6 vs. Delay Tolerant Networking (DTN). In summary, the protocol options are evaluated against the proposed exploration activities and their relative performance with respect to the criteria are assessed. An architectural approach which includes (a) the capability of multiplexing at both the network layer and the data link layer and (b) a single network layer for operations at each program phase, as these solutions are best suited to respond to the widest array of program needs and meet each of the evaluation criteria.

  2. rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks.

    PubMed

    Guo, Liyuan; Wang, Jing

    2018-01-04

    Here, we present the updated rSNPBase 3.0 database (http://rsnp3.psych.ac.cn), which provides human SNP-related regulatory elements, element-gene pairs and SNP-based regulatory networks. This database is the updated version of the SNP regulatory annotation database rSNPBase and rVarBase. In comparison to the last two versions, there are both structural and data adjustments in rSNPBase 3.0: (i) The most significant new feature is the expansion of analysis scope from SNP-related regulatory elements to include regulatory element-target gene pairs (E-G pairs), therefore it can provide SNP-based gene regulatory networks. (ii) Web function was modified according to data content and a new network search module is provided in the rSNPBase 3.0 in addition to the previous regulatory SNP (rSNP) search module. The two search modules support data query for detailed information (related-elements, element-gene pairs, and other extended annotations) on specific SNPs and SNP-related graphic networks constructed by interacting transcription factors (TFs), miRNAs and genes. (3) The type of regulatory elements was modified and enriched. To our best knowledge, the updated rSNPBase 3.0 is the first data tool supports SNP functional analysis from a regulatory network prospective, it will provide both a comprehensive understanding and concrete guidance for SNP-related regulatory studies. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Predictive regulatory models in Drosophila melanogaster by integrative inference of transcriptional networks

    PubMed Central

    Marbach, Daniel; Roy, Sushmita; Ay, Ferhat; Meyer, Patrick E.; Candeias, Rogerio; Kahveci, Tamer; Bristow, Christopher A.; Kellis, Manolis

    2012-01-01

    Gaining insights on gene regulation from large-scale functional data sets is a grand challenge in systems biology. In this article, we develop and apply methods for transcriptional regulatory network inference from diverse functional genomics data sets and demonstrate their value for gene function and gene expression prediction. We formulate the network inference problem in a machine-learning framework and use both supervised and unsupervised methods to predict regulatory edges by integrating transcription factor (TF) binding, evolutionarily conserved sequence motifs, gene expression, and chromatin modification data sets as input features. Applying these methods to Drosophila melanogaster, we predict ∼300,000 regulatory edges in a network of ∼600 TFs and 12,000 target genes. We validate our predictions using known regulatory interactions, gene functional annotations, tissue-specific expression, protein–protein interactions, and three-dimensional maps of chromosome conformation. We use the inferred network to identify putative functions for hundreds of previously uncharacterized genes, including many in nervous system development, which are independently confirmed based on their tissue-specific expression patterns. Last, we use the regulatory network to predict target gene expression levels as a function of TF expression, and find significantly higher predictive power for integrative networks than for motif or ChIP-based networks. Our work reveals the complementarity between physical evidence of regulatory interactions (TF binding, motif conservation) and functional evidence (coordinated expression or chromatin patterns) and demonstrates the power of data integration for network inference and studies of gene regulation at the systems level. PMID:22456606

  4. A Multi-Agent System Architecture for Sensor Networks

    PubMed Central

    Fuentes-Fernández, Rubén; Guijarro, María; Pajares, Gonzalo

    2009-01-01

    The design of the control systems for sensor networks presents important challenges. Besides the traditional problems about how to process the sensor data to obtain the target information, engineers need to consider additional aspects such as the heterogeneity and high number of sensors, and the flexibility of these networks regarding topologies and the sensors in them. Although there are partial approaches for resolving these issues, their integration relies on ad hoc solutions requiring important development efforts. In order to provide an effective approach for this integration, this paper proposes an architecture based on the multi-agent system paradigm with a clear separation of concerns. The architecture considers sensors as devices used by an upper layer of manager agents. These agents are able to communicate and negotiate services to achieve the required functionality. Activities are organized according to roles related with the different aspects to integrate, mainly sensor management, data processing, communication and adaptation to changes in the available devices and their capabilities. This organization largely isolates and decouples the data management from the changing network, while encouraging reuse of solutions. The use of the architecture is facilitated by a specific modelling language developed through metamodelling. A case study concerning a generic distributed system for fire fighting illustrates the approach and the comparison with related work. PMID:22303172

  5. PathCase-SB architecture and database design

    PubMed Central

    2011-01-01

    Background Integration of metabolic pathways resources and regulatory metabolic network models, and deploying new tools on the integrated platform can help perform more effective and more efficient systems biology research on understanding the regulation in metabolic networks. Therefore, the tasks of (a) integrating under a single database environment regulatory metabolic networks and existing models, and (b) building tools to help with modeling and analysis are desirable and intellectually challenging computational tasks. Description PathCase Systems Biology (PathCase-SB) is built and released. The PathCase-SB database provides data and API for multiple user interfaces and software tools. The current PathCase-SB system provides a database-enabled framework and web-based computational tools towards facilitating the development of kinetic models for biological systems. PathCase-SB aims to integrate data of selected biological data sources on the web (currently, BioModels database and KEGG), and to provide more powerful and/or new capabilities via the new web-based integrative framework. This paper describes architecture and database design issues encountered in PathCase-SB's design and implementation, and presents the current design of PathCase-SB's architecture and database. Conclusions PathCase-SB architecture and database provide a highly extensible and scalable environment with easy and fast (real-time) access to the data in the database. PathCase-SB itself is already being used by researchers across the world. PMID:22070889

  6. Gene regulatory and signaling networks exhibit distinct topological distributions of motifs

    NASA Astrophysics Data System (ADS)

    Ferreira, Gustavo Rodrigues; Nakaya, Helder Imoto; Costa, Luciano da Fontoura

    2018-04-01

    The biological processes of cellular decision making and differentiation involve a plethora of signaling pathways and gene regulatory circuits. These networks in turn exhibit a multitude of motifs playing crucial parts in regulating network activity. Here we compare the topological placement of motifs in gene regulatory and signaling networks and observe that it suggests different evolutionary strategies in motif distribution for distinct cellular subnetworks.

  7. NATO Human View Architecture and Human Networks

    NASA Technical Reports Server (NTRS)

    Handley, Holly A. H.; Houston, Nancy P.

    2010-01-01

    The NATO Human View is a system architectural viewpoint that focuses on the human as part of a system. Its purpose is to capture the human requirements and to inform on how the human impacts the system design. The viewpoint contains seven static models that include different aspects of the human element, such as roles, tasks, constraints, training and metrics. It also includes a Human Dynamics component to perform simulations of the human system under design. One of the static models, termed Human Networks, focuses on the human-to-human communication patterns that occur as a result of ad hoc or deliberate team formation, especially teams distributed across space and time. Parameters of human teams that effect system performance can be captured in this model. Human centered aspects of networks, such as differences in operational tempo (sense of urgency), priorities (common goal), and team history (knowledge of the other team members), can be incorporated. The information captured in the Human Network static model can then be included in the Human Dynamics component so that the impact of distributed teams is represented in the simulation. As the NATO militaries transform to a more networked force, the Human View architecture is an important tool that can be used to make recommendations on the proper mix of technological innovations and human interactions.

  8. Modelling and analysis of gene regulatory network using feedback control theory

    NASA Astrophysics Data System (ADS)

    El-Samad, H.; Khammash, M.

    2010-01-01

    Molecular pathways are a part of a remarkable hierarchy of regulatory networks that operate at all levels of organisation. These regulatory networks are responsible for much of the biological complexity within the cell. The dynamic character of these pathways and the prevalence of feedback regulation strategies in their operation make them amenable to systematic mathematical analysis using the same tools that have been used with success in analysing and designing engineering control systems. In this article, we aim at establishing this strong connection through various examples where the behaviour exhibited by gene networks is explained in terms of their underlying control strategies. We complement our analysis by a survey of mathematical techniques commonly used to model gene regulatory networks and analyse their dynamic behaviour.

  9. Centralized and distributed control architectures under Foundation Fieldbus network.

    PubMed

    Persechini, Maria Auxiliadora Muanis; Jota, Fábio Gonçalves

    2013-01-01

    This paper aims at discussing possible automation and control system architectures based on fieldbus networks in which the controllers can be implemented either in a centralized or in a distributed form. An experimental setup is used to demonstrate some of the addressed issues. The control and automation architecture is composed of a supervisory system, a programmable logic controller and various other devices connected to a Foundation Fieldbus H1 network. The procedures used in the network configuration, in the process modelling and in the design and implementation of controllers are described. The specificities of each one of the considered logical organizations are also discussed. Finally, experimental results are analysed using an algorithm for the assessment of control loops to compare the performances between the centralized and the distributed implementations. Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.

  10. A neural network architecture for implementation of expert systems for real time monitoring

    NASA Technical Reports Server (NTRS)

    Ramamoorthy, P. A.

    1991-01-01

    Since neural networks have the advantages of massive parallelism and simple architecture, they are good tools for implementing real time expert systems. In a rule based expert system, the antecedents of rules are in the conjunctive or disjunctive form. We constructed a multilayer feedforward type network in which neurons represent AND or OR operations of rules. Further, we developed a translator which can automatically map a given rule base into the network. Also, we proposed a new and powerful yet flexible architecture that combines the advantages of both fuzzy expert systems and neural networks. This architecture uses the fuzzy logic concepts to separate input data domains into several smaller and overlapped regions. Rule-based expert systems for time critical applications using neural networks, the automated implementation of rule-based expert systems with neural nets, and fuzzy expert systems vs. neural nets are covered.

  11. A comparison of neural network architectures for the prediction of MRR in EDM

    NASA Astrophysics Data System (ADS)

    Jena, A. R.; Das, Raja

    2017-11-01

    The aim of the research work is to predict the material removal rate of a work-piece in electrical discharge machining (EDM). Here, an effort has been made to predict the material removal rate through back-propagation neural network (BPN) and radial basis function neural network (RBFN) for a work-piece of AISI D2 steel. The input parameters for the architecture are discharge-current (Ip), pulse-duration (Ton), and duty-cycle (τ) taken for consideration to obtained the output for material removal rate of the work-piece. In the architecture, it has been observed that radial basis function neural network is comparatively faster than back-propagation neural network but logically back-propagation neural network results more real value. Therefore BPN may consider as a better process in this architecture for consistent prediction to save time and money for conducting experiments.

  12. Sieve-based relation extraction of gene regulatory networks from biological literature

    PubMed Central

    2015-01-01

    Background Relation extraction is an essential procedure in literature mining. It focuses on extracting semantic relations between parts of text, called mentions. Biomedical literature includes an enormous amount of textual descriptions of biological entities, their interactions and results of related experiments. To extract them in an explicit, computer readable format, these relations were at first extracted manually from databases. Manual curation was later replaced with automatic or semi-automatic tools with natural language processing capabilities. The current challenge is the development of information extraction procedures that can directly infer more complex relational structures, such as gene regulatory networks. Results We develop a computational approach for extraction of gene regulatory networks from textual data. Our method is designed as a sieve-based system and uses linear-chain conditional random fields and rules for relation extraction. With this method we successfully extracted the sporulation gene regulation network in the bacterium Bacillus subtilis for the information extraction challenge at the BioNLP 2013 conference. To enable extraction of distant relations using first-order models, we transform the data into skip-mention sequences. We infer multiple models, each of which is able to extract different relationship types. Following the shared task, we conducted additional analysis using different system settings that resulted in reducing the reconstruction error of bacterial sporulation network from 0.73 to 0.68, measured as the slot error rate between the predicted and the reference network. We observe that all relation extraction sieves contribute to the predictive performance of the proposed approach. Also, features constructed by considering mention words and their prefixes and suffixes are the most important features for higher accuracy of extraction. Analysis of distances between different mention types in the text shows that our choice

  13. Sieve-based relation extraction of gene regulatory networks from biological literature.

    PubMed

    Žitnik, Slavko; Žitnik, Marinka; Zupan, Blaž; Bajec, Marko

    2015-01-01

    Relation extraction is an essential procedure in literature mining. It focuses on extracting semantic relations between parts of text, called mentions. Biomedical literature includes an enormous amount of textual descriptions of biological entities, their interactions and results of related experiments. To extract them in an explicit, computer readable format, these relations were at first extracted manually from databases. Manual curation was later replaced with automatic or semi-automatic tools with natural language processing capabilities. The current challenge is the development of information extraction procedures that can directly infer more complex relational structures, such as gene regulatory networks. We develop a computational approach for extraction of gene regulatory networks from textual data. Our method is designed as a sieve-based system and uses linear-chain conditional random fields and rules for relation extraction. With this method we successfully extracted the sporulation gene regulation network in the bacterium Bacillus subtilis for the information extraction challenge at the BioNLP 2013 conference. To enable extraction of distant relations using first-order models, we transform the data into skip-mention sequences. We infer multiple models, each of which is able to extract different relationship types. Following the shared task, we conducted additional analysis using different system settings that resulted in reducing the reconstruction error of bacterial sporulation network from 0.73 to 0.68, measured as the slot error rate between the predicted and the reference network. We observe that all relation extraction sieves contribute to the predictive performance of the proposed approach. Also, features constructed by considering mention words and their prefixes and suffixes are the most important features for higher accuracy of extraction. Analysis of distances between different mention types in the text shows that our choice of transforming

  14. Reconstructing genome-wide regulatory network of E. coli using transcriptome data and predicted transcription factor activities

    PubMed Central

    2011-01-01

    Background Gene regulatory networks play essential roles in living organisms to control growth, keep internal metabolism running and respond to external environmental changes. Understanding the connections and the activity levels of regulators is important for the research of gene regulatory networks. While relevance score based algorithms that reconstruct gene regulatory networks from transcriptome data can infer genome-wide gene regulatory networks, they are unfortunately prone to false positive results. Transcription factor activities (TFAs) quantitatively reflect the ability of the transcription factor to regulate target genes. However, classic relevance score based gene regulatory network reconstruction algorithms use models do not include the TFA layer, thus missing a key regulatory element. Results This work integrates TFA prediction algorithms with relevance score based network reconstruction algorithms to reconstruct gene regulatory networks with improved accuracy over classic relevance score based algorithms. This method is called Gene expression and Transcription factor activity based Relevance Network (GTRNetwork). Different combinations of TFA prediction algorithms and relevance score functions have been applied to find the most efficient combination. When the integrated GTRNetwork method was applied to E. coli data, the reconstructed genome-wide gene regulatory network predicted 381 new regulatory links. This reconstructed gene regulatory network including the predicted new regulatory links show promising biological significances. Many of the new links are verified by known TF binding site information, and many other links can be verified from the literature and databases such as EcoCyc. The reconstructed gene regulatory network is applied to a recent transcriptome analysis of E. coli during isobutanol stress. In addition to the 16 significantly changed TFAs detected in the original paper, another 7 significantly changed TFAs have been detected by

  15. Architecture and System Engineering Development Study of Space-Based Satellite Networks for NASA Missions

    NASA Technical Reports Server (NTRS)

    Ivancic, William D.

    2003-01-01

    Traditional NASA missions, both near Earth and deep space, have been stovepipe in nature and point-to-point in architecture. Recently, NASA and others have conceptualized missions that required space-based networking. The notion of networks in space is a drastic shift in thinking and requires entirely new architectures, radio systems (antennas, modems, and media access), and possibly even new protocols. A full system engineering approach for some key mission architectures will occur that considers issues such as the science being performed, stationkeeping, antenna size, contact time, data rates, radio-link power requirements, media access techniques, and appropriate networking and transport protocols. This report highlights preliminary architecture concepts and key technologies that will be investigated.

  16. Competing endogenous RNA regulatory network in papillary thyroid carcinoma.

    PubMed

    Chen, Shouhua; Fan, Xiaobin; Gu, He; Zhang, Lili; Zhao, Wenhua

    2018-05-11

    The present study aimed to screen all types of RNAs involved in the development of papillary thyroid carcinoma (PTC). RNA‑sequencing data of PTC and normal samples were used for screening differentially expressed (DE) microRNAs (DE‑miRNAs), long non‑coding RNAs (DE‑lncRNAs) and genes (DEGs). Subsequently, lncRNA‑miRNA, miRNA‑gene (that is, miRNA‑mRNA) and gene‑gene interaction pairs were extracted and used to construct regulatory networks. Feature genes in the miRNA‑mRNA network were identified by topological analysis and recursive feature elimination analysis. A support vector machine (SVM) classifier was built using 15 feature genes, and its classification effect was validated using two microarray data sets that were downloaded from the Gene Expression Omnibus (GEO) database. In addition, Gene Ontology function and Kyoto Encyclopedia Genes and Genomes pathway enrichment analyses were conducted for genes identified in the ceRNA network. A total of 506 samples, including 447 tumor samples and 59 normal samples, were obtained from The Cancer Genome Atlas (TCGA); 16 DE‑lncRNAs, 917 DEGs and 30 DE‑miRNAs were screened. The miRNA‑mRNA regulatory network comprised 353 nodes and 577 interactions. From these data, 15 feature genes with high predictive precision (>95%) were extracted from the network and were used to form an SVM classifier with an accuracy of 96.05% (486/506) for PTC samples downloaded from TCGA, and accuracies of 96.81 and 98.46% for GEO downloaded data sets. The ceRNA regulatory network comprised 596 lines (or interactions) and 365 nodes. Genes in the ceRNA network were significantly enriched in 'neuron development', 'differentiation', 'neuroactive ligand‑receptor interaction', 'metabolism of xenobiotics by cytochrome P450', 'drug metabolism' and 'cytokine‑cytokine receptor interaction' pathways. Hox transcript antisense RNA, miRNA‑206 and kallikrein‑related peptidase 10 were nodes in the ceRNA regulatory network

  17. Proceedings of the Second Software Architecture Technology User Network (SATURN) Workshop

    DTIC Science & Technology

    2006-08-01

    Proceedings of the Second Software Architecture Technology User Network (SATURN) Workshop Robert L. Nord August 2006 TECHNICAL REPORT CMU...SEI-2006-TR-010 ESC-TR-2006-010 Software Architecture Technology Initiative Unlimited distribution subject to the copyright. This report was...Participants 3 3 Presentations 5 3.1 SATURN Opening Presentation: Future Directions of the Software Architecture Technology Initiative 5 3.2 Keynote

  18. Development of the network architecture of the Canadian MSAT system

    NASA Technical Reports Server (NTRS)

    Davies, N. George; Shoamanesh, Alireza; Leung, Victor C. M.

    1988-01-01

    A description is given of the present concept for the Canadian Mobile Satellite (MSAT) System and the development of the network architecture which will accommodate the planned family of three categories of service: a mobile radio service (MRS), a mobile telephone service (MTS), and a mobile data service (MDS). The MSAT satellite will have cross-strapped L-band and Ku-band transponders to provide communications services between L-band mobile terminals and fixed base stations supporting dispatcher-type MRS, gateway stations supporting MTS interconnections to the public telephone network, data hub stations supporting the MDS, and the network control center. The currently perceived centralized architecture with demand assignment multiple access for the circuit switched MRS, MTS and permanently assigned channels for the packet switched MDS is discussed.

  19. Development of the network architecture of the Canadian MSAT system

    NASA Astrophysics Data System (ADS)

    Davies, N. George; Shoamanesh, Alireza; Leung, Victor C. M.

    1988-05-01

    A description is given of the present concept for the Canadian Mobile Satellite (MSAT) System and the development of the network architecture which will accommodate the planned family of three categories of service: a mobile radio service (MRS), a mobile telephone service (MTS), and a mobile data service (MDS). The MSAT satellite will have cross-strapped L-band and Ku-band transponders to provide communications services between L-band mobile terminals and fixed base stations supporting dispatcher-type MRS, gateway stations supporting MTS interconnections to the public telephone network, data hub stations supporting the MDS, and the network control center. The currently perceived centralized architecture with demand assignment multiple access for the circuit switched MRS, MTS and permanently assigned channels for the packet switched MDS is discussed.

  20. Learning a Markov Logic network for supervised gene regulatory network inference

    PubMed Central

    2013-01-01

    Background Gene regulatory network inference remains a challenging problem in systems biology despite the numerous approaches that have been proposed. When substantial knowledge on a gene regulatory network is already available, supervised network inference is appropriate. Such a method builds a binary classifier able to assign a class (Regulation/No regulation) to an ordered pair of genes. Once learnt, the pairwise classifier can be used to predict new regulations. In this work, we explore the framework of Markov Logic Networks (MLN) that combine features of probabilistic graphical models with the expressivity of first-order logic rules. Results We propose to learn a Markov Logic network, e.g. a set of weighted rules that conclude on the predicate “regulates”, starting from a known gene regulatory network involved in the switch proliferation/differentiation of keratinocyte cells, a set of experimental transcriptomic data and various descriptions of genes all encoded into first-order logic. As training data are unbalanced, we use asymmetric bagging to learn a set of MLNs. The prediction of a new regulation can then be obtained by averaging predictions of individual MLNs. As a side contribution, we propose three in silico tests to assess the performance of any pairwise classifier in various network inference tasks on real datasets. A first test consists of measuring the average performance on balanced edge prediction problem; a second one deals with the ability of the classifier, once enhanced by asymmetric bagging, to update a given network. Finally our main result concerns a third test that measures the ability of the method to predict regulations with a new set of genes. As expected, MLN, when provided with only numerical discretized gene expression data, does not perform as well as a pairwise SVM in terms of AUPR. However, when a more complete description of gene properties is provided by heterogeneous sources, MLN achieves the same performance as a black

  1. Learning a Markov Logic network for supervised gene regulatory network inference.

    PubMed

    Brouard, Céline; Vrain, Christel; Dubois, Julie; Castel, David; Debily, Marie-Anne; d'Alché-Buc, Florence

    2013-09-12

    Gene regulatory network inference remains a challenging problem in systems biology despite the numerous approaches that have been proposed. When substantial knowledge on a gene regulatory network is already available, supervised network inference is appropriate. Such a method builds a binary classifier able to assign a class (Regulation/No regulation) to an ordered pair of genes. Once learnt, the pairwise classifier can be used to predict new regulations. In this work, we explore the framework of Markov Logic Networks (MLN) that combine features of probabilistic graphical models with the expressivity of first-order logic rules. We propose to learn a Markov Logic network, e.g. a set of weighted rules that conclude on the predicate "regulates", starting from a known gene regulatory network involved in the switch proliferation/differentiation of keratinocyte cells, a set of experimental transcriptomic data and various descriptions of genes all encoded into first-order logic. As training data are unbalanced, we use asymmetric bagging to learn a set of MLNs. The prediction of a new regulation can then be obtained by averaging predictions of individual MLNs. As a side contribution, we propose three in silico tests to assess the performance of any pairwise classifier in various network inference tasks on real datasets. A first test consists of measuring the average performance on balanced edge prediction problem; a second one deals with the ability of the classifier, once enhanced by asymmetric bagging, to update a given network. Finally our main result concerns a third test that measures the ability of the method to predict regulations with a new set of genes. As expected, MLN, when provided with only numerical discretized gene expression data, does not perform as well as a pairwise SVM in terms of AUPR. However, when a more complete description of gene properties is provided by heterogeneous sources, MLN achieves the same performance as a black-box model such as a

  2. A gene regulatory network armature for T-lymphocyte specification

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fung, Elizabeth-sharon

    Choice of a T-lymphoid fate by hematopoietic progenitor cells depends on sustained Notch-Delta signaling combined with tightly-regulated activities of multiple transcription factors. To dissect the regulatory network connections that mediate this process, we have used high-resolution analysis of regulatory gene expression trajectories from the beginning to the end of specification; tests of the short-term Notchdependence of these gene expression changes; and perturbation analyses of the effects of overexpression of two essential transcription factors, namely PU.l and GATA-3. Quantitative expression measurements of >50 transcription factor and marker genes have been used to derive the principal components of regulatory change through whichmore » T-cell precursors progress from primitive multipotency to T-lineage commitment. Distinct parts of the path reveal separate contributions of Notch signaling, GATA-3 activity, and downregulation of PU.l. Using BioTapestry, the results have been assembled into a draft gene regulatory network for the specification of T-cell precursors and the choice of T as opposed to myeloid dendritic or mast-cell fates. This network also accommodates effects of E proteins and mutual repression circuits of Gfil against Egr-2 and of TCF-l against PU.l as proposed elsewhere, but requires additional functions that remain unidentified. Distinctive features of this network structure include the intense dose-dependence of GATA-3 effects; the gene-specific modulation of PU.l activity based on Notch activity; the lack of direct opposition between PU.l and GATA-3; and the need for a distinct, late-acting repressive function or functions to extinguish stem and progenitor-derived regulatory gene expression.« less

  3. Actin assembly factors regulate the gelation kinetics and architecture of F-actin networks.

    PubMed

    Falzone, Tobias T; Oakes, Patrick W; Sees, Jennifer; Kovar, David R; Gardel, Margaret L

    2013-04-16

    Dynamic regulation of the actin cytoskeleton is required for diverse cellular processes. Proteins regulating the assembly kinetics of the cytoskeletal biopolymer F-actin are known to impact the architecture of actin cytoskeletal networks in vivo, but the underlying mechanisms are not well understood. Here, we demonstrate that changes to actin assembly kinetics with physiologically relevant proteins profilin and formin (mDia1 and Cdc12) have dramatic consequences on the architecture and gelation kinetics of otherwise biochemically identical cross-linked F-actin networks. Reduced F-actin nucleation rates promote the formation of a sparse network of thick bundles, whereas increased nucleation rates result in a denser network of thinner bundles. Changes to F-actin elongation rates also have marked consequences. At low elongation rates, gelation ceases and a solution of rigid bundles is formed. By contrast, rapid filament elongation accelerates dynamic arrest and promotes gelation with minimal F-actin density. These results are consistent with a recently developed model of how kinetic constraints regulate network architecture and underscore how molecular control of polymer assembly is exploited to modulate cytoskeletal architecture and material properties. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. Framewise phoneme classification with bidirectional LSTM and other neural network architectures.

    PubMed

    Graves, Alex; Schmidhuber, Jürgen

    2005-01-01

    In this paper, we present bidirectional Long Short Term Memory (LSTM) networks, and a modified, full gradient version of the LSTM learning algorithm. We evaluate Bidirectional LSTM (BLSTM) and several other network architectures on the benchmark task of framewise phoneme classification, using the TIMIT database. Our main findings are that bidirectional networks outperform unidirectional ones, and Long Short Term Memory (LSTM) is much faster and also more accurate than both standard Recurrent Neural Nets (RNNs) and time-windowed Multilayer Perceptrons (MLPs). Our results support the view that contextual information is crucial to speech processing, and suggest that BLSTM is an effective architecture with which to exploit it.

  5. Relationships between probabilistic Boolean networks and dynamic Bayesian networks as models of gene regulatory networks

    PubMed Central

    Lähdesmäki, Harri; Hautaniemi, Sampsa; Shmulevich, Ilya; Yli-Harja, Olli

    2006-01-01

    A significant amount of attention has recently been focused on modeling of gene regulatory networks. Two frequently used large-scale modeling frameworks are Bayesian networks (BNs) and Boolean networks, the latter one being a special case of its recent stochastic extension, probabilistic Boolean networks (PBNs). PBN is a promising model class that generalizes the standard rule-based interactions of Boolean networks into the stochastic setting. Dynamic Bayesian networks (DBNs) is a general and versatile model class that is able to represent complex temporal stochastic processes and has also been proposed as a model for gene regulatory systems. In this paper, we concentrate on these two model classes and demonstrate that PBNs and a certain subclass of DBNs can represent the same joint probability distribution over their common variables. The major benefit of introducing the relationships between the models is that it opens up the possibility of applying the standard tools of DBNs to PBNs and vice versa. Hence, the standard learning tools of DBNs can be applied in the context of PBNs, and the inference methods give a natural way of handling the missing values in PBNs which are often present in gene expression measurements. Conversely, the tools for controlling the stationary behavior of the networks, tools for projecting networks onto sub-networks, and efficient learning schemes can be used for DBNs. In other words, the introduced relationships between the models extend the collection of analysis tools for both model classes. PMID:17415411

  6. An Energy-Efficient and High-Quality Video Transmission Architecture in Wireless Video-Based Sensor Networks.

    PubMed

    Aghdasi, Hadi S; Abbaspour, Maghsoud; Moghadam, Mohsen Ebrahimi; Samei, Yasaman

    2008-08-04

    Technological progress in the fields of Micro Electro-Mechanical Systems (MEMS) and wireless communications and also the availability of CMOS cameras, microphones and small-scale array sensors, which may ubiquitously capture multimedia content from the field, have fostered the development of low-cost limited resources Wireless Video-based Sensor Networks (WVSN). With regards to the constraints of videobased sensor nodes and wireless sensor networks, a supporting video stream is not easy to implement with the present sensor network protocols. In this paper, a thorough architecture is presented for video transmission over WVSN called Energy-efficient and high-Quality Video transmission Architecture (EQV-Architecture). This architecture influences three layers of communication protocol stack and considers wireless video sensor nodes constraints like limited process and energy resources while video quality is preserved in the receiver side. Application, transport, and network layers are the layers in which the compression protocol, transport protocol, and routing protocol are proposed respectively, also a dropping scheme is presented in network layer. Simulation results over various environments with dissimilar conditions revealed the effectiveness of the architecture in improving the lifetime of the network as well as preserving the video quality.

  7. Modeling of a 3DTV service in the software-defined networking architecture

    NASA Astrophysics Data System (ADS)

    Wilczewski, Grzegorz

    2014-11-01

    In this article a newly developed concept towards modeling of a multimedia service offering stereoscopic motion imagery is presented. Proposed model is based on the approach of utilization of Software-defined Networking or Software Defined Networks architecture (SDN). The definition of 3D television service spanning SDN concept is identified, exposing basic characteristic of a 3DTV service in a modern networking organization layout. Furthermore, exemplary functionalities of the proposed 3DTV model are depicted. It is indicated that modeling of a 3DTV service in the Software-defined Networking architecture leads to multiplicity of improvements, especially towards flexibility of a service supporting heterogeneity of end user devices.

  8. Network Modeling Reveals Prevalent Negative Regulatory Relationships between Signaling Sectors in Arabidopsis Immune Signaling

    PubMed Central

    Sato, Masanao; Tsuda, Kenichi; Wang, Lin; Coller, John; Watanabe, Yuichiro; Glazebrook, Jane; Katagiri, Fumiaki

    2010-01-01

    Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways. Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network. The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network. We studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2). This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles for 571 immune response genes of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with Pto DC3000 AvrRpt2. The mRNA profiles were analyzed as detailed descriptions of changes in the network state resulting from the genetic perturbations. Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data. The resulting static network model accurately predicted 23 of 25 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate. The network model revealed two striking features: (i) the components of the network are highly interconnected; and (ii) negative regulatory relationships are common between signaling sectors. Complex regulatory relationships, including a novel negative regulatory relationship between the early microbe-associated molecular pattern-triggered signaling sectors and the salicylic acid sector, were further validated. We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a “sector-switching” network, which

  9. Stability Depends on Positive Autoregulation in Boolean Gene Regulatory Networks

    PubMed Central

    Pinho, Ricardo; Garcia, Victor; Irimia, Manuel; Feldman, Marcus W.

    2014-01-01

    Network motifs have been identified as building blocks of regulatory networks, including gene regulatory networks (GRNs). The most basic motif, autoregulation, has been associated with bistability (when positive) and with homeostasis and robustness to noise (when negative), but its general importance in network behavior is poorly understood. Moreover, how specific autoregulatory motifs are selected during evolution and how this relates to robustness is largely unknown. Here, we used a class of GRN models, Boolean networks, to investigate the relationship between autoregulation and network stability and robustness under various conditions. We ran evolutionary simulation experiments for different models of selection, including mutation and recombination. Each generation simulated the development of a population of organisms modeled by GRNs. We found that stability and robustness positively correlate with autoregulation; in all investigated scenarios, stable networks had mostly positive autoregulation. Assuming biological networks correspond to stable networks, these results suggest that biological networks should often be dominated by positive autoregulatory loops. This seems to be the case for most studied eukaryotic transcription factor networks, including those in yeast, flies and mammals. PMID:25375153

  10. Performance and Challenges of Service-Oriented Architecture for Wireless Sensor Networks.

    PubMed

    Alshinina, Remah; Elleithy, Khaled

    2017-03-08

    Wireless Sensor Networks (WSNs) have become essential components for a variety of environmental, surveillance, military, traffic control, and healthcare applications. These applications face critical challenges such as communication, security, power consumption, data aggregation, heterogeneities of sensor hardware, and Quality of Service (QoS) issues. Service-Oriented Architecture (SOA) is a software architecture that can be integrated with WSN applications to address those challenges. The SOA middleware bridges the gap between the high-level requirements of different applications and the hardware constraints of WSNs. This survey explores state-of-the-art approaches based on SOA and Service-Oriented Middleware (SOM) architecture that provide solutions for WSN challenges. The categories of this paper are based on approaches of SOA with and without middleware for WSNs. Additionally, features of SOA and middleware architectures for WSNs are compared to achieve more robust and efficient network performance. Design issues of SOA middleware for WSNs and its characteristics are also highlighted. The paper concludes with future research directions in SOM architecture to meet all requirements of emerging application of WSNs.

  11. Performance and Challenges of Service-Oriented Architecture for Wireless Sensor Networks

    PubMed Central

    Alshinina, Remah; Elleithy, Khaled

    2017-01-01

    Wireless Sensor Networks (WSNs) have become essential components for a variety of environmental, surveillance, military, traffic control, and healthcare applications. These applications face critical challenges such as communication, security, power consumption, data aggregation, heterogeneities of sensor hardware, and Quality of Service (QoS) issues. Service-Oriented Architecture (SOA) is a software architecture that can be integrated with WSN applications to address those challenges. The SOA middleware bridges the gap between the high-level requirements of different applications and the hardware constraints of WSNs. This survey explores state-of-the-art approaches based on SOA and Service-Oriented Middleware (SOM) architecture that provide solutions for WSN challenges. The categories of this paper are based on approaches of SOA with and without middleware for WSNs. Additionally, features of SOA and middleware architectures for WSNs are compared to achieve more robust and efficient network performance. Design issues of SOA middleware for WSNs and its characteristics are also highlighted. The paper concludes with future research directions in SOM architecture to meet all requirements of emerging application of WSNs. PMID:28282896

  12. An OSI architecture for the deep space network

    NASA Technical Reports Server (NTRS)

    Heuser, W. Randy; Cooper, Lynne P.

    1993-01-01

    The flexibility and robustness of a monitor and control system are a direct result of the underlying inter-processor communications architecture. A new architecture for monitor & Control at the Deep Space Network Communications Complexes has been developed based on the Open System Interconnection (OSI) standards. The suitability of OSI standards for DSN M&C has been proven in the laboratory. The laboratory success has resulted in choosing an OSI-based architecture for DSS-13 M&C. DSS-13 is the DSN experimental station and is not part of the 'operational' DSN; it's role is to provide an environment to test new communications concepts can be tested and conduct unique science experiments. Therefore, DSS-13 must be robust enough to support operational activities, while also being flexible enough to enable experimentation. This paper describes the M&C architecture developed for DSS-13 and the results from system and operational testing.

  13. Reconfiguration of Brain Network Architectures between Resting-State and Complexity-Dependent Cognitive Reasoning.

    PubMed

    Hearne, Luke J; Cocchi, Luca; Zalesky, Andrew; Mattingley, Jason B

    2017-08-30

    Our capacity for higher cognitive reasoning has a measurable limit. This limit is thought to arise from the brain's capacity to flexibly reconfigure interactions between spatially distributed networks. Recent work, however, has suggested that reconfigurations of task-related networks are modest when compared with intrinsic "resting-state" network architecture. Here we combined resting-state and task-driven functional magnetic resonance imaging to examine how flexible, task-specific reconfigurations associated with increasing reasoning demands are integrated within a stable intrinsic brain topology. Human participants (21 males and 28 females) underwent an initial resting-state scan, followed by a cognitive reasoning task involving different levels of complexity, followed by a second resting-state scan. The reasoning task required participants to deduce the identity of a missing element in a 4 × 4 matrix, and item difficulty was scaled parametrically as determined by relational complexity theory. Analyses revealed that external task engagement was characterized by a significant change in functional brain modules. Specifically, resting-state and null-task demand conditions were associated with more segregated brain-network topology, whereas increases in reasoning complexity resulted in merging of resting-state modules. Further increments in task complexity did not change the established modular architecture, but affected selective patterns of connectivity between frontoparietal, subcortical, cingulo-opercular, and default-mode networks. Larger increases in network efficiency within the newly established task modules were associated with higher reasoning accuracy. Our results shed light on the network architectures that underlie external task engagement, and highlight selective changes in brain connectivity supporting increases in task complexity. SIGNIFICANCE STATEMENT Humans have clear limits in their ability to solve complex reasoning problems. It is thought that

  14. An Object-Oriented Network-Centric Software Architecture for Physical Computing

    NASA Astrophysics Data System (ADS)

    Palmer, Richard

    1997-08-01

    Recent developments in object-oriented computer languages and infrastructure such as the Internet, Web browsers, and the like provide an opportunity to define a more productive computational environment for scientific programming that is based more closely on the underlying mathematics describing physics than traditional programming languages such as FORTRAN or C++. In this talk I describe an object-oriented software architecture for representing physical problems that includes classes for such common mathematical objects as geometry, boundary conditions, partial differential and integral equations, discretization and numerical solution methods, etc. In practice, a scientific program written using this architecture looks remarkably like the mathematics used to understand the problem, is typically an order of magnitude smaller than traditional FORTRAN or C++ codes, and hence easier to understand, debug, describe, etc. All objects in this architecture are ``network-enabled,'' which means that components of a software solution to a physical problem can be transparently loaded from anywhere on the Internet or other global network. The architecture is expressed as an ``API,'' or application programmers interface specification, with reference embeddings in Java, Python, and C++. A C++ class library for an early version of this API has been implemented for machines ranging from PC's to the IBM SP2, meaning that phidentical codes run on all architectures.

  15. A network architecture supporting consistent rich behavior in collaborative interactive applications.

    PubMed

    Marsh, James; Glencross, Mashhuda; Pettifer, Steve; Hubbold, Roger

    2006-01-01

    Network architectures for collaborative virtual reality have traditionally been dominated by client-server and peer-to-peer approaches, with peer-to-peer strategies typically being favored where minimizing latency is a priority, and client-server where consistency is key. With increasingly sophisticated behavior models and the demand for better support for haptics, we argue that neither approach provides sufficient support for these scenarios and, thus, a hybrid architecture is required. We discuss the relative performance of different distribution strategies in the face of real network conditions and illustrate the problems they face. Finally, we present an architecture that successfully meets many of these challenges and demonstrate its use in a distributed virtual prototyping application which supports simultaneous collaboration for assembly, maintenance, and training applications utilizing haptics.

  16. Gene Regulatory Network Inferences Using a Maximum-Relevance and Maximum-Significance Strategy

    PubMed Central

    Liu, Wei; Zhu, Wen; Liao, Bo; Chen, Xiangtao

    2016-01-01

    Recovering gene regulatory networks from expression data is a challenging problem in systems biology that provides valuable information on the regulatory mechanisms of cells. A number of algorithms based on computational models are currently used to recover network topology. However, most of these algorithms have limitations. For example, many models tend to be complicated because of the “large p, small n” problem. In this paper, we propose a novel regulatory network inference method called the maximum-relevance and maximum-significance network (MRMSn) method, which converts the problem of recovering networks into a problem of how to select the regulator genes for each gene. To solve the latter problem, we present an algorithm that is based on information theory and selects the regulator genes for a specific gene by maximizing the relevance and significance. A first-order incremental search algorithm is used to search for regulator genes. Eventually, a strict constraint is adopted to adjust all of the regulatory relationships according to the obtained regulator genes and thus obtain the complete network structure. We performed our method on five different datasets and compared our method to five state-of-the-art methods for network inference based on information theory. The results confirm the effectiveness of our method. PMID:27829000

  17. Challenges for modeling global gene regulatory networks during development: insights from Drosophila.

    PubMed

    Wilczynski, Bartek; Furlong, Eileen E M

    2010-04-15

    Development is regulated by dynamic patterns of gene expression, which are orchestrated through the action of complex gene regulatory networks (GRNs). Substantial progress has been made in modeling transcriptional regulation in recent years, including qualitative "coarse-grain" models operating at the gene level to very "fine-grain" quantitative models operating at the biophysical "transcription factor-DNA level". Recent advances in genome-wide studies have revealed an enormous increase in the size and complexity or GRNs. Even relatively simple developmental processes can involve hundreds of regulatory molecules, with extensive interconnectivity and cooperative regulation. This leads to an explosion in the number of regulatory functions, effectively impeding Boolean-based qualitative modeling approaches. At the same time, the lack of information on the biophysical properties for the majority of transcription factors within a global network restricts quantitative approaches. In this review, we explore the current challenges in moving from modeling medium scale well-characterized networks to more poorly characterized global networks. We suggest to integrate coarse- and find-grain approaches to model gene regulatory networks in cis. We focus on two very well-studied examples from Drosophila, which likely represent typical developmental regulatory modules across metazoans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  18. Regulatory networks and connected components of the neutral space. A look at functional islands

    NASA Astrophysics Data System (ADS)

    Boldhaus, G.; Klemm, K.

    2010-09-01

    The functioning of a living cell is largely determined by the structure of its regulatory network, comprising non-linear interactions between regulatory genes. An important factor for the stability and evolvability of such regulatory systems is neutrality - typically a large number of alternative network structures give rise to the necessary dynamics. Here we study the discretized regulatory dynamics of the yeast cell cycle [Li et al., PNAS, 2004] and the set of networks capable of reproducing it, which we call functional. Among these, the empirical yeast wildtype network is close to optimal with respect to sparse wiring. Under point mutations, which establish or delete single interactions, the neutral space of functional networks is fragmented into ≈ 4.7 × 108 components. One of the smaller ones contains the wildtype network. On average, functional networks reachable from the wildtype by mutations are sparser, have higher noise resilience and fewer fixed point attractors as compared with networks outside of this wildtype component.

  19. Construction of regulatory networks using expression time-series data of a genotyped population.

    PubMed

    Yeung, Ka Yee; Dombek, Kenneth M; Lo, Kenneth; Mittler, John E; Zhu, Jun; Schadt, Eric E; Bumgarner, Roger E; Raftery, Adrian E

    2011-11-29

    The inference of regulatory and biochemical networks from large-scale genomics data is a basic problem in molecular biology. The goal is to generate testable hypotheses of gene-to-gene influences and subsequently to design bench experiments to confirm these network predictions. Coexpression of genes in large-scale gene-expression data implies coregulation and potential gene-gene interactions, but provide little information about the direction of influences. Here, we use both time-series data and genetics data to infer directionality of edges in regulatory networks: time-series data contain information about the chronological order of regulatory events and genetics data allow us to map DNA variations to variations at the RNA level. We generate microarray data measuring time-dependent gene-expression levels in 95 genotyped yeast segregants subjected to a drug perturbation. We develop a Bayesian model averaging regression algorithm that incorporates external information from diverse data types to infer regulatory networks from the time-series and genetics data. Our algorithm is capable of generating feedback loops. We show that our inferred network recovers existing and novel regulatory relationships. Following network construction, we generate independent microarray data on selected deletion mutants to prospectively test network predictions. We demonstrate the potential of our network to discover de novo transcription-factor binding sites. Applying our construction method to previously published data demonstrates that our method is competitive with leading network construction algorithms in the literature.

  20. Inference of gene regulatory networks from genome-wide knockout fitness data

    PubMed Central

    Wang, Liming; Wang, Xiaodong; Arkin, Adam P.; Samoilov, Michael S.

    2013-01-01

    Motivation: Genome-wide fitness is an emerging type of high-throughput biological data generated for individual organisms by creating libraries of knockouts, subjecting them to broad ranges of environmental conditions, and measuring the resulting clone-specific fitnesses. Since fitness is an organism-scale measure of gene regulatory network behaviour, it may offer certain advantages when insights into such phenotypical and functional features are of primary interest over individual gene expression. Previous works have shown that genome-wide fitness data can be used to uncover novel gene regulatory interactions, when compared with results of more conventional gene expression analysis. Yet, to date, few algorithms have been proposed for systematically using genome-wide mutant fitness data for gene regulatory network inference. Results: In this article, we describe a model and propose an inference algorithm for using fitness data from knockout libraries to identify underlying gene regulatory networks. Unlike most prior methods, the presented approach captures not only structural, but also dynamical and non-linear nature of biomolecular systems involved. A state–space model with non-linear basis is used for dynamically describing gene regulatory networks. Network structure is then elucidated by estimating unknown model parameters. Unscented Kalman filter is used to cope with the non-linearities introduced in the model, which also enables the algorithm to run in on-line mode for practical use. Here, we demonstrate that the algorithm provides satisfying results for both synthetic data as well as empirical measurements of GAL network in yeast Saccharomyces cerevisiae and TyrR–LiuR network in bacteria Shewanella oneidensis. Availability: MATLAB code and datasets are available to download at http://www.duke.edu/∼lw174/Fitness.zip and http://genomics.lbl.gov/supplemental/fitness-bioinf/ Contact: wangx@ee.columbia.edu or mssamoilov@lbl.gov Supplementary information

  1. Security Policy for a Generic Space Exploration Communication Network Architecture

    NASA Technical Reports Server (NTRS)

    Ivancic, William D.; Sheehe, Charles J.; Vaden, Karl R.

    2016-01-01

    This document is one of three. It describes various security mechanisms and a security policy profile for a generic space-based communication architecture. Two other documents accompany this document- an Operations Concept (OpsCon) and a communication architecture document. The OpsCon should be read first followed by the security policy profile described by this document and then the architecture document. The overall goal is to design a generic space exploration communication network architecture that is affordable, deployable, maintainable, securable, evolvable, reliable, and adaptable. The architecture should also require limited reconfiguration throughout system development and deployment. System deployment includes subsystem development in a factory setting, system integration in a laboratory setting, launch preparation, launch, and deployment and operation in space.

  2. Operational Concepts for a Generic Space Exploration Communication Network Architecture

    NASA Technical Reports Server (NTRS)

    Ivancic, William D.; Vaden, Karl R.; Jones, Robert E.; Roberts, Anthony M.

    2015-01-01

    This document is one of three. It describes the Operational Concept (OpsCon) for a generic space exploration communication architecture. The purpose of this particular document is to identify communication flows and data types. Two other documents accompany this document, a security policy profile and a communication architecture document. The operational concepts should be read first followed by the security policy profile and then the architecture document. The overall goal is to design a generic space exploration communication network architecture that is affordable, deployable, maintainable, securable, evolvable, reliable, and adaptable. The architecture should also require limited reconfiguration throughout system development and deployment. System deployment includes: subsystem development in a factory setting, system integration in a laboratory setting, launch preparation, launch, and deployment and operation in space.

  3. Gap Gene Regulatory Dynamics Evolve along a Genotype Network

    PubMed Central

    Crombach, Anton; Wotton, Karl R.; Jiménez-Guri, Eva; Jaeger, Johannes

    2016-01-01

    Developmental gene networks implement the dynamic regulatory mechanisms that pattern and shape the organism. Over evolutionary time, the wiring of these networks changes, yet the patterning outcome is often preserved, a phenomenon known as “system drift.” System drift is illustrated by the gap gene network—involved in segmental patterning—in dipteran insects. In the classic model organism Drosophila melanogaster and the nonmodel scuttle fly Megaselia abdita, early activation and placement of gap gene expression domains show significant quantitative differences, yet the final patterning output of the system is essentially identical in both species. In this detailed modeling analysis of system drift, we use gene circuits which are fit to quantitative gap gene expression data in M. abdita and compare them with an equivalent set of models from D. melanogaster. The results of this comparative analysis show precisely how compensatory regulatory mechanisms achieve equivalent final patterns in both species. We discuss the larger implications of the work in terms of “genotype networks” and the ways in which the structure of regulatory networks can influence patterns of evolutionary change (evolvability). PMID:26796549

  4. Boolean dynamics of genetic regulatory networks inferred from microarray time series data

    DOE PAGES

    Martin, Shawn; Zhang, Zhaoduo; Martino, Anthony; ...

    2007-01-31

    Methods available for the inference of genetic regulatory networks strive to produce a single network, usually by optimizing some quantity to fit the experimental observations. In this paper we investigate the possibility that multiple networks can be inferred, all resulting in similar dynamics. This idea is motivated by theoretical work which suggests that biological networks are robust and adaptable to change, and that the overall behavior of a genetic regulatory network might be captured in terms of dynamical basins of attraction. We have developed and implemented a method for inferring genetic regulatory networks for time series microarray data. Our methodmore » first clusters and discretizes the gene expression data using k-means and support vector regression. We then enumerate Boolean activation–inhibition networks to match the discretized data. In conclusion, the dynamics of the Boolean networks are examined. We have tested our method on two immunology microarray datasets: an IL-2-stimulated T cell response dataset and a LPS-stimulated macrophage response dataset. In both cases, we discovered that many networks matched the data, and that most of these networks had similar dynamics.« less

  5. Transcriptional Regulatory Network Analysis of MYB Transcription Factor Family Genes in Rice.

    PubMed

    Smita, Shuchi; Katiyar, Amit; Chinnusamy, Viswanathan; Pandey, Dev M; Bansal, Kailash C

    2015-01-01

    MYB transcription factor (TF) is one of the largest TF families and regulates defense responses to various stresses, hormone signaling as well as many metabolic and developmental processes in plants. Understanding these regulatory hierarchies of gene expression networks in response to developmental and environmental cues is a major challenge due to the complex interactions between the genetic elements. Correlation analyses are useful to unravel co-regulated gene pairs governing biological process as well as identification of new candidate hub genes in response to these complex processes. High throughput expression profiling data are highly useful for construction of co-expression networks. In the present study, we utilized transcriptome data for comprehensive regulatory network studies of MYB TFs by "top-down" and "guide-gene" approaches. More than 50% of OsMYBs were strongly correlated under 50 experimental conditions with 51 hub genes via "top-down" approach. Further, clusters were identified using Markov Clustering (MCL). To maximize the clustering performance, parameter evaluation of the MCL inflation score (I) was performed in terms of enriched GO categories by measuring F-score. Comparison of co-expressed cluster and clads analyzed from phylogenetic analysis signifies their evolutionarily conserved co-regulatory role. We utilized compendium of known interaction and biological role with Gene Ontology enrichment analysis to hypothesize function of coexpressed OsMYBs. In the other part, the transcriptional regulatory network analysis by "guide-gene" approach revealed 40 putative targets of 26 OsMYB TF hubs with high correlation value utilizing 815 microarray data. The putative targets with MYB-binding cis-elements enrichment in their promoter region, functional co-occurrence as well as nuclear localization supports our finding. Specially, enrichment of MYB binding regions involved in drought-inducibility implying their regulatory role in drought response in rice

  6. CoryneRegNet 4.0 – A reference database for corynebacterial gene regulatory networks

    PubMed Central

    Baumbach, Jan

    2007-01-01

    Background Detailed information on DNA-binding transcription factors (the key players in the regulation of gene expression) and on transcriptional regulatory interactions of microorganisms deduced from literature-derived knowledge, computer predictions and global DNA microarray hybridization experiments, has opened the way for the genome-wide analysis of transcriptional regulatory networks. The large-scale reconstruction of these networks allows the in silico analysis of cell behavior in response to changing environmental conditions. We previously published CoryneRegNet, an ontology-based data warehouse of corynebacterial transcription factors and regulatory networks. Initially, it was designed to provide methods for the analysis and visualization of the gene regulatory network of Corynebacterium glutamicum. Results Now we introduce CoryneRegNet release 4.0, which integrates data on the gene regulatory networks of 4 corynebacteria, 2 mycobacteria and the model organism Escherichia coli K12. As the previous versions, CoryneRegNet provides a web-based user interface to access the database content, to allow various queries, and to support the reconstruction, analysis and visualization of regulatory networks at different hierarchical levels. In this article, we present the further improved database content of CoryneRegNet along with novel analysis features. The network visualization feature GraphVis now allows the inter-species comparisons of reconstructed gene regulatory networks and the projection of gene expression levels onto that networks. Therefore, we added stimulon data directly into the database, but also provide Web Service access to the DNA microarray analysis platform EMMA. Additionally, CoryneRegNet now provides a SOAP based Web Service server, which can easily be consumed by other bioinformatics software systems. Stimulons (imported from the database, or uploaded by the user) can be analyzed in the context of known transcriptional regulatory networks to

  7. Modeling stochasticity and robustness in gene regulatory networks.

    PubMed

    Garg, Abhishek; Mohanram, Kartik; Di Cara, Alessandro; De Micheli, Giovanni; Xenarios, Ioannis

    2009-06-15

    Understanding gene regulation in biological processes and modeling the robustness of underlying regulatory networks is an important problem that is currently being addressed by computational systems biologists. Lately, there has been a renewed interest in Boolean modeling techniques for gene regulatory networks (GRNs). However, due to their deterministic nature, it is often difficult to identify whether these modeling approaches are robust to the addition of stochastic noise that is widespread in gene regulatory processes. Stochasticity in Boolean models of GRNs has been addressed relatively sparingly in the past, mainly by flipping the expression of genes between different expression levels with a predefined probability. This stochasticity in nodes (SIN) model leads to over representation of noise in GRNs and hence non-correspondence with biological observations. In this article, we introduce the stochasticity in functions (SIF) model for simulating stochasticity in Boolean models of GRNs. By providing biological motivation behind the use of the SIF model and applying it to the T-helper and T-cell activation networks, we show that the SIF model provides more biologically robust results than the existing SIN model of stochasticity in GRNs. Algorithms are made available under our Boolean modeling toolbox, GenYsis. The software binaries can be downloaded from http://si2.epfl.ch/ approximately garg/genysis.html.

  8. Identifying the architecture of a supracellular actomyosin network that induces tissue folding

    NASA Astrophysics Data System (ADS)

    Yevick, Hannah; Stoop, Norbert; Dunkel, Jorn; Martin, Adam

    During embryonic development, the establishment of correct tissue form ensures proper tissue function. Yet, how the thousands of cells within a tissue coordinate force production to sculpt tissue shape is poorly understood. One important tissue shape change is tissue folding where a cell sheet bends to form a closed tube. Drosophila (fruit fly) embryos undergo such a folding event, called ventral furrow formation. The ventral furrow is associated with a supracellular network of actin and myosin, where actin-myosin fibers assemble and connect between cells. It is not known how this tissue-wide network grows and connects over time, how reproducible it is between embryos, and what determines its architecture. Here, we used topological feature analysis to quantitatively and dynamically map the connections and architecture of this supracellular network across hundreds of cells in the folding tissue. We identified the importance of the cell unit in setting up the tissue-scale architecture of the network. Our mathematical framework allows us to explore stereotypic properties of the myosin network such that we can investigate the reproducibility of mechanical connections for a morphogenetic process. NIH F32.

  9. The architecture of a network level intrusion detection system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Heady, R.; Luger, G.; Maccabe, A.

    1990-08-15

    This paper presents the preliminary architecture of a network level intrusion detection system. The proposed system will monitor base level information in network packets (source, destination, packet size, and time), learning the normal patterns and announcing anomalies as they occur. The goal of this research is to determine the applicability of current intrusion detection technology to the detection of network level intrusions. In particular, the authors are investigating the possibility of using this technology to detect and react to worm programs.

  10. Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens

    PubMed Central

    Chasman, Deborah; Walters, Kevin B.; Lopes, Tiago J. S.; Eisfeld, Amie J.; Kawaoka, Yoshihiro; Roy, Sushmita

    2016-01-01

    Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection. PMID:27403523

  11. Integration of a splicing regulatory network within the meiotic gene expression program of Saccharomyces cerevisiae

    PubMed Central

    Munding, Elizabeth M.; Igel, A. Haller; Shiue, Lily; Dorighi, Kristel M.; Treviño, Lisa R.; Ares, Manuel

    2010-01-01

    Splicing regulatory networks are essential components of eukaryotic gene expression programs, yet little is known about how they are integrated with transcriptional regulatory networks into coherent gene expression programs. Here we define the MER1 splicing regulatory network and examine its role in the gene expression program during meiosis in budding yeast. Mer1p splicing factor promotes splicing of just four pre-mRNAs. All four Mer1p-responsive genes also require Nam8p for splicing activation by Mer1p; however, other genes require Nam8p but not Mer1p, exposing an overlapping meiotic splicing network controlled by Nam8p. MER1 mRNA and three of the four Mer1p substrate pre-mRNAs are induced by the transcriptional regulator Ume6p. This unusual arrangement delays expression of Mer1p-responsive genes relative to other genes under Ume6p control. Products of Mer1p-responsive genes are required for initiating and completing recombination and for activation of Ndt80p, the activator of the transcriptional network required for subsequent steps in the program. Thus, the MER1 splicing regulatory network mediates the dependent relationship between the UME6 and NDT80 transcriptional regulatory networks in the meiotic gene expression program. This study reveals how splicing regulatory networks can be interlaced with transcriptional regulatory networks in eukaryotic gene expression programs. PMID:21123654

  12. Navigation Architecture for a Space Mobile Network

    NASA Technical Reports Server (NTRS)

    Valdez, Jennifer E.; Ashman, Benjamin; Gramling, Cheryl; Heckler, Gregory W.; Carpenter, Russell

    2016-01-01

    The Tracking and Data Relay Satellite System (TDRSS) Augmentation Service for Satellites (TASS) is a proposed beacon service to provide a global, space based GPS augmentation service based on the NASA Global Differential GPS (GDGPS) System. The TASS signal will be tied to the GPS time system and usable as an additional ranging and Doppler radiometric source. Additionally, it will provide data vital to autonomous navigation in the near Earth regime, including space weather information, TDRS ephemerides, Earth Orientation Parameters (EOP), and forward commanding capability. TASS benefits include enhancing situational awareness, enabling increased autonomy, and providing near real-time command access for user platforms. As NASA Headquarters' Space Communication and Navigation Office (SCaN) begins to move away from a centralized network architecture and towards a Space Mobile Network (SMN) that allows for user initiated services, autonomous navigation will be a key part of such a system. This paper explores how a TASS beacon service enables the Space Mobile Networking paradigm, what a typical user platform would require, and provides an in-depth analysis of several navigation scenarios and operations concepts. This paper provides an overview of the TASS beacon and its role within the SMN and user community. Supporting navigation analysis is presented for two user mission scenarios: an Earth observing spacecraft in low earth orbit (LEO), and a highly elliptical spacecraft in a lunar resonance orbit. These diverse flight scenarios indicate the breadth of applicability of the TASS beacon for upcoming users within the current network architecture and in the SMN.

  13. Fiber-Optic Network Architectures for Onboard Avionics Applications Investigated

    NASA Technical Reports Server (NTRS)

    Nguyen, Hung D.; Ngo, Duc H.

    2003-01-01

    This project is part of a study within the Advanced Air Transportation Technologies program undertaken at the NASA Glenn Research Center. The main focus of the program is the improvement of air transportation, with particular emphasis on air transportation safety. Current and future advances in digital data communications between an aircraft and the outside world will require high-bandwidth onboard communication networks. Radiofrequency (RF) systems, with their interconnection network based on coaxial cables and waveguides, increase the complexity of communication systems onboard modern civil and military aircraft with respect to weight, power consumption, and safety. In addition, safety and reliability concerns from electromagnetic interference between the RF components embedded in these communication systems exist. A simple, reliable, and lightweight network that is free from the effects of electromagnetic interference and capable of supporting the broadband communications needs of future onboard digital avionics systems cannot be easily implemented using existing coaxial cable-based systems. Fiber-optical communication systems can meet all these challenges of modern avionics applications in an efficient, cost-effective manner. The objective of this project is to present a number of optical network architectures for onboard RF signal distribution. Because of the emergence of a number of digital avionics devices requiring high-bandwidth connectivity, fiber-optic RF networks onboard modern aircraft will play a vital role in ensuring a low-noise, highly reliable RF communication system. Two approaches are being used for network architectures for aircraft onboard fiber-optic distribution systems: a hybrid RF-optical network and an all-optical wavelength division multiplexing (WDM) network.

  14. Building and measuring a high performance network architecture

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kramer, William T.C.; Toole, Timothy; Fisher, Chuck

    2001-04-20

    Once a year, the SC conferences present a unique opportunity to create and build one of the most complex and highest performance networks in the world. At SC2000, large-scale and complex local and wide area networking connections were demonstrated, including large-scale distributed applications running on different architectures. This project was designed to use the unique opportunity presented at SC2000 to create a testbed network environment and then use that network to demonstrate and evaluate high performance computational and communication applications. This testbed was designed to incorporate many interoperable systems and services and was designed for measurement from the very beginning.more » The end results were key insights into how to use novel, high performance networking technologies and to accumulate measurements that will give insights into the networks of the future.« less

  15. SANDS: an architecture for clinical decision support in a National Health Information Network.

    PubMed

    Wright, Adam; Sittig, Dean F

    2007-10-11

    A new architecture for clinical decision support called SANDS (Service-oriented Architecture for NHIN Decision Support) is introduced and its performance evaluated. The architecture provides a method for performing clinical decision support across a network, as in a health information exchange. Using the prototype we demonstrated that, first, a number of useful types of decision support can be carried out using our architecture; and, second, that the architecture exhibits desirable reliability and performance characteristics.

  16. Actin Assembly Factors Regulate the Gelation Kinetics and Architecture of F-actin Networks

    PubMed Central

    Falzone, Tobias T.; Oakes, Patrick W.; Sees, Jennifer; Kovar, David R.; Gardel, Margaret L.

    2013-01-01

    Dynamic regulation of the actin cytoskeleton is required for diverse cellular processes. Proteins regulating the assembly kinetics of the cytoskeletal biopolymer F-actin are known to impact the architecture of actin cytoskeletal networks in vivo, but the underlying mechanisms are not well understood. Here, we demonstrate that changes to actin assembly kinetics with physiologically relevant proteins profilin and formin (mDia1 and Cdc12) have dramatic consequences on the architecture and gelation kinetics of otherwise biochemically identical cross-linked F-actin networks. Reduced F-actin nucleation rates promote the formation of a sparse network of thick bundles, whereas increased nucleation rates result in a denser network of thinner bundles. Changes to F-actin elongation rates also have marked consequences. At low elongation rates, gelation ceases and a solution of rigid bundles is formed. By contrast, rapid filament elongation accelerates dynamic arrest and promotes gelation with minimal F-actin density. These results are consistent with a recently developed model of how kinetic constraints regulate network architecture and underscore how molecular control of polymer assembly is exploited to modulate cytoskeletal architecture and material properties. PMID:23601318

  17. State Space Model with hidden variables for reconstruction of gene regulatory networks.

    PubMed

    Wu, Xi; Li, Peng; Wang, Nan; Gong, Ping; Perkins, Edward J; Deng, Youping; Zhang, Chaoyang

    2011-01-01

    State Space Model (SSM) is a relatively new approach to inferring gene regulatory networks. It requires less computational time than Dynamic Bayesian Networks (DBN). There are two types of variables in the linear SSM, observed variables and hidden variables. SSM uses an iterative method, namely Expectation-Maximization, to infer regulatory relationships from microarray datasets. The hidden variables cannot be directly observed from experiments. How to determine the number of hidden variables has a significant impact on the accuracy of network inference. In this study, we used SSM to infer Gene regulatory networks (GRNs) from synthetic time series datasets, investigated Bayesian Information Criterion (BIC) and Principle Component Analysis (PCA) approaches to determining the number of hidden variables in SSM, and evaluated the performance of SSM in comparison with DBN. True GRNs and synthetic gene expression datasets were generated using GeneNetWeaver. Both DBN and linear SSM were used to infer GRNs from the synthetic datasets. The inferred networks were compared with the true networks. Our results show that inference precision varied with the number of hidden variables. For some regulatory networks, the inference precision of DBN was higher but SSM performed better in other cases. Although the overall performance of the two approaches is compatible, SSM is much faster and capable of inferring much larger networks than DBN. This study provides useful information in handling the hidden variables and improving the inference precision.

  18. Design mobile satellite system architecture as an integral part of the cellular access digital network

    NASA Technical Reports Server (NTRS)

    Chien, E. S. K.; Marinho, J. A.; Russell, J. E., Sr.

    1988-01-01

    The Cellular Access Digital Network (CADN) is the access vehicle through which cellular technology is brought into the mainstream of the evolving integrated telecommunications network. Beyond the integrated end-to-end digital access and per call network services provisioning of the Integrated Services Digital Network (ISDN), the CADN engenders the added capability of mobility freedom via wireless access. One key element of the CADN network architecture is the standard user to network interface that is independent of RF transmission technology. Since the Mobile Satellite System (MSS) is envisioned to not only complement but also enhance the capabilities of the terrestrial cellular telecommunications network, compatibility and interoperability between terrestrial cellular and mobile satellite systems are vitally important to provide an integrated moving telecommunications network of the future. From a network standpoint, there exist very strong commonalities between the terrestrial cellular system and the mobile satellite system. Therefore, the MSS architecture should be designed as an integral part of the CADN. This paper describes the concept of the CADN, the functional architecture of the MSS, and the user-network interface signaling protocols.

  19. An electronic regulatory document management system for a clinical trial network.

    PubMed

    Zhao, Wenle; Durkalski, Valerie; Pauls, Keith; Dillon, Catherine; Kim, Jaemyung; Kolk, Deneil; Silbergleit, Robert; Stevenson, Valerie; Palesch, Yuko

    2010-01-01

    A computerized regulatory document management system has been developed as a module in a comprehensive Clinical Trial Management System (CTMS) designed for an NIH-funded clinical trial network in order to more efficiently manage and track regulatory compliance. Within the network, several institutions and investigators are involved in multiple trials, and each trial has regulatory document requirements. Some of these documents are trial specific while others apply across multiple trials. The latter causes a possible redundancy in document collection and management. To address these and other related challenges, a central regulatory document management system was designed. This manuscript shares the design of the system as well as examples of it use in current studies. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  20. Survivable architectures for time and wavelength division multiplexed passive optical networks

    NASA Astrophysics Data System (ADS)

    Wong, Elaine

    2014-08-01

    The increased network reach and customer base of next-generation time and wavelength division multiplexed PON (TWDM-PONs) have necessitated rapid fault detection and subsequent restoration of services to its users. However, direct application of existing solutions for conventional PONs to TWDM-PONs is unsuitable as these schemes rely on the loss of signal (LOS) of upstream transmissions to trigger protection switching. As TWDM-PONs are required to potentially use sleep/doze mode optical network units (ONU), the loss of upstream transmission from a sleeping or dozing ONU could erroneously trigger protection switching. Further, TWDM-PONs require its monitoring modules for fiber/device fault detection to be more sensitive than those typically deployed in conventional PONs. To address the above issues, three survivable architectures that are compliant with TWDM-PON specifications are presented in this work. These architectures combine rapid detection and protection switching against multipoint failure, and most importantly do not rely on upstream transmissions for LOS activation. Survivability analyses as well as evaluations of the additional costs incurred to achieve survivability are performed and compared to the unprotected TWDM-PON. Network parameters that impact the maximum achievable network reach, maximum split ratio, connection availability, fault impact, and the incremental reliability costs for each proposed survivable architecture are highlighted.

  1. Genome-wide network of regulatory genes for construction of a chordate embryo.

    PubMed

    Shoguchi, Eiichi; Hamaguchi, Makoto; Satoh, Nori

    2008-04-15

    Animal development is controlled by gene regulation networks that are composed of sequence-specific transcription factors (TF) and cell signaling molecules (ST). Although housekeeping genes have been reported to show clustering in the animal genomes, whether the genes comprising a given regulatory network are physically clustered on a chromosome is uncertain. We examined this question in the present study. Ascidians are the closest living relatives of vertebrates, and their tadpole-type larva represents the basic body plan of chordates. The Ciona intestinalis genome contains 390 core TF genes and 119 major ST genes. Previous gene disruption assays led to the formulation of a basic chordate embryonic blueprint, based on over 3000 genetic interactions among 79 zygotic regulatory genes. Here, we mapped the regulatory genes, including all 79 regulatory genes, on the 14 pairs of Ciona chromosomes by fluorescent in situ hybridization (FISH). Chromosomal localization of upstream and downstream regulatory genes demonstrates that the components of coherent developmental gene networks are evenly distributed over the 14 chromosomes. Thus, this study provides the first comprehensive evidence that the physical clustering of regulatory genes, or their target genes, is not relevant for the genome-wide control of gene expression during development.

  2. Scale-space measures for graph topology link protein network architecture to function.

    PubMed

    Hulsman, Marc; Dimitrakopoulos, Christos; de Ridder, Jeroen

    2014-06-15

    The network architecture of physical protein interactions is an important determinant for the molecular functions that are carried out within each cell. To study this relation, the network architecture can be characterized by graph topological characteristics such as shortest paths and network hubs. These characteristics have an important shortcoming: they do not take into account that interactions occur across different scales. This is important because some cellular functions may involve a single direct protein interaction (small scale), whereas others require more and/or indirect interactions, such as protein complexes (medium scale) and interactions between large modules of proteins (large scale). In this work, we derive generalized scale-aware versions of known graph topological measures based on diffusion kernels. We apply these to characterize the topology of networks across all scales simultaneously, generating a so-called graph topological scale-space. The comprehensive physical interaction network in yeast is used to show that scale-space based measures consistently give superior performance when distinguishing protein functional categories and three major types of functional interactions-genetic interaction, co-expression and perturbation interactions. Moreover, we demonstrate that graph topological scale spaces capture biologically meaningful features that provide new insights into the link between function and protein network architecture. Matlab(TM) code to calculate the scale-aware topological measures (STMs) is available at http://bioinformatics.tudelft.nl/TSSA © The Author 2014. Published by Oxford University Press.

  3. MSAT signalling and network management architectures

    NASA Technical Reports Server (NTRS)

    Garland, Peter; Keelty, J. Malcolm

    1989-01-01

    Spar Aerospace has been active in the design and definition of Mobile Satellite Systems since the mid 1970's. In work sponsored by the Canadian Department of Communications, various payload configurations have evolved. In addressing the payload configuration, the requirements of the mobile user, the service provider and the satellite operator have always been the most important consideration. The current Spar 11 beam satellite design is reviewed, and its capabilities to provide flexibility and potential for network growth within the WARC87 allocations are explored. To enable the full capabilities of the payload to be realized, a large amount of ground based Switching and Network Management infrastructure will be required, when space segment becomes available. Early indications were that a single custom designed Demand Assignment Multiple Access (DAMA) switch should be implemented to provide efficient use of the space segment. As MSAT has evolved into a multiple service concept, supporting many service providers, this architecture should be reviewed. Some possible signalling and Network Management solutions are explored.

  4. Array processor architecture connection network

    NASA Technical Reports Server (NTRS)

    Barnes, George H. (Inventor); Lundstrom, Stephen F. (Inventor); Shafer, Philip E. (Inventor)

    1982-01-01

    A connection network is disclosed for use between a parallel array of processors and a parallel array of memory modules for establishing non-conflicting data communications paths between requested memory modules and requesting processors. The connection network includes a plurality of switching elements interposed between the processor array and the memory modules array in an Omega networking architecture. Each switching element includes a first and a second processor side port, a first and a second memory module side port, and control logic circuitry for providing data connections between the first and second processor ports and the first and second memory module ports. The control logic circuitry includes strobe logic for examining data arriving at the first and the second processor ports to indicate when the data arriving is requesting data from a requesting processor to a requested memory module. Further, connection circuitry is associated with the strobe logic for examining requesting data arriving at the first and the second processor ports for providing a data connection therefrom to the first and the second memory module ports in response thereto when the data connection so provided does not conflict with a pre-established data connection currently in use.

  5. Large-Scale Networked Virtual Environments: Architecture and Applications

    ERIC Educational Resources Information Center

    Lamotte, Wim; Quax, Peter; Flerackers, Eddy

    2008-01-01

    Purpose: Scalability is an important research topic in the context of networked virtual environments (NVEs). This paper aims to describe the ALVIC (Architecture for Large-scale Virtual Interactive Communities) approach to NVE scalability. Design/methodology/approach: The setup and results from two case studies are shown: a 3-D learning environment…

  6. Generation of oscillating gene regulatory network motifs

    NASA Astrophysics Data System (ADS)

    van Dorp, M.; Lannoo, B.; Carlon, E.

    2013-07-01

    Using an improved version of an evolutionary algorithm originally proposed by François and Hakim [Proc. Natl. Acad. Sci. USAPNASA60027-842410.1073/pnas.0304532101 101, 580 (2004)], we generated small gene regulatory networks in which the concentration of a target protein oscillates in time. These networks may serve as candidates for oscillatory modules to be found in larger regulatory networks and protein interaction networks. The algorithm was run for 105 times to produce a large set of oscillating modules, which were systematically classified and analyzed. The robustness of the oscillations against variations of the kinetic rates was also determined, to filter out the least robust cases. Furthermore, we show that the set of evolved networks can serve as a database of models whose behavior can be compared to experimentally observed oscillations. The algorithm found three smallest (core) oscillators in which nonlinearities and number of components are minimal. Two of those are two-gene modules: the mixed feedback loop, already discussed in the literature, and an autorepressed gene coupled with a heterodimer. The third one is a single gene module which is competitively regulated by a monomer and a dimer. The evolutionary algorithm also generated larger oscillating networks, which are in part extensions of the three core modules and in part genuinely new modules. The latter includes oscillators which do not rely on feedback induced by transcription factors, but are purely of post-transcriptional type. Analysis of post-transcriptional mechanisms of oscillation may provide useful information for circadian clock research, as recent experiments showed that circadian rhythms are maintained even in the absence of transcription.

  7. Time Shared Optical Network (TSON): a novel metro architecture for flexible multi-granular services.

    PubMed

    Zervas, Georgios S; Triay, Joan; Amaya, Norberto; Qin, Yixuan; Cervelló-Pastor, Cristina; Simeonidou, Dimitra

    2011-12-12

    This paper presents the Time Shared Optical Network (TSON) as metro mesh network architecture for guaranteed, statistically-multiplexed services. TSON proposes a flexible and tunable time-wavelength assignment along with one-way tree-based reservation and node architecture. It delivers guaranteed sub-wavelength and multi-granular network services without wavelength conversion, time-slice interchange and optical buffering. Simulation results demonstrate high network utilization, fast service delivery, and low end-to-end delay on a contention-free sub-wavelength optical transport network. In addition, implementation complexity in terms of Layer 2 aggregation, grooming and optical switching has been evaluated. © 2011 Optical Society of America

  8. Signal Correlations in Ecological Niches Can Shape the Organization and Evolution of Bacterial Gene Regulatory Networks

    PubMed Central

    Dufour, Yann S.; Donohue, Timothy J.

    2015-01-01

    Transcriptional regulation plays a significant role in the biological response of bacteria to changing environmental conditions. Therefore, mapping transcriptional regulatory networks is an important step not only in understanding how bacteria sense and interpret their environment but also to identify the functions involved in biological responses to specific conditions. Recent experimental and computational developments have facilitated the characterization of regulatory networks on a genome-wide scale in model organisms. In addition, the multiplication of complete genome sequences has encouraged comparative analyses to detect conserved regulatory elements and infer regulatory networks in other less well-studied organisms. However, transcription regulation appears to evolve rapidly, thus, creating challenges for the transfer of knowledge to nonmodel organisms. Nevertheless, the mechanisms and constraints driving the evolution of regulatory networks have been the subjects of numerous analyses, and several models have been proposed. Overall, the contributions of mutations, recombination, and horizontal gene transfer are complex. Finally, the rapid evolution of regulatory networks plays a significant role in the remarkable capacity of bacteria to adapt to new or changing environments. Conversely, the characteristics of environmental niches determine the selective pressures and can shape the structure of regulatory network accordingly. PMID:23046950

  9. Reverse Engineering of Genome-wide Gene Regulatory Networks from Gene Expression Data

    PubMed Central

    Liu, Zhi-Ping

    2015-01-01

    Transcriptional regulation plays vital roles in many fundamental biological processes. Reverse engineering of genome-wide regulatory networks from high-throughput transcriptomic data provides a promising way to characterize the global scenario of regulatory relationships between regulators and their targets. In this review, we summarize and categorize the main frameworks and methods currently available for inferring transcriptional regulatory networks from microarray gene expression profiling data. We overview each of strategies and introduce representative methods respectively. Their assumptions, advantages, shortcomings, and possible improvements and extensions are also clarified and commented. PMID:25937810

  10. Genes under weaker stabilizing selection increase network evolvability and rapid regulatory adaptation to an environmental shift.

    PubMed

    Laarits, T; Bordalo, P; Lemos, B

    2016-08-01

    Regulatory networks play a central role in the modulation of gene expression, the control of cellular differentiation, and the emergence of complex phenotypes. Regulatory networks could constrain or facilitate evolutionary adaptation in gene expression levels. Here, we model the adaptation of regulatory networks and gene expression levels to a shift in the environment that alters the optimal expression level of a single gene. Our analyses show signatures of natural selection on regulatory networks that both constrain and facilitate rapid evolution of gene expression level towards new optima. The analyses are interpreted from the standpoint of neutral expectations and illustrate the challenge to making inferences about network adaptation. Furthermore, we examine the consequence of variable stabilizing selection across genes on the strength and direction of interactions in regulatory networks and in their subsequent adaptation. We observe that directional selection on a highly constrained gene previously under strong stabilizing selection was more efficient when the gene was embedded within a network of partners under relaxed stabilizing selection pressure. The observation leads to the expectation that evolutionarily resilient regulatory networks will contain optimal ratios of genes whose expression is under weak and strong stabilizing selection. Altogether, our results suggest that the variable strengths of stabilizing selection across genes within regulatory networks might itself contribute to the long-term adaptation of complex phenotypes. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  11. Deep Space Network information system architecture study

    NASA Technical Reports Server (NTRS)

    Beswick, C. A.; Markley, R. W. (Editor); Atkinson, D. J.; Cooper, L. P.; Tausworthe, R. C.; Masline, R. C.; Jenkins, J. S.; Crowe, R. A.; Thomas, J. L.; Stoloff, M. J.

    1992-01-01

    The purpose of this article is to describe an architecture for the DSN information system in the years 2000-2010 and to provide guidelines for its evolution during the 1990's. The study scope is defined to be from the front-end areas at the antennas to the end users (spacecraft teams, principal investigators, archival storage systems, and non-NASA partners). The architectural vision provides guidance for major DSN implementation efforts during the next decade. A strong motivation for the study is an expected dramatic improvement in information-systems technologies--i.e., computer processing, automation technology (including knowledge-based systems), networking and data transport, software and hardware engineering, and human-interface technology. The proposed Ground Information System has the following major features: unified architecture from the front-end area to the end user; open-systems standards to achieve interoperability; DSN production of level 0 data; delivery of level 0 data from the Deep Space Communications Complex, if desired; dedicated telemetry processors for each receiver; security against unauthorized access and errors; and highly automated monitor and control.

  12. A statistical method for measuring activation of gene regulatory networks.

    PubMed

    Esteves, Gustavo H; Reis, Luiz F L

    2018-06-13

    Gene expression data analysis is of great importance for modern molecular biology, given our ability to measure the expression profiles of thousands of genes and enabling studies rooted in systems biology. In this work, we propose a simple statistical model for the activation measuring of gene regulatory networks, instead of the traditional gene co-expression networks. We present the mathematical construction of a statistical procedure for testing hypothesis regarding gene regulatory network activation. The real probability distribution for the test statistic is evaluated by a permutation based study. To illustrate the functionality of the proposed methodology, we also present a simple example based on a small hypothetical network and the activation measuring of two KEGG networks, both based on gene expression data collected from gastric and esophageal samples. The two KEGG networks were also analyzed for a public database, available through NCBI-GEO, presented as Supplementary Material. This method was implemented in an R package that is available at the BioConductor project website under the name maigesPack.

  13. Interconnection network architectures based on integrated orbital angular momentum emitters

    NASA Astrophysics Data System (ADS)

    Scaffardi, Mirco; Zhang, Ning; Malik, Muhammad Nouman; Lazzeri, Emma; Klitis, Charalambos; Lavery, Martin; Sorel, Marc; Bogoni, Antonella

    2018-02-01

    Novel architectures for two-layer interconnection networks based on concentric OAM emitters are presented. A scalability analysis is done in terms of devices characteristics, power budget and optical signal to noise ratio by exploiting experimentally measured parameters. The analysis shows that by exploiting optical amplifications, the proposed interconnection networks can support a number of ports higher than 100. The OAM crosstalk induced-penalty, evaluated through an experimental characterization, do not significantly affect the interconnection network performance.

  14. Dependence of physical and mechanical properties on polymer architecture for model polymer networks

    NASA Astrophysics Data System (ADS)

    Guo, Ruilan

    Effect of architecture at nanoscale on the macroscopic properties of polymer materials has long been a field of major interest, as evidenced by inhomogeneities in networks, multimodal network topologies, etc. The primary purpose of this research is to establish the architecture-property relationship of polymer networks by studying the physical and mechanical responses of a series of topologically different PTHF networks. Monodispersed allyl-tenninated PTHF precursors were synthesized through "living" cationic polymerization and functional end-capping. Model networks of various crosslink densities and inhomogeneities levels (unimodal, bimodal and clustered) were prepared by endlinking precursors via thiol-ene reaction. Thermal characteristics, i.e., glass transition, melting point, and heat of fusion, of model PTHF networks were investigated as functions of crosslink density and inhomogeneities, which showed different dependence on these two architectural parameters. Study of freezing point depression (FPD) of solvent confined in swollen networks indicated that the size of solvent microcrystals is comparable to the mesh size formed by intercrosslink chains depending on crosslink density and inhomogeneities. Relationship between crystal size and FPD provided a good reflection of the existing architecture facts in the networks. Mechanical responses of elastic chains to uniaxial strains were studied through SANS. Spatial inhomogeneities in bimodal and clustered networks gave rise to "abnormal butterfly patterns", which became more pronounced as elongation ratio increases. Radii of gyration of chains were analyzed at directions parallel and perpendicular to stretching axis. Dependence of Rg on lambda was compared to three rubber elasticity models and the molecular deformation mechanisms for unimodal, bimodal and clustered networks were explored. The thesis focused its last part on the investigation of evolution of free volume distribution of linear polymer (PE

  15. Parallel mutual information estimation for inferring gene regulatory networks on GPUs

    PubMed Central

    2011-01-01

    Background Mutual information is a measure of similarity between two variables. It has been widely used in various application domains including computational biology, machine learning, statistics, image processing, and financial computing. Previously used simple histogram based mutual information estimators lack the precision in quality compared to kernel based methods. The recently introduced B-spline function based mutual information estimation method is competitive to the kernel based methods in terms of quality but at a lower computational complexity. Results We present a new approach to accelerate the B-spline function based mutual information estimation algorithm with commodity graphics hardware. To derive an efficient mapping onto this type of architecture, we have used the Compute Unified Device Architecture (CUDA) programming model to design and implement a new parallel algorithm. Our implementation, called CUDA-MI, can achieve speedups of up to 82 using double precision on a single GPU compared to a multi-threaded implementation on a quad-core CPU for large microarray datasets. We have used the results obtained by CUDA-MI to infer gene regulatory networks (GRNs) from microarray data. The comparisons to existing methods including ARACNE and TINGe show that CUDA-MI produces GRNs of higher quality in less time. Conclusions CUDA-MI is publicly available open-source software, written in CUDA and C++ programming languages. It obtains significant speedup over sequential multi-threaded implementation by fully exploiting the compute capability of commonly used CUDA-enabled low-cost GPUs. PMID:21672264

  16. A TDMA Broadcast Satellite/Ground Architecture for the Aeronautical Telecommunications Network

    NASA Technical Reports Server (NTRS)

    Shamma, Mohammed A.; Raghavan, Rajesh S.

    2003-01-01

    An initial evaluation of a TDMA satellite broadcast architecture with an integrated ground network is proposed in this study as one option for the Aeronautical Telecommunications Network (ATN). The architecture proposed consists of a ground based network that is dedicated to the reception and transmissions of Automatic Dependent Surveillance Broadcast (ADS-B) messages from Mode-S or UAT type systems, along with tracks from primary and secondary surveillance radars. Additionally, the ground network could contain VHF Digital Link Mode 2, 3 or 4 transceivers for the reception and transmissions of Controller-Pilot Data Link Communications (CPDLC) messages and for voice. The second part of the ATN network consists of a broadcast satellite based system that is mainly dedicated for the transmission of surveillance data as well as En-route Flight Information Service Broadcast (FIS-B) to all aircraft. The system proposed integrates those two network to provide a nation wide comprehensive service utilizing near term or existing technologies and hence keeping the economic factor in prospective. The next few sections include a background introduction, the ground subnetwork, the satellite subnetwork, modeling and simulations, and conclusion and recommendations.

  17. Brain Network Architecture and Global Intelligence in Children with Focal Epilepsy.

    PubMed

    Paldino, M J; Golriz, F; Chapieski, M L; Zhang, W; Chu, Z D

    2017-02-01

    The biologic basis for intelligence rests to a large degree on the capacity for efficient integration of information across the cerebral network. We aimed to measure the relationship between network architecture and intelligence in the pediatric, epileptic brain. Patients were retrospectively identified with the following: 1) focal epilepsy; 2) brain MR imaging at 3T, including resting-state functional MR imaging; and 3) full-scale intelligence quotient measured by a pediatric neuropsychologist. The cerebral cortex was parcellated into approximately 700 gray matter network "nodes." The strength of a connection between 2 nodes was defined by the correlation between their blood oxygen level-dependent time-series. We calculated the following topologic properties: clustering coefficient, transitivity, modularity, path length, and global efficiency. A machine learning algorithm was used to measure the independent contribution of each metric to the intelligence quotient after adjusting for all other metrics. Thirty patients met the criteria (4-18 years of age); 20 patients required anesthesia during MR imaging. After we accounted for age and sex, clustering coefficient and path length were independently associated with full-scale intelligence quotient. Neither motion parameters nor general anesthesia was an important variable with regard to accurate intelligence quotient prediction by the machine learning algorithm. A longer history of epilepsy was associated with shorter path lengths ( P = .008), consistent with reorganization of the network on the basis of seizures. Considering only patients receiving anesthesia during machine learning did not alter the patterns of network architecture contributing to global intelligence. These findings support the physiologic relevance of imaging-based metrics of network architecture in the pathologic, developing brain. © 2017 by American Journal of Neuroradiology.

  18. Classification capacity of a modular neural network implementing neurally inspired architecture and training rules.

    PubMed

    Poirazi, Panayiota; Neocleous, Costas; Pattichis, Costantinos S; Schizas, Christos N

    2004-05-01

    A three-layer neural network (NN) with novel adaptive architecture has been developed. The hidden layer of the network consists of slabs of single neuron models, where neurons within a slab--but not between slabs--have the same type of activation function. The network activation functions in all three layers have adaptable parameters. The network was trained using a biologically inspired, guided-annealing learning rule on a variety of medical data. Good training/testing classification performance was obtained on all data sets tested. The performance achieved was comparable to that of SVM classifiers. It was shown that the adaptive network architecture, inspired from the modular organization often encountered in the mammalian cerebral cortex, can benefit classification performance.

  19. CoryneRegNet: an ontology-based data warehouse of corynebacterial transcription factors and regulatory networks.

    PubMed

    Baumbach, Jan; Brinkrolf, Karina; Czaja, Lisa F; Rahmann, Sven; Tauch, Andreas

    2006-02-14

    The application of DNA microarray technology in post-genomic analysis of bacterial genome sequences has allowed the generation of huge amounts of data related to regulatory networks. This data along with literature-derived knowledge on regulation of gene expression has opened the way for genome-wide reconstruction of transcriptional regulatory networks. These large-scale reconstructions can be converted into in silico models of bacterial cells that allow a systematic analysis of network behavior in response to changing environmental conditions. CoryneRegNet was designed to facilitate the genome-wide reconstruction of transcriptional regulatory networks of corynebacteria relevant in biotechnology and human medicine. During the import and integration process of data derived from experimental studies or literature knowledge CoryneRegNet generates links to genome annotations, to identified transcription factors and to the corresponding cis-regulatory elements. CoryneRegNet is based on a multi-layered, hierarchical and modular concept of transcriptional regulation and was implemented by using the relational database management system MySQL and an ontology-based data structure. Reconstructed regulatory networks can be visualized by using the yFiles JAVA graph library. As an application example of CoryneRegNet, we have reconstructed the global transcriptional regulation of a cellular module involved in SOS and stress response of corynebacteria. CoryneRegNet is an ontology-based data warehouse that allows a pertinent data management of regulatory interactions along with the genome-scale reconstruction of transcriptional regulatory networks. These models can further be combined with metabolic networks to build integrated models of cellular function including both metabolism and its transcriptional regulation.

  20. Reconstruction of the regulatory network for Bacillus subtilis and reconciliation with gene expression data

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Faria, Jose P.; Overbeek, Ross; Taylor, Ronald C.

    Here, we introduce a manually constructed and curated regulatory network model that describes the current state of knowledge of transcriptional regulation of B. subtilis. The model corresponds to an updated and enlarged version of the regulatory model of central metabolism originally proposed in 2008. We extended the original network to the whole genome by integration of information from DBTBS, a compendium of regulatory data that includes promoters, transcription factors (TFs), binding sites, motifs and regulated operons. Additionally, we consolidated our network with all the information on regulation included in the SporeWeb and Subtiwiki community-curated resources on B. subtilis. Finally, wemore » reconciled our network with data from RegPrecise, which recently released their own less comprehensive reconstruction of the regulatory network for B. subtilis. Our model describes 275 regulators and their target genes, representing 30 different mechanisms of regulation such as TFs, RNA switches, Riboswitches and small regulatory RNAs. Overall, regulatory information is included in the model for approximately 2500 of the ~4200 genes in B. subtilis 168. In an effort to further expand our knowledge of B. subtilis regulation, we reconciled our model with expression data. For this process, we reconstructed the Atomic Regulons (ARs) for B. subtilis, which are the sets of genes that share the same “ON” and “OFF” gene expression profiles across multiple samples of experimental data. We show how atomic regulons for B. subtilis are able to capture many sets of genes corresponding to regulated operons in our manually curated network. Additionally, we demonstrate how atomic regulons can be used to help expand or validate the knowledge of the regulatory networks by looking at highly correlated genes in the ARs for which regulatory information is lacking. During this process, we were also able to infer novel stimuli for hypothetical genes by exploring the genome

  1. Reconstruction of the regulatory network for Bacillus subtilis and reconciliation with gene expression data

    DOE PAGES

    Faria, Jose P.; Overbeek, Ross; Taylor, Ronald C.; ...

    2016-03-18

    Here, we introduce a manually constructed and curated regulatory network model that describes the current state of knowledge of transcriptional regulation of B. subtilis. The model corresponds to an updated and enlarged version of the regulatory model of central metabolism originally proposed in 2008. We extended the original network to the whole genome by integration of information from DBTBS, a compendium of regulatory data that includes promoters, transcription factors (TFs), binding sites, motifs and regulated operons. Additionally, we consolidated our network with all the information on regulation included in the SporeWeb and Subtiwiki community-curated resources on B. subtilis. Finally, wemore » reconciled our network with data from RegPrecise, which recently released their own less comprehensive reconstruction of the regulatory network for B. subtilis. Our model describes 275 regulators and their target genes, representing 30 different mechanisms of regulation such as TFs, RNA switches, Riboswitches and small regulatory RNAs. Overall, regulatory information is included in the model for approximately 2500 of the ~4200 genes in B. subtilis 168. In an effort to further expand our knowledge of B. subtilis regulation, we reconciled our model with expression data. For this process, we reconstructed the Atomic Regulons (ARs) for B. subtilis, which are the sets of genes that share the same “ON” and “OFF” gene expression profiles across multiple samples of experimental data. We show how atomic regulons for B. subtilis are able to capture many sets of genes corresponding to regulated operons in our manually curated network. Additionally, we demonstrate how atomic regulons can be used to help expand or validate the knowledge of the regulatory networks by looking at highly correlated genes in the ARs for which regulatory information is lacking. During this process, we were also able to infer novel stimuli for hypothetical genes by exploring the genome

  2. Combining inferred regulatory and reconstructed metabolic networks enhances phenotype prediction in yeast.

    PubMed

    Wang, Zhuo; Danziger, Samuel A; Heavner, Benjamin D; Ma, Shuyi; Smith, Jennifer J; Li, Song; Herricks, Thurston; Simeonidis, Evangelos; Baliga, Nitin S; Aitchison, John D; Price, Nathan D

    2017-05-01

    Gene regulatory and metabolic network models have been used successfully in many organisms, but inherent differences between them make networks difficult to integrate. Probabilistic Regulation Of Metabolism (PROM) provides a partial solution, but it does not incorporate network inference and underperforms in eukaryotes. We present an Integrated Deduced And Metabolism (IDREAM) method that combines statistically inferred Environment and Gene Regulatory Influence Network (EGRIN) models with the PROM framework to create enhanced metabolic-regulatory network models. We used IDREAM to predict phenotypes and genetic interactions between transcription factors and genes encoding metabolic activities in the eukaryote, Saccharomyces cerevisiae. IDREAM models contain many fewer interactions than PROM and yet produce significantly more accurate growth predictions. IDREAM consistently outperformed PROM using any of three popular yeast metabolic models and across three experimental growth conditions. Importantly, IDREAM's enhanced accuracy makes it possible to identify subtle synthetic growth defects. With experimental validation, these novel genetic interactions involving the pyruvate dehydrogenase complex suggested a new role for fatty acid-responsive factor Oaf1 in regulating acetyl-CoA production in glucose grown cells.

  3. Identification of critical regulatory genes in cancer signaling network using controllability analysis

    NASA Astrophysics Data System (ADS)

    Ravindran, Vandana; Sunitha, V.; Bagler, Ganesh

    2017-05-01

    Cancer is characterized by a complex web of regulatory mechanisms which makes it difficult to identify features that are central to its control. Molecular integrative models of cancer, generated with the help of data from experimental assays, facilitate use of control theory to probe for ways of controlling the state of such a complex dynamic network. We modeled the human cancer signaling network as a directed graph and analyzed it for its controllability, identification of driver nodes and their characterization. We identified the driver nodes using the maximum matching algorithm and classified them as backbone, peripheral and ordinary based on their role in regulatory interactions and control of the network. We found that the backbone driver nodes were key to driving the regulatory network into cancer phenotype (via mutations) as well as for steering into healthy phenotype (as drug targets). This implies that while backbone genes could lead to cancer by virtue of mutations, they are also therapeutic targets of cancer. Further, based on their impact on the size of the set of driver nodes, genes were characterized as indispensable, dispensable and neutral. Indispensable nodes within backbone of the network emerged as central to regulatory mechanisms of control of cancer. In addition to probing the cancer signaling network from the perspective of control, our findings suggest that indispensable backbone driver nodes could be potentially leveraged as therapeutic targets. This study also illustrates the application of structural controllability for studying the mechanisms underlying the regulation of complex diseases.

  4. T-SDN architecture for space and ground integrated optical transport network

    NASA Astrophysics Data System (ADS)

    Nie, Kunkun; Hu, Wenjing; Gao, Shenghua; Chang, Chengwu

    2015-11-01

    Integrated optical transport network is the development trend of the future space information backbone network. The space and ground integrated optical transport network(SGIOTN) may contain a variety of equipment and systems. Changing the network or meeting some innovation missions in the network will be an expensive implement. Software Defined Network(SDN) provides a good solution to flexibly adding process logic, timely control states and resources of the whole network, as well as shielding the differences of heterogeneous equipment and so on. According to the characteristics of SGIOTN, we propose an transport SDN architecture for it, with hierarchical control plane and data plane composed of packet networks and optical transport networks.

  5. RNA regulatory networks diversified through curvature of the PUF protein scaffold

    DOE PAGES

    Wilinski, Daniel; Qiu, Chen; Lapointe, Christopher P.; ...

    2015-09-14

    Proteins bind and control mRNAs, directing their localization, translation and stability. Members of the PUF family of RNA-binding proteins control multiple mRNAs in a single cell, and play key roles in development, stem cell maintenance and memory formation. Here we identified the mRNA targets of a S. cerevisiae PUF protein, Puf5p, by ultraviolet-crosslinking-affinity purification and high-throughput sequencing (HITS-CLIP). The binding sites recognized by Puf5p are diverse, with variable spacer lengths between two specific sequences. Each length of site correlates with a distinct biological function. Crystal structures of Puf5p–RNA complexes reveal that the protein scaffold presents an exceptionally flat and extendedmore » interaction surface relative to other PUF proteins. In complexes with RNAs of different lengths, the protein is unchanged. A single PUF protein repeat is sufficient to induce broadening of specificity. Changes in protein architecture, such as alterations in curvature, may lead to evolution of mRNA regulatory networks.« less

  6. RNA regulatory networks diversified through curvature of the PUF protein scaffold

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wilinski, Daniel; Qiu, Chen; Lapointe, Christopher P.

    Proteins bind and control mRNAs, directing their localization, translation and stability. Members of the PUF family of RNA-binding proteins control multiple mRNAs in a single cell, and play key roles in development, stem cell maintenance and memory formation. Here we identified the mRNA targets of a S. cerevisiae PUF protein, Puf5p, by ultraviolet-crosslinking-affinity purification and high-throughput sequencing (HITS-CLIP). The binding sites recognized by Puf5p are diverse, with variable spacer lengths between two specific sequences. Each length of site correlates with a distinct biological function. Crystal structures of Puf5p–RNA complexes reveal that the protein scaffold presents an exceptionally flat and extendedmore » interaction surface relative to other PUF proteins. In complexes with RNAs of different lengths, the protein is unchanged. A single PUF protein repeat is sufficient to induce broadening of specificity. Changes in protein architecture, such as alterations in curvature, may lead to evolution of mRNA regulatory networks.« less

  7. Functional architecture of Escherichia coli: new insights provided by a natural decomposition approach.

    PubMed

    Freyre-González, Julio A; Alonso-Pavón, José A; Treviño-Quintanilla, Luis G; Collado-Vides, Julio

    2008-10-27

    Previous studies have used different methods in an effort to extract the modular organization of transcriptional regulatory networks. However, these approaches are not natural, as they try to cluster strongly connected genes into a module or locate known pleiotropic transcription factors in lower hierarchical layers. Here, we unravel the transcriptional regulatory network of Escherichia coli by separating it into its key elements, thus revealing its natural organization. We also present a mathematical criterion, based on the topological features of the transcriptional regulatory network, to classify the network elements into one of two possible classes: hierarchical or modular genes. We found that modular genes are clustered into physiologically correlated groups validated by a statistical analysis of the enrichment of the functional classes. Hierarchical genes encode transcription factors responsible for coordinating module responses based on general interest signals. Hierarchical elements correlate highly with the previously studied global regulators, suggesting that this could be the first mathematical method to identify global regulators. We identified a new element in transcriptional regulatory networks never described before: intermodular genes. These are structural genes that integrate, at the promoter level, signals coming from different modules, and therefore from different physiological responses. Using the concept of pleiotropy, we have reconstructed the hierarchy of the network and discuss the role of feedforward motifs in shaping the hierarchical backbone of the transcriptional regulatory network. This study sheds new light on the design principles underpinning the organization of transcriptional regulatory networks, showing a novel nonpyramidal architecture composed of independent modules globally governed by hierarchical transcription factors, whose responses are integrated by intermodular genes.

  8. Gene regulatory network architecture in different developmental contexts influences the genetic basis of morphological evolution.

    PubMed

    Kittelmann, Sebastian; Buffry, Alexandra D; Franke, Franziska A; Almudi, Isabel; Yoth, Marianne; Sabaris, Gonzalo; Couso, Juan Pablo; Nunes, Maria D S; Frankel, Nicolás; Gómez-Skarmeta, José Luis; Pueyo-Marques, Jose; Arif, Saad; McGregor, Alistair P

    2018-05-01

    Convergent phenotypic evolution is often caused by recurrent changes at particular nodes in the underlying gene regulatory networks (GRNs). The genes at such evolutionary 'hotspots' are thought to maximally affect the phenotype with minimal pleiotropic consequences. This has led to the suggestion that if a GRN is understood in sufficient detail, the path of evolution may be predictable. The repeated evolutionary loss of larval trichomes among Drosophila species is caused by the loss of shavenbaby (svb) expression. svb is also required for development of leg trichomes, but the evolutionary gain of trichomes in the 'naked valley' on T2 femurs in Drosophila melanogaster is caused by reduced microRNA-92a (miR-92a) expression rather than changes in svb. We compared the expression and function of components between the larval and leg trichome GRNs to investigate why the genetic basis of trichome pattern evolution differs in these developmental contexts. We found key differences between the two networks in both the genes employed, and in the regulation and function of common genes. These differences in the GRNs reveal why mutations in svb are unlikely to contribute to leg trichome evolution and how instead miR-92a represents the key evolutionary switch in this context. Our work shows that variability in GRNs across different developmental contexts, as well as whether a morphological feature is lost versus gained, influence the nodes at which a GRN evolves to cause morphological change. Therefore, our findings have important implications for understanding the pathways and predictability of evolution.

  9. Molecular Evolution of the Neural Crest Regulatory Network in Ray-Finned Fish

    PubMed Central

    Kratochwil, Claudius F.; Geissler, Laura; Irisarri, Iker; Meyer, Axel

    2015-01-01

    Abstract Gene regulatory networks (GRN) are central to developmental processes. They are composed of transcription factors and signaling molecules orchestrating gene expression modules that tightly regulate the development of organisms. The neural crest (NC) is a multipotent cell population that is considered a key innovation of vertebrates. Its derivatives contribute to shaping the astounding morphological diversity of jaws, teeth, head skeleton, or pigmentation. Here, we study the molecular evolution of the NC GRN by analyzing patterns of molecular divergence for a total of 36 genes in 16 species of bony fishes. Analyses of nonsynonymous to synonymous substitution rate ratios (dN/dS) support patterns of variable selective pressures among genes deployed at different stages of NC development, consistent with the developmental hourglass model. Model-based clustering techniques of sequence features support the notion of extreme conservation of NC-genes across the entire network. Our data show that most genes are under strong purifying selection that is maintained throughout ray-finned fish evolution. Late NC development genes reveal a pattern of increased constraints in more recent lineages. Additionally, seven of the NC-genes showed signs of relaxation of purifying selection in the famously species-rich lineage of cichlid fishes. This suggests that NC genes might have played a role in the adaptive radiation of cichlids by granting flexibility in the development of NC-derived traits—suggesting an important role for NC network architecture during the diversification in vertebrates. PMID:26475317

  10. Evolution of regulatory networks towards adaptability and stability in a changing environment

    NASA Astrophysics Data System (ADS)

    Lee, Deok-Sun

    2014-11-01

    Diverse biological networks exhibit universal features distinguished from those of random networks, calling much attention to their origins and implications. Here we propose a minimal evolution model of Boolean regulatory networks, which evolve by selectively rewiring links towards enhancing adaptability to a changing environment and stability against dynamical perturbations. We find that sparse and heterogeneous connectivity patterns emerge, which show qualitative agreement with real transcriptional regulatory networks and metabolic networks. The characteristic scaling behavior of stability reflects the balance between robustness and flexibility. The scaling of fluctuation in the perturbation spread shows a dynamic crossover, which is analyzed by investigating separately the stochasticity of internal dynamics and the network structure differences depending on the evolution pathways. Our study delineates how the ambivalent pressure of evolution shapes biological networks, which can be helpful for studying general complex systems interacting with environments.

  11. A Cluster-Based Architecture to Structure the Topology of Parallel Wireless Sensor Networks

    PubMed Central

    Lloret, Jaime; Garcia, Miguel; Bri, Diana; Diaz, Juan R.

    2009-01-01

    A wireless sensor network is a self-configuring network of mobile nodes connected by wireless links where the nodes have limited capacity and energy. In many cases, the application environment requires the design of an exclusive network topology for a particular case. Cluster-based network developments and proposals in existence have been designed to build a network for just one type of node, where all nodes can communicate with any other nodes in their coverage area. Let us suppose a set of clusters of sensor nodes where each cluster is formed by different types of nodes (e.g., they could be classified by the sensed parameter using different transmitting interfaces, by the node profile or by the type of device: laptops, PDAs, sensor etc.) and exclusive networks, as virtual networks, are needed with the same type of sensed data, or the same type of devices, or even the same type of profiles. In this paper, we propose an algorithm that is able to structure the topology of different wireless sensor networks to coexist in the same environment. It allows control and management of the topology of each network. The architecture operation and the protocol messages will be described. Measurements from a real test-bench will show that the designed protocol has low bandwidth consumption and also demonstrates the viability and the scalability of the proposed architecture. Our ccluster-based algorithm is compared with other algorithms reported in the literature in terms of architecture and protocol measurements. PMID:22303185

  12. Self-growing neural network architecture using crisp and fuzzy entropy

    NASA Technical Reports Server (NTRS)

    Cios, Krzysztof J.

    1992-01-01

    The paper briefly describes the self-growing neural network algorithm, CID2, which makes decision trees equivalent to hidden layers of a neural network. The algorithm generates a feedforward architecture using crisp and fuzzy entropy measures. The results of a real-life recognition problem of distinguishing defects in a glass ribbon and of a benchmark problem of differentiating two spirals are shown and discussed.

  13. Self-growing neural network architecture using crisp and fuzzy entropy

    NASA Technical Reports Server (NTRS)

    Cios, Krzysztof J.

    1992-01-01

    The paper briefly describes the self-growing neural network algorithm, CID3, which makes decision trees equivalent to hidden layers of a neural network. The algorithm generates a feedforward architecture using crisp and fuzzy entropy measures. The results for a real-life recognition problem of distinguishing defects in a glass ribbon, and for a benchmark problen of telling two spirals apart are shown and discussed.

  14. Uncovering transcription factor and microRNA risk regulatory pathways associated with osteoarthritis by network analysis.

    PubMed

    Song, Zhenhua; Zhang, Chi; He, Lingxiao; Sui, Yanfang; Lin, Xiafei; Pan, Jingjing

    2018-06-12

    Osteoarthritis (OA) is the most common form of joint disease. The development of inflammation have been considered to play a key role during the progression of OA. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, deciphering these risk regulatory pathways is critical for elucidating the mechanisms underlying OA. We constructed an OA-specific regulatory network by integrating comprehensive curated transcription and post-transcriptional resource involving transcription factor (TF) and microRNA (miRNA). To deepen our understanding of underlying molecular mechanisms of OA, we developed an integrated systems approach to identify OA-specific risk regulatory pathways. In this study, we identified 89 significantly differentially expressed genes between normal and inflamed areas of OA patients. We found the OA-specific regulatory network was a standard scale-free network with small-world properties. It significant enriched many immune response-related functions including leukocyte differentiation, myeloid differentiation and T cell activation. Finally, 141 risk regulatory pathways were identified based on OA-specific regulatory network, which contains some known regulator of OA. The risk regulatory pathways may provide clues for the etiology of OA and be a potential resource for the discovery of novel OA-associated disease genes. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. An eConsent-based System Architecture Supporting Cooperation in Integrated Healthcare Networks.

    PubMed

    Bergmann, Joachim; Bott, Oliver J; Hoffmann, Ina; Pretschner, Dietrich P

    2005-01-01

    The economical need for efficient healthcare leads to cooperative shared care networks. A virtual electronic health record is required, which integrates patient related information but reflects the distributed infrastructure and restricts access only to those health professionals involved into the care process. Our work aims on specification and development of a system architecture fulfilling these requirements to be used in concrete regional pilot studies. Methodical analysis and specification have been performed in a healthcare network using the formal method and modelling tool MOSAIK-M. The complexity of the application field was reduced by focusing on the scenario of thyroid disease care, which still includes various interdisciplinary cooperation. Result is an architecture for a secure distributed electronic health record for integrated care networks, specified in terms of a MOSAIK-M-based system model. The architecture proposes business processes, application services, and a sophisticated security concept, providing a platform for distributed document-based, patient-centred, and secure cooperation. A corresponding system prototype has been developed for pilot studies, using advanced application server technologies. The architecture combines a consolidated patient-centred document management with a decentralized system structure without needs for replication management. An eConsent-based approach assures, that access to the distributed health record remains under control of the patient. The proposed architecture replaces message-based communication approaches, because it implements a virtual health record providing complete and current information. Acceptance of the new communication services depends on compatibility with the clinical routine. Unique and cross-institutional identification of a patient is also a challenge, but will loose significance with establishing common patient cards.

  16. Regulatory Aspects of Smart Water Networks in the U.S.

    EPA Science Inventory

    The presentation addresses regulatory aspects of smart water networks in the U.S. It will be presented at the Smart Water Networks Forum (SWAN) annual conference in London, England from April 29-30, 2015. The conference will bring together key voices in the smart water space f...

  17. Improvements to Integrated Tradespace Analysis of Communications Architectures (ITACA) Network Loading Analysis Tool

    NASA Technical Reports Server (NTRS)

    Lee, Nathaniel; Welch, Bryan W.

    2018-01-01

    NASA's SCENIC project aims to simplify and reduce the cost of space mission planning by replicating the analysis capabilities of commercially licensed software which are integrated with relevant analysis parameters specific to SCaN assets and SCaN supported user missions. SCENIC differs from current tools that perform similar analyses in that it 1) does not require any licensing fees, 2) will provide an all-in-one package for various analysis capabilities that normally requires add-ons or multiple tools to complete. As part of SCENIC's capabilities, the ITACA network loading analysis tool will be responsible for assessing the loading on a given network architecture and generating a network service schedule. ITACA will allow users to evaluate the quality of service of a given network architecture and determine whether or not the architecture will satisfy the mission's requirements. ITACA is currently under development, and the following improvements were made during the fall of 2017: optimization of runtime, augmentation of network asset pre-service configuration time, augmentation of Brent's method of root finding, augmentation of network asset FOV restrictions, augmentation of mission lifetimes, and the integration of a SCaN link budget calculation tool. The improvements resulted in (a) 25% reduction in runtime, (b) more accurate contact window predictions when compared to STK(Registered Trademark) contact window predictions, and (c) increased fidelity through the use of specific SCaN asset parameters.

  18. Evolution of network architecture in a granular material under compression

    NASA Astrophysics Data System (ADS)

    Bassett, Danielle

    As a granular material is compressed, the particles and forces within the system arrange to form complex and heterogeneous collective structures. However, capturing and characterizing the dynamic nature of the intrinsic inhomogeneity and mesoscale architecture of granular systems can be challenging. Here, we utilize multilayer networks as a framework for directly quantifying the evolution of mesoscale architecture in a compressed granular system. We examine a quasi-two-dimensional aggregate of photoelastic disks, subject to biaxial compressions through a series of small, quasistatic steps. Treating particles as network nodes and inter-particle forces as network edges, we construct a multilayer network for the system by linking together the series of static force networks that exist at each strain step. We then extract the inherent mesoscale structure from the system by using a generalization of community detection methods to multilayer networks, and we define quantitative measures to characterize the reconfiguration and evolution of this structure throughout the compression process. To test the sensitivity of the network model to particle properties, we examine whether the method can distinguish a subsystem of low-friction particles within a bath of higher-friction particles. We find that this can be done by considering the network of tangential forces, and that the community structure is better able to separate the subsystem than consideration of the local inter-particle forces alone. The results discussed throughout this study suggest that these novel network science techniques may provide a direct way to compare and classify data from systems under different external conditions or with different physical makeup. National Science Foundation (BCS-1441502, PHY-1554488, and BCS-1631550).

  19. CoryneRegNet: An ontology-based data warehouse of corynebacterial transcription factors and regulatory networks

    PubMed Central

    Baumbach, Jan; Brinkrolf, Karina; Czaja, Lisa F; Rahmann, Sven; Tauch, Andreas

    2006-01-01

    Background The application of DNA microarray technology in post-genomic analysis of bacterial genome sequences has allowed the generation of huge amounts of data related to regulatory networks. This data along with literature-derived knowledge on regulation of gene expression has opened the way for genome-wide reconstruction of transcriptional regulatory networks. These large-scale reconstructions can be converted into in silico models of bacterial cells that allow a systematic analysis of network behavior in response to changing environmental conditions. Description CoryneRegNet was designed to facilitate the genome-wide reconstruction of transcriptional regulatory networks of corynebacteria relevant in biotechnology and human medicine. During the import and integration process of data derived from experimental studies or literature knowledge CoryneRegNet generates links to genome annotations, to identified transcription factors and to the corresponding cis-regulatory elements. CoryneRegNet is based on a multi-layered, hierarchical and modular concept of transcriptional regulation and was implemented by using the relational database management system MySQL and an ontology-based data structure. Reconstructed regulatory networks can be visualized by using the yFiles JAVA graph library. As an application example of CoryneRegNet, we have reconstructed the global transcriptional regulation of a cellular module involved in SOS and stress response of corynebacteria. Conclusion CoryneRegNet is an ontology-based data warehouse that allows a pertinent data management of regulatory interactions along with the genome-scale reconstruction of transcriptional regulatory networks. These models can further be combined with metabolic networks to build integrated models of cellular function including both metabolism and its transcriptional regulation. PMID:16478536

  20. Development of the brain's functional network architecture.

    PubMed

    Vogel, Alecia C; Power, Jonathan D; Petersen, Steven E; Schlaggar, Bradley L

    2010-12-01

    A full understanding of the development of the brain's functional network architecture requires not only an understanding of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions between brain regions in both adults and children. We briefly review methods used to study functional interactions and networks with rs-fcMRI and how these methods have been used to define developmental changes in network functional connectivity. The developmental rs-fcMRI studies to date have found two general properties. First, regional interactions change from being predominately anatomically local in children to interactions spanning longer cortical distances in young adults. Second, this developmental change in functional connectivity occurs, in general, via mechanisms of segregation of local regions and integration of distant regions into disparate subnetworks.

  1. Development of the Brain's Functional Network Architecture

    PubMed Central

    Power, Jonathan D.; Petersen, Steven E.; Schlaggar, Bradley L.

    2013-01-01

    A full understanding of the development of the brain's functional network architecture requires not only an understanding of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions between brain regions in both adults and children. We briefly review methods used to study functional interactions and networks with rs-fcMRI and how these methods have been used to define developmental changes in network functional connectivity. The developmental rs-fcMRI studies to date have found two general properties. First, regional interactions change from being predominately anatomically local in children to interactions spanning longer cortical distances in young adults. Second, this developmental change in functional connectivity occurs, in general, via mechanisms of segregation of local regions and integration of distant regions into disparate subnetworks. PMID:20976563

  2. Intrinsic noise and deviations from criticality in Boolean gene-regulatory networks

    NASA Astrophysics Data System (ADS)

    Villegas, Pablo; Ruiz-Franco, José; Hidalgo, Jorge; Muñoz, Miguel A.

    2016-10-01

    Gene regulatory networks can be successfully modeled as Boolean networks. A much discussed hypothesis says that such model networks reproduce empirical findings the best if they are tuned to operate at criticality, i.e. at the borderline between their ordered and disordered phases. Critical networks have been argued to lead to a number of functional advantages such as maximal dynamical range, maximal sensitivity to environmental changes, as well as to an excellent tradeoff between stability and flexibility. Here, we study the effect of noise within the context of Boolean networks trained to learn complex tasks under supervision. We verify that quasi-critical networks are the ones learning in the fastest possible way -even for asynchronous updating rules- and that the larger the task complexity the smaller the distance to criticality. On the other hand, when additional sources of intrinsic noise in the network states and/or in its wiring pattern are introduced, the optimally performing networks become clearly subcritical. These results suggest that in order to compensate for inherent stochasticity, regulatory and other type of biological networks might become subcritical rather than being critical, all the most if the task to be performed has limited complexity.

  3. Random Evolution of Idiotypic Networks: Dynamics and Architecture

    NASA Astrophysics Data System (ADS)

    Brede, Markus; Behn, Ulrich

    The paper deals with modelling a subsystem of the immune system, the so-called idiotypic network (INW). INWs, conceived by N.K. Jerne in 1974, are functional networks of interacting antibodies and B cells. In principle, Jernes' framework provides solutions to many issues in immunology, such as immunological memory, mechanisms for antigen recognition and self/non-self discrimination. Explaining the interconnection between the elementary components, local dynamics, network formation and architecture, and possible modes of global system function appears to be an ideal playground of statistical mechanics. We present a simple cellular automaton model, based on a graph representation of the system. From a simplified description of idiotypic interactions, rules for the random evolution of networks of occupied and empty sites on these graphs are derived. In certain biologically relevant parameter ranges the resultant dynamics leads to stationary states. A stationary state is found to correspond to a specific pattern of network organization. It turns out that even these very simple rules give rise to a multitude of different kinds of patterns. We characterize these networks by classifying `static' and `dynamic' network-patterns. A type of `dynamic' network is found to display many features of real INWs.

  4. Noncoding RNA:RNA Regulatory Networks in Cancer

    PubMed Central

    Chan, Jia Jia; Tay, Yvonne

    2018-01-01

    Noncoding RNAs (ncRNAs) constitute the majority of the human transcribed genome. This largest class of RNA transcripts plays diverse roles in a multitude of cellular processes, and has been implicated in many pathological conditions, especially cancer. The different subclasses of ncRNAs include microRNAs, a class of short ncRNAs; and a variety of long ncRNAs (lncRNAs), such as lincRNAs, antisense RNAs, pseudogenes, and circular RNAs. Many studies have demonstrated the involvement of these ncRNAs in competitive regulatory interactions, known as competing endogenous RNA (ceRNA) networks, whereby lncRNAs can act as microRNA decoys to modulate gene expression. These interactions are often interconnected, thus aberrant expression of any network component could derail the complex regulatory circuitry, culminating in cancer development and progression. Recent integrative analyses have provided evidence that new computational platforms and experimental approaches can be harnessed together to distinguish key ceRNA interactions in specific cancers, which could facilitate the identification of robust biomarkers and therapeutic targets, and hence, more effective cancer therapies and better patient outcome and survival. PMID:29702599

  5. Disrupted Brain Functional Network Architecture in Chronic Tinnitus Patients

    PubMed Central

    Chen, Yu-Chen; Feng, Yuan; Xu, Jin-Jing; Mao, Cun-Nan; Xia, Wenqing; Ren, Jun; Yin, Xindao

    2016-01-01

    Purpose: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated the disruptions of multiple brain networks in tinnitus patients. Nonetheless, several studies found no differences in network processing between tinnitus patients and healthy controls (HCs). Its neural bases are poorly understood. To identify aberrant brain network architecture involved in chronic tinnitus, we compared the resting-state fMRI (rs-fMRI) patterns of tinnitus patients and HCs. Materials and Methods: Chronic tinnitus patients (n = 24) with normal hearing thresholds and age-, sex-, education- and hearing threshold-matched HCs (n = 22) participated in the current study and underwent the rs-fMRI scanning. We used degree centrality (DC) to investigate functional connectivity (FC) strength of the whole-brain network and Granger causality to analyze effective connectivity in order to explore directional aspects involved in tinnitus. Results: Compared to HCs, we found significantly increased network centrality in bilateral superior frontal gyrus (SFG). Unidirectionally, the left SFG revealed increased effective connectivity to the left middle orbitofrontal cortex (OFC), left posterior lobe of cerebellum (PLC), left postcentral gyrus, and right middle occipital gyrus (MOG) while the right SFG exhibited enhanced effective connectivity to the right supplementary motor area (SMA). In addition, the effective connectivity from the bilateral SFG to the OFC and SMA showed positive correlations with tinnitus distress. Conclusions: Rs-fMRI provides a new and novel method for identifying aberrant brain network architecture. Chronic tinnitus patients have disrupted FC strength and causal connectivity mostly in non-auditory regions, especially the prefrontal cortex (PFC). The current findings will provide a new perspective for understanding the neuropathophysiological mechanisms in chronic tinnitus. PMID:27458377

  6. Inferring Regulatory Networks by Combining Perturbation Screens and Steady State Gene Expression Profiles

    PubMed Central

    Michailidis, George

    2014-01-01

    Reconstructing transcriptional regulatory networks is an important task in functional genomics. Data obtained from experiments that perturb genes by knockouts or RNA interference contain useful information for addressing this reconstruction problem. However, such data can be limited in size and/or are expensive to acquire. On the other hand, observational data of the organism in steady state (e.g., wild-type) are more readily available, but their informational content is inadequate for the task at hand. We develop a computational approach to appropriately utilize both data sources for estimating a regulatory network. The proposed approach is based on a three-step algorithm to estimate the underlying directed but cyclic network, that uses as input both perturbation screens and steady state gene expression data. In the first step, the algorithm determines causal orderings of the genes that are consistent with the perturbation data, by combining an exhaustive search method with a fast heuristic that in turn couples a Monte Carlo technique with a fast search algorithm. In the second step, for each obtained causal ordering, a regulatory network is estimated using a penalized likelihood based method, while in the third step a consensus network is constructed from the highest scored ones. Extensive computational experiments show that the algorithm performs well in reconstructing the underlying network and clearly outperforms competing approaches that rely only on a single data source. Further, it is established that the algorithm produces a consistent estimate of the regulatory network. PMID:24586224

  7. Space Network IP Services (SNIS): An Architecture for Supporting Low Earth Orbiting IP Satellite Missions

    NASA Technical Reports Server (NTRS)

    Israel, David J.

    2005-01-01

    The NASA Space Network (SN) supports a variety of missions using the Tracking and Data Relay Satellite System (TDRSS), which includes ground stations in White Sands, New Mexico and Guam. A Space Network IP Services (SNIS) architecture is being developed to support future users with requirements for end-to-end Internet Protocol (IP) communications. This architecture will support all IP protocols, including Mobile IP, over TDRSS Single Access, Multiple Access, and Demand Access Radio Frequency (RF) links. This paper will describe this architecture and how it can enable Low Earth Orbiting IP satellite missions.

  8. Predicting gene regulatory networks of soybean nodulation from RNA-Seq transcriptome data.

    PubMed

    Zhu, Mingzhu; Dahmen, Jeremy L; Stacey, Gary; Cheng, Jianlin

    2013-09-22

    High-throughput RNA sequencing (RNA-Seq) is a revolutionary technique to study the transcriptome of a cell under various conditions at a systems level. Despite the wide application of RNA-Seq techniques to generate experimental data in the last few years, few computational methods are available to analyze this huge amount of transcription data. The computational methods for constructing gene regulatory networks from RNA-Seq expression data of hundreds or even thousands of genes are particularly lacking and urgently needed. We developed an automated bioinformatics method to predict gene regulatory networks from the quantitative expression values of differentially expressed genes based on RNA-Seq transcriptome data of a cell in different stages and conditions, integrating transcriptional, genomic and gene function data. We applied the method to the RNA-Seq transcriptome data generated for soybean root hair cells in three different development stages of nodulation after rhizobium infection. The method predicted a soybean nodulation-related gene regulatory network consisting of 10 regulatory modules common for all three stages, and 24, 49 and 70 modules separately for the first, second and third stage, each containing both a group of co-expressed genes and several transcription factors collaboratively controlling their expression under different conditions. 8 of 10 common regulatory modules were validated by at least two kinds of validations, such as independent DNA binding motif analysis, gene function enrichment test, and previous experimental data in the literature. We developed a computational method to reliably reconstruct gene regulatory networks from RNA-Seq transcriptome data. The method can generate valuable hypotheses for interpreting biological data and designing biological experiments such as ChIP-Seq, RNA interference, and yeast two hybrid experiments.

  9. Form and function in gene regulatory networks: the structure of network motifs determines fundamental properties of their dynamical state space.

    PubMed

    Ahnert, S E; Fink, T M A

    2016-07-01

    Network motifs have been studied extensively over the past decade, and certain motifs, such as the feed-forward loop, play an important role in regulatory networks. Recent studies have used Boolean network motifs to explore the link between form and function in gene regulatory networks and have found that the structure of a motif does not strongly determine its function, if this is defined in terms of the gene expression patterns the motif can produce. Here, we offer a different, higher-level definition of the 'function' of a motif, in terms of two fundamental properties of its dynamical state space as a Boolean network. One is the basin entropy, which is a complexity measure of the dynamics of Boolean networks. The other is the diversity of cyclic attractor lengths that a given motif can produce. Using these two measures, we examine all 104 topologically distinct three-node motifs and show that the structural properties of a motif, such as the presence of feedback loops and feed-forward loops, predict fundamental characteristics of its dynamical state space, which in turn determine aspects of its functional versatility. We also show that these higher-level properties have a direct bearing on real regulatory networks, as both basin entropy and cycle length diversity show a close correspondence with the prevalence, in neural and genetic regulatory networks, of the 13 connected motifs without self-interactions that have been studied extensively in the literature. © 2016 The Authors.

  10. Dynamical modeling and analysis of large cellular regulatory networks

    NASA Astrophysics Data System (ADS)

    Bérenguier, D.; Chaouiya, C.; Monteiro, P. T.; Naldi, A.; Remy, E.; Thieffry, D.; Tichit, L.

    2013-06-01

    The dynamical analysis of large biological regulatory networks requires the development of scalable methods for mathematical modeling. Following the approach initially introduced by Thomas, we formalize the interactions between the components of a network in terms of discrete variables, functions, and parameters. Model simulations result in directed graphs, called state transition graphs. We are particularly interested in reachability properties and asymptotic behaviors, which correspond to terminal strongly connected components (or "attractors") in the state transition graph. A well-known problem is the exponential increase of the size of state transition graphs with the number of network components, in particular when using the biologically realistic asynchronous updating assumption. To address this problem, we have developed several complementary methods enabling the analysis of the behavior of large and complex logical models: (i) the definition of transition priority classes to simplify the dynamics; (ii) a model reduction method preserving essential dynamical properties, (iii) a novel algorithm to compact state transition graphs and directly generate compressed representations, emphasizing relevant transient and asymptotic dynamical properties. The power of an approach combining these different methods is demonstrated by applying them to a recent multilevel logical model for the network controlling CD4+ T helper cell response to antigen presentation and to a dozen cytokines. This model accounts for the differentiation of canonical Th1 and Th2 lymphocytes, as well as of inflammatory Th17 and regulatory T cells, along with many hybrid subtypes. All these methods have been implemented into the software GINsim, which enables the definition, the analysis, and the simulation of logical regulatory graphs.

  11. Modeling Emergence in Neuroprotective Regulatory Networks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sanfilippo, Antonio P.; Haack, Jereme N.; McDermott, Jason E.

    2013-01-05

    The use of predictive modeling in the analysis of gene expression data can greatly accelerate the pace of scientific discovery in biomedical research by enabling in silico experimentation to test disease triggers and potential drug therapies. Techniques that focus on modeling emergence, such as agent-based modeling and multi-agent simulations, are of particular interest as they support the discovery of pathways that may have never been observed in the past. Thus far, these techniques have been primarily applied at the multi-cellular level, or have focused on signaling and metabolic networks. We present an approach where emergence modeling is extended to regulatorymore » networks and demonstrate its application to the discovery of neuroprotective pathways. An initial evaluation of the approach indicates that emergence modeling provides novel insights for the analysis of regulatory networks that can advance the discovery of acute treatments for stroke and other diseases.« less

  12. Planning assistance for the NASA 30/20 GHz program. Network control architecture study.

    NASA Technical Reports Server (NTRS)

    Inukai, T.; Bonnelycke, B.; Strickland, S.

    1982-01-01

    Network Control Architecture for a 30/20 GHz flight experiment system operating in the Time Division Multiple Access (TDMA) was studied. Architecture development, identification of processing functions, and performance requirements for the Master Control Station (MCS), diversity trunking stations, and Customer Premises Service (CPS) stations are covered. Preliminary hardware and software processing requirements as well as budgetary cost estimates for the network control system are given. For the trunking system control, areas covered include on board SS-TDMA switch organization, frame structure, acquisition and synchronization, channel assignment, fade detection and adaptive power control, on board oscillator control, and terrestrial network timing. For the CPS control, they include on board processing and adaptive forward error correction control.

  13. Mesh Network Architecture for Enabling Inter-Spacecraft Communication

    NASA Technical Reports Server (NTRS)

    Becker, Christopher; Merrill, Garrick

    2017-01-01

    To enable communication between spacecraft operating in a formation or small constellation, a mesh network architecture was developed and tested using a time division multiple access (TDMA) communication scheme. The network is designed to allow for the exchange of telemetry and other data between spacecraft to enable collaboration between small spacecraft. The system uses a peer-to-peer topology with no central router, so that it does not have a single point of failure. The mesh network is dynamically configurable to allow for addition and subtraction of new spacecraft into the communication network. Flight testing was performed using an unmanned aerial system (UAS) formation acting as a spacecraft analogue and providing a stressing environment to prove mesh network performance. The mesh network was primarily devised to provide low latency, high frequency communication but is flexible and can also be configured to provide higher bandwidth for applications desiring high data throughput. The network includes a relay functionality that extends the maximum range between spacecraft in the network by relaying data from node to node. The mesh network control is implemented completely in software making it hardware agnostic, thereby allowing it to function with a wide variety of existing radios and computing platforms..

  14. A Systems' Biology Approach to Study MicroRNA-Mediated Gene Regulatory Networks

    PubMed Central

    Kunz, Manfred; Vera, Julio; Wolkenhauer, Olaf

    2013-01-01

    MicroRNAs (miRNAs) are potent effectors in gene regulatory networks where aberrant miRNA expression can contribute to human diseases such as cancer. For a better understanding of the regulatory role of miRNAs in coordinating gene expression, we here present a systems biology approach combining data-driven modeling and model-driven experiments. Such an approach is characterized by an iterative process, including biological data acquisition and integration, network construction, mathematical modeling and experimental validation. To demonstrate the application of this approach, we adopt it to investigate mechanisms of collective repression on p21 by multiple miRNAs. We first construct a p21 regulatory network based on data from the literature and further expand it using algorithms that predict molecular interactions. Based on the network structure, a detailed mechanistic model is established and its parameter values are determined using data. Finally, the calibrated model is used to study the effect of different miRNA expression profiles and cooperative target regulation on p21 expression levels in different biological contexts. PMID:24350286

  15. Finding gene regulatory network candidates using the gene expression knowledge base.

    PubMed

    Venkatesan, Aravind; Tripathi, Sushil; Sanz de Galdeano, Alejandro; Blondé, Ward; Lægreid, Astrid; Mironov, Vladimir; Kuiper, Martin

    2014-12-10

    Network-based approaches for the analysis of large-scale genomics data have become well established. Biological networks provide a knowledge scaffold against which the patterns and dynamics of 'omics' data can be interpreted. The background information required for the construction of such networks is often dispersed across a multitude of knowledge bases in a variety of formats. The seamless integration of this information is one of the main challenges in bioinformatics. The Semantic Web offers powerful technologies for the assembly of integrated knowledge bases that are computationally comprehensible, thereby providing a potentially powerful resource for constructing biological networks and network-based analysis. We have developed the Gene eXpression Knowledge Base (GeXKB), a semantic web technology based resource that contains integrated knowledge about gene expression regulation. To affirm the utility of GeXKB we demonstrate how this resource can be exploited for the identification of candidate regulatory network proteins. We present four use cases that were designed from a biological perspective in order to find candidate members relevant for the gastrin hormone signaling network model. We show how a combination of specific query definitions and additional selection criteria derived from gene expression data and prior knowledge concerning candidate proteins can be used to retrieve a set of proteins that constitute valid candidates for regulatory network extensions. Semantic web technologies provide the means for processing and integrating various heterogeneous information sources. The GeXKB offers biologists such an integrated knowledge resource, allowing them to address complex biological questions pertaining to gene expression. This work illustrates how GeXKB can be used in combination with gene expression results and literature information to identify new potential candidates that may be considered for extending a gene regulatory network.

  16. Hybrid regulatory models: a statistically tractable approach to model regulatory network dynamics.

    PubMed

    Ocone, Andrea; Millar, Andrew J; Sanguinetti, Guido

    2013-04-01

    Computational modelling of the dynamics of gene regulatory networks is a central task of systems biology. For networks of small/medium scale, the dominant paradigm is represented by systems of coupled non-linear ordinary differential equations (ODEs). ODEs afford great mechanistic detail and flexibility, but calibrating these models to data is often an extremely difficult statistical problem. Here, we develop a general statistical inference framework for stochastic transcription-translation networks. We use a coarse-grained approach, which represents the system as a network of stochastic (binary) promoter and (continuous) protein variables. We derive an exact inference algorithm and an efficient variational approximation that allows scalable inference and learning of the model parameters. We demonstrate the power of the approach on two biological case studies, showing that the method allows a high degree of flexibility and is capable of testable novel biological predictions. http://homepages.inf.ed.ac.uk/gsanguin/software.html. Supplementary data are available at Bioinformatics online.

  17. A Consensus Network of Gene Regulatory Factors in the Human Frontal Lobe

    PubMed Central

    Berto, Stefano; Perdomo-Sabogal, Alvaro; Gerighausen, Daniel; Qin, Jing; Nowick, Katja

    2016-01-01

    Cognitive abilities, such as memory, learning, language, problem solving, and planning, involve the frontal lobe and other brain areas. Not much is known yet about the molecular basis of cognitive abilities, but it seems clear that cognitive abilities are determined by the interplay of many genes. One approach for analyzing the genetic networks involved in cognitive functions is to study the coexpression networks of genes with known importance for proper cognitive functions, such as genes that have been associated with cognitive disorders like intellectual disability (ID) or autism spectrum disorders (ASD). Because many of these genes are gene regulatory factors (GRFs) we aimed to provide insights into the gene regulatory networks active in the human frontal lobe. Using genome wide human frontal lobe expression data from 10 independent data sets, we first derived 10 individual coexpression networks for all GRFs including their potential target genes. We observed a high level of variability among these 10 independently derived networks, pointing out that relying on results from a single study can only provide limited biological insights. To instead focus on the most confident information from these 10 networks we developed a method for integrating such independently derived networks into a consensus network. This consensus network revealed robust GRF interactions that are conserved across the frontal lobes of different healthy human individuals. Within this network, we detected a strong central module that is enriched for 166 GRFs known to be involved in brain development and/or cognitive disorders. Interestingly, several hubs of the consensus network encode for GRFs that have not yet been associated with brain functions. Their central role in the network suggests them as excellent new candidates for playing an essential role in the regulatory network of the human frontal lobe, which should be investigated in future studies. PMID:27014338

  18. Layers of epistasis: genome-wide regulatory networks and network approaches to genome-wide association studies.

    PubMed

    Cowper-Sal lari, Richard; Cole, Michael D; Karagas, Margaret R; Lupien, Mathieu; Moore, Jason H

    2011-01-01

    The conceptual foundation of the genome-wide association study (GWAS) has advanced unchecked since its conception. A revision might seem premature as the potential of GWAS has not been fully realized. Multiple technical and practical limitations need to be overcome before GWAS can be fairly criticized. But with the completion of hundreds of studies and a deeper understanding of the genetic architecture of disease, warnings are being raised. The results compiled to date indicate that risk-associated variants lie predominantly in noncoding regions of the genome. Additionally, alternative methodologies are uncovering large and heterogeneous sets of rare variants underlying disease. The fear is that, even in its fulfillment, the current GWAS paradigm might be incapable of dissecting all kinds of phenotypes. In the following text, we review several initiatives that aim to overcome these limitations. The overarching theme of these studies is the inclusion of biological knowledge to both the analysis and interpretation of genotyping data. GWAS is uninformed of biology by design and although there is some virtue in its simplicity, it is also its most conspicuous deficiency. We propose a framework in which to integrate these novel approaches, both empirical and theoretical, in the form of a genome-wide regulatory network (GWRN). By processing experimental data into networks, emerging data types based on chromatin immunoprecipitation are made computationally tractable. This will give GWAS re-analysis efforts the most current and relevant substrates, and root them firmly on our knowledge of human disease. Copyright © 2010 John Wiley & Sons, Inc.

  19. Identification of regulatory network hubs that control lipid metabolism in Chlamydomonas reinhardtii

    DOE PAGES

    Gargouri, Mahmoud; Park, Jeong -Jin; Holguin, F. Omar; ...

    2015-05-28

    Microalgae-based biofuels are promising sources of alternative energy, but improvements throughout the production process are required to establish them as economically feasible. One of the most influential improvements would be a significant increase in lipid yields, which could be achieved by altering the regulation of lipid biosynthesis and accumulation. Chlamydomonas reinhardtii accumulates oil (triacylglycerols, TAG) in response to nitrogen (N) deprivation. Although a few important regulatory genes have been identified that are involved in controlling this process, a global understanding of the larger regulatory network has not been developed. In order to uncover this network in this species, a combinedmore » omics (transcriptomic, proteomic and metabolomic) analysis was applied to cells grown in a time course experiment after a shift from N-replete to N-depleted conditions. Changes in transcript and protein levels of 414 predicted transcription factors (TFs) and transcriptional regulators (TRs) were monitored relative to other genes. The TF and TR genes were thus classified by two separate measures: up-regulated versus down-regulated and early response versus late response relative to two phases of polar lipid synthesis (before and after TAG biosynthesis initiation). Lipidomic and primary metabolite profiling generated compound accumulation levels that were integrated with the transcript dataset and TF profiling to produce a transcriptional regulatory network. In conclusion, evaluation of this proposed regulatory network led to the identification of several regulatory hubs that control many aspects of cellular metabolism, from N assimilation and metabolism, to central metabolism, photosynthesis and lipid metabolism.« less

  20. Graphics Processing Unit–Enhanced Genetic Algorithms for Solving the Temporal Dynamics of Gene Regulatory Networks

    PubMed Central

    García-Calvo, Raúl; Guisado, JL; Diaz-del-Rio, Fernando; Córdoba, Antonio; Jiménez-Morales, Francisco

    2018-01-01

    Understanding the regulation of gene expression is one of the key problems in current biology. A promising method for that purpose is the determination of the temporal dynamics between known initial and ending network states, by using simple acting rules. The huge amount of rule combinations and the nonlinear inherent nature of the problem make genetic algorithms an excellent candidate for finding optimal solutions. As this is a computationally intensive problem that needs long runtimes in conventional architectures for realistic network sizes, it is fundamental to accelerate this task. In this article, we study how to develop efficient parallel implementations of this method for the fine-grained parallel architecture of graphics processing units (GPUs) using the compute unified device architecture (CUDA) platform. An exhaustive and methodical study of various parallel genetic algorithm schemes—master-slave, island, cellular, and hybrid models, and various individual selection methods (roulette, elitist)—is carried out for this problem. Several procedures that optimize the use of the GPU’s resources are presented. We conclude that the implementation that produces better results (both from the performance and the genetic algorithm fitness perspectives) is simulating a few thousands of individuals grouped in a few islands using elitist selection. This model comprises 2 mighty factors for discovering the best solutions: finding good individuals in a short number of generations, and introducing genetic diversity via a relatively frequent and numerous migration. As a result, we have even found the optimal solution for the analyzed gene regulatory network (GRN). In addition, a comparative study of the performance obtained by the different parallel implementations on GPU versus a sequential application on CPU is carried out. In our tests, a multifold speedup was obtained for our optimized parallel implementation of the method on medium class GPU over an equivalent

  1. Graphics Processing Unit-Enhanced Genetic Algorithms for Solving the Temporal Dynamics of Gene Regulatory Networks.

    PubMed

    García-Calvo, Raúl; Guisado, J L; Diaz-Del-Rio, Fernando; Córdoba, Antonio; Jiménez-Morales, Francisco

    2018-01-01

    Understanding the regulation of gene expression is one of the key problems in current biology. A promising method for that purpose is the determination of the temporal dynamics between known initial and ending network states, by using simple acting rules. The huge amount of rule combinations and the nonlinear inherent nature of the problem make genetic algorithms an excellent candidate for finding optimal solutions. As this is a computationally intensive problem that needs long runtimes in conventional architectures for realistic network sizes, it is fundamental to accelerate this task. In this article, we study how to develop efficient parallel implementations of this method for the fine-grained parallel architecture of graphics processing units (GPUs) using the compute unified device architecture (CUDA) platform. An exhaustive and methodical study of various parallel genetic algorithm schemes-master-slave, island, cellular, and hybrid models, and various individual selection methods (roulette, elitist)-is carried out for this problem. Several procedures that optimize the use of the GPU's resources are presented. We conclude that the implementation that produces better results (both from the performance and the genetic algorithm fitness perspectives) is simulating a few thousands of individuals grouped in a few islands using elitist selection. This model comprises 2 mighty factors for discovering the best solutions: finding good individuals in a short number of generations, and introducing genetic diversity via a relatively frequent and numerous migration. As a result, we have even found the optimal solution for the analyzed gene regulatory network (GRN). In addition, a comparative study of the performance obtained by the different parallel implementations on GPU versus a sequential application on CPU is carried out. In our tests, a multifold speedup was obtained for our optimized parallel implementation of the method on medium class GPU over an equivalent

  2. A Transcriptional Regulatory Switch Underlying B-Cell Terminal Differentiation and Its Disruption by Dioxin (S)

    EPA Science Inventory

    The terminal differentiation of B cells in lymphoid organs into antibody-secreting plasma cells upon antigen stimulation is a crucial step in the humoral immune response. The architecture of the B-cell transcriptional regulatory network consists of coupled mutually-repressive fee...

  3. An efficient optical architecture for sparsely connected neural networks

    NASA Technical Reports Server (NTRS)

    Hine, Butler P., III; Downie, John D.; Reid, Max B.

    1990-01-01

    An architecture for general-purpose optical neural network processor is presented in which the interconnections and weights are formed by directing coherent beams holographically, thereby making use of the space-bandwidth products of the recording medium for sparsely interconnected networks more efficiently that the commonly used vector-matrix multiplier, since all of the hologram area is in use. An investigation is made of the use of computer-generated holograms recorded on such updatable media as thermoplastic materials, in order to define the interconnections and weights of a neural network processor; attention is given to limits on interconnection densities, diffraction efficiencies, and weighing accuracies possible with such an updatable thin film holographic device.

  4. A Hox regulatory network establishes motor neuron pool identity and target-muscle connectivity.

    PubMed

    Dasen, Jeremy S; Tice, Bonnie C; Brenner-Morton, Susan; Jessell, Thomas M

    2005-11-04

    Spinal motor neurons acquire specialized "pool" identities that determine their ability to form selective connections with target muscles in the limb, but the molecular basis of this striking example of neuronal specificity has remained unclear. We show here that a Hox transcriptional regulatory network specifies motor neuron pool identity and connectivity. Two interdependent sets of Hox regulatory interactions operate within motor neurons, one assigning rostrocaudal motor pool position and a second directing motor pool diversity at a single segmental level. This Hox regulatory network directs the downstream transcriptional identity of motor neuron pools and defines the pattern of target-muscle connectivity.

  5. Genotet: An Interactive Web-based Visual Exploration Framework to Support Validation of Gene Regulatory Networks.

    PubMed

    Yu, Bowen; Doraiswamy, Harish; Chen, Xi; Miraldi, Emily; Arrieta-Ortiz, Mario Luis; Hafemeister, Christoph; Madar, Aviv; Bonneau, Richard; Silva, Cláudio T

    2014-12-01

    Elucidation of transcriptional regulatory networks (TRNs) is a fundamental goal in biology, and one of the most important components of TRNs are transcription factors (TFs), proteins that specifically bind to gene promoter and enhancer regions to alter target gene expression patterns. Advances in genomic technologies as well as advances in computational biology have led to multiple large regulatory network models (directed networks) each with a large corpus of supporting data and gene-annotation. There are multiple possible biological motivations for exploring large regulatory network models, including: validating TF-target gene relationships, figuring out co-regulation patterns, and exploring the coordination of cell processes in response to changes in cell state or environment. Here we focus on queries aimed at validating regulatory network models, and on coordinating visualization of primary data and directed weighted gene regulatory networks. The large size of both the network models and the primary data can make such coordinated queries cumbersome with existing tools and, in particular, inhibits the sharing of results between collaborators. In this work, we develop and demonstrate a web-based framework for coordinating visualization and exploration of expression data (RNA-seq, microarray), network models and gene-binding data (ChIP-seq). Using specialized data structures and multiple coordinated views, we design an efficient querying model to support interactive analysis of the data. Finally, we show the effectiveness of our framework through case studies for the mouse immune system (a dataset focused on a subset of key cellular functions) and a model bacteria (a small genome with high data-completeness).

  6. Memory functions reveal structural properties of gene regulatory networks

    PubMed Central

    Perez-Carrasco, Ruben

    2018-01-01

    Gene regulatory networks (GRNs) control cellular function and decision making during tissue development and homeostasis. Mathematical tools based on dynamical systems theory are often used to model these networks, but the size and complexity of these models mean that their behaviour is not always intuitive and the underlying mechanisms can be difficult to decipher. For this reason, methods that simplify and aid exploration of complex networks are necessary. To this end we develop a broadly applicable form of the Zwanzig-Mori projection. By first converting a thermodynamic state ensemble model of gene regulation into mass action reactions we derive a general method that produces a set of time evolution equations for a subset of components of a network. The influence of the rest of the network, the bulk, is captured by memory functions that describe how the subnetwork reacts to its own past state via components in the bulk. These memory functions provide probes of near-steady state dynamics, revealing information not easily accessible otherwise. We illustrate the method on a simple cross-repressive transcriptional motif to show that memory functions not only simplify the analysis of the subnetwork but also have a natural interpretation. We then apply the approach to a GRN from the vertebrate neural tube, a well characterised developmental transcriptional network composed of four interacting transcription factors. The memory functions reveal the function of specific links within the neural tube network and identify features of the regulatory structure that specifically increase the robustness of the network to initial conditions. Taken together, the study provides evidence that Zwanzig-Mori projections offer powerful and effective tools for simplifying and exploring the behaviour of GRNs. PMID:29470492

  7. Space Communications and Navigation (SCaN) Integrated Network Architecture Definition Document (ADD). Volume 1; Executive Summary; Revision 1

    NASA Technical Reports Server (NTRS)

    Younes, Badri A.; Schier, James S.

    2010-01-01

    The SCaN Program has defined an integrated network architecture that fully meets the Administrator s mandate to the Program, and will result in a NASA infrastructure capable of providing the needed and enabling communications services to future space missions. The integrated network architecture will increase SCaN operational efficiency and interoperability through standardization, commonality and technology infusion. It will enable NASA missions requiring advanced communication and tracking capabilities such as: a. Optical communication b. Antenna arraying c. Lunar and Mars Relays d. Integrated network management (service management and network control) and integrated service execution e. Enhanced tracking for navigation f. Space internetworking with DTN and IP g. End-to-end security h. Enhanced security services Moreover, the SCaN Program has created an Integrated Network Roadmap that depicts an orchestrated and coherent evolution path toward the target architecture, encompassing all aspects that concern network assets (i.e., operations and maintenance, sustaining engineering, upgrade efforts, and major development). This roadmap identifies major NASA ADPs, and shows dependencies and drivers among the various planned undertakings and timelines. The roadmap is scalable to accommodate timely adjustments in response to Agency needs, goals, objectives and funding. Future challenges to implementing this architecture include balancing user mission needs, technology development, and the availability of funding within NASA s priorities. Strategies for addressing these challenges are to: define a flexible architecture, update the architecture periodically, use ADPs to evaluate options and determine when to make decisions, and to engage the stakeholders in these evaluations. In addition, the SCaN Program will evaluate and respond to mission need dates for technical and operational capabilities to be provided by the SCaN integrated network. In that regard, the architecture

  8. A reverse engineering approach to optimize experiments for the construction of biological regulatory networks.

    PubMed

    Zhang, Xiaomeng; Shao, Bin; Wu, Yangle; Qi, Ouyang

    2013-01-01

    One of the major objectives in systems biology is to understand the relation between the topological structures and the dynamics of biological regulatory networks. In this context, various mathematical tools have been developed to deduct structures of regulatory networks from microarray expression data. In general, from a single data set, one cannot deduct the whole network structure; additional expression data are usually needed. Thus how to design a microarray expression experiment in order to get the most information is a practical problem in systems biology. Here we propose three methods, namely, maximum distance method, trajectory entropy method, and sampling method, to derive the optimal initial conditions for experiments. The performance of these methods is tested and evaluated in three well-known regulatory networks (budding yeast cell cycle, fission yeast cell cycle, and E. coli. SOS network). Based on the evaluation, we propose an efficient strategy for the design of microarray expression experiments.

  9. Establishment of apoptotic regulatory network for genetic markers of colorectal cancer.

    PubMed

    Hao, Yibin; Shan, Guoyong; Nan, Kejun

    2017-03-01

    Our purpose is to screen out genetic markers applicable to early diagnosis for colorectal cancer and to establish apoptotic regulatory network model for colorectal cancer, thereby providing theoretical evidence and targeted therapy for early diagnosis of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers applied to early diagnosis of colorectal cancer were searched to perform comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to establish apoptotic regulatory network model based on screened genetic markers, and then verification experiment was conducted. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, p53, APC, DCC and PTEN, among which DCC shows highest diagnostic efficiency. GO analysis of genetic markers found that six genetic markers played role in biological process, molecular function and cellular component. It was indicated in apoptotic regulatory network built by KEGG analysis and verification experiment that WWOX could promote tumor cell apoptotic in colorectal cancer and elevate expression level of p53. The apoptotic regulatory model of colorectal cancer established in this study provides clinically theoretical evidence and targeted therapy for early diagnosis of colorectal cancer.

  10. Predictive minimum description length principle approach to inferring gene regulatory networks.

    PubMed

    Chaitankar, Vijender; Zhang, Chaoyang; Ghosh, Preetam; Gong, Ping; Perkins, Edward J; Deng, Youping

    2011-01-01

    Reverse engineering of gene regulatory networks using information theory models has received much attention due to its simplicity, low computational cost, and capability of inferring large networks. One of the major problems with information theory models is to determine the threshold that defines the regulatory relationships between genes. The minimum description length (MDL) principle has been implemented to overcome this problem. The description length of the MDL principle is the sum of model length and data encoding length. A user-specified fine tuning parameter is used as control mechanism between model and data encoding, but it is difficult to find the optimal parameter. In this work, we propose a new inference algorithm that incorporates mutual information (MI), conditional mutual information (CMI), and predictive minimum description length (PMDL) principle to infer gene regulatory networks from DNA microarray data. In this algorithm, the information theoretic quantities MI and CMI determine the regulatory relationships between genes and the PMDL principle method attempts to determine the best MI threshold without the need of a user-specified fine tuning parameter. The performance of the proposed algorithm is evaluated using both synthetic time series data sets and a biological time series data set (Saccharomyces cerevisiae). The results show that the proposed algorithm produced fewer false edges and significantly improved the precision when compared to existing MDL algorithm.

  11. Synchronous versus asynchronous modeling of gene regulatory networks.

    PubMed

    Garg, Abhishek; Di Cara, Alessandro; Xenarios, Ioannis; Mendoza, Luis; De Micheli, Giovanni

    2008-09-01

    In silico modeling of gene regulatory networks has gained some momentum recently due to increased interest in analyzing the dynamics of biological systems. This has been further facilitated by the increasing availability of experimental data on gene-gene, protein-protein and gene-protein interactions. The two dynamical properties that are often experimentally testable are perturbations and stable steady states. Although a lot of work has been done on the identification of steady states, not much work has been reported on in silico modeling of cellular differentiation processes. In this manuscript, we provide algorithms based on reduced ordered binary decision diagrams (ROBDDs) for Boolean modeling of gene regulatory networks. Algorithms for synchronous and asynchronous transition models have been proposed and their corresponding computational properties have been analyzed. These algorithms allow users to compute cyclic attractors of large networks that are currently not feasible using existing software. Hereby we provide a framework to analyze the effect of multiple gene perturbation protocols, and their effect on cell differentiation processes. These algorithms were validated on the T-helper model showing the correct steady state identification and Th1-Th2 cellular differentiation process. The software binaries for Windows and Linux platforms can be downloaded from http://si2.epfl.ch/~garg/genysis.html.

  12. Development of Network-based Communications Architectures for Future NASA Missions

    NASA Technical Reports Server (NTRS)

    Slywczak, Richard A.

    2007-01-01

    Since the Vision for Space Exploration (VSE) announcement, NASA has been developing a communications infrastructure that combines existing terrestrial techniques with newer concepts and capabilities. The overall goal is to develop a flexible, modular, and extensible architecture that leverages and enhances terrestrial networking technologies that can either be directly applied or modified for the space regime. In addition, where existing technologies leaves gaps, new technologies must be developed. An example includes dynamic routing that accounts for constrained power and bandwidth environments. Using these enhanced technologies, NASA can develop nodes that provide characteristics, such as routing, store and forward, and access-on-demand capabilities. But with the development of the new infrastructure, challenges and obstacles will arise. The current communications infrastructure has been developed on a mission-by-mission basis rather than an end-to-end approach; this has led to a greater ground infrastructure, but has not encouraged communications between space-based assets. This alone provides one of the key challenges that NASA must encounter. With the development of the new Crew Exploration Vehicle (CEV), NASA has the opportunity to provide an integration path for the new vehicles and provide standards for their development. Some of the newer capabilities these vehicles could include are routing, security, and Software Defined Radios (SDRs). To meet these needs, the NASA/Glenn Research Center s (GRC) Network Emulation Laboratory (NEL) has been using both simulation and emulation to study and evaluate these architectures. These techniques provide options to NASA that directly impact architecture development. This paper identifies components of the infrastructure that play a pivotal role in the new NASA architecture, develops a scheme using simulation and emulation for testing these architectures and demonstrates how NASA can strengthen the new infrastructure by

  13. Cortical network architecture for context processing in primate brain

    PubMed Central

    Chao, Zenas C; Nagasaka, Yasuo; Fujii, Naotaka

    2015-01-01

    Context is information linked to a situation that can guide behavior. In the brain, context is encoded by sensory processing and can later be retrieved from memory. How context is communicated within the cortical network in sensory and mnemonic forms is unknown due to the lack of methods for high-resolution, brain-wide neuronal recording and analysis. Here, we report the comprehensive architecture of a cortical network for context processing. Using hemisphere-wide, high-density electrocorticography, we measured large-scale neuronal activity from monkeys observing videos of agents interacting in situations with different contexts. We extracted five context-related network structures including a bottom-up network during encoding and, seconds later, cue-dependent retrieval of the same network with the opposite top-down connectivity. These findings show that context is represented in the cortical network as distributed communication structures with dynamic information flows. This study provides a general methodology for recording and analyzing cortical network neuronal communication during cognition. DOI: http://dx.doi.org/10.7554/eLife.06121.001 PMID:26416139

  14. An approach for reduction of false predictions in reverse engineering of gene regulatory networks.

    PubMed

    Khan, Abhinandan; Saha, Goutam; Pal, Rajat Kumar

    2018-05-14

    A gene regulatory network discloses the regulatory interactions amongst genes, at a particular condition of the human body. The accurate reconstruction of such networks from time-series genetic expression data using computational tools offers a stiff challenge for contemporary computer scientists. This is crucial to facilitate the understanding of the proper functioning of a living organism. Unfortunately, the computational methods produce many false predictions along with the correct predictions, which is unwanted. Investigations in the domain focus on the identification of as many correct regulations as possible in the reverse engineering of gene regulatory networks to make it more reliable and biologically relevant. One way to achieve this is to reduce the number of incorrect predictions in the reconstructed networks. In the present investigation, we have proposed a novel scheme to decrease the number of false predictions by suitably combining several metaheuristic techniques. We have implemented the same using a dataset ensemble approach (i.e. combining multiple datasets) also. We have employed the proposed methodology on real-world experimental datasets of the SOS DNA Repair network of Escherichia coli and the IMRA network of Saccharomyces cerevisiae. Subsequently, we have experimented upon somewhat larger, in silico networks, namely, DREAM3 and DREAM4 Challenge networks, and 15-gene and 20-gene networks extracted from the GeneNetWeaver database. To study the effect of multiple datasets on the quality of the inferred networks, we have used four datasets in each experiment. The obtained results are encouraging enough as the proposed methodology can reduce the number of false predictions significantly, without using any supplementary prior biological information for larger gene regulatory networks. It is also observed that if a small amount of prior biological information is incorporated here, the results improve further w.r.t. the prediction of true positives

  15. Integrated network architecture for sustained human and robotic exploration

    NASA Technical Reports Server (NTRS)

    Noreen, Gary K.; Cesarone, Robert; Deutsch, Leslie; Edwards, Charlie; Soloff, Jason; Ely, Todd; Cook, Brian; Morabito, David; Hemmati, Hamid; Piazzolla, Sabino; hide

    2005-01-01

    The National Aeronautics and Space Administration (NASA) Exploration Systems Mission Directorate is planning a series of human and robotic missions to the Earth's moon and to Mars. These missions will require telecommunication and navigation services. This paper sets forth presumed requirements for such services and presents strawman lunar and Mars telecommunications network architectures to satisfy the presumed requirements.

  16. Evolution of network architecture in a granular material under compression

    NASA Astrophysics Data System (ADS)

    Papadopoulos, Lia; Puckett, James G.; Daniels, Karen E.; Bassett, Danielle S.

    2016-09-01

    As a granular material is compressed, the particles and forces within the system arrange to form complex and heterogeneous collective structures. Force chains are a prime example of such structures, and are thought to constrain bulk properties such as mechanical stability and acoustic transmission. However, capturing and characterizing the evolving nature of the intrinsic inhomogeneity and mesoscale architecture of granular systems can be challenging. A growing body of work has shown that graph theoretic approaches may provide a useful foundation for tackling these problems. Here, we extend the current approaches by utilizing multilayer networks as a framework for directly quantifying the progression of mesoscale architecture in a compressed granular system. We examine a quasi-two-dimensional aggregate of photoelastic disks, subject to biaxial compressions through a series of small, quasistatic steps. Treating particles as network nodes and interparticle forces as network edges, we construct a multilayer network for the system by linking together the series of static force networks that exist at each strain step. We then extract the inherent mesoscale structure from the system by using a generalization of community detection methods to multilayer networks, and we define quantitative measures to characterize the changes in this structure throughout the compression process. We separately consider the network of normal and tangential forces, and find that they display a different progression throughout compression. To test the sensitivity of the network model to particle properties, we examine whether the method can distinguish a subsystem of low-friction particles within a bath of higher-friction particles. We find that this can be achieved by considering the network of tangential forces, and that the community structure is better able to separate the subsystem than a purely local measure of interparticle forces alone. The results discussed throughout this study

  17. Assembly kinetics determine the architecture of α-actinin crosslinked F-actin networks.

    PubMed

    Falzone, Tobias T; Lenz, Martin; Kovar, David R; Gardel, Margaret L

    2012-05-29

    The actin cytoskeleton is organized into diverse meshworks and bundles that support many aspects of cell physiology. Understanding the self-assembly of these actin-based structures is essential for developing predictive models of cytoskeletal organization. Here we show that the competing kinetics of bundle formation with the onset of dynamic arrest arising from filament entanglements and crosslinking determine the architecture of reconstituted actin networks formed with α-actinin crosslinks. Crosslink-mediated bundle formation only occurs in dilute solutions of highly mobile actin filaments. As actin polymerization proceeds, filament mobility and bundle formation are arrested concomitantly. By controlling the onset of dynamic arrest, perturbations to actin assembly kinetics dramatically alter the architecture of biochemically identical samples. Thus, the morphology of reconstituted F-actin networks is a kinetically determined structure similar to those formed by physical gels and glasses. These results establish mechanisms controlling the structure and mechanics in diverse semiflexible biopolymer networks.

  18. The P-Mesh: A Commodity-based Scalable Network Architecture for Clusters

    NASA Technical Reports Server (NTRS)

    Nitzberg, Bill; Kuszmaul, Chris; Stockdale, Ian; Becker, Jeff; Jiang, John; Wong, Parkson; Tweten, David (Technical Monitor)

    1998-01-01

    We designed a new network architecture, the P-Mesh which combines the scalability and fault resilience of a torus with the performance of a switch. We compare the scalability, performance, and cost of the hub, switch, torus, tree, and P-Mesh architectures. The latter three are capable of scaling to thousands of nodes, however, the torus has severe performance limitations with that many processors. The tree and P-Mesh have similar latency, bandwidth, and bisection bandwidth, but the P-Mesh outperforms the switch architecture (a lower bound for tree performance) on 16-node NAB Parallel Benchmark tests by up to 23%, and costs 40% less. Further, the P-Mesh has better fault resilience characteristics. The P-Mesh architecture trades increased management overhead for lower cost, and is a good bridging technology while the price of tree uplinks is expensive.

  19. CMIP: a software package capable of reconstructing genome-wide regulatory networks using gene expression data.

    PubMed

    Zheng, Guangyong; Xu, Yaochen; Zhang, Xiujun; Liu, Zhi-Ping; Wang, Zhuo; Chen, Luonan; Zhu, Xin-Guang

    2016-12-23

    A gene regulatory network (GRN) represents interactions of genes inside a cell or tissue, in which vertexes and edges stand for genes and their regulatory interactions respectively. Reconstruction of gene regulatory networks, in particular, genome-scale networks, is essential for comparative exploration of different species and mechanistic investigation of biological processes. Currently, most of network inference methods are computationally intensive, which are usually effective for small-scale tasks (e.g., networks with a few hundred genes), but are difficult to construct GRNs at genome-scale. Here, we present a software package for gene regulatory network reconstruction at a genomic level, in which gene interaction is measured by the conditional mutual information measurement using a parallel computing framework (so the package is named CMIP). The package is a greatly improved implementation of our previous PCA-CMI algorithm. In CMIP, we provide not only an automatic threshold determination method but also an effective parallel computing framework for network inference. Performance tests on benchmark datasets show that the accuracy of CMIP is comparable to most current network inference methods. Moreover, running tests on synthetic datasets demonstrate that CMIP can handle large datasets especially genome-wide datasets within an acceptable time period. In addition, successful application on a real genomic dataset confirms its practical applicability of the package. This new software package provides a powerful tool for genomic network reconstruction to biological community. The software can be accessed at http://www.picb.ac.cn/CMIP/ .

  20. Network architectures and circuit function: testing alternative hypotheses in multifunctional networks.

    PubMed

    Leonard, J L

    2000-05-01

    Understanding how species-typical movement patterns are organized in the nervous system is a central question in neurobiology. The current explanations involve 'alphabet' models in which an individual neuron may participate in the circuit for several behaviors but each behavior is specified by a specific neural circuit. However, not all of the well-studied model systems fit the 'alphabet' model. The 'equation' model provides an alternative possibility, whereby a system of parallel motor neurons, each with a unique (but overlapping) field of innervation, can account for the production of stereotyped behavior patterns by variable circuits. That is, it is possible for such patterns to arise as emergent properties of a generalized neural network in the absence of feedback, a simple version of a 'self-organizing' behavioral system. Comparison of systems of identified neurons suggest that the 'alphabet' model may account for most observations where CPGs act to organize motor patterns. Other well-known model systems, involving architectures corresponding to feed-forward neural networks with a hidden layer, may organize patterned behavior in a manner consistent with the 'equation' model. Such architectures are found in the Mauthner and reticulospinal circuits, 'escape' locomotion in cockroaches, CNS control of Aplysia gill, and may also be important in the coordination of sensory information and motor systems in insect mushroom bodies and the vertebrate hippocampus. The hidden layer of such networks may serve as an 'internal representation' of the behavioral state and/or body position of the animal, allowing the animal to fine-tune oriented, or particularly context-sensitive, movements to the prevalent conditions. Experiments designed to distinguish between the two models in cases where they make mutually exclusive predictions provide an opportunity to elucidate the neural mechanisms by which behavior is organized in vivo and in vitro. Copyright 2000 S. Karger AG, Basel

  1. Modulation of the brain's functional network architecture in the transition from wake to sleep

    PubMed Central

    Larson-Prior, Linda J.; Power, Jonathan D.; Vincent, Justin L.; Nolan, Tracy S.; Coalson, Rebecca S.; Zempel, John; Snyder, Abraham Z.; Schlaggar, Bradley L.; Raichle, Marcus E.; Petersen, Steven E.

    2013-01-01

    The transition from quiet wakeful rest to sleep represents a period over which attention to the external environment fades. Neuroimaging methodologies have provided much information on the shift in neural activity patterns in sleep, but the dynamic restructuring of human brain networks in the transitional period from wake to sleep remains poorly understood. Analysis of electrophysiological measures and functional network connectivity of these early transitional states shows subtle shifts in network architecture that are consistent with reduced external attentiveness and increased internal and self-referential processing. Further, descent to sleep is accompanied by the loss of connectivity in anterior and posterior portions of the default-mode network and more locally organized global network architecture. These data clarify the complex and dynamic nature of the transitional period between wake and sleep and suggest the need for more studies investigating the dynamics of these processes. PMID:21854969

  2. Sensor network architecture for monitoring turtles on seashore

    NASA Astrophysics Data System (ADS)

    Carvajal-Gámez, Blanca E.; Cruz, Victor; Díaz-Casco, Manuel A.; Franco, Andrea; Escobar, Carolina; Colin, Abilene; Carreto-Arellano, Chadwick

    2017-04-01

    In the last decade, advances in information and communication technologies have made it possible to diversify the use of sensor networks in different areas of knowledge (medicine, education, militia, urbanization, protection of the environment, etc.). At present, this type of tools is used to develop applications that allow the identification and monitoring of endangered animals in their natural habitat; however, there are still limitations because some of the devices used alter the behavior of the animals, as in the case of sea turtles. Research and monitoring of sea turtles is of vital importance in identifying possible threats and ensuring their preservation, the behavior of this species (migration, reproduction, and nesting) is highly related to environmental conditions. Because of this, behavioral changes information of this species can be used to monitor global climatic conditions. This work presents the design, development and implementation of an architecture for the monitoring and identification of the sea turtle using sensor networks. This will allow to obtain information for the different investigations with a greater accuracy than the conventional techniques, through non-invasive means for the species and its habitat. The proposed architecture contemplates the use of new technology devices, selfconfigurable, with low energy consumption, interconnection with various communication protocols and sustainable energy supply (solar, wind, etc.).

  3. Shifts in the architecture of the Nationwide Health Information Network.

    PubMed

    Lenert, Leslie; Sundwall, David; Lenert, Michael Edward

    2012-01-01

    In the midst of a US $30 billion USD investment in the Nationwide Health Information Network (NwHIN) and electronic health records systems, a significant change in the architecture of the NwHIN is taking place. Prior to 2010, the focus of information exchange in the NwHIN was the Regional Health Information Organization (RHIO). Since 2010, the Office of the National Coordinator (ONC) has been sponsoring policies that promote an internet-like architecture that encourages point to-point information exchange and private health information exchange networks. The net effect of these activities is to undercut the limited business model for RHIOs, decreasing the likelihood of their success, while making the NwHIN dependent on nascent technologies for community level functions such as record locator services. These changes may impact the health of patients and communities. Independent, scientifically focused debate is needed on the wisdom of ONC's proposed changes in its strategy for the NwHIN.

  4. A Functional and Regulatory Network Associated with PIP Expression in Human Breast Cancer

    PubMed Central

    Debily, Marie-Anne; Marhomy, Sandrine El; Boulanger, Virginie; Eveno, Eric; Mariage-Samson, Régine; Camarca, Alessandra; Auffray, Charles; Piatier-Tonneau, Dominique; Imbeaud, Sandrine

    2009-01-01

    Background The PIP (prolactin-inducible protein) gene has been shown to be expressed in breast cancers, with contradictory results concerning its implication. As both the physiological role and the molecular pathways in which PIP is involved are poorly understood, we conducted combined gene expression profiling and network analysis studies on selected breast cancer cell lines presenting distinct PIP expression levels and hormonal receptor status, to explore the functional and regulatory network of PIP co-modulated genes. Principal Findings Microarray analysis allowed identification of genes co-modulated with PIP independently of modulations resulting from hormonal treatment or cell line heterogeneity. Relevant clusters of genes that can discriminate between [PIP+] and [PIP−] cells were identified. Functional and regulatory network analyses based on a knowledge database revealed a master network of PIP co-modulated genes, including many interconnecting oncogenes and tumor suppressor genes, half of which were detected as differentially expressed through high-precision measurements. The network identified appears associated with an inhibition of proliferation coupled with an increase of apoptosis and an enhancement of cell adhesion in breast cancer cell lines, and contains many genes with a STAT5 regulatory motif in their promoters. Conclusions Our global exploratory approach identified biological pathways modulated along with PIP expression, providing further support for its good prognostic value of disease-free survival in breast cancer. Moreover, our data pointed to the importance of a regulatory subnetwork associated with PIP expression in which STAT5 appears as a potential transcriptional regulator. PMID:19262752

  5. Programmable on-chip and off-chip network architecture on demand for flexible optical intra-datacenters.

    PubMed

    Rofoee, Bijan Rahimzadeh; Zervas, Georgios; Yan, Yan; Amaya, Norberto; Qin, Yixuan; Simeonidou, Dimitra

    2013-03-11

    The paper presents a novel network architecture on demand approach using on-chip and-off chip implementations, enabling programmable, highly efficient and transparent networking, well suited for intra-datacenter communications. The implemented FPGA-based adaptable line-card with on-chip design along with an architecture on demand (AoD) based off-chip flexible switching node, deliver single chip dual L2-Packet/L1-time shared optical network (TSON) server Network Interface Cards (NIC) interconnected through transparent AoD based switch. It enables hitless adaptation between Ethernet over wavelength switched network (EoWSON), and TSON based sub-wavelength switching, providing flexible bitrates, while meeting strict bandwidth, QoS requirements. The on and off-chip performance results show high throughput (9.86Ethernet, 8.68Gbps TSON), high QoS, as well as hitless switch-over.

  6. Anticipated Ethics and Regulatory Challenges in PCORnet: The National Patient-Centered Clinical Research Network.

    PubMed

    Ali, Joseph; Califf, Robert; Sugarman, Jeremy

    2016-01-01

    PCORnet, the National Patient-Centered Clinical Research Network, seeks to establish a robust national health data network for patient-centered comparative effectiveness research. This article reports the results of a PCORnet survey designed to identify the ethics and regulatory challenges anticipated in network implementation. A 12-item online survey was developed by leadership of the PCORnet Ethics and Regulatory Task Force; responses were collected from the 29 PCORnet networks. The most pressing ethics issues identified related to informed consent, patient engagement, privacy and confidentiality, and data sharing. High priority regulatory issues included IRB coordination, privacy and confidentiality, informed consent, and data sharing. Over 150 IRBs and five different approaches to managing multisite IRB review were identified within PCORnet. Further empirical and scholarly work, as well as practical and policy guidance, is essential if important initiatives that rely on comparative effectiveness research are to move forward.

  7. Navigation Architecture For A Space Mobile Network

    NASA Technical Reports Server (NTRS)

    Valdez, Jennifer E.; Ashman, Benjamin; Gramling, Cheryl; Heckler, Gregory W.; Carpenter, Russell

    2016-01-01

    The Tracking and Data Relay Satellite System (TDRSS) Augmentation Service for Satellites (TASS) is a proposed beacon service to provide a global, space-based GPS augmentation service based on the NASA Global Differential GPS (GDGPS) System. The TASS signal will be tied to the GPS time system and usable as an additional ranging and Doppler radiometric source. Additionally, it will provide data vital to autonomous navigation in the near Earth regime, including space weather information, TDRS ephemerides, Earth Orientation Parameters (EOP), and forward commanding capability. TASS benefits include enhancing situational awareness, enabling increased autonomy, and providing near real-time command access for user platforms. As NASA Headquarters Space Communication and Navigation Office (SCaN) begins to move away from a centralized network architecture and towards a Space Mobile Network (SMN) that allows for user initiated services, autonomous navigation will be a key part of such a system. This paper explores how a TASS beacon service enables the Space Mobile Networking paradigm, what a typical user platform would require, and provides an in-depth analysis of several navigation scenarios and operations concepts.

  8. Identification of Neurodegenerative Factors Using Translatome-Regulatory Network Analysis

    PubMed Central

    Brichta, Lars; Shin, William; Jackson-Lewis, Vernice; Blesa, Javier; Yap, Ee-Lynn; Walker, Zachary; Zhang, Jack; Roussarie, Jean-Pierre; Alvarez, Mariano J.; Califano, Andrea; Przedborski, Serge; Greengard, Paul

    2016-01-01

    For degenerative disorders of the central nervous system, the major obstacle to therapeutic advancement has been the challenge of identifying the key molecular mechanisms underlying neuronal loss. We developed a combinatorial approach including translational profiling and brain regulatory network analysis to search for key determinants of neuronal survival or death. Following the generation of transgenic mice for cell type-specific profiling of midbrain dopaminergic neurons, we established and compared translatome libraries reflecting the molecular signature of these cells at baseline or under degenerative stress. Analysis of these libraries by interrogating a context-specific brain regulatory network led to the identification of a repertoire of intrinsic upstream regulators that drive the dopaminergic stress response. The altered activity of these regulators was not associated with changes in their expression levels. This strategy can be generalized for the elucidation of novel molecular determinants involved in the degeneration of other classes of neurons. PMID:26214373

  9. Genome-scale cold stress response regulatory networks in ten Arabidopsis thaliana ecotypes

    PubMed Central

    2013-01-01

    Background Low temperature leads to major crop losses every year. Although several studies have been conducted focusing on diversity of cold tolerance level in multiple phenotypically divergent Arabidopsis thaliana (A. thaliana) ecotypes, genome-scale molecular understanding is still lacking. Results In this study, we report genome-scale transcript response diversity of 10 A. thaliana ecotypes originating from different geographical locations to non-freezing cold stress (10°C). To analyze the transcriptional response diversity, we initially compared transcriptome changes in all 10 ecotypes using Arabidopsis NimbleGen ATH6 microarrays. In total 6061 transcripts were significantly cold regulated (p < 0.01) in 10 ecotypes, including 498 transcription factors and 315 transposable elements. The majority of the transcripts (75%) showed ecotype specific expression pattern. By using sequence data available from Arabidopsis thaliana 1001 genome project, we further investigated sequence polymorphisms in the core cold stress regulon genes. Significant numbers of non-synonymous amino acid changes were observed in the coding region of the CBF regulon genes. Considering the limited knowledge about regulatory interactions between transcription factors and their target genes in the model plant A. thaliana, we have adopted a powerful systems genetics approach- Network Component Analysis (NCA) to construct an in-silico transcriptional regulatory network model during response to cold stress. The resulting regulatory network contained 1,275 nodes and 7,720 connections, with 178 transcription factors and 1,331 target genes. Conclusions A. thaliana ecotypes exhibit considerable variation in transcriptome level responses to non-freezing cold stress treatment. Ecotype specific transcripts and related gene ontology (GO) categories were identified to delineate natural variation of cold stress regulated differential gene expression in the model plant A. thaliana. The predicted

  10. Edge usage, motifs, and regulatory logic for cell cycling genetic networks

    NASA Astrophysics Data System (ADS)

    Zagorski, M.; Krzywicki, A.; Martin, O. C.

    2013-01-01

    The cell cycle is a tightly controlled process, yet it shows marked differences across species. Which of its structural features follow solely from the ability to control gene expression? We tackle this question in silico by examining the ensemble of all regulatory networks which satisfy the constraint of producing a given sequence of gene expressions. We focus on three cell cycle profiles coming from baker's yeast, fission yeast, and mammals. First, we show that the networks in each of the ensembles use just a few interactions that are repeatedly reused as building blocks. Second, we find an enrichment in network motifs that is similar in the two yeast cell cycle systems investigated. These motifs do not have autonomous functions, yet they reveal a regulatory logic for cell cycling based on a feed-forward cascade of activating interactions.

  11. Modularity and evolutionary constraints in a baculovirus gene regulatory network

    PubMed Central

    2013-01-01

    Background The structure of regulatory networks remains an open question in our understanding of complex biological systems. Interactions during complete viral life cycles present unique opportunities to understand how host-parasite network take shape and behave. The Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) is a large double-stranded DNA virus, whose genome may encode for 152 open reading frames (ORFs). Here we present the analysis of the ordered cascade of the AgMNPV gene expression. Results We observed an earlier onset of the expression than previously reported for other baculoviruses, especially for genes involved in DNA replication. Most ORFs were expressed at higher levels in a more permissive host cell line. Genes with more than one copy in the genome had distinct expression profiles, which could indicate the acquisition of new functionalities. The transcription gene regulatory network (GRN) for 149 ORFs had a modular topology comprising five communities of highly interconnected nodes that separated key genes that are functionally related on different communities, possibly maximizing redundancy and GRN robustness by compartmentalization of important functions. Core conserved functions showed expression synchronicity, distinct GRN features and significantly less genetic diversity, consistent with evolutionary constraints imposed in key elements of biological systems. This reduced genetic diversity also had a positive correlation with the importance of the gene in our estimated GRN, supporting a relationship between phylogenetic data of baculovirus genes and network features inferred from expression data. We also observed that gene arrangement in overlapping transcripts was conserved among related baculoviruses, suggesting a principle of genome organization. Conclusions Albeit with a reduced number of nodes (149), the AgMNPV GRN had a topology and key characteristics similar to those observed in complex cellular organisms, which indicates

  12. A modular architecture for transparent computation in recurrent neural networks.

    PubMed

    Carmantini, Giovanni S; Beim Graben, Peter; Desroches, Mathieu; Rodrigues, Serafim

    2017-01-01

    Computation is classically studied in terms of automata, formal languages and algorithms; yet, the relation between neural dynamics and symbolic representations and operations is still unclear in traditional eliminative connectionism. Therefore, we suggest a unique perspective on this central issue, to which we would like to refer as transparent connectionism, by proposing accounts of how symbolic computation can be implemented in neural substrates. In this study we first introduce a new model of dynamics on a symbolic space, the versatile shift, showing that it supports the real-time simulation of a range of automata. We then show that the Gödelization of versatile shifts defines nonlinear dynamical automata, dynamical systems evolving on a vectorial space. Finally, we present a mapping between nonlinear dynamical automata and recurrent artificial neural networks. The mapping defines an architecture characterized by its granular modularity, where data, symbolic operations and their control are not only distinguishable in activation space, but also spatially localizable in the network itself, while maintaining a distributed encoding of symbolic representations. The resulting networks simulate automata in real-time and are programmed directly, in the absence of network training. To discuss the unique characteristics of the architecture and their consequences, we present two examples: (i) the design of a Central Pattern Generator from a finite-state locomotive controller, and (ii) the creation of a network simulating a system of interactive automata that supports the parsing of garden-path sentences as investigated in psycholinguistics experiments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Coupling root architecture and pore network modeling - an attempt towards better understanding root-soil interactions

    NASA Astrophysics Data System (ADS)

    Leitner, Daniel; Bodner, Gernot; Raoof, Amir

    2013-04-01

    Understanding root-soil interactions is of high importance for environmental and agricultural management. Root uptake is an essential component in water and solute transport modeling. The amount of groundwater recharge and solute leaching significantly depends on the demand based plant extraction via its root system. Plant uptake however not only responds to the potential demand, but in most situations is limited by supply form the soil. The ability of the plant to access water and solutes in the soil is governed mainly by root distribution. Particularly under conditions of heterogeneous distribution of water and solutes in the soil, it is essential to capture the interaction between soil and roots. Root architecture models allow studying plant uptake from soil by describing growth and branching of root axes in the soil. Currently root architecture models are able to respond dynamically to water and nutrient distribution in the soil by directed growth (tropism), modified branching and enhanced exudation. The porous soil medium as rooting environment in these models is generally described by classical macroscopic water retention and sorption models, average over the pore scale. In our opinion this simplified description of the root growth medium implies several shortcomings for better understanding root-soil interactions: (i) It is well known that roots grow preferentially in preexisting pores, particularly in more rigid/dry soil. Thus the pore network contributes to the architectural form of the root system; (ii) roots themselves can influence the pore network by creating preferential flow paths (biopores) which are an essential element of structural porosity with strong impact on transport processes; (iii) plant uptake depend on both the spatial location of water/solutes in the pore network as well as the spatial distribution of roots. We therefore consider that for advancing our understanding in root-soil interactions, we need not only to extend our root models

  14. Qualitatively modelling and analysing genetic regulatory networks: a Petri net approach.

    PubMed

    Steggles, L Jason; Banks, Richard; Shaw, Oliver; Wipat, Anil

    2007-02-01

    New developments in post-genomic technology now provide researchers with the data necessary to study regulatory processes in a holistic fashion at multiple levels of biological organization. One of the major challenges for the biologist is to integrate and interpret these vast data resources to gain a greater understanding of the structure and function of the molecular processes that mediate adaptive and cell cycle driven changes in gene expression. In order to achieve this biologists require new tools and techniques to allow pathway related data to be modelled and analysed as network structures, providing valuable insights which can then be validated and investigated in the laboratory. We propose a new technique for constructing and analysing qualitative models of genetic regulatory networks based on the Petri net formalism. We take as our starting point the Boolean network approach of treating genes as binary switches and develop a new Petri net model which uses logic minimization to automate the construction of compact qualitative models. Our approach addresses the shortcomings of Boolean networks by providing access to the wide range of existing Petri net analysis techniques and by using non-determinism to cope with incomplete and inconsistent data. The ideas we present are illustrated by a case study in which the genetic regulatory network controlling sporulation in the bacterium Bacillus subtilis is modelled and analysed. The Petri net model construction tool and the data files for the B. subtilis sporulation case study are available at http://bioinf.ncl.ac.uk/gnapn.

  15. CRX ChIP-seq reveals the cis-regulatory architecture of mouse photoreceptors

    PubMed Central

    Corbo, Joseph C.; Lawrence, Karen A.; Karlstetter, Marcus; Myers, Connie A.; Abdelaziz, Musa; Dirkes, William; Weigelt, Karin; Seifert, Martin; Benes, Vladimir; Fritsche, Lars G.; Weber, Bernhard H.F.; Langmann, Thomas

    2010-01-01

    Approximately 98% of mammalian DNA is noncoding, yet we understand relatively little about the function of this enigmatic portion of the genome. The cis-regulatory elements that control gene expression reside in noncoding regions and can be identified by mapping the binding sites of tissue-specific transcription factors. Cone-rod homeobox (CRX) is a key transcription factor in photoreceptor differentiation and survival, but its in vivo targets are largely unknown. Here, we used chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq) on CRX to identify thousands of cis-regulatory regions around photoreceptor genes in adult mouse retina. CRX directly regulates downstream photoreceptor transcription factors and their target genes via a network of spatially distributed regulatory elements around each locus. CRX-bound regions act in a synergistic fashion to activate transcription and contain multiple CRX binding sites which interact in a spacing- and orientation-dependent manner to fine-tune transcript levels. CRX ChIP-seq was also performed on Nrl−/− retinas, which represent an enriched source of cone photoreceptors. Comparison with the wild-type ChIP-seq data set identified numerous rod- and cone-specific CRX-bound regions as well as many shared elements. Thus, CRX combinatorially orchestrates the transcriptional networks of both rods and cones by coordinating the expression of photoreceptor genes including most retinal disease genes. In addition, this study pinpoints thousands of noncoding regions of relevance to both Mendelian and complex retinal disease. PMID:20693478

  16. Assembly Kinetics Determine the Architecture of α-actinin Crosslinked F-actin Networks

    PubMed Central

    Falzone, Tobias T.; Lenz, Martin; Kovar, David R.; Gardel, Margaret L.

    2013-01-01

    The actin cytoskeleton is organized into diverse meshworks and bundles that support many aspects of cell physiology. Understanding the self-assembly of these actin-based structures is essential for developing predictive models of cytoskeletal organization. Here we show that the competing kinetics of bundle formation with the onset of dynamic arrest arising from filament entanglements and cross-linking determine the architecture of reconstituted actin networks formed with α-actinin cross-links. Cross-link mediated bundle formation only occurs in dilute solutions of highly mobile actin filaments. As actin polymerization proceeds, filament mobility and bundle formation are arrested concomitantly. By controlling the onset of dynamic arrest, perturbations to actin assembly kinetics dramatically alter the architecture of biochemically identical samples. Thus, the morphology of reconstituted F-actin networks is a kinetically determined structure similar to those formed by physical gels and glasses. These results establish mechanisms controlling the structure and mechanics in diverse semi-flexible biopolymer networks. PMID:22643888

  17. Design and architecture of the Mars relay network planning and analysis framework

    NASA Technical Reports Server (NTRS)

    Cheung, K. M.; Lee, C. H.

    2002-01-01

    In this paper we describe the design and architecture of the Mars Network planning and analysis framework that supports generation and validation of efficient planning and scheduling strategy. The goals are to minimize the transmitting time, minimize the delaying time, and/or maximize the network throughputs. The proposed framework would require (1) a client-server architecture to support interactive, batch, WEB, and distributed analysis and planning applications for the relay network analysis scheme, (2) a high-fidelity modeling and simulation environment that expresses link capabilities between spacecraft to spacecraft and spacecraft to Earth stations as time-varying resources, and spacecraft activities, link priority, Solar System dynamic events, the laws of orbital mechanics, and other limiting factors as spacecraft power and thermal constraints, (3) an optimization methodology that casts the resource and constraint models into a standard linear and nonlinear constrained optimization problem that lends itself to commercial off-the-shelf (COTS)planning and scheduling algorithms.

  18. Predicting Electrocardiogram and Arterial Blood Pressure Waveforms with Different Echo State Network Architectures

    DTIC Science & Technology

    2014-11-01

    networks were trained to predict an individual’s electrocardiogram (ECG) and arterial blood pressure ( ABP ) waveform data, which can potentially help...various ESN architectures for prediction tasks, and establishes the benefits of using ESN architecture designs for predicting ECG and ABP waveforms...arterial blood pressure ( ABP ) waveforms immediately prior to the machine generated alarms. When tested, the algorithm suppressed approximately 59.7

  19. A parallel implementation of the network identification by multiple regression (NIR) algorithm to reverse-engineer regulatory gene networks.

    PubMed

    Gregoretti, Francesco; Belcastro, Vincenzo; di Bernardo, Diego; Oliva, Gennaro

    2010-04-21

    The reverse engineering of gene regulatory networks using gene expression profile data has become crucial to gain novel biological knowledge. Large amounts of data that need to be analyzed are currently being produced due to advances in microarray technologies. Using current reverse engineering algorithms to analyze large data sets can be very computational-intensive. These emerging computational requirements can be met using parallel computing techniques. It has been shown that the Network Identification by multiple Regression (NIR) algorithm performs better than the other ready-to-use reverse engineering software. However it cannot be used with large networks with thousands of nodes--as is the case in biological networks--due to the high time and space complexity. In this work we overcome this limitation by designing and developing a parallel version of the NIR algorithm. The new implementation of the algorithm reaches a very good accuracy even for large gene networks, improving our understanding of the gene regulatory networks that is crucial for a wide range of biomedical applications.

  20. An algebra-based method for inferring gene regulatory networks

    PubMed Central

    2014-01-01

    Background The inference of gene regulatory networks (GRNs) from experimental observations is at the heart of systems biology. This includes the inference of both the network topology and its dynamics. While there are many algorithms available to infer the network topology from experimental data, less emphasis has been placed on methods that infer network dynamics. Furthermore, since the network inference problem is typically underdetermined, it is essential to have the option of incorporating into the inference process, prior knowledge about the network, along with an effective description of the search space of dynamic models. Finally, it is also important to have an understanding of how a given inference method is affected by experimental and other noise in the data used. Results This paper contains a novel inference algorithm using the algebraic framework of Boolean polynomial dynamical systems (BPDS), meeting all these requirements. The algorithm takes as input time series data, including those from network perturbations, such as knock-out mutant strains and RNAi experiments. It allows for the incorporation of prior biological knowledge while being robust to significant levels of noise in the data used for inference. It uses an evolutionary algorithm for local optimization with an encoding of the mathematical models as BPDS. The BPDS framework allows an effective representation of the search space for algebraic dynamic models that improves computational performance. The algorithm is validated with both simulated and experimental microarray expression profile data. Robustness to noise is tested using a published mathematical model of the segment polarity gene network in Drosophila melanogaster. Benchmarking of the algorithm is done by comparison with a spectrum of state-of-the-art network inference methods on data from the synthetic IRMA network to demonstrate that our method has good precision and recall for the network reconstruction task, while also

  1. An algebra-based method for inferring gene regulatory networks.

    PubMed

    Vera-Licona, Paola; Jarrah, Abdul; Garcia-Puente, Luis David; McGee, John; Laubenbacher, Reinhard

    2014-03-26

    The inference of gene regulatory networks (GRNs) from experimental observations is at the heart of systems biology. This includes the inference of both the network topology and its dynamics. While there are many algorithms available to infer the network topology from experimental data, less emphasis has been placed on methods that infer network dynamics. Furthermore, since the network inference problem is typically underdetermined, it is essential to have the option of incorporating into the inference process, prior knowledge about the network, along with an effective description of the search space of dynamic models. Finally, it is also important to have an understanding of how a given inference method is affected by experimental and other noise in the data used. This paper contains a novel inference algorithm using the algebraic framework of Boolean polynomial dynamical systems (BPDS), meeting all these requirements. The algorithm takes as input time series data, including those from network perturbations, such as knock-out mutant strains and RNAi experiments. It allows for the incorporation of prior biological knowledge while being robust to significant levels of noise in the data used for inference. It uses an evolutionary algorithm for local optimization with an encoding of the mathematical models as BPDS. The BPDS framework allows an effective representation of the search space for algebraic dynamic models that improves computational performance. The algorithm is validated with both simulated and experimental microarray expression profile data. Robustness to noise is tested using a published mathematical model of the segment polarity gene network in Drosophila melanogaster. Benchmarking of the algorithm is done by comparison with a spectrum of state-of-the-art network inference methods on data from the synthetic IRMA network to demonstrate that our method has good precision and recall for the network reconstruction task, while also predicting several of the

  2. Integrated Network Architecture for Sustained Human and Robotic Exploration

    NASA Technical Reports Server (NTRS)

    Noreen, Gary; Cesarone, Robert; Deutsch, Leslie; Edwards, Charles; Soloff, Jason; Ely, Todd; Cook, Brian; Morabito, David; Hemmati, Hamid; Piazolla, Sabino; hide

    2005-01-01

    The National Aeronautics and Space Administration (NASA) Exploration Systems Enterprise is planning a series of human and robotic missions to the Earth's moon and to Mars. These missions will require communication and navigation services. This paper1 sets forth presumed requirements for such services and concepts for lunar and Mars telecommunications network architectures to satisfy the presumed requirements. The paper suggests that an inexpensive ground network would suffice for missions to the near-side of the moon. A constellation of three Lunar Telecommunications Orbiters connected to an inexpensive ground network could provide continuous redundant links to a polar lunar base and its vicinity. For human and robotic missions to Mars, a pair of areostationary satellites could provide continuous redundant links between Earth and a mid-latitude Mars base in conjunction with the Deep Space Network augmented by large arrays of 12-m antennas on Earth.

  3. An Architecture for Performance Optimization in a Collaborative Knowledge-Based Approach for Wireless Sensor Networks

    PubMed Central

    Gadeo-Martos, Manuel Angel; Fernandez-Prieto, Jose Angel; Canada-Bago, Joaquin; Velasco, Juan Ramon

    2011-01-01

    Over the past few years, Intelligent Spaces (ISs) have received the attention of many Wireless Sensor Network researchers. Recently, several studies have been devoted to identify their common capacities and to set up ISs over these networks. However, little attention has been paid to integrating Fuzzy Rule-Based Systems into collaborative Wireless Sensor Networks for the purpose of implementing ISs. This work presents a distributed architecture proposal for collaborative Fuzzy Rule-Based Systems embedded in Wireless Sensor Networks, which has been designed to optimize the implementation of ISs. This architecture includes the following: (a) an optimized design for the inference engine; (b) a visual interface; (c) a module to reduce the redundancy and complexity of the knowledge bases; (d) a module to evaluate the accuracy of the new knowledge base; (e) a module to adapt the format of the rules to the structure used by the inference engine; and (f) a communications protocol. As a real-world application of this architecture and the proposed methodologies, we show an application to the problem of modeling two plagues of the olive tree: prays (olive moth, Prays oleae Bern.) and repilo (caused by the fungus Spilocaea oleagina). The results show that the architecture presented in this paper significantly decreases the consumption of resources (memory, CPU and battery) without a substantial decrease in the accuracy of the inferred values. PMID:22163687

  4. An architecture for performance optimization in a collaborative knowledge-based approach for wireless sensor networks.

    PubMed

    Gadeo-Martos, Manuel Angel; Fernandez-Prieto, Jose Angel; Canada-Bago, Joaquin; Velasco, Juan Ramon

    2011-01-01

    Over the past few years, Intelligent Spaces (ISs) have received the attention of many Wireless Sensor Network researchers. Recently, several studies have been devoted to identify their common capacities and to set up ISs over these networks. However, little attention has been paid to integrating Fuzzy Rule-Based Systems into collaborative Wireless Sensor Networks for the purpose of implementing ISs. This work presents a distributed architecture proposal for collaborative Fuzzy Rule-Based Systems embedded in Wireless Sensor Networks, which has been designed to optimize the implementation of ISs. This architecture includes the following: (a) an optimized design for the inference engine; (b) a visual interface; (c) a module to reduce the redundancy and complexity of the knowledge bases; (d) a module to evaluate the accuracy of the new knowledge base; (e) a module to adapt the format of the rules to the structure used by the inference engine; and (f) a communications protocol. As a real-world application of this architecture and the proposed methodologies, we show an application to the problem of modeling two plagues of the olive tree: prays (olive moth, Prays oleae Bern.) and repilo (caused by the fungus Spilocaea oleagina). The results show that the architecture presented in this paper significantly decreases the consumption of resources (memory, CPU and battery) without a substantial decrease in the accuracy of the inferred values.

  5. Quantifying sleep architecture dynamics and individual differences using big data and Bayesian networks

    PubMed Central

    Shelton, Christian; Mednick, Sara C.

    2018-01-01

    The pattern of sleep stages across a night (sleep architecture) is influenced by biological, behavioral, and clinical variables. However, traditional measures of sleep architecture such as stage proportions, fail to capture sleep dynamics. Here we quantify the impact of individual differences on the dynamics of sleep architecture and determine which factors or set of factors best predict the next sleep stage from current stage information. We investigated the influence of age, sex, body mass index, time of day, and sleep time on static (e.g. minutes in stage, sleep efficiency) and dynamic measures of sleep architecture (e.g. transition probabilities and stage duration distributions) using a large dataset of 3202 nights from a non-clinical population. Multi-level regressions show that sex effects duration of all Non-Rapid Eye Movement (NREM) stages, and age has a curvilinear relationship for Wake After Sleep Onset (WASO) and slow wave sleep (SWS) minutes. Bayesian network modeling reveals sleep architecture depends on time of day, total sleep time, age and sex, but not BMI. Older adults, and particularly males, have shorter bouts (more fragmentation) of Stage 2, SWS, and they transition less frequently to these stages. Additionally, we showed that the next sleep stage and its duration can be optimally predicted by the prior 2 stages and age. Our results demonstrate the potential benefit of big data and Bayesian network approaches in quantifying static and dynamic architecture of normal sleep. PMID:29641599

  6. Quantifying sleep architecture dynamics and individual differences using big data and Bayesian networks.

    PubMed

    Yetton, Benjamin D; McDevitt, Elizabeth A; Cellini, Nicola; Shelton, Christian; Mednick, Sara C

    2018-01-01

    The pattern of sleep stages across a night (sleep architecture) is influenced by biological, behavioral, and clinical variables. However, traditional measures of sleep architecture such as stage proportions, fail to capture sleep dynamics. Here we quantify the impact of individual differences on the dynamics of sleep architecture and determine which factors or set of factors best predict the next sleep stage from current stage information. We investigated the influence of age, sex, body mass index, time of day, and sleep time on static (e.g. minutes in stage, sleep efficiency) and dynamic measures of sleep architecture (e.g. transition probabilities and stage duration distributions) using a large dataset of 3202 nights from a non-clinical population. Multi-level regressions show that sex effects duration of all Non-Rapid Eye Movement (NREM) stages, and age has a curvilinear relationship for Wake After Sleep Onset (WASO) and slow wave sleep (SWS) minutes. Bayesian network modeling reveals sleep architecture depends on time of day, total sleep time, age and sex, but not BMI. Older adults, and particularly males, have shorter bouts (more fragmentation) of Stage 2, SWS, and they transition less frequently to these stages. Additionally, we showed that the next sleep stage and its duration can be optimally predicted by the prior 2 stages and age. Our results demonstrate the potential benefit of big data and Bayesian network approaches in quantifying static and dynamic architecture of normal sleep.

  7. Comparative evaluation of reverse engineering gene regulatory networks with relevance networks, graphical gaussian models and bayesian networks.

    PubMed

    Werhli, Adriano V; Grzegorczyk, Marco; Husmeier, Dirk

    2006-10-15

    An important problem in systems biology is the inference of biochemical pathways and regulatory networks from postgenomic data. Various reverse engineering methods have been proposed in the literature, and it is important to understand their relative merits and shortcomings. In the present paper, we compare the accuracy of reconstructing gene regulatory networks with three different modelling and inference paradigms: (1) Relevance networks (RNs): pairwise association scores independent of the remaining network; (2) graphical Gaussian models (GGMs): undirected graphical models with constraint-based inference, and (3) Bayesian networks (BNs): directed graphical models with score-based inference. The evaluation is carried out on the Raf pathway, a cellular signalling network describing the interaction of 11 phosphorylated proteins and phospholipids in human immune system cells. We use both laboratory data from cytometry experiments as well as data simulated from the gold-standard network. We also compare passive observations with active interventions. On Gaussian observational data, BNs and GGMs were found to outperform RNs. The difference in performance was not significant for the non-linear simulated data and the cytoflow data, though. Also, we did not observe a significant difference between BNs and GGMs on observational data in general. However, for interventional data, BNs outperform GGMs and RNs, especially when taking the edge directions rather than just the skeletons of the graphs into account. This suggests that the higher computational costs of inference with BNs over GGMs and RNs are not justified when using only passive observations, but that active interventions in the form of gene knockouts and over-expressions are required to exploit the full potential of BNs. Data, software and supplementary material are available from http://www.bioss.sari.ac.uk/staff/adriano/research.html

  8. Reverse engineering gene regulatory networks from measurement with missing values.

    PubMed

    Ogundijo, Oyetunji E; Elmas, Abdulkadir; Wang, Xiaodong

    2016-12-01

    Gene expression time series data are usually in the form of high-dimensional arrays. Unfortunately, the data may sometimes contain missing values: for either the expression values of some genes at some time points or the entire expression values of a single time point or some sets of consecutive time points. This significantly affects the performance of many algorithms for gene expression analysis that take as an input, the complete matrix of gene expression measurement. For instance, previous works have shown that gene regulatory interactions can be estimated from the complete matrix of gene expression measurement. Yet, till date, few algorithms have been proposed for the inference of gene regulatory network from gene expression data with missing values. We describe a nonlinear dynamic stochastic model for the evolution of gene expression. The model captures the structural, dynamical, and the nonlinear natures of the underlying biomolecular systems. We present point-based Gaussian approximation (PBGA) filters for joint state and parameter estimation of the system with one-step or two-step missing measurements . The PBGA filters use Gaussian approximation and various quadrature rules, such as the unscented transform (UT), the third-degree cubature rule and the central difference rule for computing the related posteriors. The proposed algorithm is evaluated with satisfying results for synthetic networks, in silico networks released as a part of the DREAM project, and the real biological network, the in vivo reverse engineering and modeling assessment (IRMA) network of yeast Saccharomyces cerevisiae . PBGA filters are proposed to elucidate the underlying gene regulatory network (GRN) from time series gene expression data that contain missing values. In our state-space model, we proposed a measurement model that incorporates the effect of the missing data points into the sequential algorithm. This approach produces a better inference of the model parameters and hence

  9. Emerging principles of regulatory evolution.

    PubMed

    Prud'homme, Benjamin; Gompel, Nicolas; Carroll, Sean B

    2007-05-15

    Understanding the genetic and molecular mechanisms governing the evolution of morphology is a major challenge in biology. Because most animals share a conserved repertoire of body-building and -patterning genes, morphological diversity appears to evolve primarily through changes in the deployment of these genes during development. The complex expression patterns of developmentally regulated genes are typically controlled by numerous independent cis-regulatory elements (CREs). It has been proposed that morphological evolution relies predominantly on changes in the architecture of gene regulatory networks and in particular on functional changes within CREs. Here, we discuss recent experimental studies that support this hypothesis and reveal some unanticipated features of how regulatory evolution occurs. From this growing body of evidence, we identify three key operating principles underlying regulatory evolution, that is, how regulatory evolution: (i) uses available genetic components in the form of preexisting and active transcription factors and CREs to generate novelty; (ii) minimizes the penalty to overall fitness by introducing discrete changes in gene expression; and (iii) allows interactions to arise among any transcription factor and downstream CRE. These principles endow regulatory evolution with a vast creative potential that accounts for both relatively modest morphological differences among closely related species and more profound anatomical divergences among groups at higher taxonomical levels.

  10. Reconstructing gene regulatory networks from knock-out data using Gaussian Noise Model and Pearson Correlation Coefficient.

    PubMed

    Mohamed Salleh, Faridah Hani; Arif, Shereena Mohd; Zainudin, Suhaila; Firdaus-Raih, Mohd

    2015-12-01

    A gene regulatory network (GRN) is a large and complex network consisting of interacting elements that, over time, affect each other's state. The dynamics of complex gene regulatory processes are difficult to understand using intuitive approaches alone. To overcome this problem, we propose an algorithm for inferring the regulatory interactions from knock-out data using a Gaussian model combines with Pearson Correlation Coefficient (PCC). There are several problems relating to GRN construction that have been outlined in this paper. We demonstrated the ability of our proposed method to (1) predict the presence of regulatory interactions between genes, (2) their directionality and (3) their states (activation or suppression). The algorithm was applied to network sizes of 10 and 50 genes from DREAM3 datasets and network sizes of 10 from DREAM4 datasets. The predicted networks were evaluated based on AUROC and AUPR. We discovered that high false positive values were generated by our GRN prediction methods because the indirect regulations have been wrongly predicted as true relationships. We achieved satisfactory results as the majority of sub-networks achieved AUROC values above 0.5. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Data-driven integration of genome-scale regulatory and metabolic network models

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Imam, Saheed; Schauble, Sascha; Brooks, Aaron N.

    Microbes are diverse and extremely versatile organisms that play vital roles in all ecological niches. Understanding and harnessing microbial systems will be key to the sustainability of our planet. One approach to improving our knowledge of microbial processes is through data-driven and mechanism-informed computational modeling. Individual models of biological networks (such as metabolism, transcription, and signaling) have played pivotal roles in driving microbial research through the years. These networks, however, are highly interconnected and function in concert a fact that has led to the development of a variety of approaches aimed at simulating the integrated functions of two or moremore » network types. Though the task of integrating these different models is fraught with new challenges, the large amounts of high-throughput data sets being generated, and algorithms being developed, means that the time is at hand for concerted efforts to build integrated regulatory-metabolic networks in a data-driven fashion. Lastly, in this perspective, we review current approaches for constructing integrated regulatory-metabolic models and outline new strategies for future development of these network models for any microbial system.« less

  12. Data-driven integration of genome-scale regulatory and metabolic network models

    DOE PAGES

    Imam, Saheed; Schauble, Sascha; Brooks, Aaron N.; ...

    2015-05-05

    Microbes are diverse and extremely versatile organisms that play vital roles in all ecological niches. Understanding and harnessing microbial systems will be key to the sustainability of our planet. One approach to improving our knowledge of microbial processes is through data-driven and mechanism-informed computational modeling. Individual models of biological networks (such as metabolism, transcription, and signaling) have played pivotal roles in driving microbial research through the years. These networks, however, are highly interconnected and function in concert a fact that has led to the development of a variety of approaches aimed at simulating the integrated functions of two or moremore » network types. Though the task of integrating these different models is fraught with new challenges, the large amounts of high-throughput data sets being generated, and algorithms being developed, means that the time is at hand for concerted efforts to build integrated regulatory-metabolic networks in a data-driven fashion. Lastly, in this perspective, we review current approaches for constructing integrated regulatory-metabolic models and outline new strategies for future development of these network models for any microbial system.« less

  13. Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages

    PubMed Central

    del Sol, Antonio; Araúzo-Bravo, Marcos J; Amoros, Dolors; Nussinov, Ruth

    2007-01-01

    Background Allosteric communications are vital for cellular signaling. Here we explore a relationship between protein architectural organization and shortcuts in signaling pathways. Results We show that protein domains consist of modules interconnected by residues that mediate signaling through the shortest pathways. These mediating residues tend to be located at the inter-modular boundaries, which are more rigid and display a larger number of long-range interactions than intra-modular regions. The inter-modular boundaries contain most of the residues centrally conserved in the protein fold, which may be crucial for information transfer between amino acids. Our approach to modular decomposition relies on a representation of protein structures as residue-interacting networks, and removal of the most central residue contacts, which are assumed to be crucial for allosteric communications. The modular decomposition of 100 multi-domain protein structures indicates that modules constitute the building blocks of domains. The analysis of 13 allosteric proteins revealed that modules characterize experimentally identified functional regions. Based on the study of an additional functionally annotated dataset of 115 proteins, we propose that high-modularity modules include functional sites and are the basic functional units. We provide examples (the Gαs subunit and P450 cytochromes) to illustrate that the modular architecture of active sites is linked to their functional specialization. Conclusion Our method decomposes protein structures into modules, allowing the study of signal transmission between functional sites. A modular configuration might be advantageous: it allows signaling proteins to expand their regulatory linkages and may elicit a broader range of control mechanisms either via modular combinations or through modulation of inter-modular linkages. PMID:17531094

  14. Cluster based architecture and network maintenance protocol for medical priority aware cognitive radio based hospital.

    PubMed

    Al Mamoon, Ishtiak; Muzahidul Islam, A K M; Baharun, Sabariah; Ahmed, Ashir; Komaki, Shozo

    2016-08-01

    Due to the rapid growth of wireless medical devices in near future, wireless healthcare services may face some inescapable issue such as medical spectrum scarcity, electromagnetic interference (EMI), bandwidth constraint, security and finally medical data communication model. To mitigate these issues, cognitive radio (CR) or opportunistic radio network enabled wireless technology is suitable for the upcoming wireless healthcare system. The up-to-date research on CR based healthcare has exposed some developments on EMI and spectrum problems. However, the investigation recommendation on system design and network model for CR enabled hospital is rare. Thus, this research designs a hierarchy based hybrid network architecture and network maintenance protocols for previously proposed CR hospital system, known as CogMed. In the previous study, the detail architecture of CogMed and its maintenance protocols were not present. The proposed architecture includes clustering concepts for cognitive base stations and non-medical devices. Two cluster head (CH selector equations are formulated based on priority of location, device, mobility rate of devices and number of accessible channels. In order to maintain the integrity of the proposed network model, node joining and node leaving protocols are also proposed. Finally, the simulation results show that the proposed network maintenance time is very low for emergency medical devices (average maintenance period 9.5 ms) and the re-clustering effects for different mobility enabled non-medical devices are also balanced.

  15. Trichomes: different regulatory networks lead to convergent structures.

    PubMed

    Serna, Laura; Martin, Cathie

    2006-06-01

    Sometimes, proteins, biological structures or even organisms have similar functions and appearances but have evolved through widely divergent pathways. There is experimental evidence to suggest that different developmental pathways have converged to produce similar outgrowths of the aerial plant epidermis, referred to as trichomes. The emerging picture suggests that trichomes in Arabidopsis thaliana and, perhaps, in cotton develop through a transcriptional regulatory network that differs from those regulating trichome formation in Antirrhinum and Solanaceous species. Several lines of evidence suggest that the duplication of a gene controlling anthocyanin production and subsequent divergence might be the major force driving trichome formation in Arabidopsis, whereas the multicellular trichomes of Antirrhinum and Solanaceous species appear to have a different regulatory origin.

  16. Exploring the bZIP transcription factor regulatory network in Neurospora crassa

    PubMed Central

    Tian, Chaoguang; Li, Jingyi; Glass, N. Louise

    2011-01-01

    Transcription factors (TFs) are key nodes of regulatory networks in eukaryotic organisms, including filamentous fungi such as Neurospora crassa. The 178 predicted DNA-binding TFs in N. crassa are distributed primarily among six gene families, which represent an ancient expansion in filamentous ascomycete genomes; 98 TF genes show detectable expression levels during vegetative growth of N. crassa, including 35 that show a significant difference in expression level between hyphae at the periphery versus hyphae in the interior of a colony. Regulatory networks within a species genome include paralogous TFs and their respective target genes (TF regulon). To investigate TF network evolution in N. crassa, we focused on the basic leucine zipper (bZIP) TF family, which contains nine members. We performed baseline transcriptional profiling during vegetative growth of the wild-type and seven isogenic, viable bZIP deletion mutants. We further characterized the regulatory network of one member of the bZIP family, NCU03905. NCU03905 encodes an Ap1-like protein (NcAp-1), which is involved in resistance to multiple stress responses, including oxidative and heavy metal stress. Relocalization of NcAp-1 from the cytoplasm to the nucleus was associated with exposure to stress. A comparison of the NcAp-1 regulon with Ap1-like regulons in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans and Aspergillus fumigatus showed both conservation and divergence. These data indicate how N. crassa responds to stress and provide information on pathway evolution. PMID:21081763

  17. Exploring the bZIP transcription factor regulatory network in Neurospora crassa.

    PubMed

    Tian, Chaoguang; Li, Jingyi; Glass, N Louise

    2011-03-01

    Transcription factors (TFs) are key nodes of regulatory networks in eukaryotic organisms, including filamentous fungi such as Neurospora crassa. The 178 predicted DNA-binding TFs in N. crassa are distributed primarily among six gene families, which represent an ancient expansion in filamentous ascomycete genomes; 98 TF genes show detectable expression levels during vegetative growth of N. crassa, including 35 that show a significant difference in expression level between hyphae at the periphery versus hyphae in the interior of a colony. Regulatory networks within a species genome include paralogous TFs and their respective target genes (TF regulon). To investigate TF network evolution in N. crassa, we focused on the basic leucine zipper (bZIP) TF family, which contains nine members. We performed baseline transcriptional profiling during vegetative growth of the wild-type and seven isogenic, viable bZIP deletion mutants. We further characterized the regulatory network of one member of the bZIP family, NCU03905. NCU03905 encodes an Ap1-like protein (NcAp-1), which is involved in resistance to multiple stress responses, including oxidative and heavy metal stress. Relocalization of NcAp-1 from the cytoplasm to the nucleus was associated with exposure to stress. A comparison of the NcAp-1 regulon with Ap1-like regulons in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans and Aspergillus fumigatus showed both conservation and divergence. These data indicate how N. crassa responds to stress and provide information on pathway evolution.

  18. Software defined network architecture based research on load balancing strategy

    NASA Astrophysics Data System (ADS)

    You, Xiaoqian; Wu, Yang

    2018-05-01

    As a new type network architecture, software defined network has the key idea of separating the control place of the network from the transmission plane, to manage and control the network in a concentrated way; in addition, the network interface is opened on the control layer and the data layer, so as to achieve programmable control of the network. Considering that only the single shortest route is taken into the calculation of traditional network data flow transmission, and congestion and resource consumption caused by excessive load of link circuits are ignored, a link circuit load based flow media business QoS gurantee system is proposed in this article to divide the flow in the network into ordinary data flow and QoS flow. In this way, it supervises the link circuit load with the controller so as to calculate reasonable route rapidly and issue the flow table to the exchanger, to finish rapid data transmission. In addition, it establishes a simulation platform to acquire optimized result through simulation experiment.

  19. Abasy Atlas: a comprehensive inventory of systems, global network properties and systems-level elements across bacteria.

    PubMed

    Ibarra-Arellano, Miguel A; Campos-González, Adrián I; Treviño-Quintanilla, Luis G; Tauch, Andreas; Freyre-González, Julio A

    2016-01-01

    The availability of databases electronically encoding curated regulatory networks and of high-throughput technologies and methods to discover regulatory interactions provides an invaluable source of data to understand the principles underpinning the organization and evolution of these networks responsible for cellular regulation. Nevertheless, data on these sources never goes beyond the regulon level despite the fact that regulatory networks are complex hierarchical-modular structures still challenging our understanding. This brings the necessity for an inventory of systems across a large range of organisms, a key step to rendering feasible comparative systems biology approaches. In this work, we take the first step towards a global understanding of the regulatory networks organization by making a cartography of the functional architectures of diverse bacteria. Abasy ( A: cross- BA: cteria SY: stems) Atlas provides a comprehensive inventory of annotated functional systems, global network properties and systems-level elements (global regulators, modular genes shaping functional systems, basal machinery genes and intermodular genes) predicted by the natural decomposition approach for reconstructed and meta-curated regulatory networks across a large range of bacteria, including pathogenically and biotechnologically relevant organisms. The meta-curation of regulatory datasets provides the most complete and reliable set of regulatory interactions currently available, which can even be projected into subsets by considering the force or weight of evidence supporting them or the systems that they belong to. Besides, Abasy Atlas provides data enabling large-scale comparative systems biology studies aimed at understanding the common principles and particular lifestyle adaptions of systems across bacteria. Abasy Atlas contains systems and system-level elements for 50 regulatory networks comprising 78 649 regulatory interactions covering 42 bacteria in nine taxa, containing

  20. Abasy Atlas: a comprehensive inventory of systems, global network properties and systems-level elements across bacteria

    PubMed Central

    Ibarra-Arellano, Miguel A.; Campos-González, Adrián I.; Treviño-Quintanilla, Luis G.; Tauch, Andreas; Freyre-González, Julio A.

    2016-01-01

    The availability of databases electronically encoding curated regulatory networks and of high-throughput technologies and methods to discover regulatory interactions provides an invaluable source of data to understand the principles underpinning the organization and evolution of these networks responsible for cellular regulation. Nevertheless, data on these sources never goes beyond the regulon level despite the fact that regulatory networks are complex hierarchical-modular structures still challenging our understanding. This brings the necessity for an inventory of systems across a large range of organisms, a key step to rendering feasible comparative systems biology approaches. In this work, we take the first step towards a global understanding of the regulatory networks organization by making a cartography of the functional architectures of diverse bacteria. Abasy (Across-bacteria systems) Atlas provides a comprehensive inventory of annotated functional systems, global network properties and systems-level elements (global regulators, modular genes shaping functional systems, basal machinery genes and intermodular genes) predicted by the natural decomposition approach for reconstructed and meta-curated regulatory networks across a large range of bacteria, including pathogenically and biotechnologically relevant organisms. The meta-curation of regulatory datasets provides the most complete and reliable set of regulatory interactions currently available, which can even be projected into subsets by considering the force or weight of evidence supporting them or the systems that they belong to. Besides, Abasy Atlas provides data enabling large-scale comparative systems biology studies aimed at understanding the common principles and particular lifestyle adaptions of systems across bacteria. Abasy Atlas contains systems and system-level elements for 50 regulatory networks comprising 78 649 regulatory interactions covering 42 bacteria in nine taxa, containing 3708

  1. Architectural impact of FDDI network on scheduling hard real-time traffic

    NASA Technical Reports Server (NTRS)

    Agrawal, Gopal; Chen, Baio; Zhao, Wei; Davari, Sadegh

    1991-01-01

    The architectural impact on guaranteeing synchronous message deadlines in FDDI (Fiber Distributed Data Interface) token ring networks is examined. The FDDI network does not have facility to support (global) priority arbitration which is a useful facility for scheduling hard real time activities. As a result, it was found that the worst case utilization of synchronous traffic in an FDDI network can be far less than that in a centralized single processor system. Nevertheless, it is proposed and analyzed that a scheduling method can guarantee deadlines of synchronous messages having traffic utilization up to 33 pct., the highest to date.

  2. F-MAP: A Bayesian approach to infer the gene regulatory network using external hints

    PubMed Central

    Shahdoust, Maryam; Mahjub, Hossein; Sadeghi, Mehdi

    2017-01-01

    The Common topological features of related species gene regulatory networks suggest reconstruction of the network of one species by using the further information from gene expressions profile of related species. We present an algorithm to reconstruct the gene regulatory network named; F-MAP, which applies the knowledge about gene interactions from related species. Our algorithm sets a Bayesian framework to estimate the precision matrix of one species microarray gene expressions dataset to infer the Gaussian Graphical model of the network. The conjugate Wishart prior is used and the information from related species is applied to estimate the hyperparameters of the prior distribution by using the factor analysis. Applying the proposed algorithm on six related species of drosophila shows that the precision of reconstructed networks is improved considerably compared to the precision of networks constructed by other Bayesian approaches. PMID:28938012

  3. Neural Network Classifier Architectures for Phoneme Recognition. CRC Technical Note No. CRC-TN-92-001.

    ERIC Educational Resources Information Center

    Treurniet, William

    A study applied artificial neural networks, trained with the back-propagation learning algorithm, to modelling phonemes extracted from the DARPA TIMIT multi-speaker, continuous speech data base. A number of proposed network architectures were applied to the phoneme classification task, ranging from the simple feedforward multilayer network to more…

  4. Reconstructing regulatory networks from the dynamic plasticity of gene expression by mutual information

    PubMed Central

    Wang, Jianxin; Chen, Bo; Wang, Yaqun; Wang, Ningtao; Garbey, Marc; Tran-Son-Tay, Roger; Berceli, Scott A.; Wu, Rongling

    2013-01-01

    The capacity of an organism to respond to its environment is facilitated by the environmentally induced alteration of gene and protein expression, i.e. expression plasticity. The reconstruction of gene regulatory networks based on expression plasticity can gain not only new insights into the causality of transcriptional and cellular processes but also the complex regulatory mechanisms that underlie biological function and adaptation. We describe an approach for network inference by integrating expression plasticity into Shannon’s mutual information. Beyond Pearson correlation, mutual information can capture non-linear dependencies and topology sparseness. The approach measures the network of dependencies of genes expressed in different environments, allowing the environment-induced plasticity of gene dependencies to be tested in unprecedented details. The approach is also able to characterize the extent to which the same genes trigger different amounts of expression in response to environmental changes. We demonstrated the usefulness of this approach through analysing gene expression data from a rabbit vein graft study that includes two distinct blood flow environments. The proposed approach provides a powerful tool for the modelling and analysis of dynamic regulatory networks using gene expression data from distinct environments. PMID:23470995

  5. Applying gene regulatory network logic to the evolution of social behavior.

    PubMed

    Baran, Nicole M; McGrath, Patrick T; Streelman, J Todd

    2017-06-06

    Animal behavior is ultimately the product of gene regulatory networks (GRNs) for brain development and neural networks for brain function. The GRN approach has advanced the fields of genomics and development, and we identify organizational similarities between networks of genes that build the brain and networks of neurons that encode brain function. In this perspective, we engage the analogy between developmental networks and neural networks, exploring the advantages of using GRN logic to study behavior. Applying the GRN approach to the brain and behavior provides a quantitative and manipulative framework for discovery. We illustrate features of this framework using the example of social behavior and the neural circuitry of aggression.

  6. From Genes to Networks: Characterizing Gene-Regulatory Interactions in Plants.

    PubMed

    Kaufmann, Kerstin; Chen, Dijun

    2017-01-01

    Plants, like other eukaryotes, have evolved complex mechanisms to coordinate gene expression during development, environmental response, and cellular homeostasis. Transcription factors (TFs), accompanied by basic cofactors and posttranscriptional regulators, are key players in gene-regulatory networks (GRNs). The coordinated control of gene activity is achieved by the interplay of these factors and by physical interactions between TFs and DNA. Here, we will briefly outline recent technological progress made to elucidate GRNs in plants. We will focus on techniques that allow us to characterize physical interactions in GRNs in plants and to analyze their regulatory consequences. Targeted manipulation allows us to test the relevance of specific gene-regulatory interactions. The combination of genome-wide experimental approaches with mathematical modeling allows us to get deeper insights into key-regulatory interactions and combinatorial control of important processes in plants.

  7. Hierarchical network architectures of carbon fiber paper supported cobalt oxide nanonet for high-capacity pseudocapacitors.

    PubMed

    Yang, Lei; Cheng, Shuang; Ding, Yong; Zhu, Xingbao; Wang, Zhong Lin; Liu, Meilin

    2012-01-11

    We present a high-capacity pseudocapacitor based on a hierarchical network architecture consisting of Co(3)O(4) nanowire network (nanonet) coated on a carbon fiber paper. With this tailored architecture, the electrode shows ideal capacitive behavior (rectangular shape of cyclic voltammograms) and large specific capacitance (1124 F/g) at high charge/discharge rate (25.34 A/g), still retaining ~94% of the capacitance at a much lower rate of 0.25 A/g. The much-improved capacity, rate capability, and cycling stability may be attributed to the unique hierarchical network structures, which improves electron/ion transport, enhances the kinetics of redox reactions, and facilitates facile stress relaxation during cycling. © 2011 American Chemical Society

  8. SANDS: a service-oriented architecture for clinical decision support in a National Health Information Network.

    PubMed

    Wright, Adam; Sittig, Dean F

    2008-12-01

    In this paper, we describe and evaluate a new distributed architecture for clinical decision support called SANDS (Service-oriented Architecture for NHIN Decision Support), which leverages current health information exchange efforts and is based on the principles of a service-oriented architecture. The architecture allows disparate clinical information systems and clinical decision support systems to be seamlessly integrated over a network according to a set of interfaces and protocols described in this paper. The architecture described is fully defined and developed, and six use cases have been developed and tested using a prototype electronic health record which links to one of the existing prototype National Health Information Networks (NHIN): drug interaction checking, syndromic surveillance, diagnostic decision support, inappropriate prescribing in older adults, information at the point of care and a simple personal health record. Some of these use cases utilize existing decision support systems, which are either commercially or freely available at present, and developed outside of the SANDS project, while other use cases are based on decision support systems developed specifically for the project. Open source code for many of these components is available, and an open source reference parser is also available for comparison and testing of other clinical information systems and clinical decision support systems that wish to implement the SANDS architecture. The SANDS architecture for decision support has several significant advantages over other architectures for clinical decision support. The most salient of these are:

  9. Large Scale Comparative Visualisation of Regulatory Networks with TRNDiff

    DOE PAGES

    Chua, Xin-Yi; Buckingham, Lawrence; Hogan, James M.; ...

    2015-06-01

    The advent of Next Generation Sequencing (NGS) technologies has seen explosive growth in genomic datasets, and dense coverage of related organisms, supporting study of subtle, strain-specific variations as a determinant of function. Such data collections present fresh and complex challenges for bioinformatics, those of comparing models of complex relationships across hundreds and even thousands of sequences. Transcriptional Regulatory Network (TRN) structures document the influence of regulatory proteins called Transcription Factors (TFs) on associated Target Genes (TGs). TRNs are routinely inferred from model systems or iterative search, and analysis at these scales requires simultaneous displays of multiple networks well beyond thosemore » of existing network visualisation tools [1]. In this paper we describe TRNDiff, an open source system supporting the comparative analysis and visualization of TRNs (and similarly structured data) from many genomes, allowing rapid identification of functional variations within species. The approach is demonstrated through a small scale multiple TRN analysis of the Fur iron-uptake system of Yersinia, suggesting a number of candidate virulence factors; and through a larger study exploiting integration with the RegPrecise database (http://regprecise.lbl.gov; [2]) - a collection of hundreds of manually curated and predicted transcription factor regulons drawn from across the entire spectrum of prokaryotic organisms.« less

  10. Construction of diagnosis system and gene regulatory networks based on microarray analysis.

    PubMed

    Hong, Chun-Fu; Chen, Ying-Chen; Chen, Wei-Chun; Tu, Keng-Chang; Tsai, Meng-Hsiun; Chan, Yung-Kuan; Yu, Shyr Shen

    2018-05-01

    A microarray analysis generally contains expression data of thousands of genes, but most of them are irrelevant to the disease of interest, making analyzing the genes concerning specific diseases complicated. Therefore, filtering out a few essential genes as well as their regulatory networks is critical, and a disease can be easily diagnosed just depending on the expression profiles of a few critical genes. In this study, a target gene screening (TGS) system, which is a microarray-based information system that integrates F-statistics, pattern recognition matching, a two-layer K-means classifier, a Parameter Detection Genetic Algorithm (PDGA), a genetic-based gene selector (GBG selector) and the association rule, was developed to screen out a small subset of genes that can discriminate malignant stages of cancers. During the first stage, F-statistic, pattern recognition matching, and a two-layer K-means classifier were applied in the system to filter out the 20 critical genes most relevant to ovarian cancer from 9600 genes, and the PDGA was used to decide the fittest values of the parameters for these critical genes. Among the 20 critical genes, 15 are associated with cancer progression. In the second stage, we further employed a GBG selector and the association rule to screen out seven target gene sets, each with only four to six genes, and each of which can precisely identify the malignancy stage of ovarian cancer based on their expression profiles. We further deduced the gene regulatory networks of the 20 critical genes by applying the Pearson correlation coefficient to evaluate the correlationship between the expression of each gene at the same stages and at different stages. Correlationships between gene pairs were calculated, and then, three regulatory networks were deduced. Their correlationships were further confirmed by the Ingenuity pathway analysis. The prognostic significances of the genes identified via regulatory networks were examined using online

  11. Unraveling gene regulatory networks from time-resolved gene expression data -- a measures comparison study

    PubMed Central

    2011-01-01

    Background Inferring regulatory interactions between genes from transcriptomics time-resolved data, yielding reverse engineered gene regulatory networks, is of paramount importance to systems biology and bioinformatics studies. Accurate methods to address this problem can ultimately provide a deeper insight into the complexity, behavior, and functions of the underlying biological systems. However, the large number of interacting genes coupled with short and often noisy time-resolved read-outs of the system renders the reverse engineering a challenging task. Therefore, the development and assessment of methods which are computationally efficient, robust against noise, applicable to short time series data, and preferably capable of reconstructing the directionality of the regulatory interactions remains a pressing research problem with valuable applications. Results Here we perform the largest systematic analysis of a set of similarity measures and scoring schemes within the scope of the relevance network approach which are commonly used for gene regulatory network reconstruction from time series data. In addition, we define and analyze several novel measures and schemes which are particularly suitable for short transcriptomics time series. We also compare the considered 21 measures and 6 scoring schemes according to their ability to correctly reconstruct such networks from short time series data by calculating summary statistics based on the corresponding specificity and sensitivity. Our results demonstrate that rank and symbol based measures have the highest performance in inferring regulatory interactions. In addition, the proposed scoring scheme by asymmetric weighting has shown to be valuable in reducing the number of false positive interactions. On the other hand, Granger causality as well as information-theoretic measures, frequently used in inference of regulatory networks, show low performance on the short time series analyzed in this study. Conclusions Our

  12. An Architecture for Cooperative Localization in Underwater Acoustic Networks

    DTIC Science & Technology

    2015-10-24

    range. (b) Independent navigation and control system onboard Iver AUVs . The cooperative localization process is highlighted in red. Figure 1: Block...Iver2 AUVs (Fig. 3) and a topside ship. While we make spe- cific notes about this three vehicle network, the architecture is vehicle independent. 3.1...Single vehicle subsystem Each vehicle executes several processes including sensor drivers, a pose estimator (Section 2), and, in the case of the AUVs

  13. Stationary and structural control in gene regulatory networks: basic concepts

    NASA Astrophysics Data System (ADS)

    Dougherty, Edward R.; Pal, Ranadip; Qian, Xiaoning; Bittner, Michael L.; Datta, Aniruddha

    2010-01-01

    A major reason for constructing gene regulatory networks is to use them as models for determining therapeutic intervention strategies by deriving ways of altering their long-run dynamics in such a way as to reduce the likelihood of entering undesirable states. In general, two paradigms have been taken for gene network intervention: (1) stationary external control is based on optimally altering the status of a control gene (or genes) over time to drive network dynamics; and (2) structural intervention involves an optimal one-time change of the network structure (wiring) to beneficially alter the long-run behaviour of the network. These intervention approaches have mainly been developed within the context of the probabilistic Boolean network model for gene regulation. This article reviews both types of intervention and applies them to reducing the metastatic competence of cells via intervention in a melanoma-related network.

  14. Advancing reversible shape memory by tuning the polymer network architecture

    DOE PAGES

    Li, Qiaoxi; Zhou, Jing; Vatankhah-Varnoosfaderani, Mohammad; ...

    2016-02-02

    Because of counteraction of a chemical network and a crystalline scaffold, semicrystalline polymer networks exhibit a peculiar behavior—reversible shape memory (RSM), which occurs naturally without applying any external force and particular structural design. There are three RSM properties: (i) range of reversible strain, (ii) rate of strain recovery, and (iii) decay of reversibility with time, which can be improved by tuning the architecture of the polymer network. Different types of poly(octylene adipate) networks were synthesized, allowing for control of cross-link density and network topology, including randomly cross-linked network by free-radical polymerization, thiol–ene clicked network with enhanced mesh uniformity, and loosemore » network with deliberately incorporated dangling chains. It is shown that the RSM properties are controlled by average cross-link density and crystal size, whereas topology of a network greatly affects its extensibility. In conclusion, we have achieved 80% maximum reversible range, 15% minimal decrease in reversibility, and fast strain recovery rate up to 0.05 K –1, i.e., ca. 5% per 10 s at a cooling rate of 5 K/min.« less

  15. Fluid and flexible minds: Intelligence reflects synchrony in the brain’s intrinsic network architecture

    PubMed Central

    Ferguson, Michael A.; Anderson, Jeffrey S.; Spreng, R. Nathan

    2017-01-01

    Human intelligence has been conceptualized as a complex system of dissociable cognitive processes, yet studies investigating the neural basis of intelligence have typically emphasized the contributions of discrete brain regions or, more recently, of specific networks of functionally connected regions. Here we take a broader, systems perspective in order to investigate whether intelligence is an emergent property of synchrony within the brain’s intrinsic network architecture. Using a large sample of resting-state fMRI and cognitive data (n = 830), we report that the synchrony of functional interactions within and across distributed brain networks reliably predicts fluid and flexible intellectual functioning. By adopting a whole-brain, systems-level approach, we were able to reliably predict individual differences in human intelligence by characterizing features of the brain’s intrinsic network architecture. These findings hold promise for the eventual development of neural markers to predict changes in intellectual function that are associated with neurodevelopment, normal aging, and brain disease.

  16. Ensuring Data Storage Security in Tree cast Routing Architecture for Sensor Networks

    NASA Astrophysics Data System (ADS)

    Kumar, K. E. Naresh; Sagar, U. Vidya; Waheed, Mohd. Abdul

    2010-10-01

    In this paper presents recent advances in technology have made low-cost, low-power wireless sensors with efficient energy consumption. A network of such nodes can coordinate among themselves for distributed sensing and processing of certain data. For which, we propose an architecture to provide a stateless solution in sensor networks for efficient routing in wireless sensor networks. This type of architecture is known as Tree Cast. We propose a unique method of address allocation, building up multiple disjoint trees which are geographically inter-twined and rooted at the data sink. Using these trees, routing messages to and from the sink node without maintaining any routing state in the sensor nodes is possible. In contrast to traditional solutions, where the IT services are under proper physical, logical and personnel controls, this routing architecture moves the application software and databases to the large data centers, where the management of the data and services may not be fully trustworthy. This unique attribute, however, poses many new security challenges which have not been well understood. In this paper, we focus on data storage security, which has always been an important aspect of quality of service. To ensure the correctness of users' data in this architecture, we propose an effective and flexible distributed scheme with two salient features, opposing to its predecessors. By utilizing the homomorphic token with distributed verification of erasure-coded data, our scheme achieves the integration of storage correctness insurance and data error localization, i.e., the identification of misbehaving server(s). Unlike most prior works, the new scheme further supports secure and efficient dynamic operations on data blocks, including: data update, delete and append. Extensive security and performance analysis shows that the proposed scheme is highly efficient and resilient against Byzantine failure, malicious data modification attack, and even server

  17. Statistical identification of gene association by CID in application of constructing ER regulatory network

    PubMed Central

    Liu, Li-Yu D; Chen, Chien-Yu; Chen, Mei-Ju M; Tsai, Ming-Shian; Lee, Cho-Han S; Phang, Tzu L; Chang, Li-Yun; Kuo, Wen-Hung; Hwa, Hsiao-Lin; Lien, Huang-Chun; Jung, Shih-Ming; Lin, Yi-Shing; Chang, King-Jen; Hsieh, Fon-Jou

    2009-01-01

    Background A variety of high-throughput techniques are now available for constructing comprehensive gene regulatory networks in systems biology. In this study, we report a new statistical approach for facilitating in silico inference of regulatory network structure. The new measure of association, coefficient of intrinsic dependence (CID), is model-free and can be applied to both continuous and categorical distributions. When given two variables X and Y, CID answers whether Y is dependent on X by examining the conditional distribution of Y given X. In this paper, we apply CID to analyze the regulatory relationships between transcription factors (TFs) (X) and their downstream genes (Y) based on clinical data. More specifically, we use estrogen receptor α (ERα) as the variable X, and the analyses are based on 48 clinical breast cancer gene expression arrays (48A). Results The analytical utility of CID was evaluated in comparison with four commonly used statistical methods, Galton-Pearson's correlation coefficient (GPCC), Student's t-test (STT), coefficient of determination (CoD), and mutual information (MI). When being compared to GPCC, CoD, and MI, CID reveals its preferential ability to discover the regulatory association where distribution of the mRNA expression levels on X and Y does not fit linear models. On the other hand, when CID is used to measure the association of a continuous variable (Y) against a discrete variable (X), it shows similar performance as compared to STT, and appears to outperform CoD and MI. In addition, this study established a two-layer transcriptional regulatory network to exemplify the usage of CID, in combination with GPCC, in deciphering gene networks based on gene expression profiles from patient arrays. Conclusion CID is shown to provide useful information for identifying associations between genes and transcription factors of interest in patient arrays. When coupled with the relationships detected by GPCC, the association

  18. The development of hub architecture in the human functional brain network.

    PubMed

    Hwang, Kai; Hallquist, Michael N; Luna, Beatriz

    2013-10-01

    Functional hubs are brain regions that play a crucial role in facilitating communication among parallel, distributed brain networks. The developmental emergence and stability of hubs, however, is not well understood. The current study used measures of network topology drawn from graph theory to investigate the development of functional hubs in 99 participants, 10-20 years of age. We found that hub architecture was evident in late childhood and was stable from adolescence to early adulthood. Connectivity between hub and non-hub ("spoke") regions, however, changed with development. From childhood to adolescence, the strength of connections between frontal hubs and cortical and subcortical spoke regions increased. From adolescence to adulthood, hub-spoke connections with frontal hubs were stable, whereas connectivity between cerebellar hubs and cortical spoke regions increased. Our findings suggest that a developmentally stable functional hub architecture provides the foundation of information flow in the brain, whereas connections between hubs and spokes continue to develop, possibly supporting mature cognitive function.

  19. Reconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis

    PubMed Central

    Chauhan, Rinki; Ravi, Janani; Datta, Pratik; Chen, Tianlong; Schnappinger, Dirk; Bassler, Kevin E.; Balázsi, Gábor; Gennaro, Maria Laura

    2016-01-01

    Accessory sigma factors, which reprogram RNA polymerase to transcribe specific gene sets, activate bacterial adaptive responses to noxious environments. Here we reconstruct the complete sigma factor regulatory network of the human pathogen Mycobacterium tuberculosis by an integrated approach. The approach combines identification of direct regulatory interactions between M. tuberculosis sigma factors in an E. coli model system, validation of selected links in M. tuberculosis, and extensive literature review. The resulting network comprises 41 direct interactions among all 13 sigma factors. Analysis of network topology reveals (i) a three-tiered hierarchy initiating at master regulators, (ii) high connectivity and (iii) distinct communities containing multiple sigma factors. These topological features are likely associated with multi-layer signal processing and specialized stress responses involving multiple sigma factors. Moreover, the identification of overrepresented network motifs, such as autoregulation and coregulation of sigma and anti-sigma factor pairs, provides structural information that is relevant for studies of network dynamics. PMID:27029515

  20. A Predictive Model of the Oxygen and Heme Regulatory Network in Yeast

    PubMed Central

    Kundaje, Anshul; Xin, Xiantong; Lan, Changgui; Lianoglou, Steve; Zhou, Mei; Zhang, Li; Leslie, Christina

    2008-01-01

    Deciphering gene regulatory mechanisms through the analysis of high-throughput expression data is a challenging computational problem. Previous computational studies have used large expression datasets in order to resolve fine patterns of coexpression, producing clusters or modules of potentially coregulated genes. These methods typically examine promoter sequence information, such as DNA motifs or transcription factor occupancy data, in a separate step after clustering. We needed an alternative and more integrative approach to study the oxygen regulatory network in Saccharomyces cerevisiae using a small dataset of perturbation experiments. Mechanisms of oxygen sensing and regulation underlie many physiological and pathological processes, and only a handful of oxygen regulators have been identified in previous studies. We used a new machine learning algorithm called MEDUSA to uncover detailed information about the oxygen regulatory network using genome-wide expression changes in response to perturbations in the levels of oxygen, heme, Hap1, and Co2+. MEDUSA integrates mRNA expression, promoter sequence, and ChIP-chip occupancy data to learn a model that accurately predicts the differential expression of target genes in held-out data. We used a novel margin-based score to extract significant condition-specific regulators and assemble a global map of the oxygen sensing and regulatory network. This network includes both known oxygen and heme regulators, such as Hap1, Mga2, Hap4, and Upc2, as well as many new candidate regulators. MEDUSA also identified many DNA motifs that are consistent with previous experimentally identified transcription factor binding sites. Because MEDUSA's regulatory program associates regulators to target genes through their promoter sequences, we directly tested the predicted regulators for OLE1, a gene specifically induced under hypoxia, by experimental analysis of the activity of its promoter. In each case, deletion of the candidate

  1. Regulatory Compliance in Multi-Tier Supplier Networks

    NASA Technical Reports Server (NTRS)

    Goossen, Emray R.; Buster, Duke A.

    2014-01-01

    Over the years, avionics systems have increased in complexity to the point where 1st tier suppliers to an aircraft OEM find it financially beneficial to outsource designs of subsystems to 2nd tier and at times to 3rd tier suppliers. Combined with challenging schedule and budgetary pressures, the environment in which safety-critical systems are being developed introduces new hurdles for regulatory agencies and industry. This new environment of both complex systems and tiered development has raised concerns in the ability of the designers to ensure safety considerations are fully addressed throughout the tier levels. This has also raised questions about the sufficiency of current regulatory guidance to ensure: proper flow down of safety awareness, avionics application understanding at the lower tiers, OEM and 1st tier oversight practices, and capabilities of lower tier suppliers. Therefore, NASA established a research project to address Regulatory Compliance in a Multi-tier Supplier Network. This research was divided into three major study efforts: 1. Describe Modern Multi-tier Avionics Development 2. Identify Current Issues in Achieving Safety and Regulatory Compliance 3. Short-term/Long-term Recommendations Toward Higher Assurance Confidence This report presents our findings of the risks, weaknesses, and our recommendations. It also includes a collection of industry-identified risks, an assessment of guideline weaknesses related to multi-tier development of complex avionics systems, and a postulation of potential modifications to guidelines to close the identified risks and weaknesses.

  2. A Novel Approach to Noise-Filtering Based on a Gain-Scheduling Neural Network Architecture

    NASA Technical Reports Server (NTRS)

    Troudet, T.; Merrill, W.

    1994-01-01

    A gain-scheduling neural network architecture is proposed to enhance the noise-filtering efficiency of feedforward neural networks, in terms of both nominal performance and robustness. The synergistic benefits of the proposed architecture are demonstrated and discussed in the context of the noise-filtering of signals that are typically encountered in aerospace control systems. The synthesis of such a gain-scheduled neurofiltering provides the robustness of linear filtering, while preserving the nominal performance advantage of conventional nonlinear neurofiltering. Quantitative performance and robustness evaluations are provided for the signal processing of pitch rate responses to typical pilot command inputs for a modern fighter aircraft model.

  3. Information theory in systems biology. Part I: Gene regulatory and metabolic networks.

    PubMed

    Mousavian, Zaynab; Kavousi, Kaveh; Masoudi-Nejad, Ali

    2016-03-01

    "A Mathematical Theory of Communication", was published in 1948 by Claude Shannon to establish a framework that is now known as information theory. In recent decades, information theory has gained much attention in the area of systems biology. The aim of this paper is to provide a systematic review of those contributions that have applied information theory in inferring or understanding of biological systems. Based on the type of system components and the interactions between them, we classify the biological systems into 4 main classes: gene regulatory, metabolic, protein-protein interaction and signaling networks. In the first part of this review, we attempt to introduce most of the existing studies on two types of biological networks, including gene regulatory and metabolic networks, which are founded on the concepts of information theory. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. PyPanda: a Python package for gene regulatory network reconstruction

    PubMed Central

    van IJzendoorn, David G.P.; Glass, Kimberly; Quackenbush, John; Kuijjer, Marieke L.

    2016-01-01

    Summary: PANDA (Passing Attributes between Networks for Data Assimilation) is a gene regulatory network inference method that uses message-passing to integrate multiple sources of ‘omics data. PANDA was originally coded in C ++. In this application note we describe PyPanda, the Python version of PANDA. PyPanda runs considerably faster than the C ++ version and includes additional features for network analysis. Availability and implementation: The open source PyPanda Python package is freely available at http://github.com/davidvi/pypanda. Contact: mkuijjer@jimmy.harvard.edu or d.g.p.van_ijzendoorn@lumc.nl PMID:27402905

  5. PyPanda: a Python package for gene regulatory network reconstruction.

    PubMed

    van IJzendoorn, David G P; Glass, Kimberly; Quackenbush, John; Kuijjer, Marieke L

    2016-11-01

    PANDA (Passing Attributes between Networks for Data Assimilation) is a gene regulatory network inference method that uses message-passing to integrate multiple sources of 'omics data. PANDA was originally coded in C ++. In this application note we describe PyPanda, the Python version of PANDA. PyPanda runs considerably faster than the C ++ version and includes additional features for network analysis. The open source PyPanda Python package is freely available at http://github.com/davidvi/pypanda CONTACT: mkuijjer@jimmy.harvard.edu or d.g.p.van_ijzendoorn@lumc.nl. © The Author 2016. Published by Oxford University Press.

  6. Prophetic Granger Causality to infer gene regulatory networks.

    PubMed

    Carlin, Daniel E; Paull, Evan O; Graim, Kiley; Wong, Christopher K; Bivol, Adrian; Ryabinin, Peter; Ellrott, Kyle; Sokolov, Artem; Stuart, Joshua M

    2017-01-01

    We introduce a novel method called Prophetic Granger Causality (PGC) for inferring gene regulatory networks (GRNs) from protein-level time series data. The method uses an L1-penalized regression adaptation of Granger Causality to model protein levels as a function of time, stimuli, and other perturbations. When combined with a data-independent network prior, the framework outperformed all other methods submitted to the HPN-DREAM 8 breast cancer network inference challenge. Our investigations reveal that PGC provides complementary information to other approaches, raising the performance of ensemble learners, while on its own achieves moderate performance. Thus, PGC serves as a valuable new tool in the bioinformatics toolkit for analyzing temporal datasets. We investigate the general and cell-specific interactions predicted by our method and find several novel interactions, demonstrating the utility of the approach in charting new tumor wiring.

  7. Prophetic Granger Causality to infer gene regulatory networks

    PubMed Central

    Carlin, Daniel E.; Paull, Evan O.; Graim, Kiley; Wong, Christopher K.; Bivol, Adrian; Ryabinin, Peter; Ellrott, Kyle; Sokolov, Artem

    2017-01-01

    We introduce a novel method called Prophetic Granger Causality (PGC) for inferring gene regulatory networks (GRNs) from protein-level time series data. The method uses an L1-penalized regression adaptation of Granger Causality to model protein levels as a function of time, stimuli, and other perturbations. When combined with a data-independent network prior, the framework outperformed all other methods submitted to the HPN-DREAM 8 breast cancer network inference challenge. Our investigations reveal that PGC provides complementary information to other approaches, raising the performance of ensemble learners, while on its own achieves moderate performance. Thus, PGC serves as a valuable new tool in the bioinformatics toolkit for analyzing temporal datasets. We investigate the general and cell-specific interactions predicted by our method and find several novel interactions, demonstrating the utility of the approach in charting new tumor wiring. PMID:29211761

  8. SDN architecture for optical packet and circuit integrated networks

    NASA Astrophysics Data System (ADS)

    Furukawa, Hideaki; Miyazawa, Takaya

    2016-02-01

    We have been developing an optical packet and circuit integrated (OPCI) network, which realizes dynamic optical path, high-density packet multiplexing, and flexible wavelength resource allocation. In the OPCI networks, a best-effort service and a QoS-guaranteed service are provided by employing optical packet switching (OPS) and optical circuit switching (OCS) respectively, and users can select these services. Different wavelength resources are assigned for OPS and OCS links, and the amount of their wavelength resources are dynamically changed in accordance with the service usage conditions. To apply OPCI networks into wide-area (core/metro) networks, we have developed an OPCI node with a distributed control mechanism. Moreover, our OPCI node works with a centralized control mechanism as well as a distributed one. It is therefore possible to realize SDN-based OPCI networks, where resource requests and a centralized configuration are carried out. In this paper, we show our SDN architecture for an OPS system that configures mapping tables between IP addresses and optical packet addresses and switching tables according to the requests from multiple users via a web interface. While OpenFlow-based centralized control protocol is coming into widespread use especially for single-administrative, small-area (LAN/data-center) networks. Here, we also show an interworking mechanism between OpenFlow-based networks (OFNs) and the OPCI network for constructing a wide-area network, and a control method of wavelength resource selection to automatically transfer diversified flows from OFNs to the OPCI network.

  9. Regulatory network involving miRNAs and genes in serous ovarian carcinoma

    PubMed Central

    Zhao, Haiyan; Xu, Hao; Xue, Luchen

    2017-01-01

    Serous ovarian carcinoma (SOC) is one of the most life-threatening types of gynecological malignancy, but the pathogenesis of SOC remains unknown. Previous studies have indicated that differentially expressed genes and microRNAs (miRNAs) serve important functions in SOC. However, genes and miRNAs are identified in a disperse form, and limited information is known about the regulatory association between miRNAs and genes in SOC. In the present study, three regulatory networks were hierarchically constructed, including a differentially-expressed network, a related network and a global network to reveal associations between each factor. In each network, there were three types of factors, which were genes, miRNAs and transcription factors that interact with each other. Focus was placed on the differentially-expressed network, in which all genes and miRNAs were differentially expressed and therefore may have affected the development of SOC. Following the comparison and analysis between the three networks, a number of signaling pathways which demonstrated differentially expressed elements were highlighted. Subsequently, the upstream and downstream elements of differentially expressed miRNAs and genes were listed, and a number of key elements (differentially expressed miRNAs, genes and TFs predicted using the P-match method) were analyzed. The differentially expressed network partially illuminated the pathogenesis of SOC. It was hypothesized that if there was no differential expression of miRNAs and genes, SOC may be prevented and treatment may be identified. The present study provided a theoretical foundation for gene therapy for SOC. PMID:29113276

  10. Construction of Gene Regulatory Networks Using Recurrent Neural Networks and Swarm Intelligence.

    PubMed

    Khan, Abhinandan; Mandal, Sudip; Pal, Rajat Kumar; Saha, Goutam

    2016-01-01

    We have proposed a methodology for the reverse engineering of biologically plausible gene regulatory networks from temporal genetic expression data. We have used established information and the fundamental mathematical theory for this purpose. We have employed the Recurrent Neural Network formalism to extract the underlying dynamics present in the time series expression data accurately. We have introduced a new hybrid swarm intelligence framework for the accurate training of the model parameters. The proposed methodology has been first applied to a small artificial network, and the results obtained suggest that it can produce the best results available in the contemporary literature, to the best of our knowledge. Subsequently, we have implemented our proposed framework on experimental (in vivo) datasets. Finally, we have investigated two medium sized genetic networks (in silico) extracted from GeneNetWeaver, to understand how the proposed algorithm scales up with network size. Additionally, we have implemented our proposed algorithm with half the number of time points. The results indicate that a reduction of 50% in the number of time points does not have an effect on the accuracy of the proposed methodology significantly, with a maximum of just over 15% deterioration in the worst case.

  11. Convolutional neural networks for event-related potential detection: impact of the architecture.

    PubMed

    Cecotti, H

    2017-07-01

    The detection of brain responses at the single-trial level in the electroencephalogram (EEG) such as event-related potentials (ERPs) is a difficult problem that requires different processing steps to extract relevant discriminant features. While most of the signal and classification techniques for the detection of brain responses are based on linear algebra, different pattern recognition techniques such as convolutional neural network (CNN), as a type of deep learning technique, have shown some interests as they are able to process the signal after limited pre-processing. In this study, we propose to investigate the performance of CNNs in relation of their architecture and in relation to how they are evaluated: a single system for each subject, or a system for all the subjects. More particularly, we want to address the change of performance that can be observed between specifying a neural network to a subject, or by considering a neural network for a group of subjects, taking advantage of a larger number of trials from different subjects. The results support the conclusion that a convolutional neural network trained on different subjects can lead to an AUC above 0.9 by using an appropriate architecture using spatial filtering and shift invariant layers.

  12. Standard Spacecraft Interfaces and IP Network Architectures: Prototyping Activities at the GSFC

    NASA Technical Reports Server (NTRS)

    Schnurr, Richard; Marquart, Jane; Lin, Michael

    2003-01-01

    Advancements in fright semiconductor technology have opened the door for IP-based networking in spacecraft architectures. The GSFC believes the same signlJicant cost savings gained using MIL-STD-1553/1773 as a standard low rate interface for spacecraft busses cun be realized for highspeed network interfaces. To that end, GSFC is developing hardware and software to support a seamless, space mission IP network based on Ethernet and MIL-STD-1553. The Ethernet network shall connect all fright computers and communications systems using interface standards defined by the CCSDS Standard Onboard InterFace (SOIF) Panel. This paper shall discuss the prototyping effort underway at GSFC and expected results.

  13. Detecting phenotype-driven transitions in regulatory network structure.

    PubMed

    Padi, Megha; Quackenbush, John

    2018-01-01

    Complex traits and diseases like human height or cancer are often not caused by a single mutation or genetic variant, but instead arise from functional changes in the underlying molecular network. Biological networks are known to be highly modular and contain dense "communities" of genes that carry out cellular processes, but these structures change between tissues, during development, and in disease. While many methods exist for inferring networks and analyzing their topologies separately, there is a lack of robust methods for quantifying differences in network structure. Here, we describe ALPACA (ALtered Partitions Across Community Architectures), a method for comparing two genome-scale networks derived from different phenotypic states to identify condition-specific modules. In simulations, ALPACA leads to more nuanced, sensitive, and robust module discovery than currently available network comparison methods. As an application, we use ALPACA to compare transcriptional networks in three contexts: angiogenic and non-angiogenic subtypes of ovarian cancer, human fibroblasts expressing transforming viral oncogenes, and sexual dimorphism in human breast tissue. In each case, ALPACA identifies modules enriched for processes relevant to the phenotype. For example, modules specific to angiogenic ovarian tumors are enriched for genes associated with blood vessel development, and modules found in female breast tissue are enriched for genes involved in estrogen receptor and ERK signaling. The functional relevance of these new modules suggests that not only can ALPACA identify structural changes in complex networks, but also that these changes may be relevant for characterizing biological phenotypes.

  14. On the role of sparseness in the evolution of modularity in gene regulatory networks

    PubMed Central

    2018-01-01

    Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases. PMID:29775459

  15. On the role of sparseness in the evolution of modularity in gene regulatory networks.

    PubMed

    Espinosa-Soto, Carlos

    2018-05-01

    Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases.

  16. Jimena: efficient computing and system state identification for genetic regulatory networks.

    PubMed

    Karl, Stefan; Dandekar, Thomas

    2013-10-11

    Boolean networks capture switching behavior of many naturally occurring regulatory networks. For semi-quantitative modeling, interpolation between ON and OFF states is necessary. The high degree polynomial interpolation of Boolean genetic regulatory networks (GRNs) in cellular processes such as apoptosis or proliferation allows for the modeling of a wider range of node interactions than continuous activator-inhibitor models, but suffers from scaling problems for networks which contain nodes with more than ~10 inputs. Many GRNs from literature or new gene expression experiments exceed those limitations and a new approach was developed. (i) As a part of our new GRN simulation framework Jimena we introduce and setup Boolean-tree-based data structures; (ii) corresponding algorithms greatly expedite the calculation of the polynomial interpolation in almost all cases, thereby expanding the range of networks which can be simulated by this model in reasonable time. (iii) Stable states for discrete models are efficiently counted and identified using binary decision diagrams. As application example, we show how system states can now be sampled efficiently in small up to large scale hormone disease networks (Arabidopsis thaliana development and immunity, pathogen Pseudomonas syringae and modulation by cytokinins and plant hormones). Jimena simulates currently available GRNs about 10-100 times faster than the previous implementation of the polynomial interpolation model and even greater gains are achieved for large scale-free networks. This speed-up also facilitates a much more thorough sampling of continuous state spaces which may lead to the identification of new stable states. Mutants of large networks can be constructed and analyzed very quickly enabling new insights into network robustness and behavior.

  17. Teledesic Global Wireless Broadband Network: Space Infrastructure Architecture, Design Features and Technologies

    NASA Technical Reports Server (NTRS)

    Stuart, James R.

    1995-01-01

    The Teledesic satellites are a new class of small satellites which demonstrate the important commercial benefits of using technologies developed for other purposes by U.S. National Laboratories. The Teledesic satellite architecture, subsystem design features, and new technologies are described. The new Teledesic satellite manufacturing, integration, and test approaches which use modern high volume production techniques and result in surprisingly low space segment costs are discussed. The constellation control and management features and attendant software architecture features are addressed. After briefly discussing the economic and technological impact on the USA commercial space industries of the space communications revolution and such large constellation projects, the paper concludes with observations on the trend toward future system architectures using networked groups of much smaller satellites.

  18. Function, dynamics and evolution of network motif modules in integrated gene regulatory networks of worm and plant.

    PubMed

    Defoort, Jonas; Van de Peer, Yves; Vermeirssen, Vanessa

    2018-06-05

    Gene regulatory networks (GRNs) consist of different molecular interactions that closely work together to establish proper gene expression in time and space. Especially in higher eukaryotes, many questions remain on how these interactions collectively coordinate gene regulation. We study high quality GRNs consisting of undirected protein-protein, genetic and homologous interactions, and directed protein-DNA, regulatory and miRNA-mRNA interactions in the worm Caenorhabditis elegans and the plant Arabidopsis thaliana. Our data-integration framework integrates interactions in composite network motifs, clusters these in biologically relevant, higher-order topological network motif modules, overlays these with gene expression profiles and discovers novel connections between modules and regulators. Similar modules exist in the integrated GRNs of worm and plant. We show how experimental or computational methodologies underlying a certain data type impact network topology. Through phylogenetic decomposition, we found that proteins of worm and plant tend to functionally interact with proteins of a similar age, while at the regulatory level TFs favor same age, but also older target genes. Despite some influence of the duplication mode difference, we also observe at the motif and module level for both species a preference for age homogeneity for undirected and age heterogeneity for directed interactions. This leads to a model where novel genes are added together to the GRNs in a specific biological functional context, regulated by one or more TFs that also target older genes in the GRNs. Overall, we detected topological, functional and evolutionary properties of GRNs that are potentially universal in all species.

  19. Integration of Steady-State and Temporal Gene Expression Data for the Inference of Gene Regulatory Networks

    PubMed Central

    Wang, Yi Kan; Hurley, Daniel G.; Schnell, Santiago; Print, Cristin G.; Crampin, Edmund J.

    2013-01-01

    We develop a new regression algorithm, cMIKANA, for inference of gene regulatory networks from combinations of steady-state and time-series gene expression data. Using simulated gene expression datasets to assess the accuracy of reconstructing gene regulatory networks, we show that steady-state and time-series data sets can successfully be combined to identify gene regulatory interactions using the new algorithm. Inferring gene networks from combined data sets was found to be advantageous when using noisy measurements collected with either lower sampling rates or a limited number of experimental replicates. We illustrate our method by applying it to a microarray gene expression dataset from human umbilical vein endothelial cells (HUVECs) which combines time series data from treatment with growth factor TNF and steady state data from siRNA knockdown treatments. Our results suggest that the combination of steady-state and time-series datasets may provide better prediction of RNA-to-RNA interactions, and may also reveal biological features that cannot be identified from dynamic or steady state information alone. Finally, we consider the experimental design of genomics experiments for gene regulatory network inference and show that network inference can be improved by incorporating steady-state measurements with time-series data. PMID:23967277

  20. SANDS: A Service-Oriented Architecture for Clinical Decision Support in a National Health Information Network

    PubMed Central

    Wright, Adam; Sittig, Dean F.

    2008-01-01

    In this paper we describe and evaluate a new distributed architecture for clinical decision support called SANDS (Service-oriented Architecture for NHIN Decision Support), which leverages current health information exchange efforts and is based on the principles of a service-oriented architecture. The architecture allows disparate clinical information systems and clinical decision support systems to be seamlessly integrated over a network according to a set of interfaces and protocols described in this paper. The architecture described is fully defined and developed, and six use cases have been developed and tested using a prototype electronic health record which links to one of the existing prototype National Health Information Networks (NHIN): drug interaction checking, syndromic surveillance, diagnostic decision support, inappropriate prescribing in older adults, information at the point of care and a simple personal health record. Some of these use cases utilize existing decision support systems, which are either commercially or freely available at present, and developed outside of the SANDS project, while other use cases are based on decision support systems developed specifically for the project. Open source code for many of these components is available, and an open source reference parser is also available for comparison and testing of other clinical information systems and clinical decision support systems that wish to implement the SANDS architecture. PMID:18434256

  1. Extended evolution: A conceptual framework for integrating regulatory networks and niche construction

    PubMed Central

    Renn, Jürgen

    2015-01-01

    ABSTRACT This paper introduces a conceptual framework for the evolution of complex systems based on the integration of regulatory network and niche construction theories. It is designed to apply equally to cases of biological, social and cultural evolution. Within the conceptual framework we focus especially on the transformation of complex networks through the linked processes of externalization and internalization of causal factors between regulatory networks and their corresponding niches and argue that these are an important part of evolutionary explanations. This conceptual framework extends previous evolutionary models and focuses on several challenges, such as the path‐dependent nature of evolutionary change, the dynamics of evolutionary innovation and the expansion of inheritance systems. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 565–577, 2015. © 2015 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution published by Wiley Periodicals, Inc. PMID:26097188

  2. Engineering tough, highly compressible, biodegradable hydrogels by tuning the network architecture.

    PubMed

    Gu, Dunyin; Tan, Shereen; Xu, Chenglong; O'Connor, Andrea J; Qiao, Greg G

    2017-06-20

    By precisely tuning the network architecture, tough, highly compressible hydrogels were engineered. The hydrogels were made by interconnecting high-functionality hydrophobic domains through linear tri-block chains, consisting of soft hydrophilic middle blocks, flanked with flexible hydrophobic blocks. In showing their applicability, the efficient encapsulation and prolonged release of hydrophobic drugs were achieved.

  3. Effective Utilization of Resources and Infrastructure for a Spaceport Network Architecture

    NASA Technical Reports Server (NTRS)

    Gill, Tracy; Larson, Wiley; Mueller, Robert; Roberson, Luke

    2012-01-01

    Providing routine, affordable access to a variety of orbital and deep space destinations requires an intricate network of ground, planetary surface, and space-based spaceports like those on Earth (land and sea), in various Earth orbits, and on other extraterrestrial surfaces. Advancements in technology and international collaboration are critical to establish a spaceport network that satisfies the requirements for private and government research, exploration, and commercial objectives. Technologies, interfaces, assembly techniques, and protocols must be adapted to enable mission critical capabilities and interoperability throughout the spaceport network. The conceptual space mission architecture must address the full range of required spaceport services, from managing propellants for a variety of spacecraft to governance structure. In order to accomplish affordability and sustainability goals, the network architecture must consider deriving propellants from in situ planetary resources to the maximum extent possible. Water on the Moon and Mars, Mars' atmospheric CO2, and O2 extracted from lunar regolith are examples of in situ resources that could be used to generate propellants for various spacecraft, orbital stages and trajectories, and the commodities to support habitation and human operations at these destinations. The ability to use in-space fuel depots containing in situ derived propellants would drastically reduce the mass required to launch long-duration or deep space missions from Earth's gravity well. Advances in transformative technologies and common capabilities, interfaces, umbilicals, commodities, protocols, and agreements will facilitate a cost-effective, safe, reliable infrastructure for a versatile network of Earth- and extraterrestrial spaceports. Defining a common infrastructure on Earth, planetary surfaces, and in space, as well as deriving propellants from in situ planetary resources to construct in-space propellant depots to serve the spaceport

  4. Chaotic Motifs in Gene Regulatory Networks

    PubMed Central

    Zhang, Zhaoyang; Ye, Weiming; Qian, Yu; Zheng, Zhigang; Huang, Xuhui; Hu, Gang

    2012-01-01

    Chaos should occur often in gene regulatory networks (GRNs) which have been widely described by nonlinear coupled ordinary differential equations, if their dimensions are no less than 3. It is therefore puzzling that chaos has never been reported in GRNs in nature and is also extremely rare in models of GRNs. On the other hand, the topic of motifs has attracted great attention in studying biological networks, and network motifs are suggested to be elementary building blocks that carry out some key functions in the network. In this paper, chaotic motifs (subnetworks with chaos) in GRNs are systematically investigated. The conclusion is that: (i) chaos can only appear through competitions between different oscillatory modes with rivaling intensities. Conditions required for chaotic GRNs are found to be very strict, which make chaotic GRNs extremely rare. (ii) Chaotic motifs are explored as the simplest few-node structures capable of producing chaos, and serve as the intrinsic source of chaos of random few-node GRNs. Several optimal motifs causing chaos with atypically high probability are figured out. (iii) Moreover, we discovered that a number of special oscillators can never produce chaos. These structures bring some advantages on rhythmic functions and may help us understand the robustness of diverse biological rhythms. (iv) The methods of dominant phase-advanced driving (DPAD) and DPAD time fraction are proposed to quantitatively identify chaotic motifs and to explain the origin of chaotic behaviors in GRNs. PMID:22792171

  5. Compartmentalized gene regulatory network of the pathogenic fungus Fusarium graminearum

    USDA-ARS?s Scientific Manuscript database

    Head blight caused by Fusarium graminearum (Fg) is a major limiting factor of wheat production with both yield loss and mycotoxin contamination. Here we report a model for global Fg gene regulatory networks (GRNs) inferred from a large collection of transcriptomic data using a machine-learning appro...

  6. Phenotypic stability and plasticity in GMP-derived cells as determined by their underlying regulatory network.

    PubMed

    Ramírez, Carlos; Mendoza, Luis

    2018-04-01

    Blood cell formation has been recognized as a suitable system to study celular differentiation mainly because of its experimental accessibility, and because it shows characteristics such as hierarchical and gradual bifurcated patterns of commitment, which are present in several developmental processes. Although hematopoiesis has been extensively studied and there is a wealth of molecular and cellular data about it, it is not clear how the underlying molecular regulatory networks define or restrict cellular differentiation processes. Here, we infer the molecular regulatory network that controls the differentiation of a blood cell subpopulation derived from the granulocyte-monocyte precursor (GMP), comprising monocytes, neutrophils, eosinophils, basophils and mast cells. We integrate published qualitative experimental data into a model to describe temporal expression patterns observed in GMP-derived cells. The model is implemented as a Boolean network, and its dynamical behavior is studied. Steady states of the network can be clearly identified with the expression profiles of monocytes, mast cells, neutrophils, basophils, and eosinophils, under wild-type and mutant backgrounds. All scripts are publicly available at https://github.com/caramirezal/RegulatoryNetworkGMPModel. lmendoza@biomedicas.unam.mx. Supplementary data are available at Bioinformatics online.

  7. On-Board Fiber-Optic Network Architectures for Radar and Avionics Signal Distribution

    NASA Technical Reports Server (NTRS)

    Alam, Mohammad F.; Atiquzzaman, Mohammed; Duncan, Bradley B.; Nguyen, Hung; Kunath, Richard

    2000-01-01

    Continued progress in both civil and military avionics applications is overstressing the capabilities of existing radio-frequency (RF) communication networks based on coaxial cables on board modem aircrafts. Future avionics systems will require high-bandwidth on- board communication links that are lightweight, immune to electromagnetic interference, and highly reliable. Fiber optic communication technology can meet all these challenges in a cost-effective manner. Recently, digital fiber-optic communication systems, where a fiber-optic network acts like a local area network (LAN) for digital data communications, have become a topic of extensive research and development. Although a fiber-optic system can be designed to transport radio-frequency (RF) signals, the digital fiber-optic systems under development today are not capable of transporting microwave and millimeter-wave RF signals used in radar and avionics systems on board an aircraft. Recent advances in fiber optic technology, especially wavelength division multiplexing (WDM), has opened a number of possibilities for designing on-board fiber optic networks, including all-optical networks for radar and avionics RF signal distribution. In this paper, we investigate a number of different novel approaches for fiber-optic transmission of on-board VHF and UHF RF signals using commercial off-the-shelf (COTS) components. The relative merits and demerits of each architecture are discussed, and the suitability of each architecture for particular applications is pointed out. All-optical approaches show better performance than other traditional approaches in terms of signal-to-noise ratio, power consumption, and weight requirements.

  8. Low-Power Direct-Sequence Spread-Spectrum Modem Architecture for Distributed Wireless Sensor Networks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chien, C; Elgorriaga, I; McConaghy, C

    2001-07-03

    Emerging CMOS and MEMS technologies enable the implementation of a large number of wireless distributed microsensors that can be easily and rapidly deployed to form highly redundant, self-configuring, and ad hoc sensor networks. To facilitate ease of deployment, these sensors should operate on battery for extended periods of time. A particular challenge in maintaining extended battery lifetime lies in achieving communications with low power. This paper presents a direct-sequence spread-spectrum modem architecture that provides robust communications for wireless sensor networks while dissipating very low power. The modem architecture has been verified in an FPGA implementation that dissipates only 33 mWmore » for both transmission and reception. The implementation can be easily mapped to an ASIC technology, with an estimated power performance of less than 1 mW.« less

  9. The Evaluation of Rekeying Protocols Within the Hubenko Architecture as Applied to Wireless Sensor Networks

    DTIC Science & Technology

    2009-03-01

    SENSOR NETWORKS THESIS Presented to the Faculty Department of Electrical and Computer Engineering Graduate School of Engineering and...hierarchical, and Secure Lock within a wireless sensor network (WSN) under the Hubenko architecture. Using a Matlab computer simulation, the impact of the...rekeying protocol should be applied given particular network parameters, such as WSN size. 10 1.3 Experimental Approach A computer simulation in

  10. Reconstructing blood stem cell regulatory network models from single-cell molecular profiles

    PubMed Central

    Hamey, Fiona K.; Nestorowa, Sonia; Kinston, Sarah J.; Kent, David G.; Wilson, Nicola K.

    2017-01-01

    Adult blood contains a mixture of mature cell types, each with specialized functions. Single hematopoietic stem cells (HSCs) have been functionally shown to generate all mature cell types for the lifetime of the organism. Differentiation of HSCs toward alternative lineages must be balanced at the population level by the fate decisions made by individual cells. Transcription factors play a key role in regulating these decisions and operate within organized regulatory programs that can be modeled as transcriptional regulatory networks. As dysregulation of single HSC fate decisions is linked to fatal malignancies such as leukemia, it is important to understand how these decisions are controlled on a cell-by-cell basis. Here we developed and applied a network inference method, exploiting the ability to infer dynamic information from single-cell snapshot expression data based on expression profiles of 48 genes in 2,167 blood stem and progenitor cells. This approach allowed us to infer transcriptional regulatory network models that recapitulated differentiation of HSCs into progenitor cell types, focusing on trajectories toward megakaryocyte–erythrocyte progenitors and lymphoid-primed multipotent progenitors. By comparing these two models, we identified and subsequently experimentally validated a difference in the regulation of nuclear factor, erythroid 2 (Nfe2) and core-binding factor, runt domain, alpha subunit 2, translocated to, 3 homolog (Cbfa2t3h) by the transcription factor Gata2. Our approach confirms known aspects of hematopoiesis, provides hypotheses about regulation of HSC differentiation, and is widely applicable to other hierarchical biological systems to uncover regulatory relationships. PMID:28584094

  11. Genetic Regulatory Networks in Embryogenesis and Evolution

    NASA Technical Reports Server (NTRS)

    1998-01-01

    The article introduces a series of papers that were originally presented at a workshop titled Genetic Regulatory Network in Embryogenesis and Evaluation. Contents include the following: evolution of cleavage programs in relationship to axial specification and body plan evolution, changes in cell lineage specification elucidate evolutionary relations in spiralia, axial patterning in the leech: developmental mechanisms and evolutionary implications, hox genes in arthropod development and evolution, heterochronic genes in development and evolution, a common theme for LIM homeobox gene function across phylogeny, and mechanisms of specification in ascidian embryos.

  12. Scalable Architecture for Federated Translational Inquiries Network (SAFTINet) Technology Infrastructure for a Distributed Data Network.

    PubMed

    Schilling, Lisa M; Kwan, Bethany M; Drolshagen, Charles T; Hosokawa, Patrick W; Brandt, Elias; Pace, Wilson D; Uhrich, Christopher; Kamerick, Michael; Bunting, Aidan; Payne, Philip R O; Stephens, William E; George, Joseph M; Vance, Mark; Giacomini, Kelli; Braddy, Jason; Green, Mika K; Kahn, Michael G

    2013-01-01

    Distributed Data Networks (DDNs) offer infrastructure solutions for sharing electronic health data from across disparate data sources to support comparative effectiveness research. Data sharing mechanisms must address technical and governance concerns stemming from network security and data disclosure laws and best practices, such as HIPAA. The Scalable Architecture for Federated Translational Inquiries Network (SAFTINet) deploys TRIAD grid technology, a common data model, detailed technical documentation, and custom software for data harmonization to facilitate data sharing in collaboration with stakeholders in the care of safety net populations. Data sharing partners host TRIAD grid nodes containing harmonized clinical data within their internal or hosted network environments. Authorized users can use a central web-based query system to request analytic data sets. SAFTINet DDN infrastructure achieved a number of data sharing objectives, including scalable and sustainable systems for ensuring harmonized data structures and terminologies and secure distributed queries. Initial implementation challenges were resolved through iterative discussions, development and implementation of technical documentation, governance, and technology solutions.

  13. TRACING CO-REGULATORY NETWORK DYNAMICS IN NOISY, SINGLE-CELL TRANSCRIPTOME TRAJECTORIES.

    PubMed

    Cordero, Pablo; Stuart, Joshua M

    2017-01-01

    The availability of gene expression data at the single cell level makes it possible to probe the molecular underpinnings of complex biological processes such as differentiation and oncogenesis. Promising new methods have emerged for reconstructing a progression 'trajectory' from static single-cell transcriptome measurements. However, it remains unclear how to adequately model the appreciable level of noise in these data to elucidate gene regulatory network rewiring. Here, we present a framework called Single Cell Inference of MorphIng Trajectories and their Associated Regulation (SCIMITAR) that infers progressions from static single-cell transcriptomes by employing a continuous parametrization of Gaussian mixtures in high-dimensional curves. SCIMITAR yields rich models from the data that highlight genes with expression and co-expression patterns that are associated with the inferred progression. Further, SCIMITAR extracts regulatory states from the implicated trajectory-evolvingco-expression networks. We benchmark the method on simulated data to show that it yields accurate cell ordering and gene network inferences. Applied to the interpretation of a single-cell human fetal neuron dataset, SCIMITAR finds progression-associated genes in cornerstone neural differentiation pathways missed by standard differential expression tests. Finally, by leveraging the rewiring of gene-gene co-expression relations across the progression, the method reveals the rise and fall of co-regulatory states and trajectory-dependent gene modules. These analyses implicate new transcription factors in neural differentiation including putative co-factors for the multi-functional NFAT pathway.

  14. Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis

    PubMed Central

    Zhang, Xueming; Huang, Yongming; Yang, Zhengpeng; Zhang, Yuguo; Zhang, Weihui; Gao, Zu-hua; Xue, Dongbo

    2017-01-01

    Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including “immune response” as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma. PMID:28355233

  15. Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis.

    PubMed

    Gao, Bo; Zhang, Xueming; Huang, Yongming; Yang, Zhengpeng; Zhang, Yuguo; Zhang, Weihui; Gao, Zu-Hua; Xue, Dongbo

    2017-01-01

    Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including "immune response" as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma.

  16. Destination-directed, packet-switched architecture for a geostationary communications satellite network

    NASA Technical Reports Server (NTRS)

    Ivancic, William D.; Shalkhauser, Mary JO; Bobinsky, Eric A.; Soni, Nitin J.; Quintana, Jorge A.; Kim, Heechul; Wager, Paul; Vanderaar, Mark

    1993-01-01

    A major goal of the Digital Systems Technology Branch at the NASA Lewis Research Center is to identify and develop critical digital components and technologies that either enable new commercial missions or significantly enhance the performance, cost efficiency, and/or reliability of existing and planned space communications systems. NASA envisions a need for low-data-rate, interactive, direct-to-the-user communications services for data, voice, facsimile, and video conferencing. The network would provide enhanced very-small-aperture terminal (VSAT) communications services and be capable of handling data rates of 64 kbps through 2.048 Mbps in 64-kbps increments. Efforts have concentrated heavily on the space segment; however, the ground segment has been considered concurrently to ensure cost efficiency and realistic operational constraints. The focus of current space segment developments is a flexible, high-throughput, fault-tolerant onboard information-switching processor (ISP) for a geostationary satellite communications network. The Digital Systems Technology Branch is investigating both circuit and packet architectures for the ISP. Destination-directed, packet-switched architectures for geostationary communications satellites are addressed.

  17. Establishment of a Spaceport Network Architecture

    NASA Technical Reports Server (NTRS)

    Larson, Wiley J.; Gill, Tracy R.; Mueller, Robert P.; Brink, Jeffrey S.

    2012-01-01

    Since the beginning of the space age, the main actors in space exploration have been governmental agencies, enabling a privileged access to space, but with very restricted and rare missions. The last decade has seen the rise of space tourism, and the founding of ambitious private space mining companies, showing the beginnings of a new exploration era, that is based on a more generalized and regular access to space and which is not limited to the Earth's vicinity. However, the cost of launching sufficient mass into orbit to sustain these inspiring challenges is prohibitive, and the necessary infrastructures to support these missions is still lacking. To provide easy and affordable access into orbital and deep space destinations, there is the need to create a network of spaceports via specific waypoint locations coupled with the use of natural resources, or In Situ Resource Utilization (ISRU), to provide a more economical solution. As part of the International Space University Space Studies Program 2012, the international and intercultural team of Operations and Service Infrastructure for Space (OASIS) proposes an interdisciplinary answer to the problem of economical space access and transportation. This paper presents a summary of a detailed report [1] of the different phases of a project for developing a network of spaceports throughout the Solar System in a timeframe of 50 years. The requirements, functions, critical technologies and mission architecture of this network of spaceports are outlined in a roadmap of the important steps and phases. The economic and financial aspects are emphasized in order to allow a sustainable development of the network in a public-private partnership via the formation of an International Spaceport Authority (ISPA). The approach includes engineering, scientific, financial, legal, policy, and societal aspects. Team OASIS intends to provide guidelines to make the development of space transportation via a spaceports logistics network

  18. Neural model of gene regulatory network: a survey on supportive meta-heuristics.

    PubMed

    Biswas, Surama; Acharyya, Sriyankar

    2016-06-01

    Gene regulatory network (GRN) is produced as a result of regulatory interactions between different genes through their coded proteins in cellular context. Having immense importance in disease detection and drug finding, GRN has been modelled through various mathematical and computational schemes and reported in survey articles. Neural and neuro-fuzzy models have been the focus of attraction in bioinformatics. Predominant use of meta-heuristic algorithms in training neural models has proved its excellence. Considering these facts, this paper is organized to survey neural modelling schemes of GRN and the efficacy of meta-heuristic algorithms towards parameter learning (i.e. weighting connections) within the model. This survey paper renders two different structure-related approaches to infer GRN which are global structure approach and substructure approach. It also describes two neural modelling schemes, such as artificial neural network/recurrent neural network based modelling and neuro-fuzzy modelling. The meta-heuristic algorithms applied so far to learn the structure and parameters of neutrally modelled GRN have been reviewed here.

  19. Post-transcriptional regulatory network of epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions

    PubMed Central

    2014-01-01

    Epithelial-to-mesenchymal transition (EMT) and its reverse process, mesenchymal-to-epithelial transition (MET), play important roles in embryogenesis, stem cell biology, and cancer progression. EMT can be regulated by many signaling pathways and regulatory transcriptional networks. Furthermore, post-transcriptional regulatory networks regulate EMT; these networks include the long non-coding RNA (lncRNA) and microRNA (miRNA) families. Specifically, the miR-200 family, miR-101, miR-506, and several lncRNAs have been found to regulate EMT. Recent studies have illustrated that several lncRNAs are overexpressed in various cancers and that they can promote tumor metastasis by inducing EMT. MiRNA controls EMT by regulating EMT transcription factors or other EMT regulators, suggesting that lncRNAs and miRNA are novel therapeutic targets for the treatment of cancer. Further efforts have shown that non-coding-mediated EMT regulation is closely associated with epigenetic regulation through promoter methylation (e.g., miR-200 or miR-506) and protein regulation (e.g., SET8 via miR-502). The formation of gene fusions has also been found to promote EMT in prostate cancer. In this review, we discuss the post-transcriptional regulatory network that is involved in EMT and MET and how targeting EMT and MET may provide effective therapeutics for human disease. PMID:24598126

  20. Integrated Regulatory and Metabolic Networks of the Marine Diatom Phaeodactylum tricornutum Predict the Response to Rising CO 2 Levels

    DOE PAGES

    Levering, Jennifer; Dupont, Christopher L.; Allen, Andrew E.; ...

    2017-02-14

    Diatoms are eukaryotic microalgae that are responsible for up to 40% of the ocean’s primary productivity. How diatoms respond to environmental perturbations such as elevated carbon concentrations in the atmosphere is currently poorly understood. We developed a transcriptional regulatory network based on various transcriptome sequencing expression libraries for different environmental responses to gain insight into the marine diatom’s metabolic and regulatory interactions and provide a comprehensive framework of responses to increasing atmospheric carbon levels. This transcriptional regulatory network was integrated with a recently published genome-scale metabolic model of Phaeodactylum tricornutum to explore the connectivity of the regulatory network and sharedmore » metabolites. The integrated regulatory and metabolic model revealed highly connected modules within carbon and nitrogen metabolism. P. tricornutum’s response to rising carbon levels was analyzed by using the recent genome-scale metabolic model with cross comparison to experimental manipulations of carbon dioxide. Using a systems biology approach, we studied the response of the marine diatom Phaeodactylum tricornutum to changing atmospheric carbon concentrations on an ocean-wide scale. By integrating an available genome-scale metabolic model and a newly developed transcriptional regulatory network inferred from transcriptome sequencing expression data, we demonstrate that carbon metabolism and nitrogen metabolism are strongly connected and the genes involved are coregulated in this model diatom. These tight regulatory constraints could play a major role during the adaptation of P. tricornutum to increasing carbon levels. The transcriptional regulatory network developed can be further used to study the effects of different environmental perturbations on P. tricornutum’s metabolism.« less

  1. Integrated Regulatory and Metabolic Networks of the Marine Diatom Phaeodactylum tricornutum Predict the Response to Rising CO 2 Levels

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Levering, Jennifer; Dupont, Christopher L.; Allen, Andrew E.

    Diatoms are eukaryotic microalgae that are responsible for up to 40% of the ocean’s primary productivity. How diatoms respond to environmental perturbations such as elevated carbon concentrations in the atmosphere is currently poorly understood. We developed a transcriptional regulatory network based on various transcriptome sequencing expression libraries for different environmental responses to gain insight into the marine diatom’s metabolic and regulatory interactions and provide a comprehensive framework of responses to increasing atmospheric carbon levels. This transcriptional regulatory network was integrated with a recently published genome-scale metabolic model of Phaeodactylum tricornutum to explore the connectivity of the regulatory network and sharedmore » metabolites. The integrated regulatory and metabolic model revealed highly connected modules within carbon and nitrogen metabolism. P. tricornutum’s response to rising carbon levels was analyzed by using the recent genome-scale metabolic model with cross comparison to experimental manipulations of carbon dioxide. Using a systems biology approach, we studied the response of the marine diatom Phaeodactylum tricornutum to changing atmospheric carbon concentrations on an ocean-wide scale. By integrating an available genome-scale metabolic model and a newly developed transcriptional regulatory network inferred from transcriptome sequencing expression data, we demonstrate that carbon metabolism and nitrogen metabolism are strongly connected and the genes involved are coregulated in this model diatom. These tight regulatory constraints could play a major role during the adaptation of P. tricornutum to increasing carbon levels. The transcriptional regulatory network developed can be further used to study the effects of different environmental perturbations on P. tricornutum’s metabolism.« less

  2. A single network adaptive critic (SNAC) architecture for optimal control synthesis for a class of nonlinear systems.

    PubMed

    Padhi, Radhakant; Unnikrishnan, Nishant; Wang, Xiaohua; Balakrishnan, S N

    2006-12-01

    Even though dynamic programming offers an optimal control solution in a state feedback form, the method is overwhelmed by computational and storage requirements. Approximate dynamic programming implemented with an Adaptive Critic (AC) neural network structure has evolved as a powerful alternative technique that obviates the need for excessive computations and storage requirements in solving optimal control problems. In this paper, an improvement to the AC architecture, called the "Single Network Adaptive Critic (SNAC)" is presented. This approach is applicable to a wide class of nonlinear systems where the optimal control (stationary) equation can be explicitly expressed in terms of the state and costate variables. The selection of this terminology is guided by the fact that it eliminates the use of one neural network (namely the action network) that is part of a typical dual network AC setup. As a consequence, the SNAC architecture offers three potential advantages: a simpler architecture, lesser computational load and elimination of the approximation error associated with the eliminated network. In order to demonstrate these benefits and the control synthesis technique using SNAC, two problems have been solved with the AC and SNAC approaches and their computational performances are compared. One of these problems is a real-life Micro-Electro-Mechanical-system (MEMS) problem, which demonstrates that the SNAC technique is applicable to complex engineering systems.

  3. On-board processing satellite network architecture and control study

    NASA Technical Reports Server (NTRS)

    Campanella, S. Joseph; Pontano, B.; Chalmers, H.

    1987-01-01

    For satellites to remain a vital part of future national and international communications, system concepts that use their inherent advantages to the fullest must be created. Network architectures that take maximum advantage of satellites equipped with onboard processing are explored. Satellite generations must accommodate various services for which satellites constitute the preferred vehicle of delivery. Such services tend to be those that are widely dispersed and present thin to medium loads to the system. Typical systems considered are thin and medium route telephony, maritime, land and aeronautical radio, VSAT data, low bit rate video teleconferencing, and high bit rate broadcast of high definition video. Delivery of services by TDMA and FDMA multiplexing techniques and combinations of the two for individual and mixed service types are studied. The possibilities offered by onboard circuit switched and packet switched architectures are examined and the results strongly support a preference for the latter. A detailed design architecture encompassing the onboard packet switch and its control, the related demand assigned TDMA burst structures, and destination packet protocols for routing traffic are presented. Fundamental onboard hardware requirements comprising speed, memory size, chip count, and power are estimated. The study concludes with identification of key enabling technologies and identifies a plan to develop a POC model.

  4. WDM-PON Architecture for FTTx Networks

    NASA Astrophysics Data System (ADS)

    Iannone, E.; Franco, P.; Santoni, S.

    Broadband services for residential users in European countries have until now largely relied on xDSL technologies, while FTTx technologies have been mainly exploited in Asia and North America. The increasing bandwidth demand and the growing penetration of new services are pushing the deployment of optical access networks, and major European operators are now announcing FTTx projects. While FTTH is recognized as the target solution to bring broadband services to residential users, the identification of an FTTx evolutionary path able to seamlessly migrate to FTTH is key to enabling a massive deployment, easing the huge investments needed. WDM-PON architecture is an interesting solution that is able to accommodate the strategic need of building a new fiber-based access infrastructure with the possibility of adapting investments to actual demands and evolving to FTTH without requiring further interventions on fiber infrastructures.

  5. Space Mobile Network: A Near Earth Communications and Navigation Architecture

    NASA Technical Reports Server (NTRS)

    Israel, David J.; Heckler, Gregory W.; Menrad, Robert J.

    2016-01-01

    This paper shares key findings of NASA's Earth Regime Network Evolution Study (ERNESt) team resulting from its 18-month effort to define a wholly new architecture-level paradigm for the exploitation of space by civil space and commercial sector organizations. Since the launch of Sputnik in October 1957 spaceflight missions have remained highly scripted activities from launch through disposal. The utilization of computer technology has enabled dramatic increases in mission complexity; but, the underlying premise that the diverse actions necessary to meet mission goals requires minute-by-minute scripting, defined weeks in advance of execution, for the life of the mission has remained. This archetype was appropriate for a "new frontier" but now risks overtly constraining the potential market-based opportunities for the innovation considered necessary to efficiently address the complexities associated with meeting communications and navigation requirements projected to be characteristics of the next era of space exploration: a growing number of missions in simultaneous execution, increased variance of mission types and growth in location/orbital regime diversity. The resulting ERNESt architectural cornerstone - the Space Mobile Network (SMN) - was envisioned as critical to creating an environment essential to meeting these future challenges in political, programmatic, technological and budgetary terms. The SMN incorporates technologies such as: Disruption Tolerant Networking (DTN) and optical communications, as well as new operations concepts such as User Initiated Services (UIS) to provide user services analogous to today's terrestrial mobile network user. Results developed in collaboration with NASA's Space Communications and Navigation (SCaN) Division and field centers are reported on. Findings have been validated via briefings to external focus groups and initial ground-based demonstrations. The SMN opens new niches for exploitation by the marketplace of mission

  6. A performance analysis of advanced I/O architectures for PC-based network file servers

    NASA Astrophysics Data System (ADS)

    Huynh, K. D.; Khoshgoftaar, T. M.

    1994-12-01

    In the personal computing and workstation environments, more and more I/O adapters are becoming complete functional subsystems that are intelligent enough to handle I/O operations on their own without much intervention from the host processor. The IBM Subsystem Control Block (SCB) architecture has been defined to enhance the potential of these intelligent adapters by defining services and conventions that deliver command information and data to and from the adapters. In recent years, a new storage architecture, the Redundant Array of Independent Disks (RAID), has been quickly gaining acceptance in the world of computing. In this paper, we would like to discuss critical system design issues that are important to the performance of a network file server. We then present a performance analysis of the SCB architecture and disk array technology in typical network file server environments based on personal computers (PCs). One of the key issues investigated in this paper is whether a disk array can outperform a group of disks (of same type, same data capacity, and same cost) operating independently, not in parallel as in a disk array.

  7. PAINT: a promoter analysis and interaction network generation tool for gene regulatory network identification.

    PubMed

    Vadigepalli, Rajanikanth; Chakravarthula, Praveen; Zak, Daniel E; Schwaber, James S; Gonye, Gregory E

    2003-01-01

    We have developed a bioinformatics tool named PAINT that automates the promoter analysis of a given set of genes for the presence of transcription factor binding sites. Based on coincidence of regulatory sites, this tool produces an interaction matrix that represents a candidate transcriptional regulatory network. This tool currently consists of (1) a database of promoter sequences of known or predicted genes in the Ensembl annotated mouse genome database, (2) various modules that can retrieve and process the promoter sequences for binding sites of known transcription factors, and (3) modules for visualization and analysis of the resulting set of candidate network connections. This information provides a substantially pruned list of genes and transcription factors that can be examined in detail in further experimental studies on gene regulation. Also, the candidate network can be incorporated into network identification methods in the form of constraints on feasible structures in order to render the algorithms tractable for large-scale systems. The tool can also produce output in various formats suitable for use in external visualization and analysis software. In this manuscript, PAINT is demonstrated in two case studies involving analysis of differentially regulated genes chosen from two microarray data sets. The first set is from a neuroblastoma N1E-115 cell differentiation experiment, and the second set is from neuroblastoma N1E-115 cells at different time intervals following exposure to neuropeptide angiotensin II. PAINT is available for use as an agent in BioSPICE simulation and analysis framework (www.biospice.org), and can also be accessed via a WWW interface at www.dbi.tju.edu/dbi/tools/paint/.

  8. Optimization of neural network architecture using genetic programming improves detection and modeling of gene-gene interactions in studies of human diseases

    PubMed Central

    Ritchie, Marylyn D; White, Bill C; Parker, Joel S; Hahn, Lance W; Moore, Jason H

    2003-01-01

    Background Appropriate definition of neural network architecture prior to data analysis is crucial for successful data mining. This can be challenging when the underlying model of the data is unknown. The goal of this study was to determine whether optimizing neural network architecture using genetic programming as a machine learning strategy would improve the ability of neural networks to model and detect nonlinear interactions among genes in studies of common human diseases. Results Using simulated data, we show that a genetic programming optimized neural network approach is able to model gene-gene interactions as well as a traditional back propagation neural network. Furthermore, the genetic programming optimized neural network is better than the traditional back propagation neural network approach in terms of predictive ability and power to detect gene-gene interactions when non-functional polymorphisms are present. Conclusion This study suggests that a machine learning strategy for optimizing neural network architecture may be preferable to traditional trial-and-error approaches for the identification and characterization of gene-gene interactions in common, complex human diseases. PMID:12846935

  9. An architecture for designing fuzzy logic controllers using neural networks

    NASA Technical Reports Server (NTRS)

    Berenji, Hamid R.

    1991-01-01

    Described here is an architecture for designing fuzzy controllers through a hierarchical process of control rule acquisition and by using special classes of neural network learning techniques. A new method for learning to refine a fuzzy logic controller is introduced. A reinforcement learning technique is used in conjunction with a multi-layer neural network model of a fuzzy controller. The model learns by updating its prediction of the plant's behavior and is related to the Sutton's Temporal Difference (TD) method. The method proposed here has the advantage of using the control knowledge of an experienced operator and fine-tuning it through the process of learning. The approach is applied to a cart-pole balancing system.

  10. An open, interoperable, and scalable prehospital information technology network architecture.

    PubMed

    Landman, Adam B; Rokos, Ivan C; Burns, Kevin; Van Gelder, Carin M; Fisher, Roger M; Dunford, James V; Cone, David C; Bogucki, Sandy

    2011-01-01

    Some of the most intractable challenges in prehospital medicine include response time optimization, inefficiencies at the emergency medical services (EMS)-emergency department (ED) interface, and the ability to correlate field interventions with patient outcomes. Information technology (IT) can address these and other concerns by ensuring that system and patient information is received when and where it is needed, is fully integrated with prior and subsequent patient information, and is securely archived. Some EMS agencies have begun adopting information technologies, such as wireless transmission of 12-lead electrocardiograms, but few agencies have developed a comprehensive plan for management of their prehospital information and integration with other electronic medical records. This perspective article highlights the challenges and limitations of integrating IT elements without a strategic plan, and proposes an open, interoperable, and scalable prehospital information technology (PHIT) architecture. The two core components of this PHIT architecture are 1) routers with broadband network connectivity to share data between ambulance devices and EMS system information services and 2) an electronic patient care report to organize and archive all electronic prehospital data. To successfully implement this comprehensive PHIT architecture, data and technology requirements must be based on best available evidence, and the system must adhere to health data standards as well as privacy and security regulations. Recent federal legislation prioritizing health information technology may position federal agencies to help design and fund PHIT architectures.

  11. Architectures and Design for Next-Generation Hybrid Circuit/Packet Networks

    NASA Astrophysics Data System (ADS)

    Vadrevu, Sree Krishna Chaitanya

    Internet traffic is increasing rapidly at an annual growth rate of 35% with aggregate traffic exceeding several Exabyte's per month. The traffic is also becoming heterogeneous in bandwidth and quality-of-service (QoS) requirements with growing popularity of cloud computing, video-on-demand (VoD), e-science, etc. Hybrid circuit/packet networks which can jointly support circuit and packet services along with the adoption of high-bit-rate transmission systems form an attractive solution to address the traffic growth. 10 Gbps and 40 Gbps transmission systems are widely deployed in telecom backbone networks such as Comcast, AT&T, etc., and network operators are considering migration to 100 Gbps and beyond. This dissertation proposes robust architectures, capacity migration strategies, and novel service frameworks for next-generation hybrid circuit/packet architectures. In this dissertation, we study two types of hybrid circuit/packet networks: a) IP-over-WDM networks, in which the packet (IP) network is overlaid on top of the circuit (optical WDM) network and b) Hybrid networks in which the circuit and packet networks are deployed side by side such as US DoE's ESnet. We investigate techniques to dynamically migrate capacity between the circuit and packet sections by exploiting traffic variations over a day, and our methods show that significant bandwidth savings can be obtained with improved reliability of services. Specifically, we investigate how idle backup circuit capacity can be used to support packet services in IP-over-WDM networks, and similarly, excess capacity in packet network to support circuit services in ESnet. Control schemes that enable our mechanisms are also discussed. In IP-over-WDM networks, with upcoming 100 Gbps and beyond, dedicated protection will induce significant under-utilization of backup resources. We investigate design strategies to loan idle circuit backup capacity to support IP/packet services. However, failure of backup circuits will

  12. Gene Regulatory Networks in Cardiac Conduction System Development

    PubMed Central

    Munshi, Nikhil V.

    2014-01-01

    The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Given its critical role in coordinating cardiac performance, a detailed analysis of the molecular mechanisms underlying conduction system formation should inform our understanding of arrhythmia pathophysiology and affect the development of novel therapeutic strategies. Historically, the ability to distinguish cells of the conduction system from neighboring working myocytes presented a major technical challenge for performing comprehensive mechanistic studies. Early lineage tracing experiments suggested that conduction cells derive from cardiomyocyte precursors, and these claims have been substantiated by using more contemporary approaches. However, regional specialization of conduction cells adds an additional layer of complexity to this system, and it appears that different components of the conduction system utilize unique modes of developmental formation. The identification of numerous transcription factors and their downstream target genes involved in regional differentiation of the conduction system has provided insight into how lineage commitment is achieved. Furthermore, by adopting cutting-edge genetic techniques in combination with sophisticated phenotyping capabilities, investigators have made substantial progress in delineating the regulatory networks that orchestrate conduction system formation and their role in cardiac rhythm and physiology. This review describes the connectivity of these gene regulatory networks in cardiac conduction system development and discusses how they provide a foundation for understanding normal and pathological human cardiac rhythms. PMID:22628576

  13. The vertebrate Hox gene regulatory network for hindbrain segmentation: Evolution and diversification: Coupling of a Hox gene regulatory network to hindbrain segmentation is an ancient trait originating at the base of vertebrates.

    PubMed

    Parker, Hugo J; Bronner, Marianne E; Krumlauf, Robb

    2016-06-01

    Hindbrain development is orchestrated by a vertebrate gene regulatory network that generates segmental patterning along the anterior-posterior axis via Hox genes. Here, we review analyses of vertebrate and invertebrate chordate models that inform upon the evolutionary origin and diversification of this network. Evidence from the sea lamprey reveals that the hindbrain regulatory network generates rhombomeric compartments with segmental Hox expression and an underlying Hox code. We infer that this basal feature was present in ancestral vertebrates and, as an evolutionarily constrained developmental state, is fundamentally important for patterning of the vertebrate hindbrain across diverse lineages. Despite the common ground plan, vertebrates exhibit neuroanatomical diversity in lineage-specific patterns, with different vertebrates revealing variations of Hox expression in the hindbrain that could underlie this diversification. Invertebrate chordates lack hindbrain segmentation but exhibit some conserved aspects of this network, with retinoic acid signaling playing a role in establishing nested domains of Hox expression. © 2016 WILEY Periodicals, Inc.

  14. Figure-ground segregation in a recurrent network architecture.

    PubMed

    Roelfsema, Pieter R; Lamme, Victor A F; Spekreijse, Henk; Bosch, Holger

    2002-05-15

    Here we propose a model of how the visual brain segregates textured scenes into figures and background. During texture segregation, locations where the properties of texture elements change abruptly are assigned to boundaries, whereas image regions that are relatively homogeneous are grouped together. Boundary detection and grouping of image regions require different connection schemes, which are accommodated in a single network architecture by implementing them in different layers. As a result, all units carry signals related to boundary detection as well as grouping of image regions, in accordance with cortical physiology. Boundaries yield an early enhancement of network responses, but at a later point, an entire figural region is grouped together, because units that respond to it are labeled with enhanced activity. The model predicts which image regions are preferentially perceived as figure or as background and reproduces the spatio-temporal profile of neuronal activity in the visual cortex during texture segregation in intact animals, as well as in animals with cortical lesions.

  15. Enhancer Variants Synergistically Drive Dysfunction of a Gene Regulatory Network In Hirschsprung Disease

    DOE PAGES

    Chatterjee, Sumantra; Kapoor, Ashish; Akiyama, Jennifer A.; ...

    2016-09-29

    Common sequence variants in cis-regulatory elements (CREs) are suspected etiological causes of complex disorders. We previously identified an intronic enhancer variant in the RET gene disrupting SOX10 binding and increasing Hirschsprung disease (HSCR) risk 4-fold. We now show that two other functionally independent CRE variants, one binding Gata2 and the other binding Rarb, also reduce Ret expression and increase risk 2- and 1.7-fold. By studying human and mouse fetal gut tissues and cell lines, we demonstrate that reduced RET expression propagates throughout its gene regulatory network, exerting effects on both its positive and negative feedback components. We also provide evidencemore » that the presence of a combination of CRE variants synergistically reduces RET expression and its effects throughout the GRN. These studies show how the effects of functionally independent non-coding variants in a coordinated gene regulatory network amplify their individually small effects, providing a model for complex disorders.« less

  16. Enhancer Variants Synergistically Drive Dysfunction of a Gene Regulatory Network In Hirschsprung Disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chatterjee, Sumantra; Kapoor, Ashish; Akiyama, Jennifer A.

    Common sequence variants in cis-regulatory elements (CREs) are suspected etiological causes of complex disorders. We previously identified an intronic enhancer variant in the RET gene disrupting SOX10 binding and increasing Hirschsprung disease (HSCR) risk 4-fold. We now show that two other functionally independent CRE variants, one binding Gata2 and the other binding Rarb, also reduce Ret expression and increase risk 2- and 1.7-fold. By studying human and mouse fetal gut tissues and cell lines, we demonstrate that reduced RET expression propagates throughout its gene regulatory network, exerting effects on both its positive and negative feedback components. We also provide evidencemore » that the presence of a combination of CRE variants synergistically reduces RET expression and its effects throughout the GRN. These studies show how the effects of functionally independent non-coding variants in a coordinated gene regulatory network amplify their individually small effects, providing a model for complex disorders.« less

  17. Reconfiguration of brain network architecture to support executive control in aging.

    PubMed

    Gallen, Courtney L; Turner, Gary R; Adnan, Areeba; D'Esposito, Mark

    2016-08-01

    Aging is accompanied by declines in executive control abilities and changes in underlying brain network architecture. Here, we examined brain networks in young and older adults during a task-free resting state and an N-back task and investigated age-related changes in the modular network organization of the brain. Compared with young adults, older adults showed larger changes in network organization between resting state and task. Although young adults exhibited increased connectivity between lateral frontal regions and other network modules during the most difficult task condition, older adults also exhibited this pattern of increased connectivity during less-demanding task conditions. Moreover, the increase in between-module connectivity in older adults was related to faster task performance and greater fractional anisotropy of the superior longitudinal fasciculus. These results demonstrate that older adults who exhibit more pronounced network changes between a resting state and task have better executive control performance and greater structural connectivity of a core frontal-posterior white matter pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. On the complexity of neural network classifiers: a comparison between shallow and deep architectures.

    PubMed

    Bianchini, Monica; Scarselli, Franco

    2014-08-01

    Recently, researchers in the artificial neural network field have focused their attention on connectionist models composed by several hidden layers. In fact, experimental results and heuristic considerations suggest that deep architectures are more suitable than shallow ones for modern applications, facing very complex problems, e.g., vision and human language understanding. However, the actual theoretical results supporting such a claim are still few and incomplete. In this paper, we propose a new approach to study how the depth of feedforward neural networks impacts on their ability in implementing high complexity functions. First, a new measure based on topological concepts is introduced, aimed at evaluating the complexity of the function implemented by a neural network, used for classification purposes. Then, deep and shallow neural architectures with common sigmoidal activation functions are compared, by deriving upper and lower bounds on their complexity, and studying how the complexity depends on the number of hidden units and the used activation function. The obtained results seem to support the idea that deep networks actually implements functions of higher complexity, so that they are able, with the same number of resources, to address more difficult problems.

  19. A multi-tiered architecture for content retrieval in mobile peer-to-peer networks.

    DOT National Transportation Integrated Search

    2012-01-01

    In this paper, we address content retrieval in Mobile Peer-to-Peer (P2P) Networks. We design a multi-tiered architecture for content : retrieval, where at Tier 1, we design a protocol for content similarity governed by a parameter that trades accu...

  20. Arabidopsis ensemble reverse-engineered gene regulatory network discloses interconnected transcription factors in oxidative stress.

    PubMed

    Vermeirssen, Vanessa; De Clercq, Inge; Van Parys, Thomas; Van Breusegem, Frank; Van de Peer, Yves

    2014-12-01

    The abiotic stress response in plants is complex and tightly controlled by gene regulation. We present an abiotic stress gene regulatory network of 200,014 interactions for 11,938 target genes by integrating four complementary reverse-engineering solutions through average rank aggregation on an Arabidopsis thaliana microarray expression compendium. This ensemble performed the most robustly in benchmarking and greatly expands upon the availability of interactions currently reported. Besides recovering 1182 known regulatory interactions, cis-regulatory motifs and coherent functionalities of target genes corresponded with the predicted transcription factors. We provide a valuable resource of 572 abiotic stress modules of coregulated genes with functional and regulatory information, from which we deduced functional relationships for 1966 uncharacterized genes and many regulators. Using gain- and loss-of-function mutants of seven transcription factors grown under control and salt stress conditions, we experimentally validated 141 out of 271 predictions (52% precision) for 102 selected genes and mapped 148 additional transcription factor-gene regulatory interactions (49% recall). We identified an intricate core oxidative stress regulatory network where NAC13, NAC053, ERF6, WRKY6, and NAC032 transcription factors interconnect and function in detoxification. Our work shows that ensemble reverse-engineering can generate robust biological hypotheses of gene regulation in a multicellular eukaryote that can be tested by medium-throughput experimental validation. © 2014 American Society of Plant Biologists. All rights reserved.

  1. Scalable Architecture for Federated Translational Inquiries Network (SAFTINet) Technology Infrastructure for a Distributed Data Network

    PubMed Central

    Schilling, Lisa M.; Kwan, Bethany M.; Drolshagen, Charles T.; Hosokawa, Patrick W.; Brandt, Elias; Pace, Wilson D.; Uhrich, Christopher; Kamerick, Michael; Bunting, Aidan; Payne, Philip R.O.; Stephens, William E.; George, Joseph M.; Vance, Mark; Giacomini, Kelli; Braddy, Jason; Green, Mika K.; Kahn, Michael G.

    2013-01-01

    Introduction: Distributed Data Networks (DDNs) offer infrastructure solutions for sharing electronic health data from across disparate data sources to support comparative effectiveness research. Data sharing mechanisms must address technical and governance concerns stemming from network security and data disclosure laws and best practices, such as HIPAA. Methods: The Scalable Architecture for Federated Translational Inquiries Network (SAFTINet) deploys TRIAD grid technology, a common data model, detailed technical documentation, and custom software for data harmonization to facilitate data sharing in collaboration with stakeholders in the care of safety net populations. Data sharing partners host TRIAD grid nodes containing harmonized clinical data within their internal or hosted network environments. Authorized users can use a central web-based query system to request analytic data sets. Discussion: SAFTINet DDN infrastructure achieved a number of data sharing objectives, including scalable and sustainable systems for ensuring harmonized data structures and terminologies and secure distributed queries. Initial implementation challenges were resolved through iterative discussions, development and implementation of technical documentation, governance, and technology solutions. PMID:25848567

  2. NIMEFI: gene regulatory network inference using multiple ensemble feature importance algorithms.

    PubMed

    Ruyssinck, Joeri; Huynh-Thu, Vân Anh; Geurts, Pierre; Dhaene, Tom; Demeester, Piet; Saeys, Yvan

    2014-01-01

    One of the long-standing open challenges in computational systems biology is the topology inference of gene regulatory networks from high-throughput omics data. Recently, two community-wide efforts, DREAM4 and DREAM5, have been established to benchmark network inference techniques using gene expression measurements. In these challenges the overall top performer was the GENIE3 algorithm. This method decomposes the network inference task into separate regression problems for each gene in the network in which the expression values of a particular target gene are predicted using all other genes as possible predictors. Next, using tree-based ensemble methods, an importance measure for each predictor gene is calculated with respect to the target gene and a high feature importance is considered as putative evidence of a regulatory link existing between both genes. The contribution of this work is twofold. First, we generalize the regression decomposition strategy of GENIE3 to other feature importance methods. We compare the performance of support vector regression, the elastic net, random forest regression, symbolic regression and their ensemble variants in this setting to the original GENIE3 algorithm. To create the ensemble variants, we propose a subsampling approach which allows us to cast any feature selection algorithm that produces a feature ranking into an ensemble feature importance algorithm. We demonstrate that the ensemble setting is key to the network inference task, as only ensemble variants achieve top performance. As second contribution, we explore the effect of using rankwise averaged predictions of multiple ensemble algorithms as opposed to only one. We name this approach NIMEFI (Network Inference using Multiple Ensemble Feature Importance algorithms) and show that this approach outperforms all individual methods in general, although on a specific network a single method can perform better. An implementation of NIMEFI has been made publicly available.

  3. NIMEFI: Gene Regulatory Network Inference using Multiple Ensemble Feature Importance Algorithms

    PubMed Central

    Ruyssinck, Joeri; Huynh-Thu, Vân Anh; Geurts, Pierre; Dhaene, Tom; Demeester, Piet; Saeys, Yvan

    2014-01-01

    One of the long-standing open challenges in computational systems biology is the topology inference of gene regulatory networks from high-throughput omics data. Recently, two community-wide efforts, DREAM4 and DREAM5, have been established to benchmark network inference techniques using gene expression measurements. In these challenges the overall top performer was the GENIE3 algorithm. This method decomposes the network inference task into separate regression problems for each gene in the network in which the expression values of a particular target gene are predicted using all other genes as possible predictors. Next, using tree-based ensemble methods, an importance measure for each predictor gene is calculated with respect to the target gene and a high feature importance is considered as putative evidence of a regulatory link existing between both genes. The contribution of this work is twofold. First, we generalize the regression decomposition strategy of GENIE3 to other feature importance methods. We compare the performance of support vector regression, the elastic net, random forest regression, symbolic regression and their ensemble variants in this setting to the original GENIE3 algorithm. To create the ensemble variants, we propose a subsampling approach which allows us to cast any feature selection algorithm that produces a feature ranking into an ensemble feature importance algorithm. We demonstrate that the ensemble setting is key to the network inference task, as only ensemble variants achieve top performance. As second contribution, we explore the effect of using rankwise averaged predictions of multiple ensemble algorithms as opposed to only one. We name this approach NIMEFI (Network Inference using Multiple Ensemble Feature Importance algorithms) and show that this approach outperforms all individual methods in general, although on a specific network a single method can perform better. An implementation of NIMEFI has been made publicly available

  4. A Bayesian connectivity-based approach to constructing probabilistic gene regulatory networks.

    PubMed

    Zhou, Xiaobo; Wang, Xiaodong; Pal, Ranadip; Ivanov, Ivan; Bittner, Michael; Dougherty, Edward R

    2004-11-22

    We have hypothesized that the construction of transcriptional regulatory networks using a method that optimizes connectivity would lead to regulation consistent with biological expectations. A key expectation is that the hypothetical networks should produce a few, very strong attractors, highly similar to the original observations, mimicking biological state stability and determinism. Another central expectation is that, since it is expected that the biological control is distributed and mutually reinforcing, interpretation of the observations should lead to a very small number of connection schemes. We propose a fully Bayesian approach to constructing probabilistic gene regulatory networks (PGRNs) that emphasizes network topology. The method computes the possible parent sets of each gene, the corresponding predictors and the associated probabilities based on a nonlinear perceptron model, using a reversible jump Markov chain Monte Carlo (MCMC) technique, and an MCMC method is employed to search the network configurations to find those with the highest Bayesian scores to construct the PGRN. The Bayesian method has been used to construct a PGRN based on the observed behavior of a set of genes whose expression patterns vary across a set of melanoma samples exhibiting two very different phenotypes with respect to cell motility and invasiveness. Key biological features have been faithfully reflected in the model. Its steady-state distribution contains attractors that are either identical or very similar to the states observed in the data, and many of the attractors are singletons, which mimics the biological propensity to stably occupy a given state. Most interestingly, the connectivity rules for the most optimal generated networks constituting the PGRN are remarkably similar, as would be expected for a network operating on a distributed basis, with strong interactions between the components.

  5. Establishment of apoptotic regulatory network for genetic markers of colorectal cancer and optimal selection of traditional Chinese medicine target.

    PubMed

    Tian, Tongde; Chen, Chuanliang; Yang, Feng; Tang, Jingwen; Pei, Junwen; Shi, Bian; Zhang, Ning; Zhang, Jianhua

    2017-03-01

    The paper aimed to screen out genetic markers applicable to early diagnosis for colorectal cancer and establish apoptotic regulatory network model for colorectal cancer, and to analyze the current situation of traditional Chinese medicine (TCM) target, thereby providing theoretical evidence for early diagnosis and targeted therapy of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers that are applied to early diagnosis of colorectal cancer were searched and performed comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. KEGG analysis was employed to establish apoptotic regulatory network model based on screened genetic markers, and optimization was conducted on TCM targets. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, P53, APC, DCC and PTEN, among which DCC has the highest diagnostic efficiency. Apoptotic regulatory network was built by KEGG analysis. Currently, it was reported that TCM has regulatory function on gene locus in apoptotic regulatory network. The apoptotic regulatory model of colorectal cancer established in this study provides theoretical evidence for early diagnosis and TCM targeted therapy of colorectal cancer in clinic.

  6. Interferon-α acutely impairs whole-brain functional connectivity network architecture - A preliminary study.

    PubMed

    Dipasquale, Ottavia; Cooper, Ella A; Tibble, Jeremy; Voon, Valerie; Baglio, Francesca; Baselli, Giuseppe; Cercignani, Mara; Harrison, Neil A

    2016-11-01

    Interferon-alpha (IFN-α) is a key mediator of antiviral immune responses used to treat Hepatitis C infection. Though clinically effective, IFN-α rapidly impairs mood, motivation and cognition, effects that can appear indistinguishable from major depression and provide powerful empirical support for the inflammation theory of depression. Though inflammation has been shown to modulate activity within discrete brain regions, how it affects distributed information processing and the architecture of whole brain functional connectivity networks have not previously been investigated. Here we use a graph theoretic analysis of resting state functional magnetic resonance imaging (rfMRI) to investigate acute effects of systemic interferon-alpha (IFN-α) on whole brain functional connectivity architecture and its relationship to IFN-α-induced mood change. Twenty-two patients with Hepatitis-C infection, initiating IFN-α-based therapy were scanned at baseline and 4h after their first IFN-α dose. The whole brain network was parcellated into 110 cortical and sub-cortical nodes based on the Oxford-Harvard Atlas and effects assessed on higher-level graph metrics, including node degree, betweenness centrality, global and local efficiency. IFN-α was associated with a significant reduction in global network connectivity (node degree) (p=0.033) and efficiency (p=0.013), indicating a global reduction of information transfer among the nodes forming the whole brain network. Effects were similar for highly connected (hub) and non-hub nodes, with no effect on betweenness centrality (p>0.1). At a local level, we identified regions with reduced efficiency of information exchange and a sub-network with decreased functional connectivity after IFN-α. Changes in local and particularly global functional connectivity correlated with associated changes in mood measured on the Profile of Mood States (POMS) questionnaire. IFN-α rapidly induced a profound shift in whole brain network structure

  7. Inferring Gene Regulatory Networks by Singular Value Decomposition and Gravitation Field Algorithm

    PubMed Central

    Zheng, Ming; Wu, Jia-nan; Huang, Yan-xin; Liu, Gui-xia; Zhou, You; Zhou, Chun-guang

    2012-01-01

    Reconstruction of gene regulatory networks (GRNs) is of utmost interest and has become a challenge computational problem in system biology. However, every existing inference algorithm from gene expression profiles has its own advantages and disadvantages. In particular, the effectiveness and efficiency of every previous algorithm is not high enough. In this work, we proposed a novel inference algorithm from gene expression data based on differential equation model. In this algorithm, two methods were included for inferring GRNs. Before reconstructing GRNs, singular value decomposition method was used to decompose gene expression data, determine the algorithm solution space, and get all candidate solutions of GRNs. In these generated family of candidate solutions, gravitation field algorithm was modified to infer GRNs, used to optimize the criteria of differential equation model, and search the best network structure result. The proposed algorithm is validated on both the simulated scale-free network and real benchmark gene regulatory network in networks database. Both the Bayesian method and the traditional differential equation model were also used to infer GRNs, and the results were used to compare with the proposed algorithm in our work. And genetic algorithm and simulated annealing were also used to evaluate gravitation field algorithm. The cross-validation results confirmed the effectiveness of our algorithm, which outperforms significantly other previous algorithms. PMID:23226565

  8. Construction of an integrated gene regulatory network link to stress-related immune system in cattle.

    PubMed

    Behdani, Elham; Bakhtiarizadeh, Mohammad Reza

    2017-10-01

    The immune system is an important biological system that is negatively impacted by stress. This study constructed an integrated regulatory network to enhance our understanding of the regulatory gene network used in the stress-related immune system. Module inference was used to construct modules of co-expressed genes with bovine leukocyte RNA-Seq data. Transcription factors (TFs) were then assigned to these modules using Lemon-Tree algorithms. In addition, the TFs assigned to each module were confirmed using the promoter analysis and protein-protein interactions data. Therefore, our integrated method identified three TFs which include one TF that is previously known to be involved in immune response (MYBL2) and two TFs (E2F8 and FOXS1) that had not been recognized previously and were identified for the first time in this study as novel regulatory candidates in immune response. This study provides valuable insights on the regulatory programs of genes involved in the stress-related immune system.

  9. New scaling relation for information transfer in biological networks

    PubMed Central

    Kim, Hyunju; Davies, Paul; Walker, Sara Imari

    2015-01-01

    We quantify characteristics of the informational architecture of two representative biological networks: the Boolean network model for the cell-cycle regulatory network of the fission yeast Schizosaccharomyces pombe (Davidich et al. 2008 PLoS ONE 3, e1672 (doi:10.1371/journal.pone.0001672)) and that of the budding yeast Saccharomyces cerevisiae (Li et al. 2004 Proc. Natl Acad. Sci. USA 101, 4781–4786 (doi:10.1073/pnas.0305937101)). We compare our results for these biological networks with the same analysis performed on ensembles of two different types of random networks: Erdös–Rényi and scale-free. We show that both biological networks share features in common that are not shared by either random network ensemble. In particular, the biological networks in our study process more information than the random networks on average. Both biological networks also exhibit a scaling relation in information transferred between nodes that distinguishes them from random, where the biological networks stand out as distinct even when compared with random networks that share important topological properties, such as degree distribution, with the biological network. We show that the most biologically distinct regime of this scaling relation is associated with a subset of control nodes that regulate the dynamics and function of each respective biological network. Information processing in biological networks is therefore interpreted as an emergent property of topology (causal structure) and dynamics (function). Our results demonstrate quantitatively how the informational architecture of biologically evolved networks can distinguish them from other classes of network architecture that do not share the same informational properties. PMID:26701883

  10. MapReduce Algorithms for Inferring Gene Regulatory Networks from Time-Series Microarray Data Using an Information-Theoretic Approach.

    PubMed

    Abduallah, Yasser; Turki, Turki; Byron, Kevin; Du, Zongxuan; Cervantes-Cervantes, Miguel; Wang, Jason T L

    2017-01-01

    Gene regulation is a series of processes that control gene expression and its extent. The connections among genes and their regulatory molecules, usually transcription factors, and a descriptive model of such connections are known as gene regulatory networks (GRNs). Elucidating GRNs is crucial to understand the inner workings of the cell and the complexity of gene interactions. To date, numerous algorithms have been developed to infer gene regulatory networks. However, as the number of identified genes increases and the complexity of their interactions is uncovered, networks and their regulatory mechanisms become cumbersome to test. Furthermore, prodding through experimental results requires an enormous amount of computation, resulting in slow data processing. Therefore, new approaches are needed to expeditiously analyze copious amounts of experimental data resulting from cellular GRNs. To meet this need, cloud computing is promising as reported in the literature. Here, we propose new MapReduce algorithms for inferring gene regulatory networks on a Hadoop cluster in a cloud environment. These algorithms employ an information-theoretic approach to infer GRNs using time-series microarray data. Experimental results show that our MapReduce program is much faster than an existing tool while achieving slightly better prediction accuracy than the existing tool.

  11. A computational approach to identify cellular heterogeneity and tissue-specific gene regulatory networks.

    PubMed

    Jambusaria, Ankit; Klomp, Jeff; Hong, Zhigang; Rafii, Shahin; Dai, Yang; Malik, Asrar B; Rehman, Jalees

    2018-06-07

    The heterogeneity of cells across tissue types represents a major challenge for studying biological mechanisms as well as for therapeutic targeting of distinct tissues. Computational prediction of tissue-specific gene regulatory networks may provide important insights into the mechanisms underlying the cellular heterogeneity of cells in distinct organs and tissues. Using three pathway analysis techniques, gene set enrichment analysis (GSEA), parametric analysis of gene set enrichment (PGSEA), alongside our novel model (HeteroPath), which assesses heterogeneously upregulated and downregulated genes within the context of pathways, we generated distinct tissue-specific gene regulatory networks. We analyzed gene expression data derived from freshly isolated heart, brain, and lung endothelial cells and populations of neurons in the hippocampus, cingulate cortex, and amygdala. In both datasets, we found that HeteroPath segregated the distinct cellular populations by identifying regulatory pathways that were not identified by GSEA or PGSEA. Using simulated datasets, HeteroPath demonstrated robustness that was comparable to what was seen using existing gene set enrichment methods. Furthermore, we generated tissue-specific gene regulatory networks involved in vascular heterogeneity and neuronal heterogeneity by performing motif enrichment of the heterogeneous genes identified by HeteroPath and linking the enriched motifs to regulatory transcription factors in the ENCODE database. HeteroPath assesses contextual bidirectional gene expression within pathways and thus allows for transcriptomic assessment of cellular heterogeneity. Unraveling tissue-specific heterogeneity of gene expression can lead to a better understanding of the molecular underpinnings of tissue-specific phenotypes.

  12. Causal structure of oscillations in gene regulatory networks: Boolean analysis of ordinary differential equation attractors.

    PubMed

    Sun, Mengyang; Cheng, Xianrui; Socolar, Joshua E S

    2013-06-01

    A common approach to the modeling of gene regulatory networks is to represent activating or repressing interactions using ordinary differential equations for target gene concentrations that include Hill function dependences on regulator gene concentrations. An alternative formulation represents the same interactions using Boolean logic with time delays associated with each network link. We consider the attractors that emerge from the two types of models in the case of a simple but nontrivial network: a figure-8 network with one positive and one negative feedback loop. We show that the different modeling approaches give rise to the same qualitative set of attractors with the exception of a possible fixed point in the ordinary differential equation model in which concentrations sit at intermediate values. The properties of the attractors are most easily understood from the Boolean perspective, suggesting that time-delay Boolean modeling is a useful tool for understanding the logic of regulatory networks.

  13. Stochastic models for regulatory networks of the genetic toggle switch.

    PubMed

    Tian, Tianhai; Burrage, Kevin

    2006-05-30

    Bistability arises within a wide range of biological systems from the lambda phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.

  14. Stochastic models for regulatory networks of the genetic toggle switch

    PubMed Central

    Tian, Tianhai; Burrage, Kevin

    2006-01-01

    Bistability arises within a wide range of biological systems from the λ phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks. PMID:16714385

  15. Software-Defined Architectures for Spectrally Efficient Cognitive Networking in Extreme Environments

    NASA Astrophysics Data System (ADS)

    Sklivanitis, Georgios

    The objective of this dissertation is the design, development, and experimental evaluation of novel algorithms and reconfigurable radio architectures for spectrally efficient cognitive networking in terrestrial, airborne, and underwater environments. Next-generation wireless communication architectures and networking protocols that maximize spectrum utilization efficiency in congested/contested or low-spectral availability (extreme) communication environments can enable a rich body of applications with unprecedented societal impact. In recent years, underwater wireless networks have attracted significant attention for military and commercial applications including oceanographic data collection, disaster prevention, tactical surveillance, offshore exploration, and pollution monitoring. Unmanned aerial systems that are autonomously networked and fully mobile can assist humans in extreme or difficult-to-reach environments and provide cost-effective wireless connectivity for devices without infrastructure coverage. Cognitive radio (CR) has emerged as a promising technology to maximize spectral efficiency in dynamically changing communication environments by adaptively reconfiguring radio communication parameters. At the same time, the fast developing technology of software-defined radio (SDR) platforms has enabled hardware realization of cognitive radio algorithms for opportunistic spectrum access. However, existing algorithmic designs and protocols for shared spectrum access do not effectively capture the interdependencies between radio parameters at the physical (PHY), medium-access control (MAC), and network (NET) layers of the network protocol stack. In addition, existing off-the-shelf radio platforms and SDR programmable architectures are far from fulfilling runtime adaptation and reconfiguration across PHY, MAC, and NET layers. Spectrum allocation in cognitive networks with multi-hop communication requirements depends on the location, network traffic load, and

  16. Fast packet switch architectures for broadband integrated services digital networks

    NASA Technical Reports Server (NTRS)

    Tobagi, Fouad A.

    1990-01-01

    Background information on networking and switching is provided, and the various architectures that have been considered for fast packet switches are described. The focus is solely on switches designed to be implemented electronically. A set of definitions and a brief description of the functionality required of fast packet switches are given. Three basic types of packet switches are identified: the shared-memory, shared-medium, and space-division types. Each of these is described, and examples are given.

  17. Social insect colony as a biological regulatory system: modelling information flow in dominance networks.

    PubMed

    Nandi, Anjan K; Sumana, Annagiri; Bhattacharya, Kunal

    2014-12-06

    Social insects provide an excellent platform to investigate flow of information in regulatory systems since their successful social organization is essentially achieved by effective information transfer through complex connectivity patterns among the colony members. Network representation of such behavioural interactions offers a powerful tool for structural as well as dynamical analysis of the underlying regulatory systems. In this paper, we focus on the dominance interaction networks in the tropical social wasp Ropalidia marginata-a species where behavioural observations indicate that such interactions are principally responsible for the transfer of information between individuals about their colony needs, resulting in a regulation of their own activities. Our research reveals that the dominance networks of R. marginata are structurally similar to a class of naturally evolved information processing networks, a fact confirmed also by the predominance of a specific substructure-the 'feed-forward loop'-a key functional component in many other information transfer networks. The dynamical analysis through Boolean modelling confirms that the networks are sufficiently stable under small fluctuations and yet capable of more efficient information transfer compared to their randomized counterparts. Our results suggest the involvement of a common structural design principle in different biological regulatory systems and a possible similarity with respect to the effect of selection on the organization levels of such systems. The findings are also consistent with the hypothesis that dominance behaviour has been shaped by natural selection to co-opt the information transfer process in such social insect species, in addition to its primal function of mediation of reproductive competition in the colony. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  18. MiRNA and TF co-regulatory network analysis for the pathology and recurrence of myocardial infarction.

    PubMed

    Lin, Ying; Sibanda, Vusumuzi Leroy; Zhang, Hong-Mei; Hu, Hui; Liu, Hui; Guo, An-Yuan

    2015-04-13

    Myocardial infarction (MI) is a leading cause of death in the world and many genes are involved in it. Transcription factor (TFs) and microRNAs (miRNAs) are key regulators of gene expression. We hypothesized that miRNAs and TFs might play combinatory regulatory roles in MI. After collecting MI candidate genes and miRNAs from various resources, we constructed a comprehensive MI-specific miRNA-TF co-regulatory network by integrating predicted and experimentally validated TF and miRNA targets. We found some hub nodes (e.g. miR-16 and miR-26) in this network are important regulators, and the network can be severed as a bridge to interpret the associations of previous results, which is shown by the case of miR-29 in this study. We also constructed a regulatory network for MI recurrence and found several important genes (e.g. DAB2, BMP6, miR-320 and miR-103), the abnormal expressions of which may be potential regulatory mechanisms and markers of MI recurrence. At last we proposed a cellular model to discuss major TF and miRNA regulators with signaling pathways in MI. This study provides more details on gene expression regulation and regulators involved in MI progression and recurrence. It also linked up and interpreted many previous results.

  19. Inferring nonlinear gene regulatory networks from gene expression data based on distance correlation.

    PubMed

    Guo, Xiaobo; Zhang, Ye; Hu, Wenhao; Tan, Haizhu; Wang, Xueqin

    2014-01-01

    Nonlinear dependence is general in regulation mechanism of gene regulatory networks (GRNs). It is vital to properly measure or test nonlinear dependence from real data for reconstructing GRNs and understanding the complex regulatory mechanisms within the cellular system. A recently developed measurement called the distance correlation (DC) has been shown powerful and computationally effective in nonlinear dependence for many situations. In this work, we incorporate the DC into inferring GRNs from the gene expression data without any underling distribution assumptions. We propose three DC-based GRNs inference algorithms: CLR-DC, MRNET-DC and REL-DC, and then compare them with the mutual information (MI)-based algorithms by analyzing two simulated data: benchmark GRNs from the DREAM challenge and GRNs generated by SynTReN network generator, and an experimentally determined SOS DNA repair network in Escherichia coli. According to both the receiver operator characteristic (ROC) curve and the precision-recall (PR) curve, our proposed algorithms significantly outperform the MI-based algorithms in GRNs inference.

  20. Inferring Nonlinear Gene Regulatory Networks from Gene Expression Data Based on Distance Correlation

    PubMed Central

    Guo, Xiaobo; Zhang, Ye; Hu, Wenhao; Tan, Haizhu; Wang, Xueqin

    2014-01-01

    Nonlinear dependence is general in regulation mechanism of gene regulatory networks (GRNs). It is vital to properly measure or test nonlinear dependence from real data for reconstructing GRNs and understanding the complex regulatory mechanisms within the cellular system. A recently developed measurement called the distance correlation (DC) has been shown powerful and computationally effective in nonlinear dependence for many situations. In this work, we incorporate the DC into inferring GRNs from the gene expression data without any underling distribution assumptions. We propose three DC-based GRNs inference algorithms: CLR-DC, MRNET-DC and REL-DC, and then compare them with the mutual information (MI)-based algorithms by analyzing two simulated data: benchmark GRNs from the DREAM challenge and GRNs generated by SynTReN network generator, and an experimentally determined SOS DNA repair network in Escherichia coli. According to both the receiver operator characteristic (ROC) curve and the precision-recall (PR) curve, our proposed algorithms significantly outperform the MI-based algorithms in GRNs inference. PMID:24551058

  1. Algebraic model checking for Boolean gene regulatory networks.

    PubMed

    Tran, Quoc-Nam

    2011-01-01

    We present a computational method in which modular and Groebner bases (GB) computation in Boolean rings are used for solving problems in Boolean gene regulatory networks (BN). In contrast to other known algebraic approaches, the degree of intermediate polynomials during the calculation of Groebner bases using our method will never grow resulting in a significant improvement in running time and memory space consumption. We also show how calculation in temporal logic for model checking can be done by means of our direct and efficient Groebner basis computation in Boolean rings. We present our experimental results in finding attractors and control strategies of Boolean networks to illustrate our theoretical arguments. The results are promising. Our algebraic approach is more efficient than the state-of-the-art model checker NuSMV on BNs. More importantly, our approach finds all solutions for the BN problems.

  2. Bottom-up GGM algorithm for constructing multiple layered hierarchical gene regulatory networks

    USDA-ARS?s Scientific Manuscript database

    Multilayered hierarchical gene regulatory networks (ML-hGRNs) are very important for understanding genetics regulation of biological pathways. However, there are currently no computational algorithms available for directly building ML-hGRNs that regulate biological pathways. A bottom-up graphic Gaus...

  3. Understanding regulatory networks requires more than computing a multitude of graph statistics. Comment on "Drivers of structural features in gene regulatory networks: From biophysical constraints to biological function" by O.C. Martin et al.

    NASA Astrophysics Data System (ADS)

    Tkačik, Gašper

    2016-07-01

    The article by O. Martin and colleagues provides a much needed systematic review of a body of work that relates the topological structure of genetic regulatory networks to evolutionary selection for function. This connection is very important. Using the current wealth of genomic data, statistical features of regulatory networks (e.g., degree distributions, motif composition, etc.) can be quantified rather easily; it is, however, often unclear how to interpret the results. On a graph theoretic level the statistical significance of the results can be evaluated by comparing observed graphs to ;randomized; ones (bravely ignoring the issue of how precisely to randomize!) and comparing the frequency of appearance of a particular network structure relative to a randomized null expectation. While this is a convenient operational test for statistical significance, its biological meaning is questionable. In contrast, an in-silico genotype-to-phenotype model makes explicit the assumptions about the network function, and thus clearly defines the expected network structures that can be compared to the case of no selection for function and, ultimately, to data.

  4. A novel role for WAVE1 in controlling actin network growth rate and architecture

    PubMed Central

    Sweeney, Meredith O.; Collins, Agnieszka; Padrick, Shae B.; Goode, Bruce L.

    2015-01-01

    Branched actin filament networks in cells are assembled through the combined activities of Arp2/3 complex and different WASP/WAVE proteins. Here we used TIRF and electron microscopy to directly compare for the first time the assembly kinetics and architectures of actin filament networks produced by Arp2/3 complex and dimerized VCA regions of WAVE1, WAVE2, or N-WASP. WAVE1 produced strikingly different networks from WAVE2 or N-WASP, which comprised unexpectedly short filaments. Further analysis showed that the WAVE1-specific activity stemmed from an inhibitory effect on filament elongation both in the presence and absence of Arp2/3 complex, which was observed even at low stoichiometries of WAVE1 to actin monomers, precluding an effect from monomer sequestration. Using a series of VCA chimeras, we mapped the elongation inhibitory effects of WAVE1 to its WH2 (“V”) domain. Further, mutating a single conserved lysine residue potently disrupted WAVE1's inhibitory effects. Taken together, our results show that WAVE1 has unique activities independent of Arp2/3 complex that can govern both the growth rates and architectures of actin filament networks. Such activities may underlie previously observed differences between the cellular functions of WAVE1 and WAVE2. PMID:25473116

  5. A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity.

    PubMed

    Li, Qingyun; Barish, Scott; Okuwa, Sumie; Maciejewski, Abigail; Brandt, Alicia T; Reinhold, Dominik; Jones, Corbin D; Volkan, Pelin Cayirlioglu

    2016-01-01

    Sensory neuron diversity is required for organisms to decipher complex environmental cues. In Drosophila, the olfactory environment is detected by 50 different olfactory receptor neuron (ORN) classes that are clustered in combinations within distinct sensilla subtypes. Each sensilla subtype houses stereotypically clustered 1-4 ORN identities that arise through asymmetric divisions from a single multipotent sensory organ precursor (SOP). How each class of SOPs acquires a unique differentiation potential that accounts for ORN diversity is unknown. Previously, we reported a critical component of SOP diversification program, Rotund (Rn), increases ORN diversity by generating novel developmental trajectories from existing precursors within each independent sensilla type lineages. Here, we show that Rn, along with BarH1/H2 (Bar), Bric-à-brac (Bab), Apterous (Ap) and Dachshund (Dac), constitutes a transcription factor (TF) network that patterns the developing olfactory tissue. This network was previously shown to pattern the segmentation of the leg, which suggests that this network is functionally conserved. In antennal imaginal discs, precursors with diverse ORN differentiation potentials are selected from concentric rings defined by unique combinations of these TFs along the proximodistal axis of the developing antennal disc. The combinatorial code that demarcates each precursor field is set up by cross-regulatory interactions among different factors within the network. Modifications of this network lead to predictable changes in the diversity of sensilla subtypes and ORN pools. In light of our data, we propose a molecular map that defines each unique SOP fate. Our results highlight the importance of the early prepatterning gene regulatory network as a modulator of SOP and terminally differentiated ORN diversity. Finally, our model illustrates how conserved developmental strategies are used to generate neuronal diversity.

  6. SPANNER: A Self-Repairing Spiking Neural Network Hardware Architecture.

    PubMed

    Liu, Junxiu; Harkin, Jim; Maguire, Liam P; McDaid, Liam J; Wade, John J

    2018-04-01

    Recent research has shown that a glial cell of astrocyte underpins a self-repair mechanism in the human brain, where spiking neurons provide direct and indirect feedbacks to presynaptic terminals. These feedbacks modulate the synaptic transmission probability of release (PR). When synaptic faults occur, the neuron becomes silent or near silent due to the low PR of synapses; whereby the PRs of remaining healthy synapses are then increased by the indirect feedback from the astrocyte cell. In this paper, a novel hardware architecture of Self-rePAiring spiking Neural NEtwoRk (SPANNER) is proposed, which mimics this self-repairing capability in the human brain. This paper demonstrates that the hardware can self-detect and self-repair synaptic faults without the conventional components for the fault detection and fault repairing. Experimental results show that SPANNER can maintain the system performance with fault densities of up to 40%, and more importantly SPANNER has only a 20% performance degradation when the self-repairing architecture is significantly damaged at a fault density of 80%.

  7. Insights into the etiology-associated gene regulatory networks in hepatocellular carcinoma from The Cancer Genome Atlas.

    PubMed

    Seshachalam, Veerabrahma Pratap; Sekar, Karthik; Hui, Kam M

    2018-04-19

    Hepatitis B virus, hepatitis C virus, alcoholic consumption and non-alcoholic fatty liver are the major known risk factors for Hepatocellular carcinoma (HCC). There have been very few studies comparing the underlying biological mechanisms associated with the different etiologies of HCC. In this study, we hypothesized the existence of different regulatory networks associated with different liver disease etiologies involved in hepatocarcinogenesis. Using upstream regulatory analysis tool in ingenuity pathway analysis software, URs were predicted using differential expressed genes for HCC to facilitate the interrogation of global gene regulation. Analysis of regulatory networks for HBV HCC revealed E2F1 as activated UR, regulating genes involved in cell cycle and DNA replication and HNF4A and HNF1A as inhibited UR. In HCV HCC, IFNG, involved in cellular movement and signaling was activated while IL1RN, MAPK1 involved in IL-22 signaling and immune response was inhibited. In Alcoholic-consumption HCC, ERBB2 involved in inflammatory response and cellular movement was activated, whereas HNF4A, NUPR1 were inhibited. For HCC derived from Non-alcoholic fatty liver disease, miR-1249-5p was activated and NUPR1 involved in cell cycle and apoptosis was inhibited. The prognostic value of representative genes identified in the regulatory networks for HBV HCC can be further validated by an independent HBV HCC dataset established in our laboratory with survival data. Our study identified functionally distinct candidate URs for HCC developed from different etiologic risk factors. Further functional validation studies of these regulatory networks could facilitate the management of HCC towards personalized medicine. This article is protected by copyright. All rights reserved.

  8. Hybrid Network Architectures for the Next Generation NAS

    NASA Technical Reports Server (NTRS)

    Madubata, Christian

    2003-01-01

    To meet the needs of the 21st Century NAS, an integrated, network-centric infrastructure is essential that is characterized by secure, high bandwidth, digital communication systems that support precision navigation capable of reducing position errors for all aircraft to within a few meters. This system will also require precision surveillance systems capable of accurately locating all aircraft, and automatically detecting any deviations from an approved path within seconds and be able to deliver high resolution weather forecasts - critical to create 4- dimensional (space and time) profiles for up to 6 hours for all atmospheric conditions affecting aviation, including wake vortices. The 21st Century NAS will be characterized by highly accurate digital data bases depicting terrain, obstacle, and airport information no matter what visibility conditions exist. This research task will be to perform a high-level requirements analysis of the applications, information and services required by the next generation National Airspace System. The investigation and analysis is expected to lead to the development and design of several national network-centric communications architectures that would be capable of supporting the Next Generation NAS.

  9. cGRNB: a web server for building combinatorial gene regulatory networks through integrated engineering of seed-matching sequence information and gene expression datasets.

    PubMed

    Xu, Huayong; Yu, Hui; Tu, Kang; Shi, Qianqian; Wei, Chaochun; Li, Yuan-Yuan; Li, Yi-Xue

    2013-01-01

    We are witnessing rapid progress in the development of methodologies for building the combinatorial gene regulatory networks involving both TFs (Transcription Factors) and miRNAs (microRNAs). There are a few tools available to do these jobs but most of them are not easy to use and not accessible online. A web server is especially needed in order to allow users to upload experimental expression datasets and build combinatorial regulatory networks corresponding to their particular contexts. In this work, we compiled putative TF-gene, miRNA-gene and TF-miRNA regulatory relationships from forward-engineering pipelines and curated them as built-in data libraries. We streamlined the R codes of our two separate forward-and-reverse engineering algorithms for combinatorial gene regulatory network construction and formalized them as two major functional modules. As a result, we released the cGRNB (combinatorial Gene Regulatory Networks Builder): a web server for constructing combinatorial gene regulatory networks through integrated engineering of seed-matching sequence information and gene expression datasets. The cGRNB enables two major network-building modules, one for MPGE (miRNA-perturbed gene expression) datasets and the other for parallel miRNA/mRNA expression datasets. A miRNA-centered two-layer combinatorial regulatory cascade is the output of the first module and a comprehensive genome-wide network involving all three types of combinatorial regulations (TF-gene, TF-miRNA, and miRNA-gene) are the output of the second module. In this article we propose cGRNB, a web server for building combinatorial gene regulatory networks through integrated engineering of seed-matching sequence information and gene expression datasets. Since parallel miRNA/mRNA expression datasets are rapidly accumulated by the advance of next-generation sequencing techniques, cGRNB will be very useful tool for researchers to build combinatorial gene regulatory networks based on expression datasets

  10. Genexpi: a toolset for identifying regulons and validating gene regulatory networks using time-course expression data.

    PubMed

    Modrák, Martin; Vohradský, Jiří

    2018-04-13

    Identifying regulons of sigma factors is a vital subtask of gene network inference. Integrating multiple sources of data is essential for correct identification of regulons and complete gene regulatory networks. Time series of expression data measured with microarrays or RNA-seq combined with static binding experiments (e.g., ChIP-seq) or literature mining may be used for inference of sigma factor regulatory networks. We introduce Genexpi: a tool to identify sigma factors by combining candidates obtained from ChIP experiments or literature mining with time-course gene expression data. While Genexpi can be used to infer other types of regulatory interactions, it was designed and validated on real biological data from bacterial regulons. In this paper, we put primary focus on CyGenexpi: a plugin integrating Genexpi with the Cytoscape software for ease of use. As a part of this effort, a plugin for handling time series data in Cytoscape called CyDataseries has been developed and made available. Genexpi is also available as a standalone command line tool and an R package. Genexpi is a useful part of gene network inference toolbox. It provides meaningful information about the composition of regulons and delivers biologically interpretable results.

  11. Regulatory gene networks that shape the development of adaptive phenotypic plasticity in a cichlid fish.

    PubMed

    Schneider, Ralf F; Li, Yuanhao; Meyer, Axel; Gunter, Helen M

    2014-09-01

    Phenotypic plasticity is the ability of organisms with a given genotype to develop different phenotypes according to environmental stimuli, resulting in individuals that are better adapted to local conditions. In spite of their ecological importance, the developmental regulatory networks underlying plastic phenotypes often remain uncharacterized. We examined the regulatory basis of diet-induced plasticity in the lower pharyngeal jaw (LPJ) of the cichlid fish Astatoreochromis alluaudi, a model species in the study of adaptive plasticity. Through raising juvenile A. alluaudi on either a hard or soft diet (hard-shelled or pulverized snails) for between 1 and 8 months, we gained insight into the temporal regulation of 19 previously identified candidate genes during the early stages of plasticity development. Plasticity in LPJ morphology was first detected between 3 and 5 months of diet treatment. The candidate genes, belonging to various functional categories, displayed dynamic expression patterns that consistently preceded the onset of morphological divergence and putatively contribute to the initiation of the plastic phenotypes. Within functional categories, we observed striking co-expression, and transcription factor binding site analysis was used to examine the prospective basis of their coregulation. We propose a regulatory network of LPJ plasticity in cichlids, presenting evidence for regulatory crosstalk between bone and muscle tissues, which putatively facilitates the development of this highly integrated trait. Through incorporating a developmental time-course into a phenotypic plasticity study, we have identified an interconnected, environmentally responsive regulatory network that shapes the development of plasticity in a key innovation of East African cichlids. © 2014 John Wiley & Sons Ltd.

  12. Inferring Regulatory Networks from Experimental Morphological Phenotypes: A Computational Method Reverse-Engineers Planarian Regeneration

    PubMed Central

    Lobo, Daniel; Levin, Michael

    2015-01-01

    Transformative applications in biomedicine require the discovery of complex regulatory networks that explain the development and regeneration of anatomical structures, and reveal what external signals will trigger desired changes of large-scale pattern. Despite recent advances in bioinformatics, extracting mechanistic pathway models from experimental morphological data is a key open challenge that has resisted automation. The fundamental difficulty of manually predicting emergent behavior of even simple networks has limited the models invented by human scientists to pathway diagrams that show necessary subunit interactions but do not reveal the dynamics that are sufficient for complex, self-regulating pattern to emerge. To finally bridge the gap between high-resolution genetic data and the ability to understand and control patterning, it is critical to develop computational tools to efficiently extract regulatory pathways from the resultant experimental shape phenotypes. For example, planarian regeneration has been studied for over a century, but despite increasing insight into the pathways that control its stem cells, no constructive, mechanistic model has yet been found by human scientists that explains more than one or two key features of its remarkable ability to regenerate its correct anatomical pattern after drastic perturbations. We present a method to infer the molecular products, topology, and spatial and temporal non-linear dynamics of regulatory networks recapitulating in silico the rich dataset of morphological phenotypes resulting from genetic, surgical, and pharmacological experiments. We demonstrated our approach by inferring complete regulatory networks explaining the outcomes of the main functional regeneration experiments in the planarian literature; By analyzing all the datasets together, our system inferred the first systems-biology comprehensive dynamical model explaining patterning in planarian regeneration. This method provides an automated

  13. Receptors rather than signals change in expression in four physiological regulatory networks during evolutionary divergence in threespine stickleback.

    PubMed

    Di Poi, Carole; Bélanger, Dominic; Amyot, Marc; Rogers, Sean; Aubin-Horth, Nadia

    2016-07-01

    The molecular mechanisms underlying behavioural evolution following colonization of novel environments are largely unknown. Molecules that interact to control equilibrium within an organism form physiological regulatory networks. It is essential to determine whether particular components of physiological regulatory networks evolve or if the network as a whole is affected in populations diverging in behavioural responses, as this may affect the nature, amplitude and number of impacted traits. We studied the regulation of four physiological regulatory networks in freshwater and marine populations of threespine stickleback raised in a common environment, which were previously characterized as showing evolutionary divergence in behaviour and stress reactivity. We measured nineteen components of these networks (ligands and receptors) using mRNA and monoamine levels in the brain, pituitary and interrenal gland, as well as hormone levels. Freshwater fish showed higher expression in the brain of adrenergic (adrb2a), serotonergic (htr2a) and dopaminergic (DRD2) receptors, but lower expression of the htr2b receptor. Freshwater fish also showed higher expression of the mc2r receptor of the glucocorticoid axis in the interrenals. Collectively, our results suggest that the inheritance of the regulation of these networks may be implicated in the evolution of behaviour and stress reactivity in association with population divergence. Our results also suggest that evolutionary change in freshwater threespine stickleback may be more associated with the expression of specific receptors rather than with global changes of all the measured constituents of the physiological regulatory networks. © 2016 John Wiley & Sons Ltd.

  14. An integrated approach to characterize transcription factor and microRNA regulatory networks involved in Schwann cell response to peripheral nerve injury

    PubMed Central

    2013-01-01

    Background The regenerative response of Schwann cells after peripheral nerve injury is a critical process directly related to the pathophysiology of a number of neurodegenerative diseases. This SC injury response is dependent on an intricate gene regulatory program coordinated by a number of transcription factors and microRNAs, but the interactions among them remain largely unknown. Uncovering the transcriptional and post-transcriptional regulatory networks governing the Schwann cell injury response is a key step towards a better understanding of Schwann cell biology and may help develop novel therapies for related diseases. Performing such comprehensive network analysis requires systematic bioinformatics methods to integrate multiple genomic datasets. Results In this study we present a computational pipeline to infer transcription factor and microRNA regulatory networks. Our approach combined mRNA and microRNA expression profiling data, ChIP-Seq data of transcription factors, and computational transcription factor and microRNA target prediction. Using mRNA and microRNA expression data collected in a Schwann cell injury model, we constructed a regulatory network and studied regulatory pathways involved in Schwann cell response to injury. Furthermore, we analyzed network motifs and obtained insights on cooperative regulation of transcription factors and microRNAs in Schwann cell injury recovery. Conclusions This work demonstrates a systematic method for gene regulatory network inference that may be used to gain new information on gene regulation by transcription factors and microRNAs. PMID:23387820

  15. Modeling workplace contact networks: The effects of organizational structure, architecture, and reporting errors on epidemic predictions.

    PubMed

    Potter, Gail E; Smieszek, Timo; Sailer, Kerstin

    2015-09-01

    Face-to-face social contacts are potentially important transmission routes for acute respiratory infections, and understanding the contact network can improve our ability to predict, contain, and control epidemics. Although workplaces are important settings for infectious disease transmission, few studies have collected workplace contact data and estimated workplace contact networks. We use contact diaries, architectural distance measures, and institutional structures to estimate social contact networks within a Swiss research institute. Some contact reports were inconsistent, indicating reporting errors. We adjust for this with a latent variable model, jointly estimating the true (unobserved) network of contacts and duration-specific reporting probabilities. We find that contact probability decreases with distance, and that research group membership, role, and shared projects are strongly predictive of contact patterns. Estimated reporting probabilities were low only for 0-5 min contacts. Adjusting for reporting error changed the estimate of the duration distribution, but did not change the estimates of covariate effects and had little effect on epidemic predictions. Our epidemic simulation study indicates that inclusion of network structure based on architectural and organizational structure data can improve the accuracy of epidemic forecasting models.

  16. Modeling workplace contact networks: The effects of organizational structure, architecture, and reporting errors on epidemic predictions

    PubMed Central

    Potter, Gail E.; Smieszek, Timo; Sailer, Kerstin

    2015-01-01

    Face-to-face social contacts are potentially important transmission routes for acute respiratory infections, and understanding the contact network can improve our ability to predict, contain, and control epidemics. Although workplaces are important settings for infectious disease transmission, few studies have collected workplace contact data and estimated workplace contact networks. We use contact diaries, architectural distance measures, and institutional structures to estimate social contact networks within a Swiss research institute. Some contact reports were inconsistent, indicating reporting errors. We adjust for this with a latent variable model, jointly estimating the true (unobserved) network of contacts and duration-specific reporting probabilities. We find that contact probability decreases with distance, and that research group membership, role, and shared projects are strongly predictive of contact patterns. Estimated reporting probabilities were low only for 0–5 min contacts. Adjusting for reporting error changed the estimate of the duration distribution, but did not change the estimates of covariate effects and had little effect on epidemic predictions. Our epidemic simulation study indicates that inclusion of network structure based on architectural and organizational structure data can improve the accuracy of epidemic forecasting models. PMID:26634122

  17. Lunar Relay Satellite Network for Space Exploration: Architecture, Technologies and Challenges

    NASA Technical Reports Server (NTRS)

    Bhasin, Kul B.; Hackenberg, Anthony W.; Slywczak, Richard A.; Bose, Prasanta; Bergamo, Marcos; Hayden, Jeffrey L.

    2006-01-01

    NASA is planning a series of short and long duration human and robotic missions to explore the Moon and then Mars. A key objective of these missions is to grow, through a series of launches, a system of systems infrastructure with the capability for safe and sustainable autonomous operations at minimum cost while maximizing the exploration capabilities and science return. An incremental implementation process will enable a buildup of the communication, navigation, networking, computing, and informatics architectures to support human exploration missions in the vicinities and on the surfaces of the Moon and Mars. These architectures will support all space and surface nodes, including other orbiters, lander vehicles, humans in spacesuits, robots, rovers, human habitats, and pressurized vehicles. This paper describes the integration of an innovative MAC and networking technology with an equally innovative position-dependent, data routing, network technology. The MAC technology provides the relay spacecraft with the capability to autonomously discover neighbor spacecraft and surface nodes, establish variable-rate links and communicate simultaneously with multiple in-space and surface clients at varying and rapidly changing distances while making optimum use of the available power. The networking technology uses attitude sensors, a time synchronization protocol and occasional orbit-corrections to maintain awareness of its instantaneous position and attitude in space as well as the orbital or surface location of its communication clients. A position-dependent data routing capability is used in the communication relay satellites to handle the movement of data among any of multiple clients (including Earth) that may be simultaneously in view; and if not in view, the relay will temporarily store the data from a client source and download it when the destination client comes into view. The integration of the MAC and data routing networking technologies would enable a relay

  18. A novel survivable architecture for hybrid WDM/TDM passive optical networks

    NASA Astrophysics Data System (ADS)

    Qiu, Yang; Chan, Chun-Kit

    2014-02-01

    A novel tree-ring survivable architecture, which consists of an organization of a wavelength-division-multiplexing (WDM) tree from optical line terminal (OLT) to remote nodes (RNs) and a time division multiplexing (TDM) ring in each RN, is proposed for hybrid WDM/TDM passive optical networks. By utilizing the cyclic property of arrayed waveguide gratings (AWGs) and the single-ring topology among a group of optical network units (ONUs) in the remote node, not only the feeder and distribution fibers, but also any fiber failures in the RN rings are protected simultaneously. Five-Gbit/s transmissions under both normal working and protection modes were experimentally demonstrated and a traffic restoration time was successfully measured.

  19. SNAVA-A real-time multi-FPGA multi-model spiking neural network simulation architecture.

    PubMed

    Sripad, Athul; Sanchez, Giovanny; Zapata, Mireya; Pirrone, Vito; Dorta, Taho; Cambria, Salvatore; Marti, Albert; Krishnamourthy, Karthikeyan; Madrenas, Jordi

    2018-01-01

    Spiking Neural Networks (SNN) for Versatile Applications (SNAVA) simulation platform is a scalable and programmable parallel architecture that supports real-time, large-scale, multi-model SNN computation. This parallel architecture is implemented in modern Field-Programmable Gate Arrays (FPGAs) devices to provide high performance execution and flexibility to support large-scale SNN models. Flexibility is defined in terms of programmability, which allows easy synapse and neuron implementation. This has been achieved by using a special-purpose Processing Elements (PEs) for computing SNNs, and analyzing and customizing the instruction set according to the processing needs to achieve maximum performance with minimum resources. The parallel architecture is interfaced with customized Graphical User Interfaces (GUIs) to configure the SNN's connectivity, to compile the neuron-synapse model and to monitor SNN's activity. Our contribution intends to provide a tool that allows to prototype SNNs faster than on CPU/GPU architectures but significantly cheaper than fabricating a customized neuromorphic chip. This could be potentially valuable to the computational neuroscience and neuromorphic engineering communities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence of Homo sapiens.

    PubMed

    Glinsky, Gennadi V

    2016-09-19

    Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Collectively, a compendium of multiple diverse families of HSRS that are functionally and structurally divergent from Great Apes could be defined as the backbone of human-specific genomic regulatory networks. Here, the conservation patterns analysis of 18,364 candidate HSRS was carried out requiring that 100% of bases must remap during the alignments of human, chimpanzee, and bonobo sequences. A total of 5,535 candidate HSRS were identified that are: (i) highly conserved in Great Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from non-human primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Genome-wide proximity placement analysis of HSRS revealed that a small fraction of topologically associating domains (TADs) contain more than half of HSRS from four distinct families. TADs that are enriched for HSRS and termed rapidly evolving in humans TADs (revTADs) comprise 0.8-10.3% of 3,127 TADs in the hESC genome. RevTADs manifest distinct correlation patterns between placements of human accelerated regions, human-specific transcription factor-binding sites, and recombination rates. There is a significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (P < 0.0001 in all instances). Present analysis supports the idea that phenotypic divergence of Homo sapiens is driven by the evolution of human

  1. Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence of Homo sapiens

    PubMed Central

    Glinsky, Gennadi V.

    2016-01-01

    Abstract Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Collectively, a compendium of multiple diverse families of HSRS that are functionally and structurally divergent from Great Apes could be defined as the backbone of human-specific genomic regulatory networks. Here, the conservation patterns analysis of 18,364 candidate HSRS was carried out requiring that 100% of bases must remap during the alignments of human, chimpanzee, and bonobo sequences. A total of 5,535 candidate HSRS were identified that are: (i) highly conserved in Great Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from non-human primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Genome-wide proximity placement analysis of HSRS revealed that a small fraction of topologically associating domains (TADs) contain more than half of HSRS from four distinct families. TADs that are enriched for HSRS and termed rapidly evolving in humans TADs (revTADs) comprise 0.8–10.3% of 3,127 TADs in the hESC genome. RevTADs manifest distinct correlation patterns between placements of human accelerated regions, human-specific transcription factor-binding sites, and recombination rates. There is a significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (P < 0.0001 in all instances). Present analysis supports the idea that phenotypic divergence of Homo sapiens is driven by the evolution of

  2. Arabidopsis Ensemble Reverse-Engineered Gene Regulatory Network Discloses Interconnected Transcription Factors in Oxidative Stress[W

    PubMed Central

    Vermeirssen, Vanessa; De Clercq, Inge; Van Parys, Thomas; Van Breusegem, Frank; Van de Peer, Yves

    2014-01-01

    The abiotic stress response in plants is complex and tightly controlled by gene regulation. We present an abiotic stress gene regulatory network of 200,014 interactions for 11,938 target genes by integrating four complementary reverse-engineering solutions through average rank aggregation on an Arabidopsis thaliana microarray expression compendium. This ensemble performed the most robustly in benchmarking and greatly expands upon the availability of interactions currently reported. Besides recovering 1182 known regulatory interactions, cis-regulatory motifs and coherent functionalities of target genes corresponded with the predicted transcription factors. We provide a valuable resource of 572 abiotic stress modules of coregulated genes with functional and regulatory information, from which we deduced functional relationships for 1966 uncharacterized genes and many regulators. Using gain- and loss-of-function mutants of seven transcription factors grown under control and salt stress conditions, we experimentally validated 141 out of 271 predictions (52% precision) for 102 selected genes and mapped 148 additional transcription factor-gene regulatory interactions (49% recall). We identified an intricate core oxidative stress regulatory network where NAC13, NAC053, ERF6, WRKY6, and NAC032 transcription factors interconnect and function in detoxification. Our work shows that ensemble reverse-engineering can generate robust biological hypotheses of gene regulation in a multicellular eukaryote that can be tested by medium-throughput experimental validation. PMID:25549671

  3. Investigation of the multifunctional gene AOP3 expands the regulatory network fine-tuning glucosinolate production in Arabidopsis

    PubMed Central

    Jensen, Lea M.; Kliebenstein, Daniel J.; Burow, Meike

    2015-01-01

    Quantitative trait loci (QTL) mapping studies enable identification of loci that are part of regulatory networks controlling various phenotypes. Detailed investigations of genes within these loci are required to ultimately understand the function of individual genes and how they interact with other players in the network. In this study, we use transgenic plants in combination with natural variation to investigate the regulatory role of the AOP3 gene found in GS-AOP locus previously suggested to contribute to the regulation of glucosinolate defense compounds. Phenotypic analysis and QTL mapping in F2 populations with different AOP3 transgenes support that the enzymatic function and the AOP3 RNA both play a significant role in controlling glucosinolate accumulation. Furthermore, we find different loci interacting with either the enzymatic activity or the RNA of AOP3 and thereby extend the regulatory network controlling glucosinolate accumulation. PMID:26442075

  4. A systems biology model of the regulatory network in Populus leaves reveals interacting regulators and conserved regulation

    PubMed Central

    2011-01-01

    Background Green plant leaves have always fascinated biologists as hosts for photosynthesis and providers of basic energy to many food webs. Today, comprehensive databases of gene expression data enable us to apply increasingly more advanced computational methods for reverse-engineering the regulatory network of leaves, and to begin to understand the gene interactions underlying complex emergent properties related to stress-response and development. These new systems biology methods are now also being applied to organisms such as Populus, a woody perennial tree, in order to understand the specific characteristics of these species. Results We present a systems biology model of the regulatory network of Populus leaves. The network is reverse-engineered from promoter information and expression profiles of leaf-specific genes measured over a large set of conditions related to stress and developmental. The network model incorporates interactions between regulators, such as synergistic and competitive relationships, by evaluating increasingly more complex regulatory mechanisms, and is therefore able to identify new regulators of leaf development not found by traditional genomics methods based on pair-wise expression similarity. The approach is shown to explain available gene function information and to provide robust prediction of expression levels in new data. We also use the predictive capability of the model to identify condition-specific regulation as well as conserved regulation between Populus and Arabidopsis. Conclusions We outline a computationally inferred model of the regulatory network of Populus leaves, and show how treating genes as interacting, rather than individual, entities identifies new regulators compared to traditional genomics analysis. Although systems biology models should be used with care considering the complexity of regulatory programs and the limitations of current genomics data, methods describing interactions can provide hypotheses about

  5. PRODIGEN: visualizing the probability landscape of stochastic gene regulatory networks in state and time space.

    PubMed

    Ma, Chihua; Luciani, Timothy; Terebus, Anna; Liang, Jie; Marai, G Elisabeta

    2017-02-15

    Visualizing the complex probability landscape of stochastic gene regulatory networks can further biologists' understanding of phenotypic behavior associated with specific genes. We present PRODIGEN (PRObability DIstribution of GEne Networks), a web-based visual analysis tool for the systematic exploration of probability distributions over simulation time and state space in such networks. PRODIGEN was designed in collaboration with bioinformaticians who research stochastic gene networks. The analysis tool combines in a novel way existing, expanded, and new visual encodings to capture the time-varying characteristics of probability distributions: spaghetti plots over one dimensional projection, heatmaps of distributions over 2D projections, enhanced with overlaid time curves to display temporal changes, and novel individual glyphs of state information corresponding to particular peaks. We demonstrate the effectiveness of the tool through two case studies on the computed probabilistic landscape of a gene regulatory network and of a toggle-switch network. Domain expert feedback indicates that our visual approach can help biologists: 1) visualize probabilities of stable states, 2) explore the temporal probability distributions, and 3) discover small peaks in the probability landscape that have potential relation to specific diseases.

  6. Micro-Computer Network Architecture for Range Instrumentation Applications - Volume 1

    DTIC Science & Technology

    1991-12-18

    AD-A247 836 MTI-R89-006-28 Micro-Computer Network Architecture for Range Instrumentation Applications Volume 1 Mitchell R. Belzer DTIC Yong M . Cho... M . Belzer, Y. Cho, J. Han 13a. TYPE OF REPORT 13b. TIME COVERED 14. DATE OF REPORT (Year, Month, Day) 15. PAGE COUNT Final Technical FROM 09SeDQ89...SpecialI I , 1 . . r l n l m s n u m mt l ~ i m I n : t l l l Contents page cover page ....................................................... 1 Report

  7. Brain in situ hybridization maps as a source for reverse-engineering transcriptional regulatory networks: Alzheimer's disease insights

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Acquaah-Mensah, George K.; Taylor, Ronald C.

    Microarray data have been a valuable resource for identifying transcriptional regulatory relationships among genes. As an example, brain region-specific transcriptional regulatory events have the potential of providing etiological insights into Alzheimer Disease (AD). However, there is often a paucity of suitable brain-region specific expression data obtained via microarrays or other high throughput means. The Allen Brain Atlas in situ hybridization (ISH) data sets (Jones et al., 2009) represent a potentially valuable alternative source of high-throughput brain region-specific gene expression data for such purposes. In this study, Allen BrainAtlasmouse ISH data in the hippocampal fields were extracted, focusing on 508 genesmore » relevant to neurodegeneration. Transcriptional regulatory networkswere learned using three high-performing network inference algorithms. Only 17% of regulatory edges from a network reverse-engineered based on brain region-specific ISH data were also found in a network constructed upon gene expression correlations inmousewhole brain microarrays, thus showing the specificity of gene expression within brain sub-regions. Furthermore, the ISH data-based networks were used to identify instructive transcriptional regulatory relationships. Ncor2, Sp3 and Usf2 form a unique three-party regulatory motif, potentially affecting memory formation pathways. Nfe2l1, Egr1 and Usf2 emerge among regulators of genes involved in AD (e.g. Dhcr24, Aplp2, Tia1, Pdrx1, Vdac1, andSyn2). Further, Nfe2l1, Egr1 and Usf2 are sensitive to dietary factors and could be among links between dietary influences and genes in the AD etiology. Thus, this approach of harnessing brain region-specific ISH data represents a rare opportunity for gleaning unique etiological insights for diseases such as AD.« less

  8. The origins and evolutionary history of human non-coding RNA regulatory networks.

    PubMed

    Sherafatian, Masih; Mowla, Seyed Javad

    2017-04-01

    The evolutionary history and origin of the regulatory function of animal non-coding RNAs are not well understood. Lack of conservation of long non-coding RNAs and small sizes of microRNAs has been major obstacles in their phylogenetic analysis. In this study, we tried to shed more light on the evolution of ncRNA regulatory networks by changing our phylogenetic strategy to focus on the evolutionary pattern of their protein coding targets. We used available target databases of miRNAs and lncRNAs to find their protein coding targets in human. We were able to recognize evolutionary hallmarks of ncRNA targets by phylostratigraphic analysis. We found the conventional 3'-UTR and lesser known 5'-UTR targets of miRNAs to be enriched at three consecutive phylostrata. Firstly, in eukaryata phylostratum corresponding to the emergence of miRNAs, our study revealed that miRNA targets function primarily in cell cycle processes. Moreover, the same overrepresentation of the targets observed in the next two consecutive phylostrata, opisthokonta and eumetazoa, corresponded to the expansion periods of miRNAs in animals evolution. Coding sequence targets of miRNAs showed a delayed rise at opisthokonta phylostratum, compared to the 3' and 5' UTR targets of miRNAs. LncRNA regulatory network was the latest to evolve at eumetazoa.

  9. Inference of hierarchical regulatory network of estrogen-dependent breast cancer through ChIP-based data

    PubMed Central

    2010-01-01

    Background Global profiling of in vivo protein-DNA interactions using ChIP-based technologies has evolved rapidly in recent years. Although many genome-wide studies have identified thousands of ERα binding sites and have revealed the associated transcription factor (TF) partners, such as AP1, FOXA1 and CEBP, little is known about ERα associated hierarchical transcriptional regulatory networks. Results In this study, we applied computational approaches to analyze three public available ChIP-based datasets: ChIP-seq, ChIP-PET and ChIP-chip, and to investigate the hierarchical regulatory network for ERα and ERα partner TFs regulation in estrogen-dependent breast cancer MCF7 cells. 16 common TFs and two common new TF partners (RORA and PITX2) were found among ChIP-seq, ChIP-chip and ChIP-PET datasets. The regulatory networks were constructed by scanning the ChIP-peak region with TF specific position weight matrix (PWM). A permutation test was performed to test the reliability of each connection of the network. We then used DREM software to perform gene ontology function analysis on the common genes. We found that FOS, PITX2, RORA and FOXA1 were involved in the up-regulated genes. We also conducted the ERα and Pol-II ChIP-seq experiments in tamoxifen resistance MCF7 cells (denoted as MCF7-T in this study) and compared the difference between MCF7 and MCF7-T cells. The result showed very little overlap between these two cells in terms of targeted genes (21.2% of common genes) and targeted TFs (25% of common TFs). The significant dissimilarity may indicate totally different transcriptional regulatory mechanisms between these two cancer cells. Conclusions Our study uncovers new estrogen-mediated regulatory networks by mining three ChIP-based data in MCF7 cells and ChIP-seq data in MCF7-T cells. We compared the different ChIP-based technologies as well as different breast cancer cells. Our computational analytical approach may guide biologists to further study the

  10. Significantly enhanced creep resistance of low volume fraction in-situ TiBw/Ti6Al4V composites by architectured network reinforcements

    PubMed Central

    Wang, S.; Huang, L. J.; Geng, L.; Scarpa, F.; Jiao, Y.; Peng, H. X.

    2017-01-01

    We present a new class of TiBw/Ti6Al4V composites with a network reinforcement architecture that exhibits a significant creep resistance compared to monolithic Ti6Al4V alloys. Creep tests performed at temperatures between 773 K and 923 K and stress range of 100 MPa-300 MPa indicate both a significant improvement of the composites creep resistance due to the network architecture made by the TiB whiskers (TiBw), and a decrease of the steady-state creep rates by augmenting the local volume fractions of TiBw in the network region. The deformation behavior is driven by a diffusion-controlled dislocation climb process. Moreover, the activation energies of these composites are significantly higher than that of Ti6Al4V alloys, indicating a higher creep resistance. The increase of the activation energy can be attributed to the TiBw architecture that severely impedes the movements of dislocation and grain boundary sliding and provides a tailoring of the stress transfer. These micromechanical mechanisms lead to a remarkable improvement of the creep resistance of these networked TiBw/Ti6Al4V composites featuring the special networked architecture. PMID:28094350

  11. A flexible data fusion architecture for persistent surveillance using ultra-low-power wireless sensor networks

    NASA Astrophysics Data System (ADS)

    Hanson, Jeffrey A.; McLaughlin, Keith L.; Sereno, Thomas J.

    2011-06-01

    We have developed a flexible, target-driven, multi-modal, physics-based fusion architecture that efficiently searches sensor detections for targets and rejects clutter while controlling the combinatoric problems that commonly arise in datadriven fusion systems. The informational constraints imposed by long lifetime requirements make systems vulnerable to false alarms. We demonstrate that our data fusion system significantly reduces false alarms while maintaining high sensitivity to threats. In addition, mission goals can vary substantially in terms of targets-of-interest, required characterization, acceptable latency, and false alarm rates. Our fusion architecture provides the flexibility to match these trade-offs with mission requirements unlike many conventional systems that require significant modifications for each new mission. We illustrate our data fusion performance with case studies that span many of the potential mission scenarios including border surveillance, base security, and infrastructure protection. In these studies, we deployed multi-modal sensor nodes - including geophones, magnetometers, accelerometers and PIR sensors - with low-power processing algorithms and low-bandwidth wireless mesh networking to create networks capable of multi-year operation. The results show our data fusion architecture maintains high sensitivities while suppressing most false alarms for a variety of environments and targets.

  12. Inference of time-delayed gene regulatory networks based on dynamic Bayesian network hybrid learning method

    PubMed Central

    Yu, Bin; Xu, Jia-Meng; Li, Shan; Chen, Cheng; Chen, Rui-Xin; Wang, Lei; Zhang, Yan; Wang, Ming-Hui

    2017-01-01

    Gene regulatory networks (GRNs) research reveals complex life phenomena from the perspective of gene interaction, which is an important research field in systems biology. Traditional Bayesian networks have a high computational complexity, and the network structure scoring model has a single feature. Information-based approaches cannot identify the direction of regulation. In order to make up for the shortcomings of the above methods, this paper presents a novel hybrid learning method (DBNCS) based on dynamic Bayesian network (DBN) to construct the multiple time-delayed GRNs for the first time, combining the comprehensive score (CS) with the DBN model. DBNCS algorithm first uses CMI2NI (conditional mutual inclusive information-based network inference) algorithm for network structure profiles learning, namely the construction of search space. Then the redundant regulations are removed by using the recursive optimization algorithm (RO), thereby reduce the false positive rate. Secondly, the network structure profiles are decomposed into a set of cliques without loss, which can significantly reduce the computational complexity. Finally, DBN model is used to identify the direction of gene regulation within the cliques and search for the optimal network structure. The performance of DBNCS algorithm is evaluated by the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in Escherichia coli, and compared with other state-of-the-art methods. The experimental results show the rationality of the algorithm design and the outstanding performance of the GRNs. PMID:29113310

  13. Inference of time-delayed gene regulatory networks based on dynamic Bayesian network hybrid learning method.

    PubMed

    Yu, Bin; Xu, Jia-Meng; Li, Shan; Chen, Cheng; Chen, Rui-Xin; Wang, Lei; Zhang, Yan; Wang, Ming-Hui

    2017-10-06

    Gene regulatory networks (GRNs) research reveals complex life phenomena from the perspective of gene interaction, which is an important research field in systems biology. Traditional Bayesian networks have a high computational complexity, and the network structure scoring model has a single feature. Information-based approaches cannot identify the direction of regulation. In order to make up for the shortcomings of the above methods, this paper presents a novel hybrid learning method (DBNCS) based on dynamic Bayesian network (DBN) to construct the multiple time-delayed GRNs for the first time, combining the comprehensive score (CS) with the DBN model. DBNCS algorithm first uses CMI2NI (conditional mutual inclusive information-based network inference) algorithm for network structure profiles learning, namely the construction of search space. Then the redundant regulations are removed by using the recursive optimization algorithm (RO), thereby reduce the false positive rate. Secondly, the network structure profiles are decomposed into a set of cliques without loss, which can significantly reduce the computational complexity. Finally, DBN model is used to identify the direction of gene regulation within the cliques and search for the optimal network structure. The performance of DBNCS algorithm is evaluated by the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in Escherichia coli , and compared with other state-of-the-art methods. The experimental results show the rationality of the algorithm design and the outstanding performance of the GRNs.

  14. EGRINs (Environmental Gene Regulatory Influence Networks) in Rice That Function in the Response to Water Deficit, High Temperature, and Agricultural Environments[OPEN

    PubMed Central

    Hafemeister, Christoph; Nicotra, Adrienne B.; Jagadish, S.V. Krishna; Bonneau, Richard; Purugganan, Michael

    2016-01-01

    Environmental gene regulatory influence networks (EGRINs) coordinate the timing and rate of gene expression in response to environmental signals. EGRINs encompass many layers of regulation, which culminate in changes in accumulated transcript levels. Here, we inferred EGRINs for the response of five tropical Asian rice (Oryza sativa) cultivars to high temperatures, water deficit, and agricultural field conditions by systematically integrating time-series transcriptome data, patterns of nucleosome-free chromatin, and the occurrence of known cis-regulatory elements. First, we identified 5447 putative target genes for 445 transcription factors (TFs) by connecting TFs with genes harboring known cis-regulatory motifs in nucleosome-free regions proximal to their transcriptional start sites. We then used network component analysis to estimate the regulatory activity for each TF based on the expression of its putative target genes. Finally, we inferred an EGRIN using the estimated transcription factor activity (TFA) as the regulator. The EGRINs include regulatory interactions between 4052 target genes regulated by 113 TFs. We resolved distinct regulatory roles for members of the heat shock factor family, including a putative regulatory connection between abiotic stress and the circadian clock. TFA estimation using network component analysis is an effective way of incorporating multiple genome-scale measurements into network inference. PMID:27655842

  15. Rhodobase, a meta-analytical tool for reconstructing gene regulatory networks in a model photosynthetic bacterium.

    PubMed

    Moskvin, Oleg V; Bolotin, Dmitry; Wang, Andrew; Ivanov, Pavel S; Gomelsky, Mark

    2011-02-01

    We present Rhodobase, a web-based meta-analytical tool for analysis of transcriptional regulation in a model anoxygenic photosynthetic bacterium, Rhodobacter sphaeroides. The gene association meta-analysis is based on the pooled data from 100 of R. sphaeroides whole-genome DNA microarrays. Gene-centric regulatory networks were visualized using the StarNet approach (Jupiter, D.C., VanBuren, V., 2008. A visual data mining tool that facilitates reconstruction of transcription regulatory networks. PLoS ONE 3, e1717) with several modifications. We developed a means to identify and visualize operons and superoperons. We designed a framework for the cross-genome search for transcription factor binding sites that takes into account high GC-content and oligonucleotide usage profile characteristic of the R. sphaeroides genome. To facilitate reconstruction of directional relationships between co-regulated genes, we screened upstream sequences (-400 to +20bp from start codons) of all genes for putative binding sites of bacterial transcription factors using a self-optimizing search method developed here. To test performance of the meta-analysis tools and transcription factor site predictions, we reconstructed selected nodes of the R. sphaeroides transcription factor-centric regulatory matrix. The test revealed regulatory relationships that correlate well with the experimentally derived data. The database of transcriptional profile correlations, the network visualization engine and the optimized search engine for transcription factor binding sites analysis are available at http://rhodobase.org. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  16. GEONETCast Americas - Architecture

    Science.gov Websites

    site map | contact us USGEO logo HOME ABOUT US Who We Are Coverage Architecture About GEOSS and GEONETCast Americas, the coverage from the satellite network, the architecture of the system, and some

  17. Examining the volume efficiency of the cortical architecture in a multi-processor network model.

    PubMed

    Ruppin, E; Schwartz, E L; Yeshurun, Y

    1993-01-01

    The convoluted form of the sheet-like mammalian cortex naturally raises the question whether there is a simple geometrical reason for the prevalence of cortical architecture in the brains of higher vertebrates. Addressing this question, we present a formal analysis of the volume occupied by a massively connected network or processors (neurons) and then consider the pertaining cortical data. Three gross macroscopic features of cortical organization are examined: the segregation of white and gray matter, the circumferential organization of the gray matter around the white matter, and the folded cortical structure. Our results testify to the efficiency of cortical architecture.

  18. Intelligent Approaches in Improving In-vehicle Network Architecture and Minimizing Power Consumption in Combat Vehicles

    DTIC Science & Technology

    2011-01-01

    4 . TITLE AND SUBTITLE INTELLIGENT APPROACHES IN IMPROVING IN-VEHICLE NETWORK ARCHITECTURE AND MINIMIZING POWER CONSUMPTION IN COMBAT VEHICLES 5a... 4 1.3 Organization...32 CHAPTER 4 – SOFTWARE RELIABILITY PREDICTION FOR COMBAT VEHICLES . 33 4.1 Introduction

  19. Enriching regulatory networks by bootstrap learning using optimised GO-based gene similarity and gene links mined from PubMed abstracts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Taylor, Ronald C.; Sanfilippo, Antonio P.; McDermott, Jason E.

    2011-02-18

    Transcriptional regulatory networks are being determined using “reverse engineering” methods that infer connections based on correlations in gene state. Corroboration of such networks through independent means such as evidence from the biomedical literature is desirable. Here, we explore a novel approach, a bootstrapping version of our previous Cross-Ontological Analytic method (XOA) that can be used for semi-automated annotation and verification of inferred regulatory connections, as well as for discovery of additional functional relationships between the genes. First, we use our annotation and network expansion method on a biological network learned entirely from the literature. We show how new relevant linksmore » between genes can be iteratively derived using a gene similarity measure based on the Gene Ontology that is optimized on the input network at each iteration. Second, we apply our method to annotation, verification, and expansion of a set of regulatory connections found by the Context Likelihood of Relatedness algorithm.« less

  20. Resource-aware system architecture model for implementation of quantum aided Byzantine agreement on quantum repeater networks

    NASA Astrophysics Data System (ADS)

    Taherkhani, Mohammand Amin; Navi, Keivan; Van Meter, Rodney

    2018-01-01

    Quantum aided Byzantine agreement is an important distributed quantum algorithm with unique features in comparison to classical deterministic and randomized algorithms, requiring only a constant expected number of rounds in addition to giving a higher level of security. In this paper, we analyze details of the high level multi-party algorithm, and propose elements of the design for the quantum architecture and circuits required at each node to run the algorithm on a quantum repeater network (QRN). Our optimization techniques have reduced the quantum circuit depth by 44% and the number of qubits in each node by 20% for a minimum five-node setup compared to the design based on the standard arithmetic circuits. These improvements lead to a quantum system architecture with 160 qubits per node, space-time product (an estimate of the required fidelity) {KQ}≈ 1.3× {10}5 per node and error threshold 1.1× {10}-6 for the total nodes in the network. The evaluation of the designed architecture shows that to execute the algorithm once on the minimum setup, we need to successfully distribute a total of 648 Bell pairs across the network, spread evenly between all pairs of nodes. This framework can be considered a starting point for establishing a road-map for light-weight demonstration of a distributed quantum application on QRNs.

  1. SignaLink 2 - a signaling pathway resource with multi-layered regulatory networks.

    PubMed

    Fazekas, Dávid; Koltai, Mihály; Türei, Dénes; Módos, Dezső; Pálfy, Máté; Dúl, Zoltán; Zsákai, Lilian; Szalay-Bekő, Máté; Lenti, Katalin; Farkas, Illés J; Vellai, Tibor; Csermely, Péter; Korcsmáros, Tamás

    2013-01-18

    Signaling networks in eukaryotes are made up of upstream and downstream subnetworks. The upstream subnetwork contains the intertwined network of signaling pathways, while the downstream regulatory part contains transcription factors and their binding sites on the DNA as well as microRNAs and their mRNA targets. Currently, most signaling and regulatory databases contain only a subsection of this network, making comprehensive analyses highly time-consuming and dependent on specific data handling expertise. The need for detailed mapping of signaling systems is also supported by the fact that several drug development failures were caused by undiscovered cross-talk or regulatory effects of drug targets. We previously created a uniformly curated signaling pathway resource, SignaLink, to facilitate the analysis of pathway cross-talks. Here, we present SignaLink 2, which significantly extends the coverage and applications of its predecessor. We developed a novel concept to integrate and utilize different subsections (i.e., layers) of the signaling network. The multi-layered (onion-like) database structure is made up of signaling pathways, their pathway regulators (e.g., scaffold and endocytotic proteins) and modifier enzymes (e.g., phosphatases, ubiquitin ligases), as well as transcriptional and post-transcriptional regulators of all of these components. The user-friendly website allows the interactive exploration of how each signaling protein is regulated. The customizable download page enables the analysis of any user-specified part of the signaling network. Compared to other signaling resources, distinctive features of SignaLink 2 are the following: 1) it involves experimental data not only from humans but from two invertebrate model organisms, C. elegans and D. melanogaster; 2) combines manual curation with large-scale datasets; 3) provides confidence scores for each interaction; 4) operates a customizable download page with multiple file formats (e.g., Bio

  2. Service oriented network architecture for control and management of home appliances

    NASA Astrophysics Data System (ADS)

    Hayakawa, Hiroshi; Koita, Takahiro; Sato, Kenya

    2005-12-01

    Recent advances in multimedia network systems and mechatronics have led to the development of a new generation of applications that associate the use of various multimedia objects with the behavior of multiple robotic actors. The connection of audio and video devices through high speed multimedia networks is expected to make the system more convenient to use. For example, many home appliances, such as a video camera, a display monitor, a video recorder, an audio system and so on, are being equipped with a communication interface in the near future. Recently some platforms (i.e. UPnP1, HAVi2 and so on) are proposed for constructing home networks; however, there are some issues to be solved to realize various services by connecting different equipment via the pervasive peer-to-peer network. UPnP offers network connectivity of PCs of intelligent home appliances, practically, which means to require a PC in the network to control other devices. Meanwhile, HAVi has been developed for intelligent AV equipments with sophisticated functions using high CPU power and large memory. Considering the targets of home alliances are embedded systems, this situation raises issues of software and hardware complexity, cost, power consumption and so on. In this study, we have proposed and developed the service oriented network architecture for control and management of home appliances, named SONICA (Service Oriented Network Interoperability for Component Adaptation), to address these issues described before.

  3. Predicting electrocardiogram and arterial blood pressure waveforms with different Echo State Network architectures.

    PubMed

    Fong, Allan; Mittu, Ranjeev; Ratwani, Raj; Reggia, James

    2014-01-01

    Alarm fatigue caused by false alarms and alerts is an extremely important issue for the medical staff in Intensive Care Units. The ability to predict electrocardiogram and arterial blood pressure waveforms can potentially help the staff and hospital systems better classify a patient's waveforms and subsequent alarms. This paper explores the use of Echo State Networks, a specific type of neural network for mining, understanding, and predicting electrocardiogram and arterial blood pressure waveforms. Several network architectures are designed and evaluated. The results show the utility of these echo state networks, particularly ones with larger integrated reservoirs, for predicting electrocardiogram waveforms and the adaptability of such models across individuals. The work presented here offers a unique approach for understanding and predicting a patient's waveforms in order to potentially improve alarm generation. We conclude with a brief discussion of future extensions of this research.

  4. Distinct tissue-specific transcriptional regulation revealed by gene regulatory networks in maize.

    PubMed

    Huang, Ji; Zheng, Juefei; Yuan, Hui; McGinnis, Karen

    2018-06-07

    Transcription factors (TFs) are proteins that can bind to DNA sequences and regulate gene expression. Many TFs are master regulators in cells that contribute to tissue-specific and cell-type-specific gene expression patterns in eukaryotes. Maize has been a model organism for over one hundred years, but little is known about its tissue-specific gene regulation through TFs. In this study, we used a network approach to elucidate gene regulatory networks (GRNs) in four tissues (leaf, root, SAM and seed) in maize. We utilized GENIE3, a machine-learning algorithm combined with large quantity of RNA-Seq expression data to construct four tissue-specific GRNs. Unlike some other techniques, this approach is not limited by high-quality Position Weighed Matrix (PWM), and can therefore predict GRNs for over 2000 TFs in maize. Although many TFs were expressed across multiple tissues, a multi-tiered analysis predicted tissue-specific regulatory functions for many transcription factors. Some well-studied TFs emerged within the four tissue-specific GRNs, and the GRN predictions matched expectations based upon published results for many of these examples. Our GRNs were also validated by ChIP-Seq datasets (KN1, FEA4 and O2). Key TFs were identified for each tissue and matched expectations for key regulators in each tissue, including GO enrichment and identity with known regulatory factors for that tissue. We also found functional modules in each network by clustering analysis with the MCL algorithm. By combining publicly available genome-wide expression data and network analysis, we can uncover GRNs at tissue-level resolution in maize. Since ChIP-Seq and PWMs are still limited in several model organisms, our study provides a uniform platform that can be adapted to any species with genome-wide expression data to construct GRNs. We also present a publicly available database, maize tissue-specific GRN (mGRN, https://www.bio.fsu.edu/mcginnislab/mgrn/ ), for easy querying. All source code

  5. Porcine Tissue-Specific Regulatory Networks Derived from Meta-Analysis of the Transcriptome

    PubMed Central

    Pérez-Montarelo, Dafne; Hudson, Nicholas J.; Fernández, Ana I.; Ramayo-Caldas, Yuliaxis; Dalrymple, Brian P.; Reverter, Antonio

    2012-01-01

    The processes that drive tissue identity and differentiation remain unclear for most tissue types. So are the gene networks and transcription factors (TF) responsible for the differential structure and function of each particular tissue, and this is particularly true for non model species with incomplete genomic resources. To better understand the regulation of genes responsible for tissue identity in pigs, we have inferred regulatory networks from a meta-analysis of 20 gene expression studies spanning 480 Porcine Affymetrix chips for 134 experimental conditions on 27 distinct tissues. We developed a mixed-model normalization approach with a covariance structure that accommodated the disparity in the origin of the individual studies, and obtained the normalized expression of 12,320 genes across the 27 tissues. Using this resource, we constructed a network, based on the co-expression patterns of 1,072 TF and 1,232 tissue specific genes. The resulting network is consistent with the known biology of tissue development. Within the network, genes clustered by tissue and tissues clustered by site of embryonic origin. These clusters were significantly enriched for genes annotated in key relevant biological processes and confirm gene functions and interactions from the literature. We implemented a Regulatory Impact Factor (RIF) metric to identify the key regulators in skeletal muscle and tissues from the central nervous systems. The normalization of the meta-analysis, the inference of the gene co-expression network and the RIF metric, operated synergistically towards a successful search for tissue-specific regulators. Novel among these findings are evidence suggesting a novel key role of ERCC3 as a muscle regulator. Together, our results recapitulate the known biology behind tissue specificity and provide new valuable insights in a less studied but valuable model species. PMID:23049964

  6. Organically Grown Architectures: Creating Decentralized, Autonomous Systems by Embryomorphic Engineering

    NASA Astrophysics Data System (ADS)

    Doursat, René

    Exploding growth growth in computational systems forces us to gradually replace rigid design and control with decentralization and autonomy. Information technologies will progress, instead, by"meta-designing" mechanisms of system self-assembly, self-regulation and evolution. Nature offers a great variety of efficient complex systems, in which numerous small elements form large-scale, adaptive patterns. The new engineering challenge is to recreate this self-organization and let it freely generate innovative designs under guidance. This article presents an original model of artificial system growth inspired by embryogenesis. A virtual organism is a lattice of cells that proliferate, migrate and self-pattern into differentiated domains. Each cell's fate is controlled by an internal gene regulatory network network. Embryomorphic engineering emphasizes hyperdistributed architectures, and their development as a prerequisite of evolutionary design.

  7. Apple miRNAs and tasiRNAs with novel regulatory networks

    PubMed Central

    2012-01-01

    Background MicroRNAs (miRNAs) and their regulatory functions have been extensively characterized in model species but whether apple has evolved similar or unique regulatory features remains unknown. Results We performed deep small RNA-seq and identified 23 conserved, 10 less-conserved and 42 apple-specific miRNAs or families with distinct expression patterns. The identified miRNAs target 118 genes representing a wide range of enzymatic and regulatory activities. Apple also conserves two TAS gene families with similar but unique trans-acting small interfering RNA (tasiRNA) biogenesis profiles and target specificities. Importantly, we found that miR159, miR828 and miR858 can collectively target up to 81 MYB genes potentially involved in diverse aspects of plant growth and development. These miRNA target sites are differentially conserved among MYBs, which is largely influenced by the location and conservation of the encoded amino acid residues in MYB factors. Finally, we found that 10 of the 19 miR828-targeted MYBs undergo small interfering RNA (siRNA) biogenesis at the 3' cleaved, highly divergent transcript regions, generating over 100 sequence-distinct siRNAs that potentially target over 70 diverse genes as confirmed by degradome analysis. Conclusions Our work identified and characterized apple miRNAs, their expression patterns, targets and regulatory functions. We also discovered that three miRNAs and the ensuing siRNAs exploit both conserved and divergent sequence features of MYB genes to initiate distinct regulatory networks targeting a multitude of genes inside and outside the MYB family. PMID:22704043

  8. BDNF and the maturation of posttranscriptional regulatory networks in human SH-SY5Y neuroblast differentiation.

    PubMed

    Goldie, Belinda J; Barnett, Michelle M; Cairns, Murray J

    2014-01-01

    The SH-SY5Y culture system is a convenient neuronal model with the potential to elaborate human/primate-specific transcription networks and pathways related to human cognitive disorders. While this system allows for the exploration of specialized features in the human genome, there is still significant debate about how this model should be implemented, and its appropriateness for answering complex functional questions related to human neural architecture. In view of these questions we sought to characterize the posttranscriptional regulatory structure of the two-stage ATRA differentiation, BDNF maturation protocol proposed by Encinas et al. (2000) using integrative whole-genome gene and microRNA (miRNA) expression analysis. We report that ATRA-BDNF induced significant increases in expression of key synaptic genes, brain-specific miRNA and miRNA biogenesis machinery, and in AChE activity, compared with ATRA alone. Functional annotation clustering associated BDNF more significantly with neuronal terms, and with synaptic terms not found in ATRA-only clusters. While our results support use of SH-SY5Y as a neuronal model, we advocate considered selection of the differentiation agent/s relative to the system being modeled.

  9. Organization of feed-forward loop motifs reveals architectural principles in natural and engineered networks.

    PubMed

    Gorochowski, Thomas E; Grierson, Claire S; di Bernardo, Mario

    2018-03-01

    Network motifs are significantly overrepresented subgraphs that have been proposed as building blocks for natural and engineered networks. Detailed functional analysis has been performed for many types of motif in isolation, but less is known about how motifs work together to perform complex tasks. To address this issue, we measure the aggregation of network motifs via methods that extract precisely how these structures are connected. Applying this approach to a broad spectrum of networked systems and focusing on the widespread feed-forward loop motif, we uncover striking differences in motif organization. The types of connection are often highly constrained, differ between domains, and clearly capture architectural principles. We show how this information can be used to effectively predict functionally important nodes in the metabolic network of Escherichia coli . Our findings have implications for understanding how networked systems are constructed from motif parts and elucidate constraints that guide their evolution.

  10. Organization of feed-forward loop motifs reveals architectural principles in natural and engineered networks

    PubMed Central

    Grierson, Claire S.

    2018-01-01

    Network motifs are significantly overrepresented subgraphs that have been proposed as building blocks for natural and engineered networks. Detailed functional analysis has been performed for many types of motif in isolation, but less is known about how motifs work together to perform complex tasks. To address this issue, we measure the aggregation of network motifs via methods that extract precisely how these structures are connected. Applying this approach to a broad spectrum of networked systems and focusing on the widespread feed-forward loop motif, we uncover striking differences in motif organization. The types of connection are often highly constrained, differ between domains, and clearly capture architectural principles. We show how this information can be used to effectively predict functionally important nodes in the metabolic network of Escherichia coli. Our findings have implications for understanding how networked systems are constructed from motif parts and elucidate constraints that guide their evolution. PMID:29670941

  11. GRN2SBML: automated encoding and annotation of inferred gene regulatory networks complying with SBML.

    PubMed

    Vlaic, Sebastian; Hoffmann, Bianca; Kupfer, Peter; Weber, Michael; Dräger, Andreas

    2013-09-01

    GRN2SBML automatically encodes gene regulatory networks derived from several inference tools in systems biology markup language. Providing a graphical user interface, the networks can be annotated via the simple object access protocol (SOAP)-based application programming interface of BioMart Central Portal and minimum information required in the annotation of models registry. Additionally, we provide an R-package, which processes the output of supported inference algorithms and automatically passes all required parameters to GRN2SBML. Therefore, GRN2SBML closes a gap in the processing pipeline between the inference of gene regulatory networks and their subsequent analysis, visualization and storage. GRN2SBML is freely available under the GNU Public License version 3 and can be downloaded from http://www.hki-jena.de/index.php/0/2/490. General information on GRN2SBML, examples and tutorials are available at the tool's web page.

  12. NetBenchmark: a bioconductor package for reproducible benchmarks of gene regulatory network inference.

    PubMed

    Bellot, Pau; Olsen, Catharina; Salembier, Philippe; Oliveras-Vergés, Albert; Meyer, Patrick E

    2015-09-29

    In the last decade, a great number of methods for reconstructing gene regulatory networks from expression data have been proposed. However, very few tools and datasets allow to evaluate accurately and reproducibly those methods. Hence, we propose here a new tool, able to perform a systematic, yet fully reproducible, evaluation of transcriptional network inference methods. Our open-source and freely available Bioconductor package aggregates a large set of tools to assess the robustness of network inference algorithms against different simulators, topologies, sample sizes and noise intensities. The benchmarking framework that uses various datasets highlights the specialization of some methods toward network types and data. As a result, it is possible to identify the techniques that have broad overall performances.

  13. Distributed video coding for wireless video sensor networks: a review of the state-of-the-art architectures.

    PubMed

    Imran, Noreen; Seet, Boon-Chong; Fong, A C M

    2015-01-01

    Distributed video coding (DVC) is a relatively new video coding architecture originated from two fundamental theorems namely, Slepian-Wolf and Wyner-Ziv. Recent research developments have made DVC attractive for applications in the emerging domain of wireless video sensor networks (WVSNs). This paper reviews the state-of-the-art DVC architectures with a focus on understanding their opportunities and gaps in addressing the operational requirements and application needs of WVSNs.

  14. Genetic control of inflorescence architecture during rice domestication

    PubMed Central

    Zhu, Zuofeng; Tan, Lubin; Fu, Yongcai; Liu, Fengxia; Cai, Hongwei; Xie, Daoxin; Wu, Feng; Wu, Jianzhong; Matsumoto, Takashi; Sun, Chuanqing

    2013-01-01

    Inflorescence architecture is a key agronomical factor determining grain yield, and thus has been a major target of cereal crop domestication. Transition from a spread panicle typical of ancestral wild rice (Oryza rufipogon Griff.) to the compact panicle of present cultivars (O. sativa L.) was a crucial event in rice domestication. Here we show that the spread panicle architecture of wild rice is controlled by a dominant gene, OsLG1, a previously reported SBP-domain transcription factor that controls rice ligule development. Association analysis indicates that a single-nucleotide polymorphism-6 in the OsLG1 regulatory region led to a compact panicle architecture in cultivars during rice domestication. We speculate that the cis-regulatory mutation can fine-tune the spatial expression of the target gene, and that selection of cis-regulatory mutations might be an efficient strategy for crop domestication. PMID:23884108

  15. JCell--a Java-based framework for inferring regulatory networks from time series data.

    PubMed

    Spieth, C; Supper, J; Streichert, F; Speer, N; Zell, A

    2006-08-15

    JCell is a Java-based application for reconstructing gene regulatory networks from experimental data. The framework provides several algorithms to identify genetic and metabolic dependencies based on experimental data conjoint with mathematical models to describe and simulate regulatory systems. Owing to the modular structure, researchers can easily implement new methods. JCell is a pure Java application with additional scripting capabilities and thus widely usable, e.g. on parallel or cluster computers. The software is freely available for download at http://www-ra.informatik.uni-tuebingen.de/software/JCell.

  16. Control of Metastatic Progression by microRNA Regulatory Networks

    PubMed Central

    Pencheva, Nora; Tavazoie, Sohail F.

    2015-01-01

    Aberrant microRNA (miRNA) expression is a defining feature of human malignancy. Specific miRNAs have been identified as promoters or suppressors of metastatic progression. These miRNAs control metastasis through divergent or convergent regulation of metastatic gene pathways. Some miRNA regulatory networks govern cell-autonomous cancer phenotypes, while others modulate the cell-extrinsic composition of the metastatic microenvironment. The use of small RNAs as probes into the molecular and cellular underpinnings of metastasis holds promise for the identification of candidate genes for potential therapeutic intervention. PMID:23728460

  17. The Role of Architectural and Learning Constraints in Neural Network Models: A Case Study on Visual Space Coding.

    PubMed

    Testolin, Alberto; De Filippo De Grazia, Michele; Zorzi, Marco

    2017-01-01

    The recent "deep learning revolution" in artificial neural networks had strong impact and widespread deployment for engineering applications, but the use of deep learning for neurocomputational modeling has been so far limited. In this article we argue that unsupervised deep learning represents an important step forward for improving neurocomputational models of perception and cognition, because it emphasizes the role of generative learning as opposed to discriminative (supervised) learning. As a case study, we present a series of simulations investigating the emergence of neural coding of visual space for sensorimotor transformations. We compare different network architectures commonly used as building blocks for unsupervised deep learning by systematically testing the type of receptive fields and gain modulation developed by the hidden neurons. In particular, we compare Restricted Boltzmann Machines (RBMs), which are stochastic, generative networks with bidirectional connections trained using contrastive divergence, with autoencoders, which are deterministic networks trained using error backpropagation. For both learning architectures we also explore the role of sparse coding, which has been identified as a fundamental principle of neural computation. The unsupervised models are then compared with supervised, feed-forward networks that learn an explicit mapping between different spatial reference frames. Our simulations show that both architectural and learning constraints strongly influenced the emergent coding of visual space in terms of distribution of tuning functions at the level of single neurons. Unsupervised models, and particularly RBMs, were found to more closely adhere to neurophysiological data from single-cell recordings in the primate parietal cortex. These results provide new insights into how basic properties of artificial neural networks might be relevant for modeling neural information processing in biological systems.

  18. The Role of Architectural and Learning Constraints in Neural Network Models: A Case Study on Visual Space Coding

    PubMed Central

    Testolin, Alberto; De Filippo De Grazia, Michele; Zorzi, Marco

    2017-01-01

    The recent “deep learning revolution” in artificial neural networks had strong impact and widespread deployment for engineering applications, but the use of deep learning for neurocomputational modeling has been so far limited. In this article we argue that unsupervised deep learning represents an important step forward for improving neurocomputational models of perception and cognition, because it emphasizes the role of generative learning as opposed to discriminative (supervised) learning. As a case study, we present a series of simulations investigating the emergence of neural coding of visual space for sensorimotor transformations. We compare different network architectures commonly used as building blocks for unsupervised deep learning by systematically testing the type of receptive fields and gain modulation developed by the hidden neurons. In particular, we compare Restricted Boltzmann Machines (RBMs), which are stochastic, generative networks with bidirectional connections trained using contrastive divergence, with autoencoders, which are deterministic networks trained using error backpropagation. For both learning architectures we also explore the role of sparse coding, which has been identified as a fundamental principle of neural computation. The unsupervised models are then compared with supervised, feed-forward networks that learn an explicit mapping between different spatial reference frames. Our simulations show that both architectural and learning constraints strongly influenced the emergent coding of visual space in terms of distribution of tuning functions at the level of single neurons. Unsupervised models, and particularly RBMs, were found to more closely adhere to neurophysiological data from single-cell recordings in the primate parietal cortex. These results provide new insights into how basic properties of artificial neural networks might be relevant for modeling neural information processing in biological systems. PMID:28377709

  19. Security Analysis of DTN Architecture and Bundle Protocol Specification for Space-Based Networks

    NASA Technical Reports Server (NTRS)

    Ivancic, William D.

    2009-01-01

    A Delay-Tolerant Network (DTN) Architecture (Request for Comment, RFC-4838) and Bundle Protocol Specification, RFC-5050, have been proposed for space and terrestrial networks. Additional security specifications have been provided via the Bundle Security Specification (currently a work in progress as an Internet Research Task Force internet-draft) and, for link-layer protocols applicable to Space networks, the Licklider Transport Protocol Security Extensions. This document provides a security analysis of the current DTN RFCs and proposed security related internet drafts with a focus on space-based communication networks, which is a rather restricted subset of DTN networks. Note, the original focus and motivation of DTN work was for the Interplanetary Internet . This document does not address general store-and-forward network overlays, just the current work being done by the Internet Research Task Force (IRTF) and the Consultative Committee for Space Data Systems (CCSDS) Space Internetworking Services Area (SIS) - DTN working group under the DTN and Bundle umbrellas. However, much of the analysis is relevant to general store-and-forward overlays.

  20. Seamless interworking architecture for WBAN in heterogeneous wireless networks with QoS guarantees.

    PubMed

    Khan, Pervez; Ullah, Niamat; Ullah, Sana; Kwak, Kyung Sup

    2011-10-01

    The IEEE 802.15.6 standard is a communication standard optimized for low-power and short-range in-body/on-body nodes to serve a variety of medical, consumer electronics and entertainment applications. Providing high mobility with guaranteed Quality of Service (QoS) to a WBAN user in heterogeneous wireless networks is a challenging task. A WBAN uses a Personal Digital Assistant (PDA) to gather data from body sensors and forwards it to a remote server through wide range wireless networks. In this paper, we present a coexistence study of WBAN with Wireless Local Area Networks (WLAN) and Wireless Wide Area Networks (WWANs). The main issue is interworking of WBAN in heterogenous wireless networks including seamless handover, QoS, emergency services, cooperation and security. We propose a Seamless Interworking Architecture (SIA) for WBAN in heterogenous wireless networks based on a cost function. The cost function is based on power consumption and data throughput costs. Our simulation results show that the proposed scheme outperforms typical approaches in terms of throughput, delay and packet loss rate.

  1. Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis.

    PubMed

    Harel, Itamar; Maezawa, Yoshiro; Avraham, Roi; Rinon, Ariel; Ma, Hsiao-Yen; Cross, Joe W; Leviatan, Noam; Hegesh, Julius; Roy, Achira; Jacob-Hirsch, Jasmine; Rechavi, Gideon; Carvajal, Jaime; Tole, Shubha; Kioussi, Chrissa; Quaggin, Susan; Tzahor, Eldad

    2012-11-13

    The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a previously undescribed player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.

  2. Heart morphogenesis gene regulatory networks revealed by temporal expression analysis.

    PubMed

    Hill, Jonathon T; Demarest, Bradley; Gorsi, Bushra; Smith, Megan; Yost, H Joseph

    2017-10-01

    During embryogenesis the heart forms as a linear tube that then undergoes multiple simultaneous morphogenetic events to obtain its mature shape. To understand the gene regulatory networks (GRNs) driving this phase of heart development, during which many congenital heart disease malformations likely arise, we conducted an RNA-seq timecourse in zebrafish from 30 hpf to 72 hpf and identified 5861 genes with altered expression. We clustered the genes by temporal expression pattern, identified transcription factor binding motifs enriched in each cluster, and generated a model GRN for the major gene batteries in heart morphogenesis. This approach predicted hundreds of regulatory interactions and found batteries enriched in specific cell and tissue types, indicating that the approach can be used to narrow the search for novel genetic markers and regulatory interactions. Subsequent analyses confirmed the GRN using two mutants, Tbx5 and nkx2-5 , and identified sets of duplicated zebrafish genes that do not show temporal subfunctionalization. This dataset provides an essential resource for future studies on the genetic/epigenetic pathways implicated in congenital heart defects and the mechanisms of cardiac transcriptional regulation. © 2017. Published by The Company of Biologists Ltd.

  3. A group LASSO-based method for robustly inferring gene regulatory networks from multiple time-course datasets.

    PubMed

    Liu, Li-Zhi; Wu, Fang-Xiang; Zhang, Wen-Jun

    2014-01-01

    As an abstract mapping of the gene regulations in the cell, gene regulatory network is important to both biological research study and practical applications. The reverse engineering of gene regulatory networks from microarray gene expression data is a challenging research problem in systems biology. With the development of biological technologies, multiple time-course gene expression datasets might be collected for a specific gene network under different circumstances. The inference of a gene regulatory network can be improved by integrating these multiple datasets. It is also known that gene expression data may be contaminated with large errors or outliers, which may affect the inference results. A novel method, Huber group LASSO, is proposed to infer the same underlying network topology from multiple time-course gene expression datasets as well as to take the robustness to large error or outliers into account. To solve the optimization problem involved in the proposed method, an efficient algorithm which combines the ideas of auxiliary function minimization and block descent is developed. A stability selection method is adapted to our method to find a network topology consisting of edges with scores. The proposed method is applied to both simulation datasets and real experimental datasets. It shows that Huber group LASSO outperforms the group LASSO in terms of both areas under receiver operating characteristic curves and areas under the precision-recall curves. The convergence analysis of the algorithm theoretically shows that the sequence generated from the algorithm converges to the optimal solution of the problem. The simulation and real data examples demonstrate the effectiveness of the Huber group LASSO in integrating multiple time-course gene expression datasets and improving the resistance to large errors or outliers.

  4. An Overlay Architecture for Throughput Optimal Multipath Routing

    DTIC Science & Technology

    2017-01-14

    1 An Overlay Architecture for Throughput Optimal Multipath Routing Nathaniel M. Jones, Georgios S. Paschos, Brooke Shrader, and Eytan Modiano...decisions. In this work, we study an overlay architecture for dynamic routing such that only a subset of devices (overlay nodes) need to make dynamic routing...a legacy network. Network overlays are frequently used to deploy new communication architectures in legacy networks [13]. To accomplish this, messages

  5. Integrated Approach to Reconstruction of Microbial Regulatory Networks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rodionov, Dmitry A; Novichkov, Pavel S

    2013-11-04

    This project had the goal(s) of development of integrated bioinformatics platform for genome-scale inference and visualization of transcriptional regulatory networks (TRNs) in bacterial genomes. The work was done in Sanford-Burnham Medical Research Institute (SBMRI, P.I. D.A. Rodionov) and Lawrence Berkeley National Laboratory (LBNL, co-P.I. P.S. Novichkov). The developed computational resources include: (1) RegPredict web-platform for TRN inference and regulon reconstruction in microbial genomes, and (2) RegPrecise database for collection, visualization and comparative analysis of transcriptional regulons reconstructed by comparative genomics. These analytical resources were selected as key components in the DOE Systems Biology KnowledgeBase (SBKB). The high-quality data accumulated inmore » RegPrecise will provide essential datasets of reference regulons in diverse microbes to enable automatic reconstruction of draft TRNs in newly sequenced genomes. We outline our progress toward the three aims of this grant proposal, which were: Develop integrated platform for genome-scale regulon reconstruction; Infer regulatory annotations in several groups of bacteria and building of reference collections of microbial regulons; and Develop KnowledgeBase on microbial transcriptional regulation.« less

  6. Segregation of striated and smooth muscle lineages by a Notch-dependent regulatory network

    PubMed Central

    2014-01-01

    Background Lineage segregation from multipotent epithelia is a central theme in development and in adult stem cell plasticity. Previously, we demonstrated that striated and smooth muscle cells share a common progenitor within their epithelium of origin, the lateral domain of the somite-derived dermomyotome. However, what controls the segregation of these muscle subtypes remains unknown. We use this in vivo bifurcation of fates as an experimental model to uncover the underlying mechanisms of lineage diversification from bipotent progenitors. Results Using the strength of spatio-temporally controlled gene missexpression in avian embryos, we report that Notch harbors distinct pro-smooth muscle activities depending on the duration of the signal; short periods prevent striated muscle development and extended periods, through Snail1, promote cell emigration from the dermomyotome towards a smooth muscle fate. Furthermore, we define a Muscle Regulatory Network, consisting of Id2, Id3, FoxC2 and Snail1, which acts in concert to promote smooth muscle by antagonizing the pro-myogenic activities of Myf5 and Pax7, which induce striated muscle fate. Notch and BMP closely regulate the network and reciprocally reinforce each other’s signal. In turn, components of the network strengthen Notch signaling, while Pax7 silences this signaling. These feedbacks augment the robustness and flexibility of the network regulating muscle subtype segregation. Conclusions Our results demarcate the details of the Muscle Regulatory Network, underlying the segregation of muscle sublineages from the lateral dermomyotome, and exhibit how factors within the network promote the smooth muscle at the expense of the striated muscle fate. This network acts as an exemplar demonstrating how lineage segregation occurs within epithelial primordia by integrating inputs from competing factors. PMID:25015411

  7. Resting State fMRI Functional Connectivity-Based Classification Using a Convolutional Neural Network Architecture

    PubMed Central

    Meszlényi, Regina J.; Buza, Krisztian; Vidnyánszky, Zoltán

    2017-01-01

    Machine learning techniques have become increasingly popular in the field of resting state fMRI (functional magnetic resonance imaging) network based classification. However, the application of convolutional networks has been proposed only very recently and has remained largely unexplored. In this paper we describe a convolutional neural network architecture for functional connectome classification called connectome-convolutional neural network (CCNN). Our results on simulated datasets and a publicly available dataset for amnestic mild cognitive impairment classification demonstrate that our CCNN model can efficiently distinguish between subject groups. We also show that the connectome-convolutional network is capable to combine information from diverse functional connectivity metrics and that models using a combination of different connectivity descriptors are able to outperform classifiers using only one metric. From this flexibility follows that our proposed CCNN model can be easily adapted to a wide range of connectome based classification or regression tasks, by varying which connectivity descriptor combinations are used to train the network. PMID:29089883

  8. Resting State fMRI Functional Connectivity-Based Classification Using a Convolutional Neural Network Architecture.

    PubMed

    Meszlényi, Regina J; Buza, Krisztian; Vidnyánszky, Zoltán

    2017-01-01

    Machine learning techniques have become increasingly popular in the field of resting state fMRI (functional magnetic resonance imaging) network based classification. However, the application of convolutional networks has been proposed only very recently and has remained largely unexplored. In this paper we describe a convolutional neural network architecture for functional connectome classification called connectome-convolutional neural network (CCNN). Our results on simulated datasets and a publicly available dataset for amnestic mild cognitive impairment classification demonstrate that our CCNN model can efficiently distinguish between subject groups. We also show that the connectome-convolutional network is capable to combine information from diverse functional connectivity metrics and that models using a combination of different connectivity descriptors are able to outperform classifiers using only one metric. From this flexibility follows that our proposed CCNN model can be easily adapted to a wide range of connectome based classification or regression tasks, by varying which connectivity descriptor combinations are used to train the network.

  9. Gene regulatory network identification from the yeast cell cycle based on a neuro-fuzzy system.

    PubMed

    Wang, B H; Lim, J W; Lim, J S

    2016-08-30

    Many studies exist for reconstructing gene regulatory networks (GRNs). In this paper, we propose a method based on an advanced neuro-fuzzy system, for gene regulatory network reconstruction from microarray time-series data. This approach uses a neural network with a weighted fuzzy function to model the relationships between genes. Fuzzy rules, which determine the regulators of genes, are very simplified through this method. Additionally, a regulator selection procedure is proposed, which extracts the exact dynamic relationship between genes, using the information obtained from the weighted fuzzy function. Time-series related features are extracted from the original data to employ the characteristics of temporal data that are useful for accurate GRN reconstruction. The microarray dataset of the yeast cell cycle was used for our study. We measured the mean squared prediction error for the efficiency of the proposed approach and evaluated the accuracy in terms of precision, sensitivity, and F-score. The proposed method outperformed the other existing approaches.

  10. Role of Graph Architecture in Controlling Dynamical Networks with Applications to Neural Systems.

    PubMed

    Kim, Jason Z; Soffer, Jonathan M; Kahn, Ari E; Vettel, Jean M; Pasqualetti, Fabio; Bassett, Danielle S

    2018-01-01

    Networked systems display complex patterns of interactions between components. In physical networks, these interactions often occur along structural connections that link components in a hard-wired connection topology, supporting a variety of system-wide dynamical behaviors such as synchronization. While descriptions of these behaviors are important, they are only a first step towards understanding and harnessing the relationship between network topology and system behavior. Here, we use linear network control theory to derive accurate closed-form expressions that relate the connectivity of a subset of structural connections (those linking driver nodes to non-driver nodes) to the minimum energy required to control networked systems. To illustrate the utility of the mathematics, we apply this approach to high-resolution connectomes recently reconstructed from Drosophila, mouse, and human brains. We use these principles to suggest an advantage of the human brain in supporting diverse network dynamics with small energetic costs while remaining robust to perturbations, and to perform clinically accessible targeted manipulation of the brain's control performance by removing single edges in the network. Generally, our results ground the expectation of a control system's behavior in its network architecture, and directly inspire new directions in network analysis and design via distributed control.

  11. Role of graph architecture in controlling dynamical networks with applications to neural systems

    NASA Astrophysics Data System (ADS)

    Kim, Jason Z.; Soffer, Jonathan M.; Kahn, Ari E.; Vettel, Jean M.; Pasqualetti, Fabio; Bassett, Danielle S.

    2018-01-01

    Networked systems display complex patterns of interactions between components. In physical networks, these interactions often occur along structural connections that link components in a hard-wired connection topology, supporting a variety of system-wide dynamical behaviours such as synchronization. Although descriptions of these behaviours are important, they are only a first step towards understanding and harnessing the relationship between network topology and system behaviour. Here, we use linear network control theory to derive accurate closed-form expressions that relate the connectivity of a subset of structural connections (those linking driver nodes to non-driver nodes) to the minimum energy required to control networked systems. To illustrate the utility of the mathematics, we apply this approach to high-resolution connectomes recently reconstructed from Drosophila, mouse, and human brains. We use these principles to suggest an advantage of the human brain in supporting diverse network dynamics with small energetic costs while remaining robust to perturbations, and to perform clinically accessible targeted manipulation of the brain's control performance by removing single edges in the network. Generally, our results ground the expectation of a control system's behaviour in its network architecture, and directly inspire new directions in network analysis and design via distributed control.

  12. MWAHCA: A Multimedia Wireless Ad Hoc Cluster Architecture

    PubMed Central

    Diaz, Juan R.; Jimenez, Jose M.; Sendra, Sandra

    2014-01-01

    Wireless Ad hoc networks provide a flexible and adaptable infrastructure to transport data over a great variety of environments. Recently, real-time audio and video data transmission has been increased due to the appearance of many multimedia applications. One of the major challenges is to ensure the quality of multimedia streams when they have passed through a wireless ad hoc network. It requires adapting the network architecture to the multimedia QoS requirements. In this paper we propose a new architecture to organize and manage cluster-based ad hoc networks in order to provide multimedia streams. Proposed architecture adapts the network wireless topology in order to improve the quality of audio and video transmissions. In order to achieve this goal, the architecture uses some information such as each node's capacity and the QoS parameters (bandwidth, delay, jitter, and packet loss). The architecture splits the network into clusters which are specialized in specific multimedia traffic. The real system performance study provided at the end of the paper will demonstrate the feasibility of the proposal. PMID:24737996

  13. MWAHCA: a multimedia wireless ad hoc cluster architecture.

    PubMed

    Diaz, Juan R; Lloret, Jaime; Jimenez, Jose M; Sendra, Sandra

    2014-01-01

    Wireless Ad hoc networks provide a flexible and adaptable infrastructure to transport data over a great variety of environments. Recently, real-time audio and video data transmission has been increased due to the appearance of many multimedia applications. One of the major challenges is to ensure the quality of multimedia streams when they have passed through a wireless ad hoc network. It requires adapting the network architecture to the multimedia QoS requirements. In this paper we propose a new architecture to organize and manage cluster-based ad hoc networks in order to provide multimedia streams. Proposed architecture adapts the network wireless topology in order to improve the quality of audio and video transmissions. In order to achieve this goal, the architecture uses some information such as each node's capacity and the QoS parameters (bandwidth, delay, jitter, and packet loss). The architecture splits the network into clusters which are specialized in specific multimedia traffic. The real system performance study provided at the end of the paper will demonstrate the feasibility of the proposal.

  14. Reverse engineering of gene regulatory networks.

    PubMed

    Cho, K H; Choo, S M; Jung, S H; Kim, J R; Choi, H S; Kim, J

    2007-05-01

    Systems biology is a multi-disciplinary approach to the study of the interactions of various cellular mechanisms and cellular components. Owing to the development of new technologies that simultaneously measure the expression of genetic information, systems biological studies involving gene interactions are increasingly prominent. In this regard, reconstructing gene regulatory networks (GRNs) forms the basis for the dynamical analysis of gene interactions and related effects on cellular control pathways. Various approaches of inferring GRNs from gene expression profiles and biological information, including machine learning approaches, have been reviewed, with a brief introduction of DNA microarray experiments as typical tools for measuring levels of messenger ribonucleic acid (mRNA) expression. In particular, the inference methods are classified according to the required input information, and the main idea of each method is elucidated by comparing its advantages and disadvantages with respect to the other methods. In addition, recent developments in this field are introduced and discussions on the challenges and opportunities for future research are provided.

  15. International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.

    PubMed

    Bal-Price, Anna; Crofton, Kevin M; Leist, Marcel; Allen, Sandra; Arand, Michael; Buetler, Timo; Delrue, Nathalie; FitzGerald, Rex E; Hartung, Thomas; Heinonen, Tuula; Hogberg, Helena; Bennekou, Susanne Hougaard; Lichtensteiger, Walter; Oggier, Daniela; Paparella, Martin; Axelstad, Marta; Piersma, Aldert; Rached, Eva; Schilter, Benoît; Schmuck, Gabriele; Stoppini, Luc; Tongiorgi, Enrico; Tiramani, Manuela; Monnet-Tschudi, Florianne; Wilks, Martin F; Ylikomi, Timo; Fritsche, Ellen

    2015-02-01

    A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.

  16. Implementing wireless sensor networks for architectural heritage conservation

    NASA Astrophysics Data System (ADS)

    Martínez-Garrido, M. I.; Aparicio, S.; Fort, R.; Izquierdo, M. A. G.; Anaya, J. J.

    2012-04-01

    Preventive conservation in architectural heritage is one of the most important aims for the development and implementation of new techniques to assess decay, lending to reduce damage before it has occurred and reducing costs in the long term. For that purpose, it is necessary to know all aspects influencing in decay evolution depending on the material under study and its internal and external conditions. Wireless sensor networks are an emerging technology and a minimally invasive technique. The use of these networks facilitates data acquisition and monitoring of a large number of variables that could provoke material damages, such as presence of harmful compounds like salts, dampness, etc. The current project presents different wireless sensors networks (WSN) and sensors used to fulfill the requirements for a complete analysis of main decay agents in a Renaissance church of the 16th century in Madrid (Spain). Current typologies and wireless technologies are studied establishing the most suitable system and the convenience of each one. Firstly, it is very important to consider that microclimate is in close correlation with material deterioration. Therefore a temperature(T) and relative humidity (RH)/moisture network has been developed, using ZigBee wireless communications protocols, and monitoring different points along the church surface. These points are recording RH/T differences depending on the height and the sensor location (inside the material or on the surface). On the other hand, T/RH button sensors have been used, minimizing aesthetical interferences, and concluding which is the most advisable way for monitoring these specific parameters. Due to the fact that microclimate is a complex phenomenon, it is necessary to examine spatial distribution and time evolution at the same time. This work shows both studies since the development expects a long term monitoring. A different wireless network has been deployed to study the effects of pollution caused by other

  17. Prior knowledge driven Granger causality analysis on gene regulatory network discovery

    DOE PAGES

    Yao, Shun; Yoo, Shinjae; Yu, Dantong

    2015-08-28

    Our study focuses on discovering gene regulatory networks from time series gene expression data using the Granger causality (GC) model. However, the number of available time points (T) usually is much smaller than the number of target genes (n) in biological datasets. The widely applied pairwise GC model (PGC) and other regularization strategies can lead to a significant number of false identifications when n>>T. In this study, we proposed a new method, viz., CGC-2SPR (CGC using two-step prior Ridge regularization) to resolve the problem by incorporating prior biological knowledge about a target gene data set. In our simulation experiments, themore » propose new methodology CGC-2SPR showed significant performance improvement in terms of accuracy over other widely used GC modeling (PGC, Ridge and Lasso) and MI-based (MRNET and ARACNE) methods. In addition, we applied CGC-2SPR to a real biological dataset, i.e., the yeast metabolic cycle, and discovered more true positive edges with CGC-2SPR than with the other existing methods. In our research, we noticed a “ 1+1>2” effect when we combined prior knowledge and gene expression data to discover regulatory networks. Based on causality networks, we made a functional prediction that the Abm1 gene (its functions previously were unknown) might be related to the yeast’s responses to different levels of glucose. In conclusion, our research improves causality modeling by combining heterogeneous knowledge, which is well aligned with the future direction in system biology. Furthermore, we proposed a method of Monte Carlo significance estimation (MCSE) to calculate the edge significances which provide statistical meanings to the discovered causality networks. All of our data and source codes will be available under the link https://bitbucket.org/dtyu/granger-causality/wiki/Home.« less

  18. A regulatory network to segregate the identity of neuronal subtypes.

    PubMed

    Lee, Seunghee; Lee, Bora; Joshi, Kaumudi; Pfaff, Samuel L; Lee, Jae W; Lee, Soo-Kyung

    2008-06-01

    Spinal motor neurons (MNs) and V2 interneurons (V2-INs) are specified by two related LIM-complexes, MN-hexamer and V2-tetramer, respectively. Here we show how multiple parallel and complementary feedback loops are integrated to assign these two cell fates accurately. While MN-hexamer response elements (REs) are specific to MN-hexamer, V2-tetramer-REs can bind both LIM-complexes. In embryonic MNs, however, two factors cooperatively suppress the aberrant activation of V2-tetramer-REs. First, LMO4 blocks V2-tetramer assembly. Second, MN-hexamer induces a repressor, Hb9, which binds V2-tetramer-REs and suppresses their activation. V2-INs use a similar approach; V2-tetramer induces a repressor, Chx10, which binds MN-hexamer-REs and blocks their activation. Thus, our study uncovers a regulatory network to segregate related cell fates, which involves reciprocal feedforward gene regulatory loops.

  19. Are genetically robust regulatory networks dynamically different from random ones?

    NASA Astrophysics Data System (ADS)

    Sevim, Volkan; Rikvold, Per Arne

    We study a genetic regulatory network model developed to demonstrate that genetic robustness can evolve through stabilizing selection for optimal phenotypes. We report preliminary results on whether such selection could result in a reorganization of the state space of the system. For the chosen parameters, the evolution moves the system slightly toward the more ordered part of the phase diagram. We also find that strong memory effects cause the Derrida annealed approximation to give erroneous predictions about the model's phase diagram.

  20. MASM: a market architecture for sensor management in distributed sensor networks

    NASA Astrophysics Data System (ADS)

    Viswanath, Avasarala; Mullen, Tracy; Hall, David; Garga, Amulya

    2005-03-01

    Rapid developments in sensor technology and its applications have energized research efforts towards devising a firm theoretical foundation for sensor management. Ubiquitous sensing, wide bandwidth communications and distributed processing provide both opportunities and challenges for sensor and process control and optimization. Traditional optimization techniques do not have the ability to simultaneously consider the wildly non-commensurate measures involved in sensor management in a single optimization routine. Market-oriented programming provides a valuable and principled paradigm to designing systems to solve this dynamic and distributed resource allocation problem. We have modeled the sensor management scenario as a competitive market, wherein the sensor manager holds a combinatorial auction to sell the various items produced by the sensors and the communication channels. However, standard auction mechanisms have been found not to be directly applicable to the sensor management domain. For this purpose, we have developed a specialized market architecture MASM (Market architecture for Sensor Management). In MASM, the mission manager is responsible for deciding task allocations to the consumers and their corresponding budgets and the sensor manager is responsible for resource allocation to the various consumers. In addition to having a modified combinatorial winner determination algorithm, MASM has specialized sensor network modules that address commensurability issues between consumers and producers in the sensor network domain. A preliminary multi-sensor, multi-target simulation environment has been implemented to test the performance of the proposed system. MASM outperformed the information theoretic sensor manager in meeting the mission objectives in the simulation experiments.