Sample records for network inference engine
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DOE Office of Scientific and Technical Information (OSTI.GOV)
McDermott, Jason E.; Costa, Michelle N.; Stevens, S.L.
A difficult problem that is currently growing rapidly due to the sharp increase in the amount of high-throughput data available for many systems is that of determining useful and informative causative influence networks. These networks can be used to predict behavior given observation of a small number of components, predict behavior at a future time point, or identify components that are critical to the functioning of the system under particular conditions. In these endeavors incorporating observations of systems from a wide variety of viewpoints can be particularly beneficial, but has often been undertaken with the objective of inferring networks thatmore » are generally applicable. The focus of the current work is to integrate both general observations and measurements taken for a particular pathology, that of ischemic stroke, to provide improved ability to produce useful predictions of systems behavior. A number of hybrid approaches have recently been proposed for network generation in which the Gene Ontology is used to filter or enrich network links inferred from gene expression data through reverse engineering methods. These approaches have been shown to improve the biological plausibility of the inferred relationships determined, but still treat knowledge-based and machine-learning inferences as incommensurable inputs. In this paper, we explore how further improvements may be achieved through a full integration of network inference insights achieved through application of the Gene Ontology and reverse engineering methods with specific reference to the construction of dynamic models of transcriptional regulatory networks. We show that integrating two approaches to network construction, one based on reverse-engineering from conditional transcriptional data, one based on reverse-engineering from in situ hybridization data, and another based on functional associations derived from Gene Ontology, using probabilities can improve results of clustering as evaluated by a predictive model of transcriptional expression levels.« less
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Variable neighborhood search for reverse engineering of gene regulatory networks.
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.
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Sambo, Francesco; de Oca, Marco A Montes; Di Camillo, Barbara; Toffolo, Gianna; Stützle, Thomas
2012-01-01
Reverse engineering is the problem of inferring the structure of a network of interactions between biological variables from a set of observations. In this paper, we propose an optimization algorithm, called MORE, for the reverse engineering of biological networks from time series data. The model inferred by MORE is a sparse system of nonlinear differential equations, complex enough to realistically describe the dynamics of a biological system. MORE tackles separately the discrete component of the problem, the determination of the biological network topology, and the continuous component of the problem, the strength of the interactions. This approach allows us both to enforce system sparsity, by globally constraining the number of edges, and to integrate a priori information about the structure of the underlying interaction network. Experimental results on simulated and real-world networks show that the mixed discrete/continuous optimization approach of MORE significantly outperforms standard continuous optimization and that MORE is competitive with the state of the art in terms of accuracy of the inferred networks.
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Narimani, Zahra; Beigy, Hamid; Ahmad, Ashar; Masoudi-Nejad, Ali; Fröhlich, Holger
2017-01-01
Inferring the structure of molecular networks from time series protein or gene expression data provides valuable information about the complex biological processes of the cell. Causal network structure inference has been approached using different methods in the past. Most causal network inference techniques, such as Dynamic Bayesian Networks and ordinary differential equations, are limited by their computational complexity and thus make large scale inference infeasible. This is specifically true if a Bayesian framework is applied in order to deal with the unavoidable uncertainty about the correct model. We devise a novel Bayesian network reverse engineering approach using ordinary differential equations with the ability to include non-linearity. Besides modeling arbitrary, possibly combinatorial and time dependent perturbations with unknown targets, one of our main contributions is the use of Expectation Propagation, an algorithm for approximate Bayesian inference over large scale network structures in short computation time. We further explore the possibility of integrating prior knowledge into network inference. We evaluate the proposed model on DREAM4 and DREAM8 data and find it competitive against several state-of-the-art existing network inference methods.
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Emmert-Streib, Frank; Glazko, Galina V.; Altay, Gökmen; de Matos Simoes, Ricardo
2012-01-01
In this paper, we present a systematic and conceptual overview of methods for inferring gene regulatory networks from observational gene expression data. Further, we discuss two classic approaches to infer causal structures and compare them with contemporary methods by providing a conceptual categorization thereof. We complement the above by surveying global and local evaluation measures for assessing the performance of inference algorithms. PMID:22408642
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Reverse engineering biological networks :applications in immune responses to bio-toxins.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Martino, Anthony A.; Sinclair, Michael B.; Davidson, George S.
Our aim is to determine the network of events, or the regulatory network, that defines an immune response to a bio-toxin. As a model system, we are studying T cell regulatory network triggered through tyrosine kinase receptor activation using a combination of pathway stimulation and time-series microarray experiments. Our approach is composed of five steps (1) microarray experiments and data error analysis, (2) data clustering, (3) data smoothing and discretization, (4) network reverse engineering, and (5) network dynamics analysis and fingerprint identification. The technological outcome of this study is a suite of experimental protocols and computational tools that reverse engineermore » regulatory networks provided gene expression data. The practical biological outcome of this work is an immune response fingerprint in terms of gene expression levels. Inferring regulatory networks from microarray data is a new field of investigation that is no more than five years old. To the best of our knowledge, this work is the first attempt that integrates experiments, error analyses, data clustering, inference, and network analysis to solve a practical problem. Our systematic approach of counting, enumeration, and sampling networks matching experimental data is new to the field of network reverse engineering. The resulting mathematical analyses and computational tools lead to new results on their own and should be useful to others who analyze and infer networks.« less
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Wisdom of crowds for robust gene network inference
Marbach, Daniel; Costello, James C.; Küffner, Robert; Vega, Nicci; Prill, Robert J.; Camacho, Diogo M.; Allison, Kyle R.; Kellis, Manolis; Collins, James J.; Stolovitzky, Gustavo
2012-01-01
Reconstructing gene regulatory networks from high-throughput data is a long-standing problem. Through the DREAM project (Dialogue on Reverse Engineering Assessment and Methods), we performed a comprehensive blind assessment of over thirty network inference methods on Escherichia coli, Staphylococcus aureus, Saccharomyces cerevisiae, and in silico microarray data. We characterize performance, data requirements, and inherent biases of different inference approaches offering guidelines for both algorithm application and development. We observe that no single inference method performs optimally across all datasets. In contrast, integration of predictions from multiple inference methods shows robust and high performance across diverse datasets. Thereby, we construct high-confidence networks for E. coli and S. aureus, each comprising ~1700 transcriptional interactions at an estimated precision of 50%. We experimentally test 53 novel interactions in E. coli, of which 23 were supported (43%). Our results establish community-based methods as a powerful and robust tool for the inference of transcriptional gene regulatory networks. PMID:22796662
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Efficient Reverse-Engineering of a Developmental Gene Regulatory Network
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 discover whether there are rules or regularities governing development and evolution of complex multi-cellular organisms. PMID:22807664
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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
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Genetic Network Inference: From Co-Expression Clustering to Reverse Engineering
NASA Technical Reports Server (NTRS)
Dhaeseleer, Patrik; Liang, Shoudan; Somogyi, Roland
2000-01-01
Advances in molecular biological, analytical, and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-duster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e., who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting, and bioengineering.
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Revealing networks from dynamics: an introduction
NASA Astrophysics Data System (ADS)
Timme, Marc; Casadiego, Jose
2014-08-01
What can we learn from the collective dynamics of a complex network about its interaction topology? Taking the perspective from nonlinear dynamics, we briefly review recent progress on how to infer structural connectivity (direct interactions) from accessing the dynamics of the units. Potential applications range from interaction networks in physics, to chemical and metabolic reactions, protein and gene regulatory networks as well as neural circuits in biology and electric power grids or wireless sensor networks in engineering. Moreover, we briefly mention some standard ways of inferring effective or functional connectivity.
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Petri Nets with Fuzzy Logic (PNFL): Reverse Engineering and Parametrization
Küffner, Robert; Petri, Tobias; Windhager, Lukas; Zimmer, Ralf
2010-01-01
Background The recent DREAM4 blind assessment provided a particularly realistic and challenging setting for network reverse engineering methods. The in silico part of DREAM4 solicited the inference of cycle-rich gene regulatory networks from heterogeneous, noisy expression data including time courses as well as knockout, knockdown and multifactorial perturbations. Methodology and Principal Findings We inferred and parametrized simulation models based on Petri Nets with Fuzzy Logic (PNFL). This completely automated approach correctly reconstructed networks with cycles as well as oscillating network motifs. PNFL was evaluated as the best performer on DREAM4 in silico networks of size 10 with an area under the precision-recall curve (AUPR) of 81%. Besides topology, we inferred a range of additional mechanistic details with good reliability, e.g. distinguishing activation from inhibition as well as dependent from independent regulation. Our models also performed well on new experimental conditions such as double knockout mutations that were not included in the provided datasets. Conclusions The inference of biological networks substantially benefits from methods that are expressive enough to deal with diverse datasets in a unified way. At the same time, overly complex approaches could generate multiple different models that explain the data equally well. PNFL appears to strike the balance between expressive power and complexity. This also applies to the intuitive representation of PNFL models combining a straightforward graphical notation with colloquial fuzzy parameters. PMID:20862218
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A Predictive Approach to Network Reverse-Engineering
NASA Astrophysics Data System (ADS)
Wiggins, Chris
2005-03-01
A central challenge of systems biology is the ``reverse engineering" of transcriptional networks: inferring which genes exert regulatory control over which other genes. Attempting such inference at the genomic scale has only recently become feasible, via data-intensive biological innovations such as DNA microrrays (``DNA chips") and the sequencing of whole genomes. In this talk we present a predictive approach to network reverse-engineering, in which we integrate DNA chip data and sequence data to build a model of the transcriptional network of the yeast S. cerevisiae capable of predicting the response of genes in unseen experiments. The technique can also be used to extract ``motifs,'' sequence elements which act as binding sites for regulatory proteins. We validate by a number of approaches and present comparison of theoretical prediction vs. experimental data, along with biological interpretations of the resulting model. En route, we will illustrate some basic notions in statistical learning theory (fitting vs. over-fitting; cross- validation; assessing statistical significance), highlighting ways in which physicists can make a unique contribution in data- driven approaches to reverse engineering.
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Schaffter, Thomas; Marbach, Daniel; Floreano, Dario
2011-08-15
Over the last decade, numerous methods have been developed for inference of regulatory networks from gene expression data. However, accurate and systematic evaluation of these methods is hampered by the difficulty of constructing adequate benchmarks and the lack of tools for a differentiated analysis of network predictions on such benchmarks. Here, we describe a novel and comprehensive method for in silico benchmark generation and performance profiling of network inference methods available to the community as an open-source software called GeneNetWeaver (GNW). In addition to the generation of detailed dynamical models of gene regulatory networks to be used as benchmarks, GNW provides a network motif analysis that reveals systematic prediction errors, thereby indicating potential ways of improving inference methods. The accuracy of network inference methods is evaluated using standard metrics such as precision-recall and receiver operating characteristic curves. We show how GNW can be used to assess the performance and identify the strengths and weaknesses of six inference methods. Furthermore, we used GNW to provide the international Dialogue for Reverse Engineering Assessments and Methods (DREAM) competition with three network inference challenges (DREAM3, DREAM4 and DREAM5). GNW is available at http://gnw.sourceforge.net along with its Java source code, user manual and supporting data. Supplementary data are available at Bioinformatics online. dario.floreano@epfl.ch.
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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.
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Mobile Context Provider for Social Networking
NASA Astrophysics Data System (ADS)
Santos, André C.; Cardoso, João M. P.; Ferreira, Diogo R.; Diniz, Pedro C.
The ability to infer user context based on a mobile device together with a set of external sensors opens up the way to new context-aware services and applications. In this paper, we describe a mobile context provider that makes use of sensors available in a smartphone as well as sensors externally connected via bluetooth. We describe the system architecture from sensor data acquisition to feature extraction, context inference and the publication of context information to well-known social networking services such as Twitter and Hi5. In the current prototype, context inference is based on decision trees, but the middleware allows the integration of other inference engines. Experimental results suggest that the proposed solution is a promising approach to provide user context to both local and network-level services.
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An algebra-based method for inferring gene regulatory networks.
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 dynamic patterns present in the network. Boolean polynomial dynamical systems provide a powerful modeling framework for the reverse engineering of gene regulatory networks, that enables a rich mathematical structure on the model search space. A C++ implementation of the method, distributed under LPGL license, is available, together with the source code, at http://www.paola-vera-licona.net/Software/EARevEng/REACT.html.
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Modeling Diagnostic Assessments with Bayesian Networks
ERIC Educational Resources Information Center
Almond, Russell G.; DiBello, Louis V.; Moulder, Brad; Zapata-Rivera, Juan-Diego
2007-01-01
This paper defines Bayesian network models and examines their applications to IRT-based cognitive diagnostic modeling. These models are especially suited to building inference engines designed to be synchronous with the finer grained student models that arise in skills diagnostic assessment. Aspects of the theory and use of Bayesian network models…
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An algebra-based method for inferring gene regulatory networks
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 predicting several of the dynamic patterns present in the network. Conclusions Boolean polynomial dynamical systems provide a powerful modeling framework for the reverse engineering of gene regulatory networks, that enables a rich mathematical structure on the model search space. A C++ implementation of the method, distributed under LPGL license, is available, together with the source code, at http://www.paola-vera-licona.net/Software/EARevEng/REACT.html. PMID:24669835
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Ambroise, Jérôme; Robert, Annie; Macq, Benoit; Gala, Jean-Luc
2012-01-06
An important challenge in system biology is the inference of biological networks from postgenomic data. Among these biological networks, a gene transcriptional regulatory network focuses on interactions existing between transcription factors (TFs) and and their corresponding target genes. A large number of reverse engineering algorithms were proposed to infer such networks from gene expression profiles, but most current methods have relatively low predictive performances. In this paper, we introduce the novel TNIFSED method (Transcriptional Network Inference from Functional Similarity and Expression Data), that infers a transcriptional network from the integration of correlations and partial correlations of gene expression profiles and gene functional similarities through a supervised classifier. In the current work, TNIFSED was applied to predict the transcriptional network in Escherichia coli and in Saccharomyces cerevisiae, using datasets of 445 and 170 affymetrix arrays, respectively. Using the area under the curve of the receiver operating characteristics and the F-measure as indicators, we showed the predictive performance of TNIFSED to be better than unsupervised state-of-the-art methods. TNIFSED performed slightly worse than the supervised SIRENE algorithm for the target genes identification of the TF having a wide range of yet identified target genes but better for TF having only few identified target genes. Our results indicate that TNIFSED is complementary to the SIRENE algorithm, and particularly suitable to discover target genes of "orphan" TFs.
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The design and application of a Transportable Inference Engine (TIE1)
NASA Technical Reports Server (NTRS)
Mclean, David R.
1986-01-01
A Transportable Inference Engine (TIE1) system has been developed by the author as part of the Interactive Experimenter Planning System (IEPS) task which is involved with developing expert systems in support of the Spacecraft Control Programs Branch at Goddard Space Flight Center in Greenbelt, Maryland. Unlike traditional inference engines, TIE1 is written in the C programming language. In the TIE1 system, knowledge is represented by a hierarchical network of objects which have rule frames. The TIE1 search algorithm uses a set of strategies, including backward chaining, to obtain the values of goals. The application of TIE1 to a spacecraft scheduling problem is described. This application involves the development of a strategies interpreter which uses TIE1 to do constraint checking.
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Reverse Engineering Cellular Networks with Information Theoretic Methods
Villaverde, Alejandro F.; Ross, John; Banga, Julio R.
2013-01-01
Building mathematical models of cellular networks lies at the core of systems biology. It involves, among other tasks, the reconstruction of the structure of interactions between molecular components, which is known as network inference or reverse engineering. Information theory can help in the goal of extracting as much information as possible from the available data. A large number of methods founded on these concepts have been proposed in the literature, not only in biology journals, but in a wide range of areas. Their critical comparison is difficult due to the different focuses and the adoption of different terminologies. Here we attempt to review some of the existing information theoretic methodologies for network inference, and clarify their differences. While some of these methods have achieved notable success, many challenges remain, among which we can mention dealing with incomplete measurements, noisy data, counterintuitive behaviour emerging from nonlinear relations or feedback loops, and computational burden of dealing with large data sets. PMID:24709703
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Fuzzy/Neural Software Estimates Costs of Rocket-Engine Tests
NASA Technical Reports Server (NTRS)
Douglas, Freddie; Bourgeois, Edit Kaminsky
2005-01-01
The Highly Accurate Cost Estimating Model (HACEM) is a software system for estimating the costs of testing rocket engines and components at Stennis Space Center. HACEM is built on a foundation of adaptive-network-based fuzzy inference systems (ANFIS) a hybrid software concept that combines the adaptive capabilities of neural networks with the ease of development and additional benefits of fuzzy-logic-based systems. In ANFIS, fuzzy inference systems are trained by use of neural networks. HACEM includes selectable subsystems that utilize various numbers and types of inputs, various numbers of fuzzy membership functions, and various input-preprocessing techniques. The inputs to HACEM are parameters of specific tests or series of tests. These parameters include test type (component or engine test), number and duration of tests, and thrust level(s) (in the case of engine tests). The ANFIS in HACEM are trained by use of sets of these parameters, along with costs of past tests. Thereafter, the user feeds HACEM a simple input text file that contains the parameters of a planned test or series of tests, the user selects the desired HACEM subsystem, and the subsystem processes the parameters into an estimate of cost(s).
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Lee, Wei-Po; Hsiao, Yu-Ting; Hwang, Wei-Che
2014-01-16
To improve the tedious task of reconstructing gene networks through testing experimentally the possible interactions between genes, it becomes a trend to adopt the automated reverse engineering procedure instead. Some evolutionary algorithms have been suggested for deriving network parameters. However, to infer large networks by the evolutionary algorithm, it is necessary to address two important issues: premature convergence and high computational cost. To tackle the former problem and to enhance the performance of traditional evolutionary algorithms, it is advisable to use parallel model evolutionary algorithms. To overcome the latter and to speed up the computation, it is advocated to adopt the mechanism of cloud computing as a promising solution: most popular is the method of MapReduce programming model, a fault-tolerant framework to implement parallel algorithms for inferring large gene networks. This work presents a practical framework to infer large gene networks, by developing and parallelizing a hybrid GA-PSO optimization method. Our parallel method is extended to work with the Hadoop MapReduce programming model and is executed in different cloud computing environments. To evaluate the proposed approach, we use a well-known open-source software GeneNetWeaver to create several yeast S. cerevisiae sub-networks and use them to produce gene profiles. Experiments have been conducted and the results have been analyzed. They show that our parallel approach can be successfully used to infer networks with desired behaviors and the computation time can be largely reduced. Parallel population-based algorithms can effectively determine network parameters and they perform better than the widely-used sequential algorithms in gene network inference. These parallel algorithms can be distributed to the cloud computing environment to speed up the computation. By coupling the parallel model population-based optimization method and the parallel computational framework, high quality solutions can be obtained within relatively short time. This integrated approach is a promising way for inferring large networks.
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2014-01-01
Background To improve the tedious task of reconstructing gene networks through testing experimentally the possible interactions between genes, it becomes a trend to adopt the automated reverse engineering procedure instead. Some evolutionary algorithms have been suggested for deriving network parameters. However, to infer large networks by the evolutionary algorithm, it is necessary to address two important issues: premature convergence and high computational cost. To tackle the former problem and to enhance the performance of traditional evolutionary algorithms, it is advisable to use parallel model evolutionary algorithms. To overcome the latter and to speed up the computation, it is advocated to adopt the mechanism of cloud computing as a promising solution: most popular is the method of MapReduce programming model, a fault-tolerant framework to implement parallel algorithms for inferring large gene networks. Results This work presents a practical framework to infer large gene networks, by developing and parallelizing a hybrid GA-PSO optimization method. Our parallel method is extended to work with the Hadoop MapReduce programming model and is executed in different cloud computing environments. To evaluate the proposed approach, we use a well-known open-source software GeneNetWeaver to create several yeast S. cerevisiae sub-networks and use them to produce gene profiles. Experiments have been conducted and the results have been analyzed. They show that our parallel approach can be successfully used to infer networks with desired behaviors and the computation time can be largely reduced. Conclusions Parallel population-based algorithms can effectively determine network parameters and they perform better than the widely-used sequential algorithms in gene network inference. These parallel algorithms can be distributed to the cloud computing environment to speed up the computation. By coupling the parallel model population-based optimization method and the parallel computational framework, high quality solutions can be obtained within relatively short time. This integrated approach is a promising way for inferring large networks. PMID:24428926
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Experiments on neural network architectures for fuzzy logic
NASA Technical Reports Server (NTRS)
Keller, James M.
1991-01-01
The use of fuzzy logic to model and manage uncertainty in a rule-based system places high computational demands on an inference engine. In an earlier paper, the authors introduced a trainable neural network structure for fuzzy logic. These networks can learn and extrapolate complex relationships between possibility distributions for the antecedents and consequents in the rules. Here, the power of these networks is further explored. The insensitivity of the output to noisy input distributions (which are likely if the clauses are generated from real data) is demonstrated as well as the ability of the networks to internalize multiple conjunctive clause and disjunctive clause rules. Since different rules with the same variables can be encoded in a single network, this approach to fuzzy logic inference provides a natural mechanism for rule conflict resolution.
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Gene network analysis: from heart development to cardiac therapy.
Ferrazzi, Fulvia; Bellazzi, Riccardo; Engel, Felix B
2015-03-01
Networks offer a flexible framework to represent and analyse the complex interactions between components of cellular systems. In particular gene networks inferred from expression data can support the identification of novel hypotheses on regulatory processes. In this review we focus on the use of gene network analysis in the study of heart development. Understanding heart development will promote the elucidation of the aetiology of congenital heart disease and thus possibly improve diagnostics. Moreover, it will help to establish cardiac therapies. For example, understanding cardiac differentiation during development will help to guide stem cell differentiation required for cardiac tissue engineering or to enhance endogenous repair mechanisms. We introduce different methodological frameworks to infer networks from expression data such as Boolean and Bayesian networks. Then we present currently available temporal expression data in heart development and discuss the use of network-based approaches in published studies. Collectively, our literature-based analysis indicates that gene network analysis constitutes a promising opportunity to infer therapy-relevant regulatory processes in heart development. However, the use of network-based approaches has so far been limited by the small amount of samples in available datasets. Thus, we propose to acquire high-resolution temporal expression data to improve the mathematical descriptions of regulatory processes obtained with gene network inference methodologies. Especially probabilistic methods that accommodate the intrinsic variability of biological systems have the potential to contribute to a deeper understanding of heart development.
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Reverse Engineering of Genome-wide Gene Regulatory Networks from Gene Expression Data
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
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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
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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.
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Automated Interpretation of LIBS Spectra using a Fuzzy Logic Inference Engine
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jeremy J. Hatch; Timothy R. McJunkin; Cynthia Hanson
2012-02-01
Automated interpretation of laser-induced breakdown spectroscopy (LIBS) data is necessary due to the plethora of spectra that can be acquired in a relatively short time. However, traditional chemometric and artificial neural network methods that have been employed are not always transparent to a skilled user. A fuzzy logic approach to data interpretation has now been adapted to LIBS spectral interpretation. A fuzzy logic inference engine (FLIE) was used to differentiate between various copper containing and stainless steel alloys as well as unknowns. Results using FLIE indicate a high degree of confidence in spectral assignment.
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Mass Conservation and Inference of Metabolic Networks from High-Throughput Mass Spectrometry Data
Bandaru, Pradeep; Bansal, Mukesh
2011-01-01
Abstract We present a step towards the metabolome-wide computational inference of cellular metabolic reaction networks from metabolic profiling data, such as mass spectrometry. The reconstruction is based on identification of irreducible statistical interactions among the metabolite activities using the ARACNE reverse-engineering algorithm and on constraining possible metabolic transformations to satisfy the conservation of mass. The resulting algorithms are validated on synthetic data from an abridged computational model of Escherichia coli metabolism. Precision rates upwards of 50% are routinely observed for identification of full metabolic reactions, and recalls upwards of 20% are also seen. PMID:21314454
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Decision Support Systems for Launch and Range Operations Using Jess
NASA Technical Reports Server (NTRS)
Thirumalainambi, Rajkumar
2007-01-01
The virtual test bed for launch and range operations developed at NASA Ames Research Center consists of various independent expert systems advising on weather effects, toxic gas dispersions and human health risk assessment during space-flight operations. An individual dedicated server supports each expert system and the master system gather information from the dedicated servers to support the launch decision-making process. Since the test bed is based on the web system, reducing network traffic and optimizing the knowledge base is critical to its success of real-time or near real-time operations. Jess, a fast rule engine and powerful scripting environment developed at Sandia National Laboratory has been adopted to build the expert systems providing robustness and scalability. Jess also supports XML representation of knowledge base with forward and backward chaining inference mechanism. Facts added - to working memory during run-time operations facilitates analyses of multiple scenarios. Knowledge base can be distributed with one inference engine performing the inference process. This paper discusses details of the knowledge base and inference engine using Jess for a launch and range virtual test bed.
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A Hybrid Stochastic-Neuro-Fuzzy Model-Based System for In-Flight Gas Turbine Engine Diagnostics
2001-04-05
Margin (ADM) and (ii) Fault Detection Margin (FDM). Key Words: ANFIS, Engine Health Monitoring , Gas Path Analysis, and Stochastic Analysis Adaptive Network...The paper illustrates the application of a hybrid Stochastic- Fuzzy -Inference Model-Based System (StoFIS) to fault diagnostics and prognostics for both...operational history monitored on-line by the engine health management (EHM) system. To capture the complex functional relationships between different
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NASA Astrophysics Data System (ADS)
Ma, Chuang; Chen, Han-Shuang; Lai, Ying-Cheng; Zhang, Hai-Feng
2018-02-01
Complex networks hosting binary-state dynamics arise in a variety of contexts. In spite of previous works, to fully reconstruct the network structure from observed binary data remains challenging. We articulate a statistical inference based approach to this problem. In particular, exploiting the expectation-maximization (EM) algorithm, we develop a method to ascertain the neighbors of any node in the network based solely on binary data, thereby recovering the full topology of the network. A key ingredient of our method is the maximum-likelihood estimation of the probabilities associated with actual or nonexistent links, and we show that the EM algorithm can distinguish the two kinds of probability values without any ambiguity, insofar as the length of the available binary time series is reasonably long. Our method does not require any a priori knowledge of the detailed dynamical processes, is parameter-free, and is capable of accurate reconstruction even in the presence of noise. We demonstrate the method using combinations of distinct types of binary dynamical processes and network topologies, and provide a physical understanding of the underlying reconstruction mechanism. Our statistical inference based reconstruction method contributes an additional piece to the rapidly expanding "toolbox" of data based reverse engineering of complex networked systems.
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Ma, Chuang; Chen, Han-Shuang; Lai, Ying-Cheng; Zhang, Hai-Feng
2018-02-01
Complex networks hosting binary-state dynamics arise in a variety of contexts. In spite of previous works, to fully reconstruct the network structure from observed binary data remains challenging. We articulate a statistical inference based approach to this problem. In particular, exploiting the expectation-maximization (EM) algorithm, we develop a method to ascertain the neighbors of any node in the network based solely on binary data, thereby recovering the full topology of the network. A key ingredient of our method is the maximum-likelihood estimation of the probabilities associated with actual or nonexistent links, and we show that the EM algorithm can distinguish the two kinds of probability values without any ambiguity, insofar as the length of the available binary time series is reasonably long. Our method does not require any a priori knowledge of the detailed dynamical processes, is parameter-free, and is capable of accurate reconstruction even in the presence of noise. We demonstrate the method using combinations of distinct types of binary dynamical processes and network topologies, and provide a physical understanding of the underlying reconstruction mechanism. Our statistical inference based reconstruction method contributes an additional piece to the rapidly expanding "toolbox" of data based reverse engineering of complex networked systems.
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Sequential defense against random and intentional attacks in complex networks.
Chen, Pin-Yu; Cheng, Shin-Ming
2015-02-01
Network robustness against attacks is one of the most fundamental researches in network science as it is closely associated with the reliability and functionality of various networking paradigms. However, despite the study on intrinsic topological vulnerabilities to node removals, little is known on the network robustness when network defense mechanisms are implemented, especially for networked engineering systems equipped with detection capabilities. In this paper, a sequential defense mechanism is first proposed in complex networks for attack inference and vulnerability assessment, where the data fusion center sequentially infers the presence of an attack based on the binary attack status reported from the nodes in the network. The network robustness is evaluated in terms of the ability to identify the attack prior to network disruption under two major attack schemes, i.e., random and intentional attacks. We provide a parametric plug-in model for performance evaluation on the proposed mechanism and validate its effectiveness and reliability via canonical complex network models and real-world large-scale network topology. The results show that the sequential defense mechanism greatly improves the network robustness and mitigates the possibility of network disruption by acquiring limited attack status information from a small subset of nodes in the network.
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Praveen, Paurush; Fröhlich, Holger
2013-01-01
Inferring regulatory networks from experimental data via probabilistic graphical models is a popular framework to gain insights into biological systems. However, the inherent noise in experimental data coupled with a limited sample size reduces the performance of network reverse engineering. Prior knowledge from existing sources of biological information can address this low signal to noise problem by biasing the network inference towards biologically plausible network structures. Although integrating various sources of information is desirable, their heterogeneous nature makes this task challenging. We propose two computational methods to incorporate various information sources into a probabilistic consensus structure prior to be used in graphical model inference. Our first model, called Latent Factor Model (LFM), assumes a high degree of correlation among external information sources and reconstructs a hidden variable as a common source in a Bayesian manner. The second model, a Noisy-OR, picks up the strongest support for an interaction among information sources in a probabilistic fashion. Our extensive computational studies on KEGG signaling pathways as well as on gene expression data from breast cancer and yeast heat shock response reveal that both approaches can significantly enhance the reconstruction accuracy of Bayesian Networks compared to other competing methods as well as to the situation without any prior. Our framework allows for using diverse information sources, like pathway databases, GO terms and protein domain data, etc. and is flexible enough to integrate new sources, if available.
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PREMER: a Tool to Infer Biological Networks.
Villaverde, Alejandro F; Becker, Kolja; Banga, Julio R
2017-10-04
Inferring the structure of unknown cellular networks is a main challenge in computational biology. Data-driven approaches based on information theory can determine the existence of interactions among network nodes automatically. However, the elucidation of certain features - such as distinguishing between direct and indirect interactions or determining the direction of a causal link - requires estimating information-theoretic quantities in a multidimensional space. This can be a computationally demanding task, which acts as a bottleneck for the application of elaborate algorithms to large-scale network inference problems. The computational cost of such calculations can be alleviated by the use of compiled programs and parallelization. To this end we have developed PREMER (Parallel Reverse Engineering with Mutual information & Entropy Reduction), a software toolbox that can run in parallel and sequential environments. It uses information theoretic criteria to recover network topology and determine the strength and causality of interactions, and allows incorporating prior knowledge, imputing missing data, and correcting outliers. PREMER is a free, open source software tool that does not require any commercial software. Its core algorithms are programmed in FORTRAN 90 and implement OpenMP directives. It has user interfaces in Python and MATLAB/Octave, and runs on Windows, Linux and OSX (https://sites.google.com/site/premertoolbox/).
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MoCha: Molecular Characterization of Unknown Pathways.
Lobo, Daniel; Hammelman, Jennifer; Levin, Michael
2016-04-01
Automated methods for the reverse-engineering of complex regulatory networks are paving the way for the inference of mechanistic comprehensive models directly from experimental data. These novel methods can infer not only the relations and parameters of the known molecules defined in their input datasets, but also unknown components and pathways identified as necessary by the automated algorithms. Identifying the molecular nature of these unknown components is a crucial step for making testable predictions and experimentally validating the models, yet no specific and efficient tools exist to aid in this process. To this end, we present here MoCha (Molecular Characterization), a tool optimized for the search of unknown proteins and their pathways from a given set of known interacting proteins. MoCha uses the comprehensive dataset of protein-protein interactions provided by the STRING database, which currently includes more than a billion interactions from over 2,000 organisms. MoCha is highly optimized, performing typical searches within seconds. We demonstrate the use of MoCha with the characterization of unknown components from reverse-engineered models from the literature. MoCha is useful for working on network models by hand or as a downstream step of a model inference engine workflow and represents a valuable and efficient tool for the characterization of unknown pathways using known data from thousands of organisms. MoCha and its source code are freely available online under the GPLv3 license.
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The accurate reconstruction of gene regulatory networks from large scale molecular profile datasets represents one of the grand challenges of Systems Biology. The Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) represents one of the most effective tools to accomplish this goal. However, the initial Fixed Bandwidth (FB) implementation is both inefficient and unable to deal with sample sets providing largely uneven coverage of the probability density space.
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A Survey of Statistical Models for Reverse Engineering Gene Regulatory Networks
Huang, Yufei; Tienda-Luna, Isabel M.; Wang, Yufeng
2009-01-01
Statistical models for reverse engineering gene regulatory networks are surveyed in this article. To provide readers with a system-level view of the modeling issues in this research, a graphical modeling framework is proposed. This framework serves as the scaffolding on which the review of different models can be systematically assembled. Based on the framework, we review many existing models for many aspects of gene regulation; the pros and cons of each model are discussed. In addition, network inference algorithms are also surveyed under the graphical modeling framework by the categories of point solutions and probabilistic solutions and the connections and differences among the algorithms are provided. This survey has the potential to elucidate the development and future of reverse engineering GRNs and bring statistical signal processing closer to the core of this research. PMID:20046885
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A Multimetric Approach for Handoff Decision in Heterogeneous Wireless Networks
NASA Astrophysics Data System (ADS)
Kustiawan, I.; Purnama, W.
2018-02-01
Seamless mobility and service continuity anywhere at any time are an important issue in the wireless Internet. This research proposes a scheme to make handoff decisions effectively in heterogeneous wireless networks using a fuzzy system. Our design lies in an inference engine which takes RSS (received signal strength), data rate, network latency, and user preference as strategic determinants. The logic of our engine is realized on a UE (user equipment) side in faster reaction to network dynamics while roaming across different radio access technologies. The fuzzy system handles four metrics jointly to deduce a moderate decision about when to initiate handoff. The performance of our design is evaluated by simulating move-out mobility scenarios. Simulation results show that our scheme outperforms other approaches in terms of reducing unnecessary handoff.
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VINE: A Variational Inference -Based Bayesian Neural Network Engine
2018-01-01
networks are trained using the same dataset and hyper parameter settings as discussed. Table 1 Performance evaluation of the proposed transfer learning...multiplication/addition/subtraction. These operations can be implemented using nested loops in which various iterations of a loop are independent of...each other. This introduces an opportunity for optimization where a loop may be unrolled fully or partially to increase parallelism at the cost of
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Kaiser, Jacob L; Bland, Cassidy L; Klinke, David J
2016-03-01
Cancer arises from a deregulation of both intracellular and intercellular networks that maintain system homeostasis. Identifying the architecture of these networks and how they are changed in cancer is a pre-requisite for designing drugs to restore homeostasis. Since intercellular networks only appear in intact systems, it is difficult to identify how these networks become altered in human cancer using many of the common experimental models. To overcome this, we used the diversity in normal and malignant human tissue samples from the Cancer Genome Atlas (TCGA) database of human breast cancer to identify the topology associated with intercellular networks in vivo. To improve the underlying biological signals, we constructed Bayesian networks using metagene constructs, which represented groups of genes that are concomitantly associated with different immune and cancer states. We also used bootstrap resampling to establish the significance associated with the inferred networks. In short, we found opposing relationships between cell proliferation and epithelial-to-mesenchymal transformation (EMT) with regards to macrophage polarization. These results were consistent across multiple carcinomas in that proliferation was associated with a type 1 cell-mediated anti-tumor immune response and EMT was associated with a pro-tumor anti-inflammatory response. To address the identifiability of these networks from other datasets, we could identify the relationship between EMT and macrophage polarization with fewer samples when the Bayesian network was generated from malignant samples alone. However, the relationship between proliferation and macrophage polarization was identified with fewer samples when the samples were taken from a combination of the normal and malignant samples. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:470-479, 2016. © 2016 American Institute of Chemical Engineers.
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Recursive regularization for inferring gene networks from time-course gene expression profiles
Shimamura, Teppei; Imoto, Seiya; Yamaguchi, Rui; Fujita, André; Nagasaki, Masao; Miyano, Satoru
2009-01-01
Background Inferring gene networks from time-course microarray experiments with vector autoregressive (VAR) model is the process of identifying functional associations between genes through multivariate time series. This problem can be cast as a variable selection problem in Statistics. One of the promising methods for variable selection is the elastic net proposed by Zou and Hastie (2005). However, VAR modeling with the elastic net succeeds in increasing the number of true positives while it also results in increasing the number of false positives. Results By incorporating relative importance of the VAR coefficients into the elastic net, we propose a new class of regularization, called recursive elastic net, to increase the capability of the elastic net and estimate gene networks based on the VAR model. The recursive elastic net can reduce the number of false positives gradually by updating the importance. Numerical simulations and comparisons demonstrate that the proposed method succeeds in reducing the number of false positives drastically while keeping the high number of true positives in the network inference and achieves two or more times higher true discovery rate (the proportion of true positives among the selected edges) than the competing methods even when the number of time points is small. We also compared our method with various reverse-engineering algorithms on experimental data of MCF-7 breast cancer cells stimulated with two ErbB ligands, EGF and HRG. Conclusion The recursive elastic net is a powerful tool for inferring gene networks from time-course gene expression profiles. PMID:19386091
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Praveen, Paurush; Fröhlich, Holger
2013-01-01
Inferring regulatory networks from experimental data via probabilistic graphical models is a popular framework to gain insights into biological systems. However, the inherent noise in experimental data coupled with a limited sample size reduces the performance of network reverse engineering. Prior knowledge from existing sources of biological information can address this low signal to noise problem by biasing the network inference towards biologically plausible network structures. Although integrating various sources of information is desirable, their heterogeneous nature makes this task challenging. We propose two computational methods to incorporate various information sources into a probabilistic consensus structure prior to be used in graphical model inference. Our first model, called Latent Factor Model (LFM), assumes a high degree of correlation among external information sources and reconstructs a hidden variable as a common source in a Bayesian manner. The second model, a Noisy-OR, picks up the strongest support for an interaction among information sources in a probabilistic fashion. Our extensive computational studies on KEGG signaling pathways as well as on gene expression data from breast cancer and yeast heat shock response reveal that both approaches can significantly enhance the reconstruction accuracy of Bayesian Networks compared to other competing methods as well as to the situation without any prior. Our framework allows for using diverse information sources, like pathway databases, GO terms and protein domain data, etc. and is flexible enough to integrate new sources, if available. PMID:23826291
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Impact of environmental inputs on reverse-engineering approach to network structures.
Wu, Jianhua; Sinfield, James L; Buchanan-Wollaston, Vicky; Feng, Jianfeng
2009-12-04
Uncovering complex network structures from a biological system is one of the main topic in system biology. The network structures can be inferred by the dynamical Bayesian network or Granger causality, but neither techniques have seriously taken into account the impact of environmental inputs. With considerations of natural rhythmic dynamics of biological data, we propose a system biology approach to reveal the impact of environmental inputs on network structures. We first represent the environmental inputs by a harmonic oscillator and combine them with Granger causality to identify environmental inputs and then uncover the causal network structures. We also generalize it to multiple harmonic oscillators to represent various exogenous influences. This system approach is extensively tested with toy models and successfully applied to a real biological network of microarray data of the flowering genes of the model plant Arabidopsis Thaliana. The aim is to identify those genes that are directly affected by the presence of the sunlight and uncover the interactive network structures associating with flowering metabolism. We demonstrate that environmental inputs are crucial for correctly inferring network structures. Harmonic causal method is proved to be a powerful technique to detect environment inputs and uncover network structures, especially when the biological data exhibit periodic oscillations.
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Predictive minimum description length principle approach to inferring gene regulatory networks.
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.
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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.
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Data fusion and classification using a hybrid intrinsic cellular inference network
NASA Astrophysics Data System (ADS)
Woodley, Robert; Walenz, Brett; Seiffertt, John; Robinette, Paul; Wunsch, Donald
2010-04-01
Hybrid Intrinsic Cellular Inference Network (HICIN) is designed for battlespace decision support applications. We developed an automatic method of generating hypotheses for an entity-attribute classifier. The capability and effectiveness of a domain specific ontology was used to generate automatic categories for data classification. Heterogeneous data is clustered using an Adaptive Resonance Theory (ART) inference engine on a sample (unclassified) data set. The data set is the Lahman baseball database. The actual data is immaterial to the architecture, however, parallels in the data can be easily drawn (i.e., "Team" maps to organization, "Runs scored/allowed" to Measure of organization performance (positive/negative), "Payroll" to organization resources, etc.). Results show that HICIN classifiers create known inferences from the heterogonous data. These inferences are not explicitly stated in the ontological description of the domain and are strictly data driven. HICIN uses data uncertainty handling to reduce errors in the classification. The uncertainty handling is based on subjective logic. The belief mass allows evidence from multiple sources to be mathematically combined to increase or discount an assertion. In military operations the ability to reduce uncertainty will be vital in the data fusion operation.
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DOT National Transportation Integrated Search
2008-05-06
The present study used commercial motor vehicle (CMV) crash data from NCDOTs Traffic Engineering Accident : Analysis System (TEAAS) to infer the presence and relative extent of STAA dimensioned vehicles operating : beyond the 3-mile buffer of the ...
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Reverse engineering and analysis of large genome-scale gene networks
Aluru, Maneesha; Zola, Jaroslaw; Nettleton, Dan; Aluru, Srinivas
2013-01-01
Reverse engineering the whole-genome networks of complex multicellular organisms continues to remain a challenge. While simpler models easily scale to large number of genes and gene expression datasets, more accurate models are compute intensive limiting their scale of applicability. To enable fast and accurate reconstruction of large networks, we developed Tool for Inferring Network of Genes (TINGe), a parallel mutual information (MI)-based program. The novel features of our approach include: (i) B-spline-based formulation for linear-time computation of MI, (ii) a novel algorithm for direct permutation testing and (iii) development of parallel algorithms to reduce run-time and facilitate construction of large networks. We assess the quality of our method by comparison with ARACNe (Algorithm for the Reconstruction of Accurate Cellular Networks) and GeneNet and demonstrate its unique capability by reverse engineering the whole-genome network of Arabidopsis thaliana from 3137 Affymetrix ATH1 GeneChips in just 9 min on a 1024-core cluster. We further report on the development of a new software Gene Network Analyzer (GeNA) for extracting context-specific subnetworks from a given set of seed genes. Using TINGe and GeNA, we performed analysis of 241 Arabidopsis AraCyc 8.0 pathways, and the results are made available through the web. PMID:23042249
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A novel gene network inference algorithm using predictive minimum description length approach.
Chaitankar, Vijender; Ghosh, Preetam; Perkins, Edward J; Gong, Ping; Deng, Youping; Zhang, Chaoyang
2010-05-28
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 which 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 proposed a new inference algorithm which incorporated 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 was evaluated using both synthetic time series data sets and a biological time series data set for the yeast Saccharomyces cerevisiae. The benchmark quantities precision and recall were used as performance measures. The results show that the proposed algorithm produced less false edges and significantly improved the precision, as compared to the existing algorithm. For further analysis the performance of the algorithms was observed over different sizes of data. We have proposed a new algorithm that implements the PMDL principle for inferring gene regulatory networks from time series DNA microarray data that eliminates the need of a fine tuning parameter. The evaluation results obtained from both synthetic and actual biological data sets show that the PMDL principle is effective in determining the MI threshold and the developed algorithm improves precision of gene regulatory network inference. Based on the sensitivity analysis of all tested cases, an optimal CMI threshold value has been identified. Finally it was observed that the performance of the algorithms saturates at a certain threshold of data size.
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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 study is intended to serve as a guide for choosing a particular combination of similarity measures and scoring schemes suitable for reconstruction of gene regulatory networks from short time series data. We show that further improvement of algorithms for reverse engineering can be obtained if one considers measures that are rooted in the study of symbolic dynamics or ranks, in contrast to the application of common similarity measures which do not consider the temporal character of the employed data. Moreover, we establish that the asymmetric weighting scoring scheme together with symbol based measures (for low noise level) and rank based measures (for high noise level) are the most suitable choices. PMID:21771321
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A prior-based integrative framework for functional transcriptional regulatory network inference
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
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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, highly generalizable framework for identifying the underlying control mechanisms responsible for the dynamic regulation of growth and form. PMID:26042810
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Bal, Mert; Amasyali, M Fatih; Sever, Hayri; Kose, Guven; Demirhan, Ayse
2014-01-01
The importance of the decision support systems is increasingly supporting the decision making process in cases of uncertainty and the lack of information and they are widely used in various fields like engineering, finance, medicine, and so forth, Medical decision support systems help the healthcare personnel to select optimal method during the treatment of the patients. Decision support systems are intelligent software systems that support decision makers on their decisions. The design of decision support systems consists of four main subjects called inference mechanism, knowledge-base, explanation module, and active memory. Inference mechanism constitutes the basis of decision support systems. There are various methods that can be used in these mechanisms approaches. Some of these methods are decision trees, artificial neural networks, statistical methods, rule-based methods, and so forth. In decision support systems, those methods can be used separately or a hybrid system, and also combination of those methods. In this study, synthetic data with 10, 100, 1000, and 2000 records have been produced to reflect the probabilities on the ALARM network. The accuracy of 11 machine learning methods for the inference mechanism of medical decision support system is compared on various data sets.
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Rational Modular RNA Engineering Based on In Vivo Profiling of Structural Accessibility.
Leistra, Abigail N; Amador, Paul; Buvanendiran, Aishwarya; Moon-Walker, Alex; Contreras, Lydia M
2017-12-15
Bacterial small RNAs (sRNAs) have been established as powerful parts for controlling gene expression. However, development and application of engineered sRNAs has primarily focused on regulating novel synthetic targets. In this work, we demonstrate a rational modular RNA engineering approach that uses in vivo structural accessibility measurements to tune the regulatory activity of a multisubstrate sRNA for differential control of its native target network. Employing the CsrB global sRNA regulator as a model system, we use published in vivo structural accessibility data to infer the contribution of its local structures (substructures) to function and select a subset for engineering. We then modularly recombine the selected substructures, differentially representing those of presumed high or low functional contribution, to build a library of 21 CsrB variants. Using fluorescent translational reporter assays, we demonstrate that the CsrB variants achieve a 5-fold gradient of control of well-characterized Csr network targets. Interestingly, results suggest that less conserved local structures within long, multisubstrate sRNAs may represent better targets for rational engineering than their well-conserved counterparts. Lastly, mapping the impact of sRNA variants on a signature Csr network phenotype indicates the potential of this approach for tuning the activity of global sRNA regulators in the context of metabolic engineering applications.
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Evaluating a common semi-mechanistic mathematical model of gene-regulatory networks
2015-01-01
Modeling and simulation of gene-regulatory networks (GRNs) has become an important aspect of modern systems biology investigations into mechanisms underlying gene regulation. A key challenge in this area is the automated inference (reverse-engineering) of dynamic, mechanistic GRN models from gene expression time-course data. Common mathematical formalisms for representing such models capture two aspects simultaneously within a single parameter: (1) Whether or not a gene is regulated, and if so, the type of regulator (activator or repressor), and (2) the strength of influence of the regulator (if any) on the target or effector gene. To accommodate both roles, "generous" boundaries or limits for possible values of this parameter are commonly allowed in the reverse-engineering process. This approach has several important drawbacks. First, in the absence of good guidelines, there is no consensus on what limits are reasonable. Second, because the limits may vary greatly among different reverse-engineering experiments, the concrete values obtained for the models may differ considerably, and thus it is difficult to compare models. Third, if high values are chosen as limits, the search space of the model inference process becomes very large, adding unnecessary computational load to the already complex reverse-engineering process. In this study, we demonstrate that restricting the limits to the [−1, +1] interval is sufficient to represent the essential features of GRN systems and offers a reduction of the search space without loss of quality in the resulting models. To show this, we have carried out reverse-engineering studies on data generated from artificial and experimentally determined from real GRN systems. PMID:26356485
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Jaeger, Johannes; Crombach, Anton
2012-01-01
We propose an approach to evolutionary systems biology which is based on reverse engineering of gene regulatory networks and in silico evolutionary simulations. We infer regulatory parameters for gene networks by fitting computational models to quantitative expression data. This allows us to characterize the regulatory structure and dynamical repertoire of evolving gene regulatory networks with a reasonable amount of experimental and computational effort. We use the resulting network models to identify those regulatory interactions that are conserved, and those that have diverged between different species. Moreover, we use the models obtained by data fitting as starting points for simulations of evolutionary transitions between species. These simulations enable us to investigate whether such transitions are random, or whether they show stereotypical series of regulatory changes which depend on the structure and dynamical repertoire of an evolving network. Finally, we present a case study-the gap gene network in dipterans (flies, midges, and mosquitoes)-to illustrate the practical application of the proposed methodology, and to highlight the kind of biological insights that can be gained by this approach.
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Extracting information from multiplex networks
NASA Astrophysics Data System (ADS)
Iacovacci, Jacopo; Bianconi, Ginestra
2016-06-01
Multiplex networks are generalized network structures that are able to describe networks in which the same set of nodes are connected by links that have different connotations. Multiplex networks are ubiquitous since they describe social, financial, engineering, and biological networks as well. Extending our ability to analyze complex networks to multiplex network structures increases greatly the level of information that is possible to extract from big data. For these reasons, characterizing the centrality of nodes in multiplex networks and finding new ways to solve challenging inference problems defined on multiplex networks are fundamental questions of network science. In this paper, we discuss the relevance of the Multiplex PageRank algorithm for measuring the centrality of nodes in multilayer networks and we characterize the utility of the recently introduced indicator function Θ ˜ S for describing their mesoscale organization and community structure. As working examples for studying these measures, we consider three multiplex network datasets coming for social science.
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Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Chen, Jian; Liu, Long
By combining advanced omics technology and computational modeling, systems biologists have identified and inferred thousands of regulatory events and system-wide interactions of the bacterium Bacillus subtilis, which is commonly used both in the laboratory and in industry. This dissection of the multiple layers of regulatory networks and their interactions has provided invaluable information for unraveling regulatory mechanisms and guiding metabolic engineering. In this review, we discuss recent advances in the systems biology and metabolic engineering of B. subtilis and highlight current gaps in our understanding of global metabolism and global pathway engineering in this organism. We also propose future perspectives in the systems biology of B. subtilis and suggest ways that this approach can be used to guide metabolic engineering. Specifically, although hundreds of regulatory events have been identified or inferred via systems biology approaches, systematic investigation of the functionality of these events in vivo has lagged, thereby preventing the elucidation of regulatory mechanisms and further rational pathway engineering. In metabolic engineering, ignoring the engineering of multilayer regulation hinders metabolic flux redistribution. Post-translational engineering, allosteric engineering, and dynamic pathway analyses and control will also contribute to the modulation and control of the metabolism of engineered B. subtilis, ultimately producing the desired cellular traits. We hope this review will aid metabolic engineers in making full use of available systems biology datasets and approaches for the design and perfection of microbial cell factories through global metabolism optimization. Copyright © 2016 Elsevier Inc. All rights reserved.
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Network inference using informative priors.
Mukherjee, Sach; Speed, Terence P
2008-09-23
Recent years have seen much interest in the study of systems characterized by multiple interacting components. A class of statistical models called graphical models, in which graphs are used to represent probabilistic relationships between variables, provides a framework for formal inference regarding such systems. In many settings, the object of inference is the network structure itself. This problem of "network inference" is well known to be a challenging one. However, in scientific settings there is very often existing information regarding network connectivity. A natural idea then is to take account of such information during inference. This article addresses the question of incorporating prior information into network inference. We focus on directed models called Bayesian networks, and use Markov chain Monte Carlo to draw samples from posterior distributions over network structures. We introduce prior distributions on graphs capable of capturing information regarding network features including edges, classes of edges, degree distributions, and sparsity. We illustrate our approach in the context of systems biology, applying our methods to network inference in cancer signaling.
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A comparative study of covariance selection models for the inference of gene regulatory networks.
Stifanelli, Patrizia F; Creanza, Teresa M; Anglani, Roberto; Liuzzi, Vania C; Mukherjee, Sayan; Schena, Francesco P; Ancona, Nicola
2013-10-01
The inference, or 'reverse-engineering', of gene regulatory networks from expression data and the description of the complex dependency structures among genes are open issues in modern molecular biology. In this paper we compared three regularized methods of covariance selection for the inference of gene regulatory networks, developed to circumvent the problems raising when the number of observations n is smaller than the number of genes p. The examined approaches provided three alternative estimates of the inverse covariance matrix: (a) the 'PINV' method is based on the Moore-Penrose pseudoinverse, (b) the 'RCM' method performs correlation between regression residuals and (c) 'ℓ(2C)' method maximizes a properly regularized log-likelihood function. Our extensive simulation studies showed that ℓ(2C) outperformed the other two methods having the most predictive partial correlation estimates and the highest values of sensitivity to infer conditional dependencies between genes even when a few number of observations was available. The application of this method for inferring gene networks of the isoprenoid biosynthesis pathways in Arabidopsis thaliana allowed to enlighten a negative partial correlation coefficient between the two hubs in the two isoprenoid pathways and, more importantly, provided an evidence of cross-talk between genes in the plastidial and the cytosolic pathways. When applied to gene expression data relative to a signature of HRAS oncogene in human cell cultures, the method revealed 9 genes (p-value<0.0005) directly interacting with HRAS, sharing the same Ras-responsive binding site for the transcription factor RREB1. This result suggests that the transcriptional activation of these genes is mediated by a common transcription factor downstream of Ras signaling. Software implementing the methods in the form of Matlab scripts are available at: http://users.ba.cnr.it/issia/iesina18/CovSelModelsCodes.zip. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
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Souza, Terezinha M; Kleinjans, Jos C S; Jennen, Danyel G J
2017-01-01
Perturbation of biological networks is often observed during exposure to xenobiotics, and the identification of disturbed processes, their dynamic traits, and dose-response relationships are some of the current challenges for elucidating the mechanisms determining adverse outcomes. In this scenario, reverse engineering of gene regulatory networks (GRNs) from expression data may provide a system-level snapshot embedded within accurate molecular events. Here, we investigate the composition of GRNs inferred from groups of chemicals with two distinct outcomes, namely carcinogenicity [azathioprine (AZA) and cyclophosphamide (CYC)] and drug-induced liver injury (DILI; diclofenac, nitrofurantoin, and propylthiouracil), and a non-carcinogenic/non-DILI group (aspirin, diazepam, and omeprazole). For this, we analyzed publicly available exposed in vitro human data, taking into account dose and time dependencies. Dose-Time Network Identification (DTNI) was applied to gene sets from exposed primary human hepatocytes using four stress pathways, namely endoplasmic reticulum (ER), NF-κB, NRF2, and TP53. Inferred GRNs suggested case specificity, varying in interactions, starting nodes, and target genes across groups. DILI and carcinogenic compounds were shown to directly affect all pathway-based GRNs, while non-DILI/non-carcinogenic chemicals only affected NF-κB. NF-κB-based GRNs clearly illustrated group-specific disturbances, with the cancer-related casein kinase CSNK2A1 being a target gene only in the carcinogenic group, and opposite regulation of NF-κB subunits being observed in DILI and non-DILI/non-carcinogenic groups. Target genes in NRF2-based GRNs shared by DILI and carcinogenic compounds suggested markers of hepatotoxicity. Finally, we indicate several of these group-specific interactions as potentially novel. In summary, our reversed-engineered GRNs are capable of revealing dose dependent, chemical-specific mechanisms of action in stress-related biological networks.
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State Space Model with hidden variables for reconstruction of gene regulatory networks.
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.
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A unified design space of synthetic stripe-forming networks
Schaerli, Yolanda; Munteanu, Andreea; Gili, Magüi; Cotterell, James; Sharpe, James; Isalan, Mark
2014-01-01
Synthetic biology is a promising tool to study the function and properties of gene regulatory networks. Gene circuits with predefined behaviours have been successfully built and modelled, but largely on a case-by-case basis. Here we go beyond individual networks and explore both computationally and synthetically the design space of possible dynamical mechanisms for 3-node stripe-forming networks. First, we computationally test every possible 3-node network for stripe formation in a morphogen gradient. We discover four different dynamical mechanisms to form a stripe and identify the minimal network of each group. Next, with the help of newly established engineering criteria we build these four networks synthetically and show that they indeed operate with four fundamentally distinct mechanisms. Finally, this close match between theory and experiment allows us to infer and subsequently build a 2-node network that represents the archetype of the explored design space. PMID:25247316
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Hurley, Daniel; Araki, Hiromitsu; Tamada, Yoshinori; Dunmore, Ben; Sanders, Deborah; Humphreys, Sally; Affara, Muna; Imoto, Seiya; Yasuda, Kaori; Tomiyasu, Yuki; Tashiro, Kosuke; Savoie, Christopher; Cho, Vicky; Smith, Stephen; Kuhara, Satoru; Miyano, Satoru; Charnock-Jones, D. Stephen; Crampin, Edmund J.; Print, Cristin G.
2012-01-01
Gene regulatory networks inferred from RNA abundance data have generated significant interest, but despite this, gene network approaches are used infrequently and often require input from bioinformaticians. We have assembled a suite of tools for analysing regulatory networks, and we illustrate their use with microarray datasets generated in human endothelial cells. We infer a range of regulatory networks, and based on this analysis discuss the strengths and limitations of network inference from RNA abundance data. We welcome contact from researchers interested in using our inference and visualization tools to answer biological questions. PMID:22121215
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Reverse engineering a gene network using an asynchronous parallel evolution strategy
2010-01-01
Background The use of reverse engineering methods to infer gene regulatory networks by fitting mathematical models to gene expression data is becoming increasingly popular and successful. However, increasing model complexity means that more powerful global optimisation techniques are required for model fitting. The parallel Lam Simulated Annealing (pLSA) algorithm has been used in such approaches, but recent research has shown that island Evolutionary Strategies can produce faster, more reliable results. However, no parallel island Evolutionary Strategy (piES) has yet been demonstrated to be effective for this task. Results Here, we present synchronous and asynchronous versions of the piES algorithm, and apply them to a real reverse engineering problem: inferring parameters in the gap gene network. We find that the asynchronous piES exhibits very little communication overhead, and shows significant speed-up for up to 50 nodes: the piES running on 50 nodes is nearly 10 times faster than the best serial algorithm. We compare the asynchronous piES to pLSA on the same test problem, measuring the time required to reach particular levels of residual error, and show that it shows much faster convergence than pLSA across all optimisation conditions tested. Conclusions Our results demonstrate that the piES is consistently faster and more reliable than the pLSA algorithm on this problem, and scales better with increasing numbers of nodes. In addition, the piES is especially well suited to further improvements and adaptations: Firstly, the algorithm's fast initial descent speed and high reliability make it a good candidate for being used as part of a global/local search hybrid algorithm. Secondly, it has the potential to be used as part of a hierarchical evolutionary algorithm, which takes advantage of modern multi-core computing architectures. PMID:20196855
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Reverse engineering gene regulatory networks from measurement with missing values.
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, more accurate prediction of the underlying GRN compared to when using the conventional Gaussian approximation (GA) filters ignoring the missing data points.
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Zou, Cunlu; Ladroue, Christophe; Guo, Shuixia; Feng, Jianfeng
2010-06-21
Reverse-engineering approaches such as Bayesian network inference, ordinary differential equations (ODEs) and information theory are widely applied to deriving causal relationships among different elements such as genes, proteins, metabolites, neurons, brain areas and so on, based upon multi-dimensional spatial and temporal data. There are several well-established reverse-engineering approaches to explore causal relationships in a dynamic network, such as ordinary differential equations (ODE), Bayesian networks, information theory and Granger Causality. Here we focused on Granger causality both in the time and frequency domain and in local and global networks, and applied our approach to experimental data (genes and proteins). For a small gene network, Granger causality outperformed all the other three approaches mentioned above. A global protein network of 812 proteins was reconstructed, using a novel approach. The obtained results fitted well with known experimental findings and predicted many experimentally testable results. In addition to interactions in the time domain, interactions in the frequency domain were also recovered. The results on the proteomic data and gene data confirm that Granger causality is a simple and accurate approach to recover the network structure. Our approach is general and can be easily applied to other types of temporal data.
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Inference of neuronal network spike dynamics and topology from calcium imaging data
Lütcke, Henry; Gerhard, Felipe; Zenke, Friedemann; Gerstner, Wulfram; Helmchen, Fritjof
2013-01-01
Two-photon calcium imaging enables functional analysis of neuronal circuits by inferring action potential (AP) occurrence (“spike trains”) from cellular fluorescence signals. It remains unclear how experimental parameters such as signal-to-noise ratio (SNR) and acquisition rate affect spike inference and whether additional information about network structure can be extracted. Here we present a simulation framework for quantitatively assessing how well spike dynamics and network topology can be inferred from noisy calcium imaging data. For simulated AP-evoked calcium transients in neocortical pyramidal cells, we analyzed the quality of spike inference as a function of SNR and data acquisition rate using a recently introduced peeling algorithm. Given experimentally attainable values of SNR and acquisition rate, neural spike trains could be reconstructed accurately and with up to millisecond precision. We then applied statistical neuronal network models to explore how remaining uncertainties in spike inference affect estimates of network connectivity and topological features of network organization. We define the experimental conditions suitable for inferring whether the network has a scale-free structure and determine how well hub neurons can be identified. Our findings provide a benchmark for future calcium imaging studies that aim to reliably infer neuronal network properties. PMID:24399936
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Network inference using informative priors
Mukherjee, Sach; Speed, Terence P.
2008-01-01
Recent years have seen much interest in the study of systems characterized by multiple interacting components. A class of statistical models called graphical models, in which graphs are used to represent probabilistic relationships between variables, provides a framework for formal inference regarding such systems. In many settings, the object of inference is the network structure itself. This problem of “network inference” is well known to be a challenging one. However, in scientific settings there is very often existing information regarding network connectivity. A natural idea then is to take account of such information during inference. This article addresses the question of incorporating prior information into network inference. We focus on directed models called Bayesian networks, and use Markov chain Monte Carlo to draw samples from posterior distributions over network structures. We introduce prior distributions on graphs capable of capturing information regarding network features including edges, classes of edges, degree distributions, and sparsity. We illustrate our approach in the context of systems biology, applying our methods to network inference in cancer signaling. PMID:18799736
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Mathematical inference and control of molecular networks from perturbation experiments
NASA Astrophysics Data System (ADS)
Mohammed-Rasheed, Mohammed
One of the main challenges facing biologists and mathematicians in the post genomic era is to understand the behavior of molecular networks and harness this understanding into an educated intervention of the cell. The cell maintains its function via an elaborate network of interconnecting positive and negative feedback loops of genes, RNA and proteins that send different signals to a large number of pathways and molecules. These structures are referred to as genetic regulatory networks (GRNs) or molecular networks. GRNs can be viewed as dynamical systems with inherent properties and mechanisms, such as steady-state equilibriums and stability, that determine the behavior of the cell. The biological relevance of the mathematical concepts are important as they may predict the differentiation of a stem cell, the maintenance of a normal cell, the development of cancer and its aberrant behavior, and the design of drugs and response to therapy. Uncovering the underlying GRN structure from gene/protein expression data, e.g., microarrays or perturbation experiments, is called inference or reverse engineering of the molecular network. Because of the high cost and time consuming nature of biological experiments, the number of available measurements or experiments is very small compared to the number of molecules (genes, RNA and proteins). In addition, the observations are noisy, where the noise is due to the measurements imperfections as well as the inherent stochasticity of genetic expression levels. Intra-cellular activities and extra-cellular environmental attributes are also another source of variability. Thus, the inference of GRNs is, in general, an under-determined problem with a highly noisy set of observations. The ultimate goal of GRN inference and analysis is to be able to intervene within the network, in order to force it away from undesirable cellular states and into desirable ones. However, it remains a major challenge to design optimal intervention strategies in order to affect the time evolution of molecular activity in a desirable manner. In this proposal, we address both the inference and control problems of GRNs. In the first part of the thesis, we consider the control problem. We assume that we are given a general topology network structure, whose dynamics follow a discrete-time Markov chain model. We subsequently develop a comprehensive framework for optimal perturbation control of the network. The aim of the perturbation is to drive the network away from undesirable steady-states and to force it to converge to a unique desirable steady-state. The proposed framework does not make any assumptions about the topology of the initial network (e.g., ergodicity, weak and strong connectivity), and is thus applicable to general topology networks. We define the optimal perturbation as the minimum-energy perturbation measured in terms of the Frobenius norm between the initial and perturbed networks. We subsequently demonstrate that there exists at most one optimal perturbation that forces the network into the desirable steady-state. In the event where the optimal perturbation does not exist, we construct a family of sub-optimal perturbations that approximate the optimal solution arbitrarily closely. In the second part of the thesis, we address the inference problem of GRNs from time series data. We model the dynamics of the molecules using a system of ordinary differential equations corrupted by additive white noise. For large-scale networks, we formulate the inference problem as a constrained maximum likelihood estimation problem. We derive the molecular interactions that maximize the likelihood function while constraining the network to be sparse. We further propose a procedure to recover weak interactions based on the Bayesian information criterion. For small-size networks, we investigated the inference of a globally stable 7-gene melanoma genetic regulatory network from genetic perturbation experiments. We considered five melanoma cell lines, who exhibit different motility/invasion behavior under the same perturbation experiment of gene Wnt5a. The results of the simulations validate both the steady state levels and the experimental data of the perturbation experiments of all five cell lines. The goal of this study is to answer important questions that link the response of the network to perturbations, as measured by the experiments, to its structure, i.e., connectivity. Answers to these questions shed novel insights on the structure of networks and how they react to perturbations.
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Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J.; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco
2016-01-01
Abstract The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks in a wide spectrum of biological systems. PMID:27124473
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Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antczak, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco
2016-04-01
The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks in a wide spectrum of biological systems.
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In silico model-based inference: a contemporary approach for hypothesis testing in network biology.
Klinke, David J
2014-01-01
Inductive inference plays a central role in the study of biological systems where one aims to increase their understanding of the system by reasoning backwards from uncertain observations to identify causal relationships among components of the system. These causal relationships are postulated from prior knowledge as a hypothesis or simply a model. Experiments are designed to test the model. Inferential statistics are used to establish a level of confidence in how well our postulated model explains the acquired data. This iterative process, commonly referred to as the scientific method, either improves our confidence in a model or suggests that we revisit our prior knowledge to develop a new model. Advances in technology impact how we use prior knowledge and data to formulate models of biological networks and how we observe cellular behavior. However, the approach for model-based inference has remained largely unchanged since Fisher, Neyman and Pearson developed the ideas in the early 1900s that gave rise to what is now known as classical statistical hypothesis (model) testing. Here, I will summarize conventional methods for model-based inference and suggest a contemporary approach to aid in our quest to discover how cells dynamically interpret and transmit information for therapeutic aims that integrates ideas drawn from high performance computing, Bayesian statistics, and chemical kinetics. © 2014 American Institute of Chemical Engineers.
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MIDER: Network Inference with Mutual Information Distance and Entropy Reduction
Villaverde, Alejandro F.; Ross, John; Morán, Federico; Banga, Julio R.
2014-01-01
The prediction of links among variables from a given dataset is a task referred to as network inference or reverse engineering. It is an open problem in bioinformatics and systems biology, as well as in other areas of science. Information theory, which uses concepts such as mutual information, provides a rigorous framework for addressing it. While a number of information-theoretic methods are already available, most of them focus on a particular type of problem, introducing assumptions that limit their generality. Furthermore, many of these methods lack a publicly available implementation. Here we present MIDER, a method for inferring network structures with information theoretic concepts. It consists of two steps: first, it provides a representation of the network in which the distance among nodes indicates their statistical closeness. Second, it refines the prediction of the existing links to distinguish between direct and indirect interactions and to assign directionality. The method accepts as input time-series data related to some quantitative features of the network nodes (such as e.g. concentrations, if the nodes are chemical species). It takes into account time delays between variables, and allows choosing among several definitions and normalizations of mutual information. It is general purpose: it may be applied to any type of network, cellular or otherwise. A Matlab implementation including source code and data is freely available (http://www.iim.csic.es/~gingproc/mider.html). The performance of MIDER has been evaluated on seven different benchmark problems that cover the main types of cellular networks, including metabolic, gene regulatory, and signaling. Comparisons with state of the art information–theoretic methods have demonstrated the competitive performance of MIDER, as well as its versatility. Its use does not demand any a priori knowledge from the user; the default settings and the adaptive nature of the method provide good results for a wide range of problems without requiring tuning. PMID:24806471
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MIDER: network inference with mutual information distance and entropy reduction.
Villaverde, Alejandro F; Ross, John; Morán, Federico; Banga, Julio R
2014-01-01
The prediction of links among variables from a given dataset is a task referred to as network inference or reverse engineering. It is an open problem in bioinformatics and systems biology, as well as in other areas of science. Information theory, which uses concepts such as mutual information, provides a rigorous framework for addressing it. While a number of information-theoretic methods are already available, most of them focus on a particular type of problem, introducing assumptions that limit their generality. Furthermore, many of these methods lack a publicly available implementation. Here we present MIDER, a method for inferring network structures with information theoretic concepts. It consists of two steps: first, it provides a representation of the network in which the distance among nodes indicates their statistical closeness. Second, it refines the prediction of the existing links to distinguish between direct and indirect interactions and to assign directionality. The method accepts as input time-series data related to some quantitative features of the network nodes (such as e.g. concentrations, if the nodes are chemical species). It takes into account time delays between variables, and allows choosing among several definitions and normalizations of mutual information. It is general purpose: it may be applied to any type of network, cellular or otherwise. A Matlab implementation including source code and data is freely available (http://www.iim.csic.es/~gingproc/mider.html). The performance of MIDER has been evaluated on seven different benchmark problems that cover the main types of cellular networks, including metabolic, gene regulatory, and signaling. Comparisons with state of the art information-theoretic methods have demonstrated the competitive performance of MIDER, as well as its versatility. Its use does not demand any a priori knowledge from the user; the default settings and the adaptive nature of the method provide good results for a wide range of problems without requiring tuning.
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Inferring Phylogenetic Networks Using PhyloNet.
Wen, Dingqiao; Yu, Yun; Zhu, Jiafan; Nakhleh, Luay
2018-07-01
PhyloNet was released in 2008 as a software package for representing and analyzing phylogenetic networks. At the time of its release, the main functionalities in PhyloNet consisted of measures for comparing network topologies and a single heuristic for reconciling gene trees with a species tree. Since then, PhyloNet has grown significantly. The software package now includes a wide array of methods for inferring phylogenetic networks from data sets of unlinked loci while accounting for both reticulation (e.g., hybridization) and incomplete lineage sorting. In particular, PhyloNet now allows for maximum parsimony, maximum likelihood, and Bayesian inference of phylogenetic networks from gene tree estimates. Furthermore, Bayesian inference directly from sequence data (sequence alignments or biallelic markers) is implemented. Maximum parsimony is based on an extension of the "minimizing deep coalescences" criterion to phylogenetic networks, whereas maximum likelihood and Bayesian inference are based on the multispecies network coalescent. All methods allow for multiple individuals per species. As computing the likelihood of a phylogenetic network is computationally hard, PhyloNet allows for evaluation and inference of networks using a pseudolikelihood measure. PhyloNet summarizes the results of the various analyzes and generates phylogenetic networks in the extended Newick format that is readily viewable by existing visualization software.
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Genetic network inference as a series of discrimination tasks.
Kimura, Shuhei; Nakayama, Satoshi; Hatakeyama, Mariko
2009-04-01
Genetic network inference methods based on sets of differential equations generally require a great deal of time, as the equations must be solved many times. To reduce the computational cost, researchers have proposed other methods for inferring genetic networks by solving sets of differential equations only a few times, or even without solving them at all. When we try to obtain reasonable network models using these methods, however, we must estimate the time derivatives of the gene expression levels with great precision. In this study, we propose a new method to overcome the drawbacks of inference methods based on sets of differential equations. Our method infers genetic networks by obtaining classifiers capable of predicting the signs of the derivatives of the gene expression levels. For this purpose, we defined a genetic network inference problem as a series of discrimination tasks, then solved the defined series of discrimination tasks with a linear programming machine. Our experimental results demonstrated that the proposed method is capable of correctly inferring genetic networks, and doing so more than 500 times faster than the other inference methods based on sets of differential equations. Next, we applied our method to actual expression data of the bacterial SOS DNA repair system. And finally, we demonstrated that our approach relates to the inference method based on the S-system model. Though our method provides no estimation of the kinetic parameters, it should be useful for researchers interested only in the network structure of a target system. Supplementary data are available at Bioinformatics online.
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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 reconstruction using network and transcriptomic data), we show that the formalism used to build FRANK can to some extent be a reasonable model for gene regulatory networks in real cells.
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System and method for responding to ground and flight system malfunctions
NASA Technical Reports Server (NTRS)
Anderson, Julie J. (Inventor); Fussell, Ronald M. (Inventor)
2010-01-01
A system for on-board anomaly resolution for a vehicle has a data repository. The data repository stores data related to different systems, subsystems, and components of the vehicle. The data stored is encoded in a tree-based structure. A query engine is coupled to the data repository. The query engine provides a user and automated interface and provides contextual query to the data repository. An inference engine is coupled to the query engine. The inference engine compares current anomaly data to contextual data stored in the data repository using inference rules. The inference engine generates a potential solution to the current anomaly by referencing the data stored in the data repository.
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Reverse engineering of gene regulatory networks.
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.
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Inferring causal molecular networks: empirical assessment through a community-based effort
Hill, Steven M.; Heiser, Laura M.; Cokelaer, Thomas; Unger, Michael; Nesser, Nicole K.; Carlin, Daniel E.; Zhang, Yang; Sokolov, Artem; Paull, Evan O.; Wong, Chris K.; Graim, Kiley; Bivol, Adrian; Wang, Haizhou; Zhu, Fan; Afsari, Bahman; Danilova, Ludmila V.; Favorov, Alexander V.; Lee, Wai Shing; Taylor, Dane; Hu, Chenyue W.; Long, Byron L.; Noren, David P.; Bisberg, Alexander J.; Mills, Gordon B.; Gray, Joe W.; Kellen, Michael; Norman, Thea; Friend, Stephen; Qutub, Amina A.; Fertig, Elana J.; Guan, Yuanfang; Song, Mingzhou; Stuart, Joshua M.; Spellman, Paul T.; Koeppl, Heinz; Stolovitzky, Gustavo; Saez-Rodriguez, Julio; Mukherjee, Sach
2016-01-01
Inferring molecular networks is a central challenge in computational biology. However, it has remained unclear whether causal, rather than merely correlational, relationships can be effectively inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge that focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results constitute the most comprehensive assessment of causal network inference in a mammalian setting carried out to date and suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess the causal validity of inferred molecular networks. PMID:26901648
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NASA Astrophysics Data System (ADS)
Zhang, Daili
Increasing societal demand for automation has led to considerable efforts to control large-scale complex systems, especially in the area of autonomous intelligent control methods. The control system of a large-scale complex system needs to satisfy four system level requirements: robustness, flexibility, reusability, and scalability. Corresponding to the four system level requirements, there arise four major challenges. First, it is difficult to get accurate and complete information. Second, the system may be physically highly distributed. Third, the system evolves very quickly. Fourth, emergent global behaviors of the system can be caused by small disturbances at the component level. The Multi-Agent Based Control (MABC) method as an implementation of distributed intelligent control has been the focus of research since the 1970s, in an effort to solve the above-mentioned problems in controlling large-scale complex systems. However, to the author's best knowledge, all MABC systems for large-scale complex systems with significant uncertainties are problem-specific and thus difficult to extend to other domains or larger systems. This situation is partly due to the control architecture of multiple agents being determined by agent to agent coupling and interaction mechanisms. Therefore, the research objective of this dissertation is to develop a comprehensive, generalized framework for the control system design of general large-scale complex systems with significant uncertainties, with the focus on distributed control architecture design and distributed inference engine design. A Hybrid Multi-Agent Based Control (HyMABC) architecture is proposed by combining hierarchical control architecture and module control architecture with logical replication rings. First, it decomposes a complex system hierarchically; second, it combines the components in the same level as a module, and then designs common interfaces for all of the components in the same module; third, replications are made for critical agents and are organized into logical rings. This architecture maintains clear guidelines for complexity decomposition and also increases the robustness of the whole system. Multiple Sectioned Dynamic Bayesian Networks (MSDBNs) as a distributed dynamic probabilistic inference engine, can be embedded into the control architecture to handle uncertainties of general large-scale complex systems. MSDBNs decomposes a large knowledge-based system into many agents. Each agent holds its partial perspective of a large problem domain by representing its knowledge as a Dynamic Bayesian Network (DBN). Each agent accesses local evidence from its corresponding local sensors and communicates with other agents through finite message passing. If the distributed agents can be organized into a tree structure, satisfying the running intersection property and d-sep set requirements, globally consistent inferences are achievable in a distributed way. By using different frequencies for local DBN agent belief updating and global system belief updating, it balances the communication cost with the global consistency of inferences. In this dissertation, a fully factorized Boyen-Koller (BK) approximation algorithm is used for local DBN agent belief updating, and the static Junction Forest Linkage Tree (JFLT) algorithm is used for global system belief updating. MSDBNs assume a static structure and a stable communication network for the whole system. However, for a real system, sub-Bayesian networks as nodes could be lost, and the communication network could be shut down due to partial damage in the system. Therefore, on-line and automatic MSDBNs structure formation is necessary for making robust state estimations and increasing survivability of the whole system. A Distributed Spanning Tree Optimization (DSTO) algorithm, a Distributed D-Sep Set Satisfaction (DDSSS) algorithm, and a Distributed Running Intersection Satisfaction (DRIS) algorithm are proposed in this dissertation. Combining these three distributed algorithms and a Distributed Belief Propagation (DBP) algorithm in MSDBNs makes state estimations robust to partial damage in the whole system. Combining the distributed control architecture design and the distributed inference engine design leads to a process of control system design for a general large-scale complex system. As applications of the proposed methodology, the control system design of a simplified ship chilled water system and a notional ship chilled water system have been demonstrated step by step. Simulation results not only show that the proposed methodology gives a clear guideline for control system design for general large-scale complex systems with dynamic and uncertain environment, but also indicate that the combination of MSDBNs and HyMABC can provide excellent performance for controlling general large-scale complex systems.
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A Bayesian Active Learning Experimental Design for Inferring Signaling Networks.
Ness, Robert O; Sachs, Karen; Mallick, Parag; Vitek, Olga
2018-06-21
Machine learning methods for learning network structure are applied to quantitative proteomics experiments and reverse-engineer intracellular signal transduction networks. They provide insight into the rewiring of signaling within the context of a disease or a phenotype. To learn the causal patterns of influence between proteins in the network, the methods require experiments that include targeted interventions that fix the activity of specific proteins. However, the interventions are costly and add experimental complexity. We describe an active learning strategy for selecting optimal interventions. Our approach takes as inputs pathway databases and historic data sets, expresses them in form of prior probability distributions on network structures, and selects interventions that maximize their expected contribution to structure learning. Evaluations on simulated and real data show that the strategy reduces the detection error of validated edges as compared with an unguided choice of interventions and avoids redundant interventions, thereby increasing the effectiveness of the experiment.
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Generic comparison of protein inference engines.
Claassen, Manfred; Reiter, Lukas; Hengartner, Michael O; Buhmann, Joachim M; Aebersold, Ruedi
2012-04-01
Protein identifications, instead of peptide-spectrum matches, constitute the biologically relevant result of shotgun proteomics studies. How to appropriately infer and report protein identifications has triggered a still ongoing debate. This debate has so far suffered from the lack of appropriate performance measures that allow us to objectively assess protein inference approaches. This study describes an intuitive, generic and yet formal performance measure and demonstrates how it enables experimentalists to select an optimal protein inference strategy for a given collection of fragment ion spectra. We applied the performance measure to systematically explore the benefit of excluding possibly unreliable protein identifications, such as single-hit wonders. Therefore, we defined a family of protein inference engines by extending a simple inference engine by thousands of pruning variants, each excluding a different specified set of possibly unreliable identifications. We benchmarked these protein inference engines on several data sets representing different proteomes and mass spectrometry platforms. Optimally performing inference engines retained all high confidence spectral evidence, without posterior exclusion of any type of protein identifications. Despite the diversity of studied data sets consistently supporting this rule, other data sets might behave differently. In order to ensure maximal reliable proteome coverage for data sets arising in other studies we advocate abstaining from rigid protein inference rules, such as exclusion of single-hit wonders, and instead consider several protein inference approaches and assess these with respect to the presented performance measure in the specific application context.
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Robust Strategy for Rocket Engine Health Monitoring
NASA Technical Reports Server (NTRS)
Santi, L. Michael
2001-01-01
Monitoring the health of rocket engine systems is essentially a two-phase process. The acquisition phase involves sensing physical conditions at selected locations, converting physical inputs to electrical signals, conditioning the signals as appropriate to establish scale or filter interference, and recording results in a form that is easy to interpret. The inference phase involves analysis of results from the acquisition phase, comparison of analysis results to established health measures, and assessment of health indications. A variety of analytical tools may be employed in the inference phase of health monitoring. These tools can be separated into three broad categories: statistical, rule based, and model based. Statistical methods can provide excellent comparative measures of engine operating health. They require well-characterized data from an ensemble of "typical" engines, or "golden" data from a specific test assumed to define the operating norm in order to establish reliable comparative measures. Statistical methods are generally suitable for real-time health monitoring because they do not deal with the physical complexities of engine operation. The utility of statistical methods in rocket engine health monitoring is hindered by practical limits on the quantity and quality of available data. This is due to the difficulty and high cost of data acquisition, the limited number of available test engines, and the problem of simulating flight conditions in ground test facilities. In addition, statistical methods incur a penalty for disregarding flow complexity and are therefore limited in their ability to define performance shift causality. Rule based methods infer the health state of the engine system based on comparison of individual measurements or combinations of measurements with defined health norms or rules. This does not mean that rule based methods are necessarily simple. Although binary yes-no health assessment can sometimes be established by relatively simple rules, the causality assignment needed for refined health monitoring often requires an exceptionally complex rule base involving complicated logical maps. Structuring the rule system to be clear and unambiguous can be difficult, and the expert input required to maintain a large logic network and associated rule base can be prohibitive.
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Identification of Boolean Network Models From Time Series Data Incorporating Prior Knowledge.
Leifeld, Thomas; Zhang, Zhihua; Zhang, Ping
2018-01-01
Motivation: Mathematical models take an important place in science and engineering. A model can help scientists to explain dynamic behavior of a system and to understand the functionality of system components. Since length of a time series and number of replicates is limited by the cost of experiments, Boolean networks as a structurally simple and parameter-free logical model for gene regulatory networks have attracted interests of many scientists. In order to fit into the biological contexts and to lower the data requirements, biological prior knowledge is taken into consideration during the inference procedure. In the literature, the existing identification approaches can only deal with a subset of possible types of prior knowledge. Results: We propose a new approach to identify Boolean networks from time series data incorporating prior knowledge, such as partial network structure, canalizing property, positive and negative unateness. Using vector form of Boolean variables and applying a generalized matrix multiplication called the semi-tensor product (STP), each Boolean function can be equivalently converted into a matrix expression. Based on this, the identification problem is reformulated as an integer linear programming problem to reveal the system matrix of Boolean model in a computationally efficient way, whose dynamics are consistent with the important dynamics captured in the data. By using prior knowledge the number of candidate functions can be reduced during the inference. Hence, identification incorporating prior knowledge is especially suitable for the case of small size time series data and data without sufficient stimuli. The proposed approach is illustrated with the help of a biological model of the network of oxidative stress response. Conclusions: The combination of efficient reformulation of the identification problem with the possibility to incorporate various types of prior knowledge enables the application of computational model inference to systems with limited amount of time series data. The general applicability of this methodological approach makes it suitable for a variety of biological systems and of general interest for biological and medical research.
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On the Inference of Functional Circadian Networks Using Granger Causality
Pourzanjani, Arya; Herzog, Erik D.; Petzold, Linda R.
2015-01-01
Being able to infer one way direct connections in an oscillatory network such as the suprachiastmatic nucleus (SCN) of the mammalian brain using time series data is difficult but crucial to understanding network dynamics. Although techniques have been developed for inferring networks from time series data, there have been no attempts to adapt these techniques to infer directional connections in oscillatory time series, while accurately distinguishing between direct and indirect connections. In this paper an adaptation of Granger Causality is proposed that allows for inference of circadian networks and oscillatory networks in general called Adaptive Frequency Granger Causality (AFGC). Additionally, an extension of this method is proposed to infer networks with large numbers of cells called LASSO AFGC. The method was validated using simulated data from several different networks. For the smaller networks the method was able to identify all one way direct connections without identifying connections that were not present. For larger networks of up to twenty cells the method shows excellent performance in identifying true and false connections; this is quantified by an area-under-the-curve (AUC) 96.88%. We note that this method like other Granger Causality-based methods, is based on the detection of high frequency signals propagating between cell traces. Thus it requires a relatively high sampling rate and a network that can propagate high frequency signals. PMID:26413748
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Inferring microbial interactions in thermophilic and mesophilic anaerobic digestion of hog waste
Shaw, Grace Tzun-Wen; Liu, An-Chi; Weng, Chieh-Yin; Chou, Chu-Yang
2017-01-01
Anaerobic digestion (AnD) is a microbiological process that converts organic waste materials into biogas. Because of its high methane content, biogas is a combustible energy source and serves as an important environmental technology commonly used in the management of animal waste generated on large animal farms. Much work has been done on hardware design and process engineering for the generation of biogas. However, little is known about the complexity of the microbiology in this process. In particular, how microbes interact in the digester and eventually breakdown and convert organic matter into biogas is still regarded as a “black box.” We used 16S rRNA sequencing as a tool to study the microbial community in laboratory hog waste digesters under tightly controlled conditions, and systematically unraveled the distinct interaction networks of two microbial communities from mesophilic (MAnD) and thermophilic anaerobic digestion (TAnD). Under thermophilic conditions, the well-known association between hydrogen-producing bacteria, e.g., Ruminococcaceae and Prevotellaceae, and hydrotrophic methanogens, Methanomicrobiaceae, was reverse engineered by their interactive topological niches. The inferred interaction network provides a sketch enabling the determination of microbial interactive relationships that conventional strategy of finding differential taxa was hard to achieve. This research is still in its infancy, but it can help to depict the dynamics of microbial ecosystems and to lay the groundwork for understanding how microorganisms cohabit in the anaerobic digester. PMID:28732056
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Inferring microbial interactions in thermophilic and mesophilic anaerobic digestion of hog waste.
Shaw, Grace Tzun-Wen; Liu, An-Chi; Weng, Chieh-Yin; Chou, Chu-Yang; Wang, Daryi
2017-01-01
Anaerobic digestion (AnD) is a microbiological process that converts organic waste materials into biogas. Because of its high methane content, biogas is a combustible energy source and serves as an important environmental technology commonly used in the management of animal waste generated on large animal farms. Much work has been done on hardware design and process engineering for the generation of biogas. However, little is known about the complexity of the microbiology in this process. In particular, how microbes interact in the digester and eventually breakdown and convert organic matter into biogas is still regarded as a "black box." We used 16S rRNA sequencing as a tool to study the microbial community in laboratory hog waste digesters under tightly controlled conditions, and systematically unraveled the distinct interaction networks of two microbial communities from mesophilic (MAnD) and thermophilic anaerobic digestion (TAnD). Under thermophilic conditions, the well-known association between hydrogen-producing bacteria, e.g., Ruminococcaceae and Prevotellaceae, and hydrotrophic methanogens, Methanomicrobiaceae, was reverse engineered by their interactive topological niches. The inferred interaction network provides a sketch enabling the determination of microbial interactive relationships that conventional strategy of finding differential taxa was hard to achieve. This research is still in its infancy, but it can help to depict the dynamics of microbial ecosystems and to lay the groundwork for understanding how microorganisms cohabit in the anaerobic digester.
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Carrera, Javier; Rodrigo, Guillermo; Jaramillo, Alfonso; Elena, Santiago F
2009-01-01
Background Understanding the molecular mechanisms plants have evolved to adapt their biological activities to a constantly changing environment is an intriguing question and one that requires a systems biology approach. Here we present a network analysis of genome-wide expression data combined with reverse-engineering network modeling to dissect the transcriptional control of Arabidopsis thaliana. The regulatory network is inferred by using an assembly of microarray data containing steady-state RNA expression levels from several growth conditions, developmental stages, biotic and abiotic stresses, and a variety of mutant genotypes. Results We show that the A. thaliana regulatory network has the characteristic properties of hierarchical networks. We successfully applied our quantitative network model to predict the full transcriptome of the plant for a set of microarray experiments not included in the training dataset. We also used our model to analyze the robustness in expression levels conferred by network motifs such as the coherent feed-forward loop. In addition, the meta-analysis presented here has allowed us to identify regulatory and robust genetic structures. Conclusions These data suggest that A. thaliana has evolved high connectivity in terms of transcriptional regulation among cellular functions involved in response and adaptation to changing environments, while gene networks constitutively expressed or less related to stress response are characterized by a lower connectivity. Taken together, these findings suggest conserved regulatory strategies that have been selected during the evolutionary history of this eukaryote. PMID:19754933
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NASA Astrophysics Data System (ADS)
Lobo, Daniel; Lobikin, Maria; Levin, Michael
2017-01-01
Progress in regenerative medicine requires reverse-engineering cellular control networks to infer perturbations with desired systems-level outcomes. Such dynamic models allow phenotypic predictions for novel perturbations to be rapidly assessed in silico. Here, we analyzed a Xenopus model of conversion of melanocytes to a metastatic-like phenotype only previously observed in an all-or-none manner. Prior in vivo genetic and pharmacological experiments showed that individual animals either fully convert or remain normal, at some characteristic frequency after a given perturbation. We developed a Machine Learning method which inferred a model explaining this complex, stochastic all-or-none dataset. We then used this model to ask how a new phenotype could be generated: animals in which only some of the melanocytes converted. Systematically performing in silico perturbations, the model predicted that a combination of altanserin (5HTR2 inhibitor), reserpine (VMAT inhibitor), and VP16-XlCreb1 (constitutively active CREB) would break the all-or-none concordance. Remarkably, applying the predicted combination of three reagents in vivo revealed precisely the expected novel outcome, resulting in partial conversion of melanocytes within individuals. This work demonstrates the capability of automated analysis of dynamic models of signaling networks to discover novel phenotypes and predictively identify specific manipulations that can reach them.
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Orhan, A Emin; Ma, Wei Ji
2017-07-26
Animals perform near-optimal probabilistic inference in a wide range of psychophysical tasks. Probabilistic inference requires trial-to-trial representation of the uncertainties associated with task variables and subsequent use of this representation. Previous work has implemented such computations using neural networks with hand-crafted and task-dependent operations. We show that generic neural networks trained with a simple error-based learning rule perform near-optimal probabilistic inference in nine common psychophysical tasks. In a probabilistic categorization task, error-based learning in a generic network simultaneously explains a monkey's learning curve and the evolution of qualitative aspects of its choice behavior. In all tasks, the number of neurons required for a given level of performance grows sublinearly with the input population size, a substantial improvement on previous implementations of probabilistic inference. The trained networks develop a novel sparsity-based probabilistic population code. Our results suggest that probabilistic inference emerges naturally in generic neural networks trained with error-based learning rules.Behavioural tasks often require probability distributions to be inferred about task specific variables. Here, the authors demonstrate that generic neural networks can be trained using a simple error-based learning rule to perform such probabilistic computations efficiently without any need for task specific operations.
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Mapping edge-based traffic measurements onto the internal links in MPLS network
NASA Astrophysics Data System (ADS)
Zhao, Guofeng; Tang, Hong; Zhang, Yi
2004-09-01
Applying multi-protocol label switching techniques to IP-based backbone for traffic engineering goals has shown advantageous. Obtaining a volume of load on each internal link of the network is crucial for traffic engineering applying. Though collecting can be available for each link, such as applying traditional SNMP scheme, the approach may cause heavy processing load and sharply degrade the throughput of the core routers. Then monitoring merely at the edge of the network and mapping the measurements onto the core provides a good alternative way. In this paper, we explore a scheme for traffic mapping with edge-based measurements in MPLS network. It is supposed that the volume of traffic on each internal link over the domain would be mapped onto by measurements available only at ingress nodes. We apply path-based measurements at ingress nodes without enabling measurements in the core of the network. We propose a method that can infer a path from the ingress to the egress node using label distribution protocol without collecting routing data from core routers. Based on flow theory and queuing theory, we prove that our approach is effective and present the algorithm for traffic mapping. We also show performance simulation results that indicate potential of our approach.
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Algorithm Optimally Orders Forward-Chaining Inference Rules
NASA Technical Reports Server (NTRS)
James, Mark
2008-01-01
People typically develop knowledge bases in a somewhat ad hoc manner by incrementally adding rules with no specific organization. This often results in a very inefficient execution of those rules since they are so often order sensitive. This is relevant to tasks like Deep Space Network in that it allows the knowledge base to be incrementally developed and have it automatically ordered for efficiency. Although data flow analysis was first developed for use in compilers for producing optimal code sequences, its usefulness is now recognized in many software systems including knowledge-based systems. However, this approach for exhaustively computing data-flow information cannot directly be applied to inference systems because of the ubiquitous execution of the rules. An algorithm is presented that efficiently performs a complete producer/consumer analysis for each antecedent and consequence clause in a knowledge base to optimally order the rules to minimize inference cycles. An algorithm was developed that optimally orders a knowledge base composed of forwarding chaining inference rules such that independent inference cycle executions are minimized, thus, resulting in significantly faster execution. This algorithm was integrated into the JPL tool Spacecraft Health Inference Engine (SHINE) for verification and it resulted in a significant reduction in inference cycles for what was previously considered an ordered knowledge base. For a knowledge base that is completely unordered, then the improvement is much greater.
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MaxEnt analysis of a water distribution network in Canberra, ACT, Australia
NASA Astrophysics Data System (ADS)
Waldrip, Steven H.; Niven, Robert K.; Abel, Markus; Schlegel, Michael; Noack, Bernd R.
2015-01-01
A maximum entropy (MaxEnt) method is developed to infer the state of a pipe flow network, for situations in which there is insufficient information to form a closed equation set. This approach substantially extends existing deterministic methods for the analysis of engineered flow networks (e.g. Newton's method or the Hardy Cross scheme). The network is represented as an undirected graph structure, in which the uncertainty is represented by a continuous relative entropy on the space of internal and external flow rates. The head losses (potential differences) on the network are treated as dependent variables, using specified pipe-flow resistance functions. The entropy is maximised subject to "observable" constraints on the mean values of certain flow rates and/or potential differences, and also "physical" constraints arising from the frictional properties of each pipe and from Kirchhoff's nodal and loop laws. A numerical method is developed in Matlab for solution of the integral equation system, based on multidimensional quadrature. Several nonlinear resistance functions (e.g. power-law and Colebrook) are investigated, necessitating numerical solution of the implicit Lagrangian by a double iteration scheme. The method is applied to a 1123-node, 1140-pipe water distribution network for the suburb of Torrens in the Australian Capital Territory, Australia, using network data supplied by water authority ACTEW Corporation Limited. A number of different assumptions are explored, including various network geometric representations, prior probabilities and constraint settings, yielding useful predictions of network demand and performance. We also propose this methodology be used in conjunction with in-flow monitoring systems, to obtain better inferences of user consumption without large investments in monitoring equipment and maintenance.
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NASA Astrophysics Data System (ADS)
El-Sebakhy, Emad A.
2009-09-01
Pressure-volume-temperature properties are very important in the reservoir engineering computations. There are many empirical approaches for predicting various PVT properties based on empirical correlations and statistical regression models. Last decade, researchers utilized neural networks to develop more accurate PVT correlations. These achievements of neural networks open the door to data mining techniques to play a major role in oil and gas industry. Unfortunately, the developed neural networks correlations are often limited, and global correlations are usually less accurate compared to local correlations. Recently, adaptive neuro-fuzzy inference systems have been proposed as a new intelligence framework for both prediction and classification based on fuzzy clustering optimization criterion and ranking. This paper proposes neuro-fuzzy inference systems for estimating PVT properties of crude oil systems. This new framework is an efficient hybrid intelligence machine learning scheme for modeling the kind of uncertainty associated with vagueness and imprecision. We briefly describe the learning steps and the use of the Takagi Sugeno and Kang model and Gustafson-Kessel clustering algorithm with K-detected clusters from the given database. It has featured in a wide range of medical, power control system, and business journals, often with promising results. A comparative study will be carried out to compare their performance of this new framework with the most popular modeling techniques, such as neural networks, nonlinear regression, and the empirical correlations algorithms. The results show that the performance of neuro-fuzzy systems is accurate, reliable, and outperform most of the existing forecasting techniques. Future work can be achieved by using neuro-fuzzy systems for clustering the 3D seismic data, identification of lithofacies types, and other reservoir characterization.
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Meyer, Patrick E; Lafitte, Frédéric; Bontempi, Gianluca
2008-10-29
This paper presents the R/Bioconductor package minet (version 1.1.6) which provides a set of functions to infer mutual information networks from a dataset. Once fed with a microarray dataset, the package returns a network where nodes denote genes, edges model statistical dependencies between genes and the weight of an edge quantifies the statistical evidence of a specific (e.g transcriptional) gene-to-gene interaction. Four different entropy estimators are made available in the package minet (empirical, Miller-Madow, Schurmann-Grassberger and shrink) as well as four different inference methods, namely relevance networks, ARACNE, CLR and MRNET. Also, the package integrates accuracy assessment tools, like F-scores, PR-curves and ROC-curves in order to compare the inferred network with a reference one. The package minet provides a series of tools for inferring transcriptional networks from microarray data. It is freely available from the Comprehensive R Archive Network (CRAN) as well as from the Bioconductor website.
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De Cegli, Rossella; Iacobacci, Simona; Flore, Gemma; Gambardella, Gennaro; Mao, Lei; Cutillo, Luisa; Lauria, Mario; Klose, Joachim; Illingworth, Elizabeth; Banfi, Sandro; di Bernardo, Diego
2013-01-01
Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology 'reverse engineering' approaches. We 'reverse engineered' an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators of gene expression ('hubs'). We discovered that E130012A19Rik (E13), highly expressed in mouse ES cells as compared with differentiated cells, was a central 'hub' of the network. We demonstrated that E13 is a protein-coding gene implicated in regulating the commitment towards the different neuronal subtypes and glia cells. The overexpression and knock-down of E13 in ES cell lines, undergoing differentiation into neurons and glia cells, caused a strong up-regulation of the glutamatergic neurons marker Vglut2 and a strong down-regulation of the GABAergic neurons marker GAD65 and of the radial glia marker Blbp. We confirmed E13 expression in the cerebral cortex of adult mice and during development. By immuno-based affinity purification, we characterized protein partners of E13, involved in the Polycomb complex. Our results suggest a role of E13 in regulating the division between glutamatergic projection neurons and GABAergic interneurons and glia cells possibly by epigenetic-mediated transcriptional regulation.
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Network inference from multimodal data: A review of approaches from infectious disease transmission.
Ray, Bisakha; Ghedin, Elodie; Chunara, Rumi
2016-12-01
Networks inference problems are commonly found in multiple biomedical subfields such as genomics, metagenomics, neuroscience, and epidemiology. Networks are useful for representing a wide range of complex interactions ranging from those between molecular biomarkers, neurons, and microbial communities, to those found in human or animal populations. Recent technological advances have resulted in an increasing amount of healthcare data in multiple modalities, increasing the preponderance of network inference problems. Multi-domain data can now be used to improve the robustness and reliability of recovered networks from unimodal data. For infectious diseases in particular, there is a body of knowledge that has been focused on combining multiple pieces of linked information. Combining or analyzing disparate modalities in concert has demonstrated greater insight into disease transmission than could be obtained from any single modality in isolation. This has been particularly helpful in understanding incidence and transmission at early stages of infections that have pandemic potential. Novel pieces of linked information in the form of spatial, temporal, and other covariates including high-throughput sequence data, clinical visits, social network information, pharmaceutical prescriptions, and clinical symptoms (reported as free-text data) also encourage further investigation of these methods. The purpose of this review is to provide an in-depth analysis of multimodal infectious disease transmission network inference methods with a specific focus on Bayesian inference. We focus on analytical Bayesian inference-based methods as this enables recovering multiple parameters simultaneously, for example, not just the disease transmission network, but also parameters of epidemic dynamics. Our review studies their assumptions, key inference parameters and limitations, and ultimately provides insights about improving future network inference methods in multiple applications. Copyright © 2016 Elsevier Inc. All rights reserved.
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Functional networks inference from rule-based machine learning models.
Lazzarini, Nicola; Widera, Paweł; Williamson, Stuart; Heer, Rakesh; Krasnogor, Natalio; Bacardit, Jaume
2016-01-01
Functional networks play an important role in the analysis of biological processes and systems. The inference of these networks from high-throughput (-omics) data is an area of intense research. So far, the similarity-based inference paradigm (e.g. gene co-expression) has been the most popular approach. It assumes a functional relationship between genes which are expressed at similar levels across different samples. An alternative to this paradigm is the inference of relationships from the structure of machine learning models. These models are able to capture complex relationships between variables, that often are different/complementary to the similarity-based methods. We propose a protocol to infer functional networks from machine learning models, called FuNeL. It assumes, that genes used together within a rule-based machine learning model to classify the samples, might also be functionally related at a biological level. The protocol is first tested on synthetic datasets and then evaluated on a test suite of 8 real-world datasets related to human cancer. The networks inferred from the real-world data are compared against gene co-expression networks of equal size, generated with 3 different methods. The comparison is performed from two different points of view. We analyse the enriched biological terms in the set of network nodes and the relationships between known disease-associated genes in a context of the network topology. The comparison confirms both the biological relevance and the complementary character of the knowledge captured by the FuNeL networks in relation to similarity-based methods and demonstrates its potential to identify known disease associations as core elements of the network. Finally, using a prostate cancer dataset as a case study, we confirm that the biological knowledge captured by our method is relevant to the disease and consistent with the specialised literature and with an independent dataset not used in the inference process. The implementation of our network inference protocol is available at: http://ico2s.org/software/funel.html.
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Inferring Time-Varying Network Topologies from Gene Expression Data
2007-01-01
Most current methods for gene regulatory network identification lead to the inference of steady-state networks, that is, networks prevalent over all times, a hypothesis which has been challenged. There has been a need to infer and represent networks in a dynamic, that is, time-varying fashion, in order to account for different cellular states affecting the interactions amongst genes. In this work, we present an approach, regime-SSM, to understand gene regulatory networks within such a dynamic setting. The approach uses a clustering method based on these underlying dynamics, followed by system identification using a state-space model for each learnt cluster—to infer a network adjacency matrix. We finally indicate our results on the mouse embryonic kidney dataset as well as the T-cell activation-based expression dataset and demonstrate conformity with reported experimental evidence. PMID:18309363
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Inferring time-varying network topologies from gene expression data.
Rao, Arvind; Hero, Alfred O; States, David J; Engel, James Douglas
2007-01-01
Most current methods for gene regulatory network identification lead to the inference of steady-state networks, that is, networks prevalent over all times, a hypothesis which has been challenged. There has been a need to infer and represent networks in a dynamic, that is, time-varying fashion, in order to account for different cellular states affecting the interactions amongst genes. In this work, we present an approach, regime-SSM, to understand gene regulatory networks within such a dynamic setting. The approach uses a clustering method based on these underlying dynamics, followed by system identification using a state-space model for each learnt cluster--to infer a network adjacency matrix. We finally indicate our results on the mouse embryonic kidney dataset as well as the T-cell activation-based expression dataset and demonstrate conformity with reported experimental evidence.
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Inference of scale-free networks from gene expression time series.
Daisuke, Tominaga; Horton, Paul
2006-04-01
Quantitative time-series observation of gene expression is becoming possible, for example by cell array technology. However, there are no practical methods with which to infer network structures using only observed time-series data. As most computational models of biological networks for continuous time-series data have a high degree of freedom, it is almost impossible to infer the correct structures. On the other hand, it has been reported that some kinds of biological networks, such as gene networks and metabolic pathways, may have scale-free properties. We hypothesize that the architecture of inferred biological network models can be restricted to scale-free networks. We developed an inference algorithm for biological networks using only time-series data by introducing such a restriction. We adopt the S-system as the network model, and a distributed genetic algorithm to optimize models to fit its simulated results to observed time series data. We have tested our algorithm on a case study (simulated data). We compared optimization under no restriction, which allows for a fully connected network, and under the restriction that the total number of links must equal that expected from a scale free network. The restriction reduced both false positive and false negative estimation of the links and also the differences between model simulation and the given time-series data.
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Multi-Objective data analysis using Bayesian Inference for MagLIF experiments
NASA Astrophysics Data System (ADS)
Knapp, Patrick; Glinksy, Michael; Evans, Matthew; Gom, Matth; Han, Stephanie; Harding, Eric; Slutz, Steve; Hahn, Kelly; Harvey-Thompson, Adam; Geissel, Matthias; Ampleford, David; Jennings, Christopher; Schmit, Paul; Smith, Ian; Schwarz, Jens; Peterson, Kyle; Jones, Brent; Rochau, Gregory; Sinars, Daniel
2017-10-01
The MagLIF concept has recently demonstrated Gbar pressures and confinement of charged fusion products at stagnation. We present a new analysis methodology that allows for integration of multiple diagnostics including nuclear, x-ray imaging, and x-ray power to determine the temperature, pressure, liner areal density, and mix fraction. A simplified hot-spot model is used with a Bayesian inference network to determine the most probable model parameters that describe the observations while simultaneously revealing the principal uncertainties in the analysis. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA-0003525.
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Performance Optimization Control of ECH using Fuzzy Inference Application
NASA Astrophysics Data System (ADS)
Dubey, Abhay Kumar
Electro-chemical honing (ECH) is a hybrid electrolytic precision micro-finishing technology that, by combining physico-chemical actions of electro-chemical machining and conventional honing processes, provides the controlled functional surfaces-generation and fast material removal capabilities in a single operation. Process multi-performance optimization has become vital for utilizing full potential of manufacturing processes to meet the challenging requirements being placed on the surface quality, size, tolerances and production rate of engineering components in this globally competitive scenario. This paper presents an strategy that integrates the Taguchi matrix experimental design, analysis of variances and fuzzy inference system (FIS) to formulate a robust practical multi-performance optimization methodology for complex manufacturing processes like ECH, which involve several control variables. Two methodologies one using a genetic algorithm tuning of FIS (GA-tuned FIS) and another using an adaptive network based fuzzy inference system (ANFIS) have been evaluated for a multi-performance optimization case study of ECH. The actual experimental results confirm their potential for a wide range of machining conditions employed in ECH.
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Multi-Agent Inference in Social Networks: A Finite Population Learning Approach.
Fan, Jianqing; Tong, Xin; Zeng, Yao
When people in a society want to make inference about some parameter, each person may want to use data collected by other people. Information (data) exchange in social networks is usually costly, so to make reliable statistical decisions, people need to trade off the benefits and costs of information acquisition. Conflicts of interests and coordination problems will arise in the process. Classical statistics does not consider people's incentives and interactions in the data collection process. To address this imperfection, this work explores multi-agent Bayesian inference problems with a game theoretic social network model. Motivated by our interest in aggregate inference at the societal level, we propose a new concept, finite population learning , to address whether with high probability, a large fraction of people in a given finite population network can make "good" inference. Serving as a foundation, this concept enables us to study the long run trend of aggregate inference quality as population grows.
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Reasoning about Causal Relationships: Inferences on Causal Networks
Rottman, Benjamin Margolin; Hastie, Reid
2013-01-01
Over the last decade, a normative framework for making causal inferences, Bayesian Probabilistic Causal Networks, has come to dominate psychological studies of inference based on causal relationships. The following causal networks—[X→Y→Z, X←Y→Z, X→Y←Z]—supply answers for questions like, “Suppose both X and Y occur, what is the probability Z occurs?” or “Suppose you intervene and make Y occur, what is the probability Z occurs?” In this review, we provide a tutorial for how normatively to calculate these inferences. Then, we systematically detail the results of behavioral studies comparing human qualitative and quantitative judgments to the normative calculations for many network structures and for several types of inferences on those networks. Overall, when the normative calculations imply that an inference should increase, judgments usually go up; when calculations imply a decrease, judgments usually go down. However, two systematic deviations appear. First, people’s inferences violate the Markov assumption. For example, when inferring Z from the structure X→Y→Z, people think that X is relevant even when Y completely mediates the relationship between X and Z. Second, even when people’s inferences are directionally consistent with the normative calculations, they are often not as sensitive to the parameters and the structure of the network as they should be. We conclude with a discussion of productive directions for future research. PMID:23544658
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Inferring explicit weighted consensus networks to represent alternative evolutionary histories
2013-01-01
Background The advent of molecular biology techniques and constant increase in availability of genetic material have triggered the development of many phylogenetic tree inference methods. However, several reticulate evolution processes, such as horizontal gene transfer and hybridization, have been shown to blur the species evolutionary history by causing discordance among phylogenies inferred from different genes. Methods To tackle this problem, we hereby describe a new method for inferring and representing alternative (reticulate) evolutionary histories of species as an explicit weighted consensus network which can be constructed from a collection of gene trees with or without prior knowledge of the species phylogeny. Results We provide a way of building a weighted phylogenetic network for each of the following reticulation mechanisms: diploid hybridization, intragenic recombination and complete or partial horizontal gene transfer. We successfully tested our method on some synthetic and real datasets to infer the above-mentioned evolutionary events which may have influenced the evolution of many species. Conclusions Our weighted consensus network inference method allows one to infer, visualize and validate statistically major conflicting signals induced by the mechanisms of reticulate evolution. The results provided by the new method can be used to represent the inferred conflicting signals by means of explicit and easy-to-interpret phylogenetic networks. PMID:24359207
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Data-driven reverse engineering of signaling pathways using ensembles of dynamic models.
Henriques, David; Villaverde, Alejandro F; Rocha, Miguel; Saez-Rodriguez, Julio; Banga, Julio R
2017-02-01
Despite significant efforts and remarkable progress, the inference of signaling networks from experimental data remains very challenging. The problem is particularly difficult when the objective is to obtain a dynamic model capable of predicting the effect of novel perturbations not considered during model training. The problem is ill-posed due to the nonlinear nature of these systems, the fact that only a fraction of the involved proteins and their post-translational modifications can be measured, and limitations on the technologies used for growing cells in vitro, perturbing them, and measuring their variations. As a consequence, there is a pervasive lack of identifiability. To overcome these issues, we present a methodology called SELDOM (enSEmbLe of Dynamic lOgic-based Models), which builds an ensemble of logic-based dynamic models, trains them to experimental data, and combines their individual simulations into an ensemble prediction. It also includes a model reduction step to prune spurious interactions and mitigate overfitting. SELDOM is a data-driven method, in the sense that it does not require any prior knowledge of the system: the interaction networks that act as scaffolds for the dynamic models are inferred from data using mutual information. We have tested SELDOM on a number of experimental and in silico signal transduction case-studies, including the recent HPN-DREAM breast cancer challenge. We found that its performance is highly competitive compared to state-of-the-art methods for the purpose of recovering network topology. More importantly, the utility of SELDOM goes beyond basic network inference (i.e. uncovering static interaction networks): it builds dynamic (based on ordinary differential equation) models, which can be used for mechanistic interpretations and reliable dynamic predictions in new experimental conditions (i.e. not used in the training). For this task, SELDOM's ensemble prediction is not only consistently better than predictions from individual models, but also often outperforms the state of the art represented by the methods used in the HPN-DREAM challenge.
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Data-driven reverse engineering of signaling pathways using ensembles of dynamic models
Henriques, David; Villaverde, Alejandro F.; Banga, Julio R.
2017-01-01
Despite significant efforts and remarkable progress, the inference of signaling networks from experimental data remains very challenging. The problem is particularly difficult when the objective is to obtain a dynamic model capable of predicting the effect of novel perturbations not considered during model training. The problem is ill-posed due to the nonlinear nature of these systems, the fact that only a fraction of the involved proteins and their post-translational modifications can be measured, and limitations on the technologies used for growing cells in vitro, perturbing them, and measuring their variations. As a consequence, there is a pervasive lack of identifiability. To overcome these issues, we present a methodology called SELDOM (enSEmbLe of Dynamic lOgic-based Models), which builds an ensemble of logic-based dynamic models, trains them to experimental data, and combines their individual simulations into an ensemble prediction. It also includes a model reduction step to prune spurious interactions and mitigate overfitting. SELDOM is a data-driven method, in the sense that it does not require any prior knowledge of the system: the interaction networks that act as scaffolds for the dynamic models are inferred from data using mutual information. We have tested SELDOM on a number of experimental and in silico signal transduction case-studies, including the recent HPN-DREAM breast cancer challenge. We found that its performance is highly competitive compared to state-of-the-art methods for the purpose of recovering network topology. More importantly, the utility of SELDOM goes beyond basic network inference (i.e. uncovering static interaction networks): it builds dynamic (based on ordinary differential equation) models, which can be used for mechanistic interpretations and reliable dynamic predictions in new experimental conditions (i.e. not used in the training). For this task, SELDOM’s ensemble prediction is not only consistently better than predictions from individual models, but also often outperforms the state of the art represented by the methods used in the HPN-DREAM challenge. PMID:28166222
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Bayesian Inference and Online Learning in Poisson Neuronal Networks.
Huang, Yanping; Rao, Rajesh P N
2016-08-01
Motivated by the growing evidence for Bayesian computation in the brain, we show how a two-layer recurrent network of Poisson neurons can perform both approximate Bayesian inference and learning for any hidden Markov model. The lower-layer sensory neurons receive noisy measurements of hidden world states. The higher-layer neurons infer a posterior distribution over world states via Bayesian inference from inputs generated by sensory neurons. We demonstrate how such a neuronal network with synaptic plasticity can implement a form of Bayesian inference similar to Monte Carlo methods such as particle filtering. Each spike in a higher-layer neuron represents a sample of a particular hidden world state. The spiking activity across the neural population approximates the posterior distribution over hidden states. In this model, variability in spiking is regarded not as a nuisance but as an integral feature that provides the variability necessary for sampling during inference. We demonstrate how the network can learn the likelihood model, as well as the transition probabilities underlying the dynamics, using a Hebbian learning rule. We present results illustrating the ability of the network to perform inference and learning for arbitrary hidden Markov models.
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Inferring causal molecular networks: empirical assessment through a community-based effort.
Hill, Steven M; Heiser, Laura M; Cokelaer, Thomas; Unger, Michael; Nesser, Nicole K; Carlin, Daniel E; Zhang, Yang; Sokolov, Artem; Paull, Evan O; Wong, Chris K; Graim, Kiley; Bivol, Adrian; Wang, Haizhou; Zhu, Fan; Afsari, Bahman; Danilova, Ludmila V; Favorov, Alexander V; Lee, Wai Shing; Taylor, Dane; Hu, Chenyue W; Long, Byron L; Noren, David P; Bisberg, Alexander J; Mills, Gordon B; Gray, Joe W; Kellen, Michael; Norman, Thea; Friend, Stephen; Qutub, Amina A; Fertig, Elana J; Guan, Yuanfang; Song, Mingzhou; Stuart, Joshua M; Spellman, Paul T; Koeppl, Heinz; Stolovitzky, Gustavo; Saez-Rodriguez, Julio; Mukherjee, Sach
2016-04-01
It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense.
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Inferring Network Controls from Topology Using the Chomp Database
2015-12-03
AFRL-AFOSR-VA-TR-2016-0033 INFERRING NETWORK CONTROLS FROM TOPOLOGY USING THE CHOMP DATABASE John Harer DUKE UNIVERSITY Final Report 12/03/2015...INFERRING NETWORK CONTROLS FROM TOPOLOGY USING THE CHOMP DATABASE 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA9550-10-1-0436 5c. PROGRAM ELEMENT NUMBER 6...area of Topological Data Analysis (TDA) and it’s application to dynamical systems. The role of this work in the Complex Networks program is based on
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Boolean dynamics of genetic regulatory networks inferred from microarray time series data
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
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Evaluation of artificial time series microarray data for dynamic gene regulatory network inference.
Xenitidis, P; Seimenis, I; Kakolyris, S; Adamopoulos, A
2017-08-07
High-throughput technology like microarrays is widely used in the inference of gene regulatory networks (GRNs). We focused on time series data since we are interested in the dynamics of GRNs and the identification of dynamic networks. We evaluated the amount of information that exists in artificial time series microarray data and the ability of an inference process to produce accurate models based on them. We used dynamic artificial gene regulatory networks in order to create artificial microarray data. Key features that characterize microarray data such as the time separation of directly triggered genes, the percentage of directly triggered genes and the triggering function type were altered in order to reveal the limits that are imposed by the nature of microarray data on the inference process. We examined the effect of various factors on the inference performance such as the network size, the presence of noise in microarray data, and the network sparseness. We used a system theory approach and examined the relationship between the pole placement of the inferred system and the inference performance. We examined the relationship between the inference performance in the time domain and the true system parameter identification. Simulation results indicated that time separation and the percentage of directly triggered genes are crucial factors. Also, network sparseness, the triggering function type and noise in input data affect the inference performance. When two factors were simultaneously varied, it was found that variation of one parameter significantly affects the dynamic response of the other. Crucial factors were also examined using a real GRN and acquired results confirmed simulation findings with artificial data. Different initial conditions were also used as an alternative triggering approach. Relevant results confirmed that the number of datasets constitutes the most significant parameter with regard to the inference performance. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Data based identification and prediction of nonlinear and complex dynamical systems
NASA Astrophysics Data System (ADS)
Wang, Wen-Xu; Lai, Ying-Cheng; Grebogi, Celso
2016-07-01
The problem of reconstructing nonlinear and complex dynamical systems from measured data or time series is central to many scientific disciplines including physical, biological, computer, and social sciences, as well as engineering and economics. The classic approach to phase-space reconstruction through the methodology of delay-coordinate embedding has been practiced for more than three decades, but the paradigm is effective mostly for low-dimensional dynamical systems. Often, the methodology yields only a topological correspondence of the original system. There are situations in various fields of science and engineering where the systems of interest are complex and high dimensional with many interacting components. A complex system typically exhibits a rich variety of collective dynamics, and it is of great interest to be able to detect, classify, understand, predict, and control the dynamics using data that are becoming increasingly accessible due to the advances of modern information technology. To accomplish these goals, especially prediction and control, an accurate reconstruction of the original system is required. Nonlinear and complex systems identification aims at inferring, from data, the mathematical equations that govern the dynamical evolution and the complex interaction patterns, or topology, among the various components of the system. With successful reconstruction of the system equations and the connecting topology, it may be possible to address challenging and significant problems such as identification of causal relations among the interacting components and detection of hidden nodes. The "inverse" problem thus presents a grand challenge, requiring new paradigms beyond the traditional delay-coordinate embedding methodology. The past fifteen years have witnessed rapid development of contemporary complex graph theory with broad applications in interdisciplinary science and engineering. The combination of graph, information, and nonlinear dynamical systems theories with tools from statistical physics, optimization, engineering control, applied mathematics, and scientific computing enables the development of a number of paradigms to address the problem of nonlinear and complex systems reconstruction. In this Review, we describe the recent advances in this forefront and rapidly evolving field, with a focus on compressive sensing based methods. In particular, compressive sensing is a paradigm developed in recent years in applied mathematics, electrical engineering, and nonlinear physics to reconstruct sparse signals using only limited data. It has broad applications ranging from image compression/reconstruction to the analysis of large-scale sensor networks, and it has become a powerful technique to obtain high-fidelity signals for applications where sufficient observations are not available. We will describe in detail how compressive sensing can be exploited to address a diverse array of problems in data based reconstruction of nonlinear and complex networked systems. The problems include identification of chaotic systems and prediction of catastrophic bifurcations, forecasting future attractors of time-varying nonlinear systems, reconstruction of complex networks with oscillatory and evolutionary game dynamics, detection of hidden nodes, identification of chaotic elements in neuronal networks, reconstruction of complex geospatial networks and nodal positioning, and reconstruction of complex spreading networks with binary data.. A number of alternative methods, such as those based on system response to external driving, synchronization, and noise-induced dynamical correlation, will also be discussed. Due to the high relevance of network reconstruction to biological sciences, a special section is devoted to a brief survey of the current methods to infer biological networks. Finally, a number of open problems including control and controllability of complex nonlinear dynamical networks are discussed. The methods outlined in this Review are principled on various concepts in complexity science and engineering such as phase transitions, bifurcations, stabilities, and robustness. The methodologies have the potential to significantly improve our ability to understand a variety of complex dynamical systems ranging from gene regulatory systems to social networks toward the ultimate goal of controlling such systems.
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Craddock, Travis J. A.; Fletcher, Mary Ann; Klimas, Nancy G.
2015-01-01
There is a growing appreciation for the network biology that regulates the coordinated expression of molecular and cellular markers however questions persist regarding the identifiability of these networks. Here we explore some of the issues relevant to recovering directed regulatory networks from time course data collected under experimental constraints typical of in vivo studies. NetSim simulations of sparsely connected biological networks were used to evaluate two simple feature selection techniques used in the construction of linear Ordinary Differential Equation (ODE) models, namely truncation of terms versus latent vector projection. Performance was compared with ODE-based Time Series Network Identification (TSNI) integral, and the information-theoretic Time-Delay ARACNE (TD-ARACNE). Projection-based techniques and TSNI integral outperformed truncation-based selection and TD-ARACNE on aggregate networks with edge densities of 10-30%, i.e. transcription factor, protein-protein cliques and immune signaling networks. All were more robust to noise than truncation-based feature selection. Performance was comparable on the in silico 10-node DREAM 3 network, a 5-node Yeast synthetic network designed for In vivo Reverse-engineering and Modeling Assessment (IRMA) and a 9-node human HeLa cell cycle network of similar size and edge density. Performance was more sensitive to the number of time courses than to sample frequency and extrapolated better to larger networks by grouping experiments. In all cases performance declined rapidly in larger networks with lower edge density. Limited recovery and high false positive rates obtained overall bring into question our ability to generate informative time course data rather than the design of any particular reverse engineering algorithm. PMID:25984725
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Inferring Centrality from Network Snapshots
Shao, Haibin; Mesbahi, Mehran; Li, Dewei; Xi, Yugeng
2017-01-01
The topology and dynamics of a complex network shape its functionality. However, the topologies of many large-scale networks are either unavailable or incomplete. Without the explicit knowledge of network topology, we show how the data generated from the network dynamics can be utilised to infer the tempo centrality, which is proposed to quantify the influence of nodes in a consensus network. We show that the tempo centrality can be used to construct an accurate estimate of both the propagation rate of influence exerted on consensus networks and the Kirchhoff index of the underlying graph. Moreover, the tempo centrality also encodes the disturbance rejection of nodes in a consensus network. Our findings provide an approach to infer the performance of a consensus network from its temporal data. PMID:28098166
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Inferring Centrality from Network Snapshots
NASA Astrophysics Data System (ADS)
Shao, Haibin; Mesbahi, Mehran; Li, Dewei; Xi, Yugeng
2017-01-01
The topology and dynamics of a complex network shape its functionality. However, the topologies of many large-scale networks are either unavailable or incomplete. Without the explicit knowledge of network topology, we show how the data generated from the network dynamics can be utilised to infer the tempo centrality, which is proposed to quantify the influence of nodes in a consensus network. We show that the tempo centrality can be used to construct an accurate estimate of both the propagation rate of influence exerted on consensus networks and the Kirchhoff index of the underlying graph. Moreover, the tempo centrality also encodes the disturbance rejection of nodes in a consensus network. Our findings provide an approach to infer the performance of a consensus network from its temporal data.
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A Hierarchical Poisson Log-Normal Model for Network Inference from RNA Sequencing Data
Gallopin, Mélina; Rau, Andrea; Jaffrézic, Florence
2013-01-01
Gene network inference from transcriptomic data is an important methodological challenge and a key aspect of systems biology. Although several methods have been proposed to infer networks from microarray data, there is a need for inference methods able to model RNA-seq data, which are count-based and highly variable. In this work we propose a hierarchical Poisson log-normal model with a Lasso penalty to infer gene networks from RNA-seq data; this model has the advantage of directly modelling discrete data and accounting for inter-sample variance larger than the sample mean. Using real microRNA-seq data from breast cancer tumors and simulations, we compare this method to a regularized Gaussian graphical model on log-transformed data, and a Poisson log-linear graphical model with a Lasso penalty on power-transformed data. For data simulated with large inter-sample dispersion, the proposed model performs better than the other methods in terms of sensitivity, specificity and area under the ROC curve. These results show the necessity of methods specifically designed for gene network inference from RNA-seq data. PMID:24147011
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Qualitative Discovery in Medical Databases
NASA Technical Reports Server (NTRS)
Maluf, David A.
2000-01-01
Implication rules have been used in uncertainty reasoning systems to confirm and draw hypotheses or conclusions. However a major bottleneck in developing such systems lies in the elicitation of these rules. This paper empirically examines the performance of evidential inferencing with implication networks generated using a rule induction tool called KAT. KAT utilizes an algorithm for the statistical analysis of empirical case data, and hence reduces the knowledge engineering efforts and biases in subjective implication certainty assignment. The paper describes several experiments in which real-world diagnostic problems were investigated; namely, medical diagnostics. In particular, it attempts to show that: (1) with a limited number of case samples, KAT is capable of inducing implication networks useful for making evidential inferences based on partial observations, and (2) observation driven by a network entropy optimization mechanism is effective in reducing the uncertainty of predicted events.
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An inference engine for embedded diagnostic systems
NASA Technical Reports Server (NTRS)
Fox, Barry R.; Brewster, Larry T.
1987-01-01
The implementation of an inference engine for embedded diagnostic systems is described. The system consists of two distinct parts. The first is an off-line compiler which accepts a propositional logical statement of the relationship between facts and conclusions and produces data structures required by the on-line inference engine. The second part consists of the inference engine and interface routines which accept assertions of fact and return the conclusions which necessarily follow. Given a set of assertions, it will generate exactly the conclusions which logically follow. At the same time, it will detect any inconsistencies which may propagate from an inconsistent set of assertions or a poorly formulated set of rules. The memory requirements are fixed and the worst case execution times are bounded at compile time. The data structures and inference algorithms are very simple and well understood. The data structures and algorithms are described in detail. The system has been implemented on Lisp, Pascal, and Modula-2.
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Information Theory, Inference and Learning Algorithms
NASA Astrophysics Data System (ADS)
Mackay, David J. C.
2003-10-01
Information theory and inference, often taught separately, are here united in one entertaining textbook. These topics lie at the heart of many exciting areas of contemporary science and engineering - communication, signal processing, data mining, machine learning, pattern recognition, computational neuroscience, bioinformatics, and cryptography. This textbook introduces theory in tandem with applications. Information theory is taught alongside practical communication systems, such as arithmetic coding for data compression and sparse-graph codes for error-correction. A toolbox of inference techniques, including message-passing algorithms, Monte Carlo methods, and variational approximations, are developed alongside applications of these tools to clustering, convolutional codes, independent component analysis, and neural networks. The final part of the book describes the state of the art in error-correcting codes, including low-density parity-check codes, turbo codes, and digital fountain codes -- the twenty-first century standards for satellite communications, disk drives, and data broadcast. Richly illustrated, filled with worked examples and over 400 exercises, some with detailed solutions, David MacKay's groundbreaking book is ideal for self-learning and for undergraduate or graduate courses. Interludes on crosswords, evolution, and sex provide entertainment along the way. In sum, this is a textbook on information, communication, and coding for a new generation of students, and an unparalleled entry point into these subjects for professionals in areas as diverse as computational biology, financial engineering, and machine learning.
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Causal Inference and Explaining Away in a Spiking Network
Moreno-Bote, Rubén; Drugowitsch, Jan
2015-01-01
While the brain uses spiking neurons for communication, theoretical research on brain computations has mostly focused on non-spiking networks. The nature of spike-based algorithms that achieve complex computations, such as object probabilistic inference, is largely unknown. Here we demonstrate that a family of high-dimensional quadratic optimization problems with non-negativity constraints can be solved exactly and efficiently by a network of spiking neurons. The network naturally imposes the non-negativity of causal contributions that is fundamental to causal inference, and uses simple operations, such as linear synapses with realistic time constants, and neural spike generation and reset non-linearities. The network infers the set of most likely causes from an observation using explaining away, which is dynamically implemented by spike-based, tuned inhibition. The algorithm performs remarkably well even when the network intrinsically generates variable spike trains, the timing of spikes is scrambled by external sources of noise, or the network is mistuned. This type of network might underlie tasks such as odor identification and classification. PMID:26621426
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Causal Inference and Explaining Away in a Spiking Network.
Moreno-Bote, Rubén; Drugowitsch, Jan
2015-12-01
While the brain uses spiking neurons for communication, theoretical research on brain computations has mostly focused on non-spiking networks. The nature of spike-based algorithms that achieve complex computations, such as object probabilistic inference, is largely unknown. Here we demonstrate that a family of high-dimensional quadratic optimization problems with non-negativity constraints can be solved exactly and efficiently by a network of spiking neurons. The network naturally imposes the non-negativity of causal contributions that is fundamental to causal inference, and uses simple operations, such as linear synapses with realistic time constants, and neural spike generation and reset non-linearities. The network infers the set of most likely causes from an observation using explaining away, which is dynamically implemented by spike-based, tuned inhibition. The algorithm performs remarkably well even when the network intrinsically generates variable spike trains, the timing of spikes is scrambled by external sources of noise, or the network is mistuned. This type of network might underlie tasks such as odor identification and classification.
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Inference of gene regulatory networks from time series by Tsallis entropy
2011-01-01
Background The inference of gene regulatory networks (GRNs) from large-scale expression profiles is one of the most challenging problems of Systems Biology nowadays. Many techniques and models have been proposed for this task. However, it is not generally possible to recover the original topology with great accuracy, mainly due to the short time series data in face of the high complexity of the networks and the intrinsic noise of the expression measurements. In order to improve the accuracy of GRNs inference methods based on entropy (mutual information), a new criterion function is here proposed. Results In this paper we introduce the use of generalized entropy proposed by Tsallis, for the inference of GRNs from time series expression profiles. The inference process is based on a feature selection approach and the conditional entropy is applied as criterion function. In order to assess the proposed methodology, the algorithm is applied to recover the network topology from temporal expressions generated by an artificial gene network (AGN) model as well as from the DREAM challenge. The adopted AGN is based on theoretical models of complex networks and its gene transference function is obtained from random drawing on the set of possible Boolean functions, thus creating its dynamics. On the other hand, DREAM time series data presents variation of network size and its topologies are based on real networks. The dynamics are generated by continuous differential equations with noise and perturbation. By adopting both data sources, it is possible to estimate the average quality of the inference with respect to different network topologies, transfer functions and network sizes. Conclusions A remarkable improvement of accuracy was observed in the experimental results by reducing the number of false connections in the inferred topology by the non-Shannon entropy. The obtained best free parameter of the Tsallis entropy was on average in the range 2.5 ≤ q ≤ 3.5 (hence, subextensive entropy), which opens new perspectives for GRNs inference methods based on information theory and for investigation of the nonextensivity of such networks. The inference algorithm and criterion function proposed here were implemented and included in the DimReduction software, which is freely available at http://sourceforge.net/projects/dimreduction and http://code.google.com/p/dimreduction/. PMID:21545720
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Saxena, Anupam; Lipson, Hod; Valero-Cuevas, Francisco J.
2012-01-01
In systems and computational biology, much effort is devoted to functional identification of systems and networks at the molecular-or cellular scale. However, similarly important networks exist at anatomical scales such as the tendon network of human fingers: the complex array of collagen fibers that transmits and distributes muscle forces to finger joints. This network is critical to the versatility of the human hand, and its function has been debated since at least the 16th century. Here, we experimentally infer the structure (both topology and parameter values) of this network through sparse interrogation with force inputs. A population of models representing this structure co-evolves in simulation with a population of informative future force inputs via the predator-prey estimation-exploration algorithm. Model fitness depends on their ability to explain experimental data, while the fitness of future force inputs depends on causing maximal functional discrepancy among current models. We validate our approach by inferring two known synthetic Latex networks, and one anatomical tendon network harvested from a cadaver's middle finger. We find that functionally similar but structurally diverse models can exist within a narrow range of the training set and cross-validation errors. For the Latex networks, models with low training set error [<4%] and resembling the known network have the smallest cross-validation errors [∼5%]. The low training set [<4%] and cross validation [<7.2%] errors for models for the cadaveric specimen demonstrate what, to our knowledge, is the first experimental inference of the functional structure of complex anatomical networks. This work expands current bioinformatics inference approaches by demonstrating that sparse, yet informative interrogation of biological specimens holds significant computational advantages in accurate and efficient inference over random testing, or assuming model topology and only inferring parameters values. These findings also hold clues to both our evolutionary history and the development of versatile machines. PMID:23144601
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Saxena, Anupam; Lipson, Hod; Valero-Cuevas, Francisco J
2012-01-01
In systems and computational biology, much effort is devoted to functional identification of systems and networks at the molecular-or cellular scale. However, similarly important networks exist at anatomical scales such as the tendon network of human fingers: the complex array of collagen fibers that transmits and distributes muscle forces to finger joints. This network is critical to the versatility of the human hand, and its function has been debated since at least the 16(th) century. Here, we experimentally infer the structure (both topology and parameter values) of this network through sparse interrogation with force inputs. A population of models representing this structure co-evolves in simulation with a population of informative future force inputs via the predator-prey estimation-exploration algorithm. Model fitness depends on their ability to explain experimental data, while the fitness of future force inputs depends on causing maximal functional discrepancy among current models. We validate our approach by inferring two known synthetic Latex networks, and one anatomical tendon network harvested from a cadaver's middle finger. We find that functionally similar but structurally diverse models can exist within a narrow range of the training set and cross-validation errors. For the Latex networks, models with low training set error [<4%] and resembling the known network have the smallest cross-validation errors [∼5%]. The low training set [<4%] and cross validation [<7.2%] errors for models for the cadaveric specimen demonstrate what, to our knowledge, is the first experimental inference of the functional structure of complex anatomical networks. This work expands current bioinformatics inference approaches by demonstrating that sparse, yet informative interrogation of biological specimens holds significant computational advantages in accurate and efficient inference over random testing, or assuming model topology and only inferring parameters values. These findings also hold clues to both our evolutionary history and the development of versatile machines.
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Deng, Yue; Zenil, Hector; Tegnér, Jesper; Kiani, Narsis A
2017-12-15
The use of differential equations (ODE) is one of the most promising approaches to network inference. The success of ODE-based approaches has, however, been limited, due to the difficulty in estimating parameters and by their lack of scalability. Here, we introduce a novel method and pipeline to reverse engineer gene regulatory networks from gene expression of time series and perturbation data based upon an improvement on the calculation scheme of the derivatives and a pre-filtration step to reduce the number of possible links. The method introduces a linear differential equation model with adaptive numerical differentiation that is scalable to extremely large regulatory networks. We demonstrate the ability of this method to outperform current state-of-the-art methods applied to experimental and synthetic data using test data from the DREAM4 and DREAM5 challenges. Our method displays greater accuracy and scalability. We benchmark the performance of the pipeline with respect to dataset size and levels of noise. We show that the computation time is linear over various network sizes. The Matlab code of the HiDi implementation is available at: www.complexitycalculator.com/HiDiScript.zip. hzenilc@gmail.com or narsis.kiani@ki.se. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
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CompareSVM: supervised, Support Vector Machine (SVM) inference of gene regularity networks.
Gillani, Zeeshan; Akash, Muhammad Sajid Hamid; Rahaman, M D Matiur; Chen, Ming
2014-11-30
Predication of gene regularity network (GRN) from expression data is a challenging task. There are many methods that have been developed to address this challenge ranging from supervised to unsupervised methods. Most promising methods are based on support vector machine (SVM). There is a need for comprehensive analysis on prediction accuracy of supervised method SVM using different kernels on different biological experimental conditions and network size. We developed a tool (CompareSVM) based on SVM to compare different kernel methods for inference of GRN. Using CompareSVM, we investigated and evaluated different SVM kernel methods on simulated datasets of microarray of different sizes in detail. The results obtained from CompareSVM showed that accuracy of inference method depends upon the nature of experimental condition and size of the network. For network with nodes (<200) and average (over all sizes of networks), SVM Gaussian kernel outperform on knockout, knockdown, and multifactorial datasets compared to all the other inference methods. For network with large number of nodes (~500), choice of inference method depend upon nature of experimental condition. CompareSVM is available at http://bis.zju.edu.cn/CompareSVM/ .
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Multi-Agent Inference in Social Networks: A Finite Population Learning Approach
Tong, Xin; Zeng, Yao
2016-01-01
When people in a society want to make inference about some parameter, each person may want to use data collected by other people. Information (data) exchange in social networks is usually costly, so to make reliable statistical decisions, people need to trade off the benefits and costs of information acquisition. Conflicts of interests and coordination problems will arise in the process. Classical statistics does not consider people’s incentives and interactions in the data collection process. To address this imperfection, this work explores multi-agent Bayesian inference problems with a game theoretic social network model. Motivated by our interest in aggregate inference at the societal level, we propose a new concept, finite population learning, to address whether with high probability, a large fraction of people in a given finite population network can make “good” inference. Serving as a foundation, this concept enables us to study the long run trend of aggregate inference quality as population grows. PMID:27076691
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Gene network inference by fusing data from diverse distributions
Žitnik, Marinka; Zupan, Blaž
2015-01-01
Motivation: Markov networks are undirected graphical models that are widely used to infer relations between genes from experimental data. Their state-of-the-art inference procedures assume the data arise from a Gaussian distribution. High-throughput omics data, such as that from next generation sequencing, often violates this assumption. Furthermore, when collected data arise from multiple related but otherwise nonidentical distributions, their underlying networks are likely to have common features. New principled statistical approaches are needed that can deal with different data distributions and jointly consider collections of datasets. Results: We present FuseNet, a Markov network formulation that infers networks from a collection of nonidentically distributed datasets. Our approach is computationally efficient and general: given any number of distributions from an exponential family, FuseNet represents model parameters through shared latent factors that define neighborhoods of network nodes. In a simulation study, we demonstrate good predictive performance of FuseNet in comparison to several popular graphical models. We show its effectiveness in an application to breast cancer RNA-sequencing and somatic mutation data, a novel application of graphical models. Fusion of datasets offers substantial gains relative to inference of separate networks for each dataset. Our results demonstrate that network inference methods for non-Gaussian data can help in accurate modeling of the data generated by emergent high-throughput technologies. Availability and implementation: Source code is at https://github.com/marinkaz/fusenet. Contact: blaz.zupan@fri.uni-lj.si Supplementary information: Supplementary information is available at Bioinformatics online. PMID:26072487
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Inferring Gene Regulatory Networks by Singular Value Decomposition and Gravitation Field Algorithm
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
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Integration of multi-omics data for integrative gene regulatory network inference.
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.
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Integration of multi-omics data for integrative gene regulatory network inference
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
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Pecevski, Dejan; Buesing, Lars; Maass, Wolfgang
2011-01-01
An important open problem of computational neuroscience is the generic organization of computations in networks of neurons in the brain. We show here through rigorous theoretical analysis that inherent stochastic features of spiking neurons, in combination with simple nonlinear computational operations in specific network motifs and dendritic arbors, enable networks of spiking neurons to carry out probabilistic inference through sampling in general graphical models. In particular, it enables them to carry out probabilistic inference in Bayesian networks with converging arrows (“explaining away”) and with undirected loops, that occur in many real-world tasks. Ubiquitous stochastic features of networks of spiking neurons, such as trial-to-trial variability and spontaneous activity, are necessary ingredients of the underlying computational organization. We demonstrate through computer simulations that this approach can be scaled up to neural emulations of probabilistic inference in fairly large graphical models, yielding some of the most complex computations that have been carried out so far in networks of spiking neurons. PMID:22219717
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Foo, Mathias; Gherman, Iulia; Zhang, Peijun; Bates, Declan G; Denby, Katherine J
2018-05-23
Crop disease leads to significant waste worldwide, both pre- and postharvest, with subsequent economic and sustainability consequences. Disease outcome is determined both by the plants' response to the pathogen and by the ability of the pathogen to suppress defense responses and manipulate the plant to enhance colonization. The defense response of a plant is characterized by significant transcriptional reprogramming mediated by underlying gene regulatory networks, and components of these networks are often targeted by attacking pathogens. Here, using gene expression data from Botrytis cinerea-infected Arabidopsis plants, we develop a systematic approach for mitigating the effects of pathogen-induced network perturbations, using the tools of synthetic biology. We employ network inference and system identification techniques to build an accurate model of an Arabidopsis defense subnetwork that contains key genes determining susceptibility of the plant to the pathogen attack. Once validated against time-series data, we use this model to design and test perturbation mitigation strategies based on the use of genetic feedback control. We show how a synthetic feedback controller can be designed to attenuate the effect of external perturbations on the transcription factor CHE in our subnetwork. We investigate and compare two approaches for implementing such a controller biologically-direct implementation of the genetic feedback controller, and rewiring the regulatory regions of multiple genes-to achieve the network motif required to implement the controller. Our results highlight the potential of combining feedback control theory with synthetic biology for engineering plants with enhanced resilience to environmental stress.
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Kimura, Shuhei; Sato, Masanao; Okada-Hatakeyama, Mariko
2013-01-01
The inference of a genetic network is a problem in which mutual interactions among genes are inferred from time-series of gene expression levels. While a number of models have been proposed to describe genetic networks, this study focuses on a mathematical model proposed by Vohradský. Because of its advantageous features, several researchers have proposed the inference methods based on Vohradský's model. When trying to analyze large-scale networks consisting of dozens of genes, however, these methods must solve high-dimensional non-linear function optimization problems. In order to resolve the difficulty of estimating the parameters of the Vohradský's model, this study proposes a new method that defines the problem as several two-dimensional function optimization problems. Through numerical experiments on artificial genetic network inference problems, we showed that, although the computation time of the proposed method is not the shortest, the method has the ability to estimate parameters of Vohradský's models more effectively with sufficiently short computation times. This study then applied the proposed method to an actual inference problem of the bacterial SOS DNA repair system, and succeeded in finding several reasonable regulations. PMID:24386175
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Application of temporal LNC logic in artificial intelligence
NASA Astrophysics Data System (ADS)
Adamek, Marek; Mulawka, Jan
2016-09-01
This paper presents the temporal logic inference engine developed in our university. It is an attempt to demonstrate implementation and practical application of temporal logic LNC developed in Cardinal Stefan Wyszynski University in Warsaw.1 The paper describes the fundamentals of LNC logic, architecture and implementation of inference engine. The practical application is shown by providing the solution for popular in Artificial Intelligence problem of Missionaries and Cannibals in terms of LNC logic. Both problem formulation and inference engine are described in details.
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The Role of Probability-Based Inference in an Intelligent Tutoring System.
ERIC Educational Resources Information Center
Mislevy, Robert J.; Gitomer, Drew H.
Probability-based inference in complex networks of interdependent variables is an active topic in statistical research, spurred by such diverse applications as forecasting, pedigree analysis, troubleshooting, and medical diagnosis. This paper concerns the role of Bayesian inference networks for updating student models in intelligent tutoring…
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Mason, Robert A.; Just, Marcel Adam
2010-01-01
Cortical activity associated with generating an inference was measured using fMRI. Participants read three-sentence passages that differed in whether or not an inference needed to be drawn to understand them. The inference was based on either a protagonist’s intention or a physical consequence of a character’s action. Activation was expected in Theory of Mind brain regions for the passages based on protagonists’ intentions but not for the physical consequence passages. The activation measured in the right temporo-parietal junction was greater in the intentional passages than in the consequence passages, consistent with predictions from a Theory of Mind perspective. In contrast, there was increased occipital activation in the physical inference passages. For both types of passage, the cortical activity related to the reading of the critical inference sentence demonstrated a recruitment of a common inference cortical network. This general inference-related activation appeared bilaterally in the language processing areas (the inferior frontal gyrus, the temporal gyrus, and the angular gyrus), as well as in the medial to superior frontal gyrus, which has been found to be active in Theory of Mind tasks. These findings are consistent with the hypothesis that component areas of the discourse processing network are recruited as needed based on the nature of the inference. A Protagonist monitoring and synthesis network is proposed as a more accurate account for Theory of Mind activation during narrative comprehension. PMID:21229617
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Social networks help to infer causality in the tumor microenvironment.
Crespo, Isaac; Doucey, Marie-Agnès; Xenarios, Ioannis
2016-03-15
Networks have become a popular way to conceptualize a system of interacting elements, such as electronic circuits, social communication, metabolism or gene regulation. Network inference, analysis, and modeling techniques have been developed in different areas of science and technology, such as computer science, mathematics, physics, and biology, with an active interdisciplinary exchange of concepts and approaches. However, some concepts seem to belong to a specific field without a clear transferability to other domains. At the same time, it is increasingly recognized that within some biological systems--such as the tumor microenvironment--where different types of resident and infiltrating cells interact to carry out their functions, the complexity of the system demands a theoretical framework, such as statistical inference, graph analysis and dynamical models, in order to asses and study the information derived from high-throughput experimental technologies. In this article we propose to adopt and adapt the concepts of influence and investment from the world of social network analysis to biological problems, and in particular to apply this approach to infer causality in the tumor microenvironment. We showed that constructing a bidirectional network of influence between cell and cell communication molecules allowed us to determine the direction of inferred regulations at the expression level and correctly recapitulate cause-effect relationships described in literature. This work constitutes an example of a transfer of knowledge and concepts from the world of social network analysis to biomedical research, in particular to infer network causality in biological networks. This causality elucidation is essential to model the homeostatic response of biological systems to internal and external factors, such as environmental conditions, pathogens or treatments.
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Enhancing gene regulatory network inference through data integration with markov random fields
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
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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
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Integrated Module and Gene-Specific Regulatory Inference Implicates Upstream Signaling Networks
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
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Consistency of biological networks inferred from microarray and sequencing data.
Vinciotti, Veronica; Wit, Ernst C; Jansen, Rick; de Geus, Eco J C N; Penninx, Brenda W J H; Boomsma, Dorret I; 't Hoen, Peter A C
2016-06-24
Sparse Gaussian graphical models are popular for inferring biological networks, such as gene regulatory networks. In this paper, we investigate the consistency of these models across different data platforms, such as microarray and next generation sequencing, on the basis of a rich dataset containing samples that are profiled under both techniques as well as a large set of independent samples. Our analysis shows that individual node variances can have a remarkable effect on the connectivity of the resulting network. Their inconsistency across platforms and the fact that the variability level of a node may not be linked to its regulatory role mean that, failing to scale the data prior to the network analysis, leads to networks that are not reproducible across different platforms and that may be misleading. Moreover, we show how the reproducibility of networks across different platforms is significantly higher if networks are summarised in terms of enrichment amongst functional groups of interest, such as pathways, rather than at the level of individual edges. Careful pre-processing of transcriptional data and summaries of networks beyond individual edges can improve the consistency of network inference across platforms. However, caution is needed at this stage in the (over)interpretation of gene regulatory networks inferred from biological data.
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Automatic inference of multicellular regulatory networks using informative priors.
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.
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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
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Causal inference in biology networks with integrated belief propagation.
Chang, Rui; Karr, Jonathan R; Schadt, Eric E
2015-01-01
Inferring causal relationships among molecular and higher order phenotypes is a critical step in elucidating the complexity of living systems. Here we propose a novel method for inferring causality that is no longer constrained by the conditional dependency arguments that limit the ability of statistical causal inference methods to resolve causal relationships within sets of graphical models that are Markov equivalent. Our method utilizes Bayesian belief propagation to infer the responses of perturbation events on molecular traits given a hypothesized graph structure. A distance measure between the inferred response distribution and the observed data is defined to assess the 'fitness' of the hypothesized causal relationships. To test our algorithm, we infer causal relationships within equivalence classes of gene networks in which the form of the functional interactions that are possible are assumed to be nonlinear, given synthetic microarray and RNA sequencing data. We also apply our method to infer causality in real metabolic network with v-structure and feedback loop. We show that our method can recapitulate the causal structure and recover the feedback loop only from steady-state data which conventional method cannot.
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Reasoning and Knowledge Acquisition Framework for 5G Network Analytics
2017-01-01
Autonomic self-management is a key challenge for next-generation networks. This paper proposes an automated analysis framework to infer knowledge in 5G networks with the aim to understand the network status and to predict potential situations that might disrupt the network operability. The framework is based on the Endsley situational awareness model, and integrates automated capabilities for metrics discovery, pattern recognition, prediction techniques and rule-based reasoning to infer anomalous situations in the current operational context. Those situations should then be mitigated, either proactive or reactively, by a more complex decision-making process. The framework is driven by a use case methodology, where the network administrator is able to customize the knowledge inference rules and operational parameters. The proposal has also been instantiated to prove its adaptability to a real use case. To this end, a reference network traffic dataset was used to identify suspicious patterns and to predict the behavior of the monitored data volume. The preliminary results suggest a good level of accuracy on the inference of anomalous traffic volumes based on a simple configuration. PMID:29065473
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Reasoning and Knowledge Acquisition Framework for 5G Network Analytics.
Sotelo Monge, Marco Antonio; Maestre Vidal, Jorge; García Villalba, Luis Javier
2017-10-21
Autonomic self-management is a key challenge for next-generation networks. This paper proposes an automated analysis framework to infer knowledge in 5G networks with the aim to understand the network status and to predict potential situations that might disrupt the network operability. The framework is based on the Endsley situational awareness model, and integrates automated capabilities for metrics discovery, pattern recognition, prediction techniques and rule-based reasoning to infer anomalous situations in the current operational context. Those situations should then be mitigated, either proactive or reactively, by a more complex decision-making process. The framework is driven by a use case methodology, where the network administrator is able to customize the knowledge inference rules and operational parameters. The proposal has also been instantiated to prove its adaptability to a real use case. To this end, a reference network traffic dataset was used to identify suspicious patterns and to predict the behavior of the monitored data volume. The preliminary results suggest a good level of accuracy on the inference of anomalous traffic volumes based on a simple configuration.
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IMNN: Information Maximizing Neural Networks
NASA Astrophysics Data System (ADS)
Charnock, Tom; Lavaux, Guilhem; Wandelt, Benjamin D.
2018-04-01
This software trains artificial neural networks to find non-linear functionals of data that maximize Fisher information: information maximizing neural networks (IMNNs). As compressing large data sets vastly simplifies both frequentist and Bayesian inference, important information may be inadvertently missed. Likelihood-free inference based on automatically derived IMNN summaries produces summaries that are good approximations to sufficient statistics. IMNNs are robustly capable of automatically finding optimal, non-linear summaries of the data even in cases where linear compression fails: inferring the variance of Gaussian signal in the presence of noise, inferring cosmological parameters from mock simulations of the Lyman-α forest in quasar spectra, and inferring frequency-domain parameters from LISA-like detections of gravitational waveforms. In this final case, the IMNN summary outperforms linear data compression by avoiding the introduction of spurious likelihood maxima.
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Mason, Robert A; Just, Marcel Adam
2011-02-01
Cortical activity associated with generating an inference was measured using fMRI. Participants read three-sentence passages that differed in whether or not an inference needed to be drawn to understand them. The inference was based on either a protagonist's intention or a physical consequence of a character's action. Activation was expected in Theory of Mind brain regions for the passages based on protagonists' intentions but not for the physical consequence passages. The activation measured in the right temporo-parietal junction was greater in the intentional passages than in the consequence passages, consistent with predictions from a Theory of Mind perspective. In contrast, there was increased occipital activation in the physical inference passages. For both types of passage, the cortical activity related to the reading of the critical inference sentence demonstrated a recruitment of a common inference cortical network. This general inference-related activation appeared bilaterally in the language processing areas (the inferior frontal gyrus, the temporal gyrus, and the angular gyrus), as well as in the medial to superior frontal gyrus, which has been found to be active in Theory of Mind tasks. These findings are consistent with the hypothesis that component areas of the discourse processing network are recruited as needed based on the nature of the inference. A Protagonist monitoring and synthesis network is proposed as a more accurate account for Theory of Mind activation during narrative comprehension. Copyright © 2010 Wiley-Liss, Inc.
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NIMEFI: gene regulatory network inference using multiple ensemble feature importance algorithms.
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.
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PIA: An Intuitive Protein Inference Engine with a Web-Based User Interface.
Uszkoreit, Julian; Maerkens, Alexandra; Perez-Riverol, Yasset; Meyer, Helmut E; Marcus, Katrin; Stephan, Christian; Kohlbacher, Oliver; Eisenacher, Martin
2015-07-02
Protein inference connects the peptide spectrum matches (PSMs) obtained from database search engines back to proteins, which are typically at the heart of most proteomics studies. Different search engines yield different PSMs and thus different protein lists. Analysis of results from one or multiple search engines is often hampered by different data exchange formats and lack of convenient and intuitive user interfaces. We present PIA, a flexible software suite for combining PSMs from different search engine runs and turning these into consistent results. PIA can be integrated into proteomics data analysis workflows in several ways. A user-friendly graphical user interface can be run either locally or (e.g., for larger core facilities) from a central server. For automated data processing, stand-alone tools are available. PIA implements several established protein inference algorithms and can combine results from different search engines seamlessly. On several benchmark data sets, we show that PIA can identify a larger number of proteins at the same protein FDR when compared to that using inference based on a single search engine. PIA supports the majority of established search engines and data in the mzIdentML standard format. It is implemented in Java and freely available at https://github.com/mpc-bioinformatics/pia.
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An Intuitive Dashboard for Bayesian Network Inference
NASA Astrophysics Data System (ADS)
Reddy, Vikas; Charisse Farr, Anna; Wu, Paul; Mengersen, Kerrie; Yarlagadda, Prasad K. D. V.
2014-03-01
Current Bayesian network software packages provide good graphical interface for users who design and develop Bayesian networks for various applications. However, the intended end-users of these networks may not necessarily find such an interface appealing and at times it could be overwhelming, particularly when the number of nodes in the network is large. To circumvent this problem, this paper presents an intuitive dashboard, which provides an additional layer of abstraction, enabling the end-users to easily perform inferences over the Bayesian networks. Unlike most software packages, which display the nodes and arcs of the network, the developed tool organises the nodes based on the cause-and-effect relationship, making the user-interaction more intuitive and friendly. In addition to performing various types of inferences, the users can conveniently use the tool to verify the behaviour of the developed Bayesian network. The tool has been developed using QT and SMILE libraries in C++.
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Multi-user investigation organizer
NASA Technical Reports Server (NTRS)
Panontin, Tina L. (Inventor); Williams, James F. (Inventor); Carvalho, Robert E. (Inventor); Sturken, Ian (Inventor); Wolfe, Shawn R. (Inventor); Gawdiak, Yuri O. (Inventor); Keller, Richard M. (Inventor)
2009-01-01
A system that allows a team of geographically dispersed users to collaboratively analyze a mishap event. The system includes a reconfigurable ontology, including instances that are related to and characterize the mishap, a semantic network that receives, indexes and stores, for retrieval, viewing and editing, the instances and links between the instances, a network browser interface for retrieving and viewing screens that present the instances and links to other instances and that allow editing thereof, and a rule-based inference engine, including a collection of rules associated with establishment of links between the instances. A possible conclusion arising from analysis of the mishap event may be characterized as one or more of: not a credible conclusion; an unlikely conclusion; a credible conclusion; conclusion needs analysis; conclusion needs supporting data; conclusion proposed to be closed; and an un-reviewed conclusion.
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Soft computing methods for geoidal height transformation
NASA Astrophysics Data System (ADS)
Akyilmaz, O.; Özlüdemir, M. T.; Ayan, T.; Çelik, R. N.
2009-07-01
Soft computing techniques, such as fuzzy logic and artificial neural network (ANN) approaches, have enabled researchers to create precise models for use in many scientific and engineering applications. Applications that can be employed in geodetic studies include the estimation of earth rotation parameters and the determination of mean sea level changes. Another important field of geodesy in which these computing techniques can be applied is geoidal height transformation. We report here our use of a conventional polynomial model, the Adaptive Network-based Fuzzy (or in some publications, Adaptive Neuro-Fuzzy) Inference System (ANFIS), an ANN and a modified ANN approach to approximate geoid heights. These approximation models have been tested on a number of test points. The results obtained through the transformation processes from ellipsoidal heights into local levelling heights have also been compared.
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Shin, Junha; Lee, Insuk
2015-01-01
Phylogenetic profiling, a network inference method based on gene inheritance profiles, has been widely used to construct functional gene networks in microbes. However, its utility for network inference in higher eukaryotes has been limited. An improved algorithm with an in-depth understanding of pathway evolution may overcome this limitation. In this study, we investigated the effects of taxonomic structures on co-inheritance analysis using 2,144 reference species in four query species: Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana, and Homo sapiens. We observed three clusters of reference species based on a principal component analysis of the phylogenetic profiles, which correspond to the three domains of life—Archaea, Bacteria, and Eukaryota—suggesting that pathways inherit primarily within specific domains or lower-ranked taxonomic groups during speciation. Hence, the co-inheritance pattern within a taxonomic group may be eroded by confounding inheritance patterns from irrelevant taxonomic groups. We demonstrated that co-inheritance analysis within domains substantially improved network inference not only in microbe species but also in the higher eukaryotes, including humans. Although we observed two sub-domain clusters of reference species within Eukaryota, co-inheritance analysis within these sub-domain taxonomic groups only marginally improved network inference. Therefore, we conclude that co-inheritance analysis within domains is the optimal approach to network inference with the given reference species. The construction of a series of human gene networks with increasing sample sizes of the reference species for each domain revealed that the size of the high-accuracy networks increased as additional reference species genomes were included, suggesting that within-domain co-inheritance analysis will continue to expand human gene networks as genomes of additional species are sequenced. Taken together, we propose that co-inheritance analysis within the domains of life will greatly potentiate the use of the expected onslaught of sequenced genomes in the study of molecular pathways in higher eukaryotes. PMID:26394049
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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
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A Scalable Approach to Probabilistic Latent Space Inference of Large-Scale Networks
Yin, Junming; Ho, Qirong; Xing, Eric P.
2014-01-01
We propose a scalable approach for making inference about latent spaces of large networks. With a succinct representation of networks as a bag of triangular motifs, a parsimonious statistical model, and an efficient stochastic variational inference algorithm, we are able to analyze real networks with over a million vertices and hundreds of latent roles on a single machine in a matter of hours, a setting that is out of reach for many existing methods. When compared to the state-of-the-art probabilistic approaches, our method is several orders of magnitude faster, with competitive or improved accuracy for latent space recovery and link prediction. PMID:25400487
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An approach for reduction of false predictions in reverse engineering of gene regulatory networks.
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. Copyright © 2018 Elsevier Ltd. All rights reserved.
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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.
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Explaining Inference on a Population of Independent Agents Using Bayesian Networks
ERIC Educational Resources Information Center
Sutovsky, Peter
2013-01-01
The main goal of this research is to design, implement, and evaluate a novel explanation method, the hierarchical explanation method (HEM), for explaining Bayesian network (BN) inference when the network is modeling a population of conditionally independent agents, each of which is modeled as a subnetwork. For example, consider disease-outbreak…
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ERIC Educational Resources Information Center
Peng, Yefei
2010-01-01
An ontology mapping neural network (OMNN) is proposed in order to learn and infer correspondences among ontologies. It extends the Identical Elements Neural Network (IENN)'s ability to represent and map complex relationships. The learning dynamics of simultaneous (interlaced) training of similar tasks interact at the shared connections of the…
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Inference of cancer-specific gene regulatory networks using soft computing rules.
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.
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A Modular Artificial Intelligence Inference Engine System (MAIS) for support of on orbit experiments
NASA Technical Reports Server (NTRS)
Hancock, Thomas M., III
1994-01-01
This paper describes a Modular Artificial Intelligence Inference Engine System (MAIS) support tool that would provide health and status monitoring, cognitive replanning, analysis and support of on-orbit Space Station, Spacelab experiments and systems.
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Towards a Rigorous Assessment of Systems Biology Models: The DREAM3 Challenges
Prill, Robert J.; Marbach, Daniel; Saez-Rodriguez, Julio; Sorger, Peter K.; Alexopoulos, Leonidas G.; Xue, Xiaowei; Clarke, Neil D.; Altan-Bonnet, Gregoire; Stolovitzky, Gustavo
2010-01-01
Background Systems biology has embraced computational modeling in response to the quantitative nature and increasing scale of contemporary data sets. The onslaught of data is accelerating as molecular profiling technology evolves. The Dialogue for Reverse Engineering Assessments and Methods (DREAM) is a community effort to catalyze discussion about the design, application, and assessment of systems biology models through annual reverse-engineering challenges. Methodology and Principal Findings We describe our assessments of the four challenges associated with the third DREAM conference which came to be known as the DREAM3 challenges: signaling cascade identification, signaling response prediction, gene expression prediction, and the DREAM3 in silico network challenge. The challenges, based on anonymized data sets, tested participants in network inference and prediction of measurements. Forty teams submitted 413 predicted networks and measurement test sets. Overall, a handful of best-performer teams were identified, while a majority of teams made predictions that were equivalent to random. Counterintuitively, combining the predictions of multiple teams (including the weaker teams) can in some cases improve predictive power beyond that of any single method. Conclusions DREAM provides valuable feedback to practitioners of systems biology modeling. Lessons learned from the predictions of the community provide much-needed context for interpreting claims of efficacy of algorithms described in the scientific literature. PMID:20186320
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Inferring Plasmodium vivax Transmission Networks from Tempo-Spatial Surveillance Data
Shi, Benyun; Liu, Jiming; Zhou, Xiao-Nong; Yang, Guo-Jing
2014-01-01
Background The transmission networks of Plasmodium vivax characterize how the parasite transmits from one location to another, which are informative and insightful for public health policy makers to accurately predict the patterns of its geographical spread. However, such networks are not apparent from surveillance data because P. vivax transmission can be affected by many factors, such as the biological characteristics of mosquitoes and the mobility of human beings. Here, we pay special attention to the problem of how to infer the underlying transmission networks of P. vivax based on available tempo-spatial patterns of reported cases. Methodology We first define a spatial transmission model, which involves representing both the heterogeneous transmission potential of P. vivax at individual locations and the mobility of infected populations among different locations. Based on the proposed transmission model, we further introduce a recurrent neural network model to infer the transmission networks from surveillance data. Specifically, in this model, we take into account multiple real-world factors, including the length of P. vivax incubation period, the impact of malaria control at different locations, and the total number of imported cases. Principal Findings We implement our proposed models by focusing on the P. vivax transmission among 62 towns in Yunnan province, People's Republic China, which have been experiencing high malaria transmission in the past years. By conducting scenario analysis with respect to different numbers of imported cases, we can (i) infer the underlying P. vivax transmission networks, (ii) estimate the number of imported cases for each individual town, and (iii) quantify the roles of individual towns in the geographical spread of P. vivax. Conclusion The demonstrated models have presented a general means for inferring the underlying transmission networks from surveillance data. The inferred networks will offer new insights into how to improve the predictability of P. vivax transmission. PMID:24516684
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Construction of regulatory networks using expression time-series data of a genotyped population.
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.
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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.
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Audain, Enrique; Uszkoreit, Julian; Sachsenberg, Timo; Pfeuffer, Julianus; Liang, Xiao; Hermjakob, Henning; Sanchez, Aniel; Eisenacher, Martin; Reinert, Knut; Tabb, David L; Kohlbacher, Oliver; Perez-Riverol, Yasset
2017-01-06
In mass spectrometry-based shotgun proteomics, protein identifications are usually the desired result. However, most of the analytical methods are based on the identification of reliable peptides and not the direct identification of intact proteins. Thus, assembling peptides identified from tandem mass spectra into a list of proteins, referred to as protein inference, is a critical step in proteomics research. Currently, different protein inference algorithms and tools are available for the proteomics community. Here, we evaluated five software tools for protein inference (PIA, ProteinProphet, Fido, ProteinLP, MSBayesPro) using three popular database search engines: Mascot, X!Tandem, and MS-GF+. All the algorithms were evaluated using a highly customizable KNIME workflow using four different public datasets with varying complexities (different sample preparation, species and analytical instruments). We defined a set of quality control metrics to evaluate the performance of each combination of search engines, protein inference algorithm, and parameters on each dataset. We show that the results for complex samples vary not only regarding the actual numbers of reported protein groups but also concerning the actual composition of groups. Furthermore, the robustness of reported proteins when using databases of differing complexities is strongly dependant on the applied inference algorithm. Finally, merging the identifications of multiple search engines does not necessarily increase the number of reported proteins, but does increase the number of peptides per protein and thus can generally be recommended. Protein inference is one of the major challenges in MS-based proteomics nowadays. Currently, there are a vast number of protein inference algorithms and implementations available for the proteomics community. Protein assembly impacts in the final results of the research, the quantitation values and the final claims in the research manuscript. Even though protein inference is a crucial step in proteomics data analysis, a comprehensive evaluation of the many different inference methods has never been performed. Previously Journal of proteomics has published multiple studies about other benchmark of bioinformatics algorithms (PMID: 26585461; PMID: 22728601) in proteomics studies making clear the importance of those studies for the proteomics community and the journal audience. This manuscript presents a new bioinformatics solution based on the KNIME/OpenMS platform that aims at providing a fair comparison of protein inference algorithms (https://github.com/KNIME-OMICS). Six different algorithms - ProteinProphet, MSBayesPro, ProteinLP, Fido and PIA- were evaluated using the highly customizable workflow on four public datasets with varying complexities. Five popular database search engines Mascot, X!Tandem, MS-GF+ and combinations thereof were evaluated for every protein inference tool. In total >186 proteins lists were analyzed and carefully compare using three metrics for quality assessments of the protein inference results: 1) the numbers of reported proteins, 2) peptides per protein, and the 3) number of uniquely reported proteins per inference method, to address the quality of each inference method. We also examined how many proteins were reported by choosing each combination of search engines, protein inference algorithms and parameters on each dataset. The results show that using 1) PIA or Fido seems to be a good choice when studying the results of the analyzed workflow, regarding not only the reported proteins and the high-quality identifications, but also the required runtime. 2) Merging the identifications of multiple search engines gives almost always more confident results and increases the number of peptides per protein group. 3) The usage of databases containing not only the canonical, but also known isoforms of proteins has a small impact on the number of reported proteins. The detection of specific isoforms could, concerning the question behind the study, compensate for slightly shorter reports using the parsimonious reports. 4) The current workflow can be easily extended to support new algorithms and search engine combinations. Copyright © 2016. Published by Elsevier B.V.
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Inferring gene and protein interactions using PubMed citations and consensus Bayesian networks.
Deeter, Anthony; Dalman, Mark; Haddad, Joseph; Duan, Zhong-Hui
2017-01-01
The PubMed database offers an extensive set of publication data that can be useful, yet inherently complex to use without automated computational techniques. Data repositories such as the Genomic Data Commons (GDC) and the Gene Expression Omnibus (GEO) offer experimental data storage and retrieval as well as curated gene expression profiles. Genetic interaction databases, including Reactome and Ingenuity Pathway Analysis, offer pathway and experiment data analysis using data curated from these publications and data repositories. We have created a method to generate and analyze consensus networks, inferring potential gene interactions, using large numbers of Bayesian networks generated by data mining publications in the PubMed database. Through the concept of network resolution, these consensus networks can be tailored to represent possible genetic interactions. We designed a set of experiments to confirm that our method is stable across variation in both sample and topological input sizes. Using gene product interactions from the KEGG pathway database and data mining PubMed publication abstracts, we verify that regardless of the network resolution or the inferred consensus network, our method is capable of inferring meaningful gene interactions through consensus Bayesian network generation with multiple, randomized topological orderings. Our method can not only confirm the existence of currently accepted interactions, but has the potential to hypothesize new ones as well. We show our method confirms the existence of known gene interactions such as JAK-STAT-PI3K-AKT-mTOR, infers novel gene interactions such as RAS- Bcl-2 and RAS-AKT, and found significant pathway-pathway interactions between the JAK-STAT signaling and Cardiac Muscle Contraction KEGG pathways.
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A Topological Criterion for Filtering Information in Complex Brain Networks
Latora, Vito; Chavez, Mario
2017-01-01
In many biological systems, the network of interactions between the elements can only be inferred from experimental measurements. In neuroscience, non-invasive imaging tools are extensively used to derive either structural or functional brain networks in-vivo. As a result of the inference process, we obtain a matrix of values corresponding to a fully connected and weighted network. To turn this into a useful sparse network, thresholding is typically adopted to cancel a percentage of the weakest connections. The structural properties of the resulting network depend on how much of the inferred connectivity is eventually retained. However, how to objectively fix this threshold is still an open issue. We introduce a criterion, the efficiency cost optimization (ECO), to select a threshold based on the optimization of the trade-off between the efficiency of a network and its wiring cost. We prove analytically and we confirm through numerical simulations that the connection density maximizing this trade-off emphasizes the intrinsic properties of a given network, while preserving its sparsity. Moreover, this density threshold can be determined a-priori, since the number of connections to filter only depends on the network size according to a power-law. We validate this result on several brain networks, from micro- to macro-scales, obtained with different imaging modalities. Finally, we test the potential of ECO in discriminating brain states with respect to alternative filtering methods. ECO advances our ability to analyze and compare biological networks, inferred from experimental data, in a fast and principled way. PMID:28076353
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Dynamic modelling of microRNA regulation during mesenchymal stem cell differentiation.
Weber, Michael; Sotoca, Ana M; Kupfer, Peter; Guthke, Reinhard; van Zoelen, Everardus J
2013-11-12
Network inference from gene expression data is a typical approach to reconstruct gene regulatory networks. During chondrogenic differentiation of human mesenchymal stem cells (hMSCs), a complex transcriptional network is active and regulates the temporal differentiation progress. As modulators of transcriptional regulation, microRNAs (miRNAs) play a critical role in stem cell differentiation. Integrated network inference aimes at determining interrelations between miRNAs and mRNAs on the basis of expression data as well as miRNA target predictions. We applied the NetGenerator tool in order to infer an integrated gene regulatory network. Time series experiments were performed to measure mRNA and miRNA abundances of TGF-beta1+BMP2 stimulated hMSCs. Network nodes were identified by analysing temporal expression changes, miRNA target gene predictions, time series correlation and literature knowledge. Network inference was performed using NetGenerator to reconstruct a dynamical regulatory model based on the measured data and prior knowledge. The resulting model is robust against noise and shows an optimal trade-off between fitting precision and inclusion of prior knowledge. It predicts the influence of miRNAs on the expression of chondrogenic marker genes and therefore proposes novel regulatory relations in differentiation control. By analysing the inferred network, we identified a previously unknown regulatory effect of miR-524-5p on the expression of the transcription factor SOX9 and the chondrogenic marker genes COL2A1, ACAN and COL10A1. Genome-wide exploration of miRNA-mRNA regulatory relationships is a reasonable approach to identify miRNAs which have so far not been associated with the investigated differentiation process. The NetGenerator tool is able to identify valid gene regulatory networks on the basis of miRNA and mRNA time series data.
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F-OWL: An Inference Engine for Semantic Web
NASA Technical Reports Server (NTRS)
Zou, Youyong; Finin, Tim; Chen, Harry
2004-01-01
Understanding and using the data and knowledge encoded in semantic web documents requires an inference engine. F-OWL is an inference engine for the semantic web language OWL language based on F-logic, an approach to defining frame-based systems in logic. F-OWL is implemented using XSB and Flora-2 and takes full advantage of their features. We describe how F-OWL computes ontology entailment and compare it with other description logic based approaches. We also describe TAGA, a trading agent environment that we have used as a test bed for F-OWL and to explore how multiagent systems can use semantic web concepts and technology.
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Image feature based GPS trace filtering for road network generation and road segmentation
Yuan, Jiangye; Cheriyadat, Anil M.
2015-10-19
We propose a new method to infer road networks from GPS trace data and accurately segment road regions in high-resolution aerial images. Unlike previous efforts that rely on GPS traces alone, we exploit image features to infer road networks from noisy trace data. The inferred road network is used to guide road segmentation. We show that the number of image segments spanned by the traces and the trace orientation validated with image features are important attributes for identifying GPS traces on road regions. Based on filtered traces , we construct road networks and integrate them with image features to segmentmore » road regions. Lastly, our experiments show that the proposed method produces more accurate road networks than the leading method that uses GPS traces alone, and also achieves high accuracy in segmenting road regions even with very noisy GPS data.« less
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Image feature based GPS trace filtering for road network generation and road segmentation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yuan, Jiangye; Cheriyadat, Anil M.
We propose a new method to infer road networks from GPS trace data and accurately segment road regions in high-resolution aerial images. Unlike previous efforts that rely on GPS traces alone, we exploit image features to infer road networks from noisy trace data. The inferred road network is used to guide road segmentation. We show that the number of image segments spanned by the traces and the trace orientation validated with image features are important attributes for identifying GPS traces on road regions. Based on filtered traces , we construct road networks and integrate them with image features to segmentmore » road regions. Lastly, our experiments show that the proposed method produces more accurate road networks than the leading method that uses GPS traces alone, and also achieves high accuracy in segmenting road regions even with very noisy GPS data.« less
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NIMEFI: Gene Regulatory Network Inference using Multiple Ensemble Feature Importance Algorithms
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. PMID:24667482
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Integrating Information in Biological Ontologies and Molecular Networks to Infer Novel Terms.
Li, Le; Yip, Kevin Y
2016-12-15
Currently most terms and term-term relationships in Gene Ontology (GO) are defined manually, which creates cost, consistency and completeness issues. Recent studies have demonstrated the feasibility of inferring GO automatically from biological networks, which represents an important complementary approach to GO construction. These methods (NeXO and CliXO) are unsupervised, which means 1) they cannot use the information contained in existing GO, 2) the way they integrate biological networks may not optimize the accuracy, and 3) they are not customized to infer the three different sub-ontologies of GO. Here we present a semi-supervised method called Unicorn that extends these previous methods to tackle the three problems. Unicorn uses a sub-tree of an existing GO sub-ontology as training part to learn parameters in integrating multiple networks. Cross-validation results show that Unicorn reliably inferred the left-out parts of each specific GO sub-ontology. In addition, by training Unicorn with an old version of GO together with biological networks, it successfully re-discovered some terms and term-term relationships present only in a new version of GO. Unicorn also successfully inferred some novel terms that were not contained in GO but have biological meanings well-supported by the literature. Source code of Unicorn is available at http://yiplab.cse.cuhk.edu.hk/unicorn/.
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Lavoie, Marie-Audrey; Vistoli, Damien; Sutliff, Stephanie; Jackson, Philip L; Achim, Amélie M
2016-08-01
Theory of mind (ToM) refers to the ability to infer the mental states of others. Behavioral measures of ToM usually present information about both a character and the context in which this character is placed, and these different pieces of information can be used to infer the character's mental states. A set of brain regions designated as the ToM brain network is recognized to support (ToM) inferences. Different brain regions within that network could however support different ToM processes. This functional magnetic resonance imaging (fMRI) study aimed to distinguish the brain regions supporting two aspects inherent to many ToM tasks, i.e., the ability to infer or represent mental states and the ability to use the context to adjust these inferences. Nineteen healthy subjects were scanned during the REMICS task, a novel task designed to orthogonally manipulate mental state inferences (as opposed to physical inferences) and contextual adjustments of inferences (as opposed to inferences that do not require contextual adjustments). We observed that mental state inferences and contextual adjustments, which are important aspects of most behavioral ToM tasks, rely on distinct brain regions or subregions within the classical brain network activated in previous ToM research. Notably, an interesting dissociation emerged within the medial prefrontal cortex (mPFC) and temporo-parietal junctions (TPJ) such that the inferior part of these brain regions responded to mental state inferences while the superior part of these brain regions responded to the requirement for contextual adjustments. This study provides evidence that the overall set of brain regions activated during ToM tasks supports different processes, and highlights that cognitive processes related to contextual adjustments have an important role in ToM and should be further studied. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Genie Inference Engine Rule Writer’s Guide.
1987-08-01
33 APPENDIX D. Animal Bootstrap File.............................................................. 39...APPENDIX E. Sample Run of Animal Identification Expert System.......................... 43 APPENDIX F. Numeric Test Knowledge Base...and other data s.tructures stored in the knowledge base (KB), queries the user for input, and draws conclusions. Genie (GENeric Inference Engine) is
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Analysis and Design of Complex Network Environments
2014-02-01
entanglements among un- measured variables. This “potential entanglement ” type of network complexity is previously unaddressed in the literature, yet it...Appreciating the power of structural representations that allow for potential entanglement among unmeasured variables to simplify network inference problems...rely on the idea of subsystems and allows for potential entanglement among unmeasured states. As a result, inferring a system’s signal structure
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Inferring topologies via driving-based generalized synchronization of two-layer networks
NASA Astrophysics Data System (ADS)
Wang, Yingfei; Wu, Xiaoqun; Feng, Hui; Lu, Jun-an; Xu, Yuhua
2016-05-01
The interaction topology among the constituents of a complex network plays a crucial role in the network’s evolutionary mechanisms and functional behaviors. However, some network topologies are usually unknown or uncertain. Meanwhile, coupling delays are ubiquitous in various man-made and natural networks. Hence, it is necessary to gain knowledge of the whole or partial topology of a complex dynamical network by taking into consideration communication delay. In this paper, topology identification of complex dynamical networks is investigated via generalized synchronization of a two-layer network. Particularly, based on the LaSalle-type invariance principle of stochastic differential delay equations, an adaptive control technique is proposed by constructing an auxiliary layer and designing proper control input and updating laws so that the unknown topology can be recovered upon successful generalized synchronization. Numerical simulations are provided to illustrate the effectiveness of the proposed method. The technique provides a certain theoretical basis for topology inference of complex networks. In particular, when the considered network is composed of systems with high-dimension or complicated dynamics, a simpler response layer can be constructed, which is conducive to circuit design. Moreover, it is practical to take into consideration perturbations caused by control input. Finally, the method is applicable to infer topology of a subnetwork embedded within a complex system and locate hidden sources. We hope the results can provide basic insight into further research endeavors on understanding practical and economical topology inference of networks.
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Logic-centered architecture for ubiquitous health monitoring.
Lewandowski, Jacek; Arochena, Hisbel E; Naguib, Raouf N G; Chao, Kuo-Ming; Garcia-Perez, Alexeis
2014-09-01
One of the key points to maintain and boost research and development in the area of smart wearable systems (SWS) is the development of integrated architectures for intelligent services, as well as wearable systems and devices for health and wellness management. This paper presents such a generic architecture for multiparametric, intelligent and ubiquitous wireless sensing platforms. It is a transparent, smartphone-based sensing framework with customizable wireless interfaces and plug'n'play capability to easily interconnect third party sensor devices. It caters to wireless body, personal, and near-me area networks. A pivotal part of the platform is the integrated inference engine/runtime environment that allows the mobile device to serve as a user-adaptable personal health assistant. The novelty of this system lays in a rapid visual development and remote deployment model. The complementary visual Inference Engine Editor that comes with the package enables artificial intelligence specialists, alongside with medical experts, to build data processing models by assembling different components and instantly deploying them (remotely) on patient mobile devices. In this paper, the new logic-centered software architecture for ubiquitous health monitoring applications is described, followed by a discussion as to how it helps to shift focus from software and hardware development, to medical and health process-centered design of new SWS applications.
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Du, Yuanwei; Guo, Yubin
2015-01-01
The intrinsic mechanism of multimorbidity is difficult to recognize and prediction and diagnosis are difficult to carry out accordingly. Bayesian networks can help to diagnose multimorbidity in health care, but it is difficult to obtain the conditional probability table (CPT) because of the lack of clinically statistical data. Today, expert knowledge and experience are increasingly used in training Bayesian networks in order to help predict or diagnose diseases, but the CPT in Bayesian networks is usually irrational or ineffective for ignoring realistic constraints especially in multimorbidity. In order to solve these problems, an evidence reasoning (ER) approach is employed to extract and fuse inference data from experts using a belief distribution and recursive ER algorithm, based on which evidence reasoning method for constructing conditional probability tables in Bayesian network of multimorbidity is presented step by step. A multimorbidity numerical example is used to demonstrate the method and prove its feasibility and application. Bayesian network can be determined as long as the inference assessment is inferred by each expert according to his/her knowledge or experience. Our method is more effective than existing methods for extracting expert inference data accurately and is fused effectively for constructing CPTs in a Bayesian network of multimorbidity.
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Inference of financial networks using the normalised mutual information rate.
Goh, Yong Kheng; Hasim, Haslifah M; Antonopoulos, Chris G
2018-01-01
In this paper, we study data from financial markets, using the normalised Mutual Information Rate. We show how to use it to infer the underlying network structure of interrelations in the foreign currency exchange rates and stock indices of 15 currency areas. We first present the mathematical method and discuss its computational aspects, and apply it to artificial data from chaotic dynamics and to correlated normal-variates data. We then apply the method to infer the structure of the financial system from the time-series of currency exchange rates and stock indices. In particular, we study and reveal the interrelations among the various foreign currency exchange rates and stock indices in two separate networks, of which we also study their structural properties. Our results show that both inferred networks are small-world networks, sharing similar properties and having differences in terms of assortativity. Importantly, our work shows that global economies tend to connect with other economies world-wide, rather than creating small groups of local economies. Finally, the consistent interrelations depicted among the 15 currency areas are further supported by a discussion from the viewpoint of economics.
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Chockalingam, Sriram; Aluru, Maneesha; Aluru, Srinivas
2016-09-19
Pre-processing of microarray data is a well-studied problem. Furthermore, all popular platforms come with their own recommended best practices for differential analysis of genes. However, for genome-scale network inference using microarray data collected from large public repositories, these methods filter out a considerable number of genes. This is primarily due to the effects of aggregating a diverse array of experiments with different technical and biological scenarios. Here we introduce a pre-processing pipeline suitable for inferring genome-scale gene networks from large microarray datasets. We show that partitioning of the available microarray datasets according to biological relevance into tissue- and process-specific categories significantly extends the limits of downstream network construction. We demonstrate the effectiveness of our pre-processing pipeline by inferring genome-scale networks for the model plant Arabidopsis thaliana using two different construction methods and a collection of 11,760 Affymetrix ATH1 microarray chips. Our pre-processing pipeline and the datasets used in this paper are made available at http://alurulab.cc.gatech.edu/microarray-pp.
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Inference of financial networks using the normalised mutual information rate
2018-01-01
In this paper, we study data from financial markets, using the normalised Mutual Information Rate. We show how to use it to infer the underlying network structure of interrelations in the foreign currency exchange rates and stock indices of 15 currency areas. We first present the mathematical method and discuss its computational aspects, and apply it to artificial data from chaotic dynamics and to correlated normal-variates data. We then apply the method to infer the structure of the financial system from the time-series of currency exchange rates and stock indices. In particular, we study and reveal the interrelations among the various foreign currency exchange rates and stock indices in two separate networks, of which we also study their structural properties. Our results show that both inferred networks are small-world networks, sharing similar properties and having differences in terms of assortativity. Importantly, our work shows that global economies tend to connect with other economies world-wide, rather than creating small groups of local economies. Finally, the consistent interrelations depicted among the 15 currency areas are further supported by a discussion from the viewpoint of economics. PMID:29420644
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A sub-space greedy search method for efficient Bayesian Network inference.
Zhang, Qing; Cao, Yong; Li, Yong; Zhu, Yanming; Sun, Samuel S M; Guo, Dianjing
2011-09-01
Bayesian network (BN) has been successfully used to infer the regulatory relationships of genes from microarray dataset. However, one major limitation of BN approach is the computational cost because the calculation time grows more than exponentially with the dimension of the dataset. In this paper, we propose a sub-space greedy search method for efficient Bayesian Network inference. Particularly, this method limits the greedy search space by only selecting gene pairs with higher partial correlation coefficients. Using both synthetic and real data, we demonstrate that the proposed method achieved comparable results with standard greedy search method yet saved ∼50% of the computational time. We believe that sub-space search method can be widely used for efficient BN inference in systems biology. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-01-04
...,846B; TA-W-81,846C; TA-W-81,846D] Goodman Networks, Inc. Core Network Engineering (Deployment Engineering) Division Alpharetta, GA; Goodman Networks, Inc. Core Network Engineering (Deployment Engineering) Division Hunt Valley, MD; Goodman Networks, Inc. Core Network Engineering (Deployment Engineering) Division...
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Privacy Vulnerability of Published Anonymous Mobility Traces
Ma, Chris Y. T.; Yau, David K. Y.; Yip, Nung Kwan; ...
2013-06-01
Mobility traces of people and vehicles have been collected and published to assist the design and evaluation of mobile networks, such as large-scale urban sensing networks. Although the published traces are often made anonymous in that the true identities of nodes are replaced by random identifiers, the privacy concern remains. This is because in real life, nodes are open to observations in public spaces, or they may voluntarily or inadvertently disclose partial knowledge of their whereabouts. Thus, snapshots of nodes’ location information can be learned by interested third parties, e.g., directly through chance/engineered meetings between the nodes and their observers,more » or indirectly through casual conversations or other information sources about people. In this paper, we investigate how an adversary, when equipped with a small amount of the snapshot information termed as side information, can infer an extended view of the whereabouts of a victim node appearing in an anonymous trace. Our results quantify the loss of victim nodes’ privacy as a function of the nodal mobility, the inference strategies of adversaries, and any noise that may appear in the trace or the side information. Generally, our results indicate that the privacy concern is significant in that a relatively small amount of side information is sufficient for the adversary to infer the true identity (either uniquely or with high probability) of a victim in a set of anonymous traces. For instance, an adversary is able to identify the trace of 30%-50% of the victims when she has collected 10 pieces of side information about a victim.« less
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Veiga, Diogo F. T.; Dutta, Bhaskar; Balaźsi, Gábor
2011-01-01
The escalating amount of genome-scale data demands a pragmatic stance from the research community. How can we utilize this deluge of information to better understand biology, cure diseases, or engage cells in bioremediation or biomaterial production for various purposes? A research pipeline moving new sequence, expression and binding data towards practical end goals seems to be necessary. While most individual researchers are not motivated by such well-articulated pragmatic end goals, the scientific community has already self-organized itself to successfully convert genomic data into fundamentally new biological knowledge and practical applications. Here we review two important steps in this workflow: network inference and network response identification, applied to transcriptional regulatory networks. Among network inference methods, we concentrate on relevance networks due to their conceptual simplicity. We classify and discuss network response identification approaches as either data-centric or network-centric. Finally, we conclude with an outlook on what is still missing from these approaches and what may be ahead on the road to biological discovery. PMID:20174676
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Semi-Supervised Multi-View Learning for Gene Network Reconstruction
Ceci, Michelangelo; Pio, Gianvito; Kuzmanovski, Vladimir; Džeroski, Sašo
2015-01-01
The task of gene regulatory network reconstruction from high-throughput data is receiving increasing attention in recent years. As a consequence, many inference methods for solving this task have been proposed in the literature. It has been recently observed, however, that no single inference method performs optimally across all datasets. It has also been shown that the integration of predictions from multiple inference methods is more robust and shows high performance across diverse datasets. Inspired by this research, in this paper, we propose a machine learning solution which learns to combine predictions from multiple inference methods. While this approach adds additional complexity to the inference process, we expect it would also carry substantial benefits. These would come from the automatic adaptation to patterns on the outputs of individual inference methods, so that it is possible to identify regulatory interactions more reliably when these patterns occur. This article demonstrates the benefits (in terms of accuracy of the reconstructed networks) of the proposed method, which exploits an iterative, semi-supervised ensemble-based algorithm. The algorithm learns to combine the interactions predicted by many different inference methods in the multi-view learning setting. The empirical evaluation of the proposed algorithm on a prokaryotic model organism (E. coli) and on a eukaryotic model organism (S. cerevisiae) clearly shows improved performance over the state of the art methods. The results indicate that gene regulatory network reconstruction for the real datasets is more difficult for S. cerevisiae than for E. coli. The software, all the datasets used in the experiments and all the results are available for download at the following link: http://figshare.com/articles/Semi_supervised_Multi_View_Learning_for_Gene_Network_Reconstruction/1604827. PMID:26641091
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A Prize-Collecting Steiner Tree Approach for Transduction Network Inference
NASA Astrophysics Data System (ADS)
Bailly-Bechet, Marc; Braunstein, Alfredo; Zecchina, Riccardo
Into the cell, information from the environment is mainly propagated via signaling pathways which form a transduction network. Here we propose a new algorithm to infer transduction networks from heterogeneous data, using both the protein interaction network and expression datasets. We formulate the inference problem as an optimization task, and develop a message-passing, probabilistic and distributed formalism to solve it. We apply our algorithm to the pheromone response in the baker’s yeast S. cerevisiae. We are able to find the backbone of the known structure of the MAPK cascade of pheromone response, validating our algorithm. More importantly, we make biological predictions about some proteins whose role could be at the interface between pheromone response and other cellular functions.
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NASA Astrophysics Data System (ADS)
Lee, K. David; Colony, Mike
2011-06-01
Modeling and simulation has been established as a cost-effective means of supporting the development of requirements, exploring doctrinal alternatives, assessing system performance, and performing design trade-off analysis. The Army's constructive simulation for the evaluation of equipment effectiveness in small combat unit operations is currently limited to representation of situation awareness without inclusion of the many uncertainties associated with real world combat environments. The goal of this research is to provide an ability to model situation awareness and decision process uncertainties in order to improve evaluation of the impact of battlefield equipment on ground soldier and small combat unit decision processes. Our Army Probabilistic Inference and Decision Engine (Army-PRIDE) system provides this required uncertainty modeling through the application of two critical techniques that allow Bayesian network technology to be applied to real-time applications. (Object-Oriented Bayesian Network methodology and Object-Oriented Inference technique). In this research, we implement decision process and situation awareness models for a reference scenario using Army-PRIDE and demonstrate its ability to model a variety of uncertainty elements, including: confidence of source, information completeness, and information loss. We also demonstrate that Army-PRIDE improves the realism of the current constructive simulation's decision processes through Monte Carlo simulation.
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Inferring gene and protein interactions using PubMed citations and consensus Bayesian networks
Dalman, Mark; Haddad, Joseph; Duan, Zhong-Hui
2017-01-01
The PubMed database offers an extensive set of publication data that can be useful, yet inherently complex to use without automated computational techniques. Data repositories such as the Genomic Data Commons (GDC) and the Gene Expression Omnibus (GEO) offer experimental data storage and retrieval as well as curated gene expression profiles. Genetic interaction databases, including Reactome and Ingenuity Pathway Analysis, offer pathway and experiment data analysis using data curated from these publications and data repositories. We have created a method to generate and analyze consensus networks, inferring potential gene interactions, using large numbers of Bayesian networks generated by data mining publications in the PubMed database. Through the concept of network resolution, these consensus networks can be tailored to represent possible genetic interactions. We designed a set of experiments to confirm that our method is stable across variation in both sample and topological input sizes. Using gene product interactions from the KEGG pathway database and data mining PubMed publication abstracts, we verify that regardless of the network resolution or the inferred consensus network, our method is capable of inferring meaningful gene interactions through consensus Bayesian network generation with multiple, randomized topological orderings. Our method can not only confirm the existence of currently accepted interactions, but has the potential to hypothesize new ones as well. We show our method confirms the existence of known gene interactions such as JAK-STAT-PI3K-AKT-mTOR, infers novel gene interactions such as RAS- Bcl-2 and RAS-AKT, and found significant pathway-pathway interactions between the JAK-STAT signaling and Cardiac Muscle Contraction KEGG pathways. PMID:29049295
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A New Modified Histogram Matching Normalization for Time Series Microarray Analysis.
Astola, Laura; Molenaar, Jaap
2014-07-01
Microarray data is often utilized in inferring regulatory networks. Quantile normalization (QN) is a popular method to reduce array-to-array variation. We show that in the context of time series measurements QN may not be the best choice for this task, especially not if the inference is based on continuous time ODE model. We propose an alternative normalization method that is better suited for network inference from time series data.
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Inferring Boolean network states from partial information
2013-01-01
Networks of molecular interactions regulate key processes in living cells. Therefore, understanding their functionality is a high priority in advancing biological knowledge. Boolean networks are often used to describe cellular networks mathematically and are fitted to experimental datasets. The fitting often results in ambiguities since the interpretation of the measurements is not straightforward and since the data contain noise. In order to facilitate a more reliable mapping between datasets and Boolean networks, we develop an algorithm that infers network trajectories from a dataset distorted by noise. We analyze our algorithm theoretically and demonstrate its accuracy using simulation and microarray expression data. PMID:24006954
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Incorporating time-delays in S-System model for reverse engineering genetic networks.
Chowdhury, Ahsan Raja; Chetty, Madhu; Vinh, Nguyen Xuan
2013-06-18
In any gene regulatory network (GRN), the complex interactions occurring amongst transcription factors and target genes can be either instantaneous or time-delayed. However, many existing modeling approaches currently applied for inferring GRNs are unable to represent both these interactions simultaneously. As a result, all these approaches cannot detect important interactions of the other type. S-System model, a differential equation based approach which has been increasingly applied for modeling GRNs, also suffers from this limitation. In fact, all S-System based existing modeling approaches have been designed to capture only instantaneous interactions, and are unable to infer time-delayed interactions. In this paper, we propose a novel Time-Delayed S-System (TDSS) model which uses a set of delay differential equations to represent the system dynamics. The ability to incorporate time-delay parameters in the proposed S-System model enables simultaneous modeling of both instantaneous and time-delayed interactions. Furthermore, the delay parameters are not limited to just positive integer values (corresponding to time stamps in the data), but can also take fractional values. Moreover, we also propose a new criterion for model evaluation exploiting the sparse and scale-free nature of GRNs to effectively narrow down the search space, which not only reduces the computation time significantly but also improves model accuracy. The evaluation criterion systematically adapts the max-min in-degrees and also systematically balances the effect of network accuracy and complexity during optimization. The four well-known performance measures applied to the experimental studies on synthetic networks with various time-delayed regulations clearly demonstrate that the proposed method can capture both instantaneous and delayed interactions correctly with high precision. The experiments carried out on two well-known real-life networks, namely IRMA and SOS DNA repair network in Escherichia coli show a significant improvement compared with other state-of-the-art approaches for GRN modeling.
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NASA Astrophysics Data System (ADS)
Thakar, Juilee; Albert, Réka
The following sections are included: * Introduction * Boolean Network Concepts and History * Extensions of the Classical Boolean Framework * Boolean Inference Methods and Examples in Biology * Dynamic Boolean Models: Examples in Plant Biology, Developmental Biology and Immunology * Conclusions * References
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Multiple hot-deck imputation for network inference from RNA sequencing data.
Imbert, Alyssa; Valsesia, Armand; Le Gall, Caroline; Armenise, Claudia; Lefebvre, Gregory; Gourraud, Pierre-Antoine; Viguerie, Nathalie; Villa-Vialaneix, Nathalie
2018-05-15
Network inference provides a global view of the relations existing between gene expression in a given transcriptomic experiment (often only for a restricted list of chosen genes). However, it is still a challenging problem: even if the cost of sequencing techniques has decreased over the last years, the number of samples in a given experiment is still (very) small compared to the number of genes. We propose a method to increase the reliability of the inference when RNA-seq expression data have been measured together with an auxiliary dataset that can provide external information on gene expression similarity between samples. Our statistical approach, hd-MI, is based on imputation for samples without available RNA-seq data that are considered as missing data but are observed on the secondary dataset. hd-MI can improve the reliability of the inference for missing rates up to 30% and provides more stable networks with a smaller number of false positive edges. On a biological point of view, hd-MI was also found relevant to infer networks from RNA-seq data acquired in adipose tissue during a nutritional intervention in obese individuals. In these networks, novel links between genes were highlighted, as well as an improved comparability between the two steps of the nutritional intervention. Software and sample data are available as an R package, RNAseqNet, that can be downloaded from the Comprehensive R Archive Network (CRAN). alyssa.imbert@inra.fr or nathalie.villa-vialaneix@inra.fr. Supplementary data are available at Bioinformatics online.
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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.
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Inferring Nonlinear Gene Regulatory Networks from Gene Expression Data Based on Distance Correlation
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
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Prediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference
Jiang, Jing; Lu, Weiqiang; Li, Weihua; Liu, Guixia; Zhou, Weixing; Huang, Jin; Tang, Yun
2012-01-01
Drug-target interaction (DTI) is the basis of drug discovery and design. It is time consuming and costly to determine DTI experimentally. Hence, it is necessary to develop computational methods for the prediction of potential DTI. Based on complex network theory, three supervised inference methods were developed here to predict DTI and used for drug repositioning, namely drug-based similarity inference (DBSI), target-based similarity inference (TBSI) and network-based inference (NBI). Among them, NBI performed best on four benchmark data sets. Then a drug-target network was created with NBI based on 12,483 FDA-approved and experimental drug-target binary links, and some new DTIs were further predicted. In vitro assays confirmed that five old drugs, namely montelukast, diclofenac, simvastatin, ketoconazole, and itraconazole, showed polypharmacological features on estrogen receptors or dipeptidyl peptidase-IV with half maximal inhibitory or effective concentration ranged from 0.2 to 10 µM. Moreover, simvastatin and ketoconazole showed potent antiproliferative activities on human MDA-MB-231 breast cancer cell line in MTT assays. The results indicated that these methods could be powerful tools in prediction of DTIs and drug repositioning. PMID:22589709
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Chen, Shuonan; Mar, Jessica C
2018-06-19
A fundamental fact in biology states that genes do not operate in isolation, and yet, methods that infer regulatory networks for single cell gene expression data have been slow to emerge. With single cell sequencing methods now becoming accessible, general network inference algorithms that were initially developed for data collected from bulk samples may not be suitable for single cells. Meanwhile, although methods that are specific for single cell data are now emerging, whether they have improved performance over general methods is unknown. In this study, we evaluate the applicability of five general methods and three single cell methods for inferring gene regulatory networks from both experimental single cell gene expression data and in silico simulated data. Standard evaluation metrics using ROC curves and Precision-Recall curves against reference sets sourced from the literature demonstrated that most of the methods performed poorly when they were applied to either experimental single cell data, or simulated single cell data, which demonstrates their lack of performance for this task. Using default settings, network methods were applied to the same datasets. Comparisons of the learned networks highlighted the uniqueness of some predicted edges for each method. The fact that different methods infer networks that vary substantially reflects the underlying mathematical rationale and assumptions that distinguish network methods from each other. This study provides a comprehensive evaluation of network modeling algorithms applied to experimental single cell gene expression data and in silico simulated datasets where the network structure is known. Comparisons demonstrate that most of these assessed network methods are not able to predict network structures from single cell expression data accurately, even if they are specifically developed for single cell methods. Also, single cell methods, which usually depend on more elaborative algorithms, in general have less similarity to each other in the sets of edges detected. The results from this study emphasize the importance for developing more accurate optimized network modeling methods that are compatible for single cell data. Newly-developed single cell methods may uniquely capture particular features of potential gene-gene relationships, and caution should be taken when we interpret these results.
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Inconsistencies in spontaneous and intentional trait inferences.
Ma, Ning; Vandekerckhove, Marie; Baetens, Kris; Van Overwalle, Frank; Seurinck, Ruth; Fias, Wim
2012-11-01
This study explores the fMRI correlates of observers making trait inferences about other people under conflicting social cues. Participants were presented with several behavioral descriptions involving an agent that implied a particular trait. The last behavior was either consistent or inconsistent with the previously implied trait. This was done under instructions that elicited either spontaneous trait inferences ('read carefully') or intentional trait inferences ('infer a trait'). The results revealed that when the behavioral descriptions violated earlier trait implications, regardless of instruction, the medial prefrontal cortex (mPFC) was more strongly recruited as well as the domain-general conflict network including the posterior medial frontal cortex (pmFC) and the right prefrontal cortex (rPFC). These latter two areas were more strongly activated under intentional than spontaneous instructions. These findings suggest that when trait-relevant behavioral information is inconsistent, not only is activity increased in the mentalizing network responsible for trait processing, but control is also passed to a higher level conflict monitoring network in order to detect and resolve the contradiction.
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A hybrid neural networks-fuzzy logic-genetic algorithm for grade estimation
NASA Astrophysics Data System (ADS)
Tahmasebi, Pejman; Hezarkhani, Ardeshir
2012-05-01
The grade estimation is a quite important and money/time-consuming stage in a mine project, which is considered as a challenge for the geologists and mining engineers due to the structural complexities in mineral ore deposits. To overcome this problem, several artificial intelligence techniques such as Artificial Neural Networks (ANN) and Fuzzy Logic (FL) have recently been employed with various architectures and properties. However, due to the constraints of both methods, they yield the desired results only under the specific circumstances. As an example, one major problem in FL is the difficulty of constructing the membership functions (MFs).Other problems such as architecture and local minima could also be located in ANN designing. Therefore, a new methodology is presented in this paper for grade estimation. This method which is based on ANN and FL is called "Coactive Neuro-Fuzzy Inference System" (CANFIS) which combines two approaches, ANN and FL. The combination of these two artificial intelligence approaches is achieved via the verbal and numerical power of intelligent systems. To improve the performance of this system, a Genetic Algorithm (GA) - as a well-known technique to solve the complex optimization problems - is also employed to optimize the network parameters including learning rate, momentum of the network and the number of MFs for each input. A comparison of these techniques (ANN, Adaptive Neuro-Fuzzy Inference System or ANFIS) with this new method (CANFIS-GA) is also carried out through a case study in Sungun copper deposit, located in East-Azerbaijan, Iran. The results show that CANFIS-GA could be a faster and more accurate alternative to the existing time-consuming methodologies for ore grade estimation and that is, therefore, suggested to be applied for grade estimation in similar problems.
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A hybrid neural networks-fuzzy logic-genetic algorithm for grade estimation
Tahmasebi, Pejman; Hezarkhani, Ardeshir
2012-01-01
The grade estimation is a quite important and money/time-consuming stage in a mine project, which is considered as a challenge for the geologists and mining engineers due to the structural complexities in mineral ore deposits. To overcome this problem, several artificial intelligence techniques such as Artificial Neural Networks (ANN) and Fuzzy Logic (FL) have recently been employed with various architectures and properties. However, due to the constraints of both methods, they yield the desired results only under the specific circumstances. As an example, one major problem in FL is the difficulty of constructing the membership functions (MFs).Other problems such as architecture and local minima could also be located in ANN designing. Therefore, a new methodology is presented in this paper for grade estimation. This method which is based on ANN and FL is called “Coactive Neuro-Fuzzy Inference System” (CANFIS) which combines two approaches, ANN and FL. The combination of these two artificial intelligence approaches is achieved via the verbal and numerical power of intelligent systems. To improve the performance of this system, a Genetic Algorithm (GA) – as a well-known technique to solve the complex optimization problems – is also employed to optimize the network parameters including learning rate, momentum of the network and the number of MFs for each input. A comparison of these techniques (ANN, Adaptive Neuro-Fuzzy Inference System or ANFIS) with this new method (CANFIS–GA) is also carried out through a case study in Sungun copper deposit, located in East-Azerbaijan, Iran. The results show that CANFIS–GA could be a faster and more accurate alternative to the existing time-consuming methodologies for ore grade estimation and that is, therefore, suggested to be applied for grade estimation in similar problems. PMID:25540468
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Inference of Gene Regulatory Networks Using Time-Series Data: A Survey
Sima, Chao; Hua, Jianping; Jung, Sungwon
2009-01-01
The advent of high-throughput technology like microarrays has provided the platform for studying how different cellular components work together, thus created an enormous interest in mathematically modeling biological network, particularly gene regulatory network (GRN). Of particular interest is the modeling and inference on time-series data, which capture a more thorough picture of the system than non-temporal data do. We have given an extensive review of methodologies that have been used on time-series data. In realizing that validation is an impartible part of the inference paradigm, we have also presented a discussion on the principles and challenges in performance evaluation of different methods. This survey gives a panoramic view on these topics, with anticipation that the readers will be inspired to improve and/or expand GRN inference and validation tool repository. PMID:20190956
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A New Modified Histogram Matching Normalization for Time Series Microarray Analysis
Astola, Laura; Molenaar, Jaap
2014-01-01
Microarray data is often utilized in inferring regulatory networks. Quantile normalization (QN) is a popular method to reduce array-to-array variation. We show that in the context of time series measurements QN may not be the best choice for this task, especially not if the inference is based on continuous time ODE model. We propose an alternative normalization method that is better suited for network inference from time series data. PMID:27600344
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Nonparametric Bayesian inference of the microcanonical stochastic block model
NASA Astrophysics Data System (ADS)
Peixoto, Tiago P.
2017-01-01
A principled approach to characterize the hidden modular structure of networks is to formulate generative models and then infer their parameters from data. When the desired structure is composed of modules or "communities," a suitable choice for this task is the stochastic block model (SBM), where nodes are divided into groups, and the placement of edges is conditioned on the group memberships. Here, we present a nonparametric Bayesian method to infer the modular structure of empirical networks, including the number of modules and their hierarchical organization. We focus on a microcanonical variant of the SBM, where the structure is imposed via hard constraints, i.e., the generated networks are not allowed to violate the patterns imposed by the model. We show how this simple model variation allows simultaneously for two important improvements over more traditional inference approaches: (1) deeper Bayesian hierarchies, with noninformative priors replaced by sequences of priors and hyperpriors, which not only remove limitations that seriously degrade the inference on large networks but also reveal structures at multiple scales; (2) a very efficient inference algorithm that scales well not only for networks with a large number of nodes and edges but also with an unlimited number of modules. We show also how this approach can be used to sample modular hierarchies from the posterior distribution, as well as to perform model selection. We discuss and analyze the differences between sampling from the posterior and simply finding the single parameter estimate that maximizes it. Furthermore, we expose a direct equivalence between our microcanonical approach and alternative derivations based on the canonical SBM.
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Integrating Information in Biological Ontologies and Molecular Networks to Infer Novel Terms
Li, Le; Yip, Kevin Y.
2016-01-01
Currently most terms and term-term relationships in Gene Ontology (GO) are defined manually, which creates cost, consistency and completeness issues. Recent studies have demonstrated the feasibility of inferring GO automatically from biological networks, which represents an important complementary approach to GO construction. These methods (NeXO and CliXO) are unsupervised, which means 1) they cannot use the information contained in existing GO, 2) the way they integrate biological networks may not optimize the accuracy, and 3) they are not customized to infer the three different sub-ontologies of GO. Here we present a semi-supervised method called Unicorn that extends these previous methods to tackle the three problems. Unicorn uses a sub-tree of an existing GO sub-ontology as training part to learn parameters in integrating multiple networks. Cross-validation results show that Unicorn reliably inferred the left-out parts of each specific GO sub-ontology. In addition, by training Unicorn with an old version of GO together with biological networks, it successfully re-discovered some terms and term-term relationships present only in a new version of GO. Unicorn also successfully inferred some novel terms that were not contained in GO but have biological meanings well-supported by the literature.Availability: Source code of Unicorn is available at http://yiplab.cse.cuhk.edu.hk/unicorn/. PMID:27976738
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Najafi, Shahriar; Flintsch, Gerardo W; Khaleghian, Seyedmeysam
2016-05-01
Minimizing roadway crashes and fatalities is one of the primary objectives of highway engineers, and can be achieved in part through appropriate maintenance practices. Maintaining an appropriate level of friction is a crucial maintenance practice, due to the effect it has on roadway safety. This paper presents a fuzzy logic inference system that predicts the rate of vehicle crashes based on traffic level, speed limit, and surface friction. Mamdani and Sugeno fuzzy controllers were used to develop the model. The application of the proposed fuzzy control system in a real-time slippery road warning system is demonstrated as a proof of concept. The results of this study provide a decision support model for highway agencies to monitor their network's friction and make appropriate judgments to correct deficiencies based on crash risk. Furthermore, this model can be implemented in the connected vehicle environment to warn drivers of potentially slippery locations. Published by Elsevier Ltd.
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Goyal, Ravi; De Gruttola, Victor
2018-01-30
Analysis of sexual history data intended to describe sexual networks presents many challenges arising from the fact that most surveys collect information on only a very small fraction of the population of interest. In addition, partners are rarely identified and responses are subject to reporting biases. Typically, each network statistic of interest, such as mean number of sexual partners for men or women, is estimated independently of other network statistics. There is, however, a complex relationship among networks statistics; and knowledge of these relationships can aid in addressing concerns mentioned earlier. We develop a novel method that constrains a posterior predictive distribution of a collection of network statistics in order to leverage the relationships among network statistics in making inference about network properties of interest. The method ensures that inference on network properties is compatible with an actual network. Through extensive simulation studies, we also demonstrate that use of this method can improve estimates in settings where there is uncertainty that arises both from sampling and from systematic reporting bias compared with currently available approaches to estimation. To illustrate the method, we apply it to estimate network statistics using data from the Chicago Health and Social Life Survey. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
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Mandal, Sudip; Saha, Goutam; Pal, Rajat Kumar
2017-08-01
Correct inference of genetic regulations inside a cell from the biological database like time series microarray data is one of the greatest challenges in post genomic era for biologists and researchers. Recurrent Neural Network (RNN) is one of the most popular and simple approach to model the dynamics as well as to infer correct dependencies among genes. Inspired by the behavior of social elephants, we propose a new metaheuristic namely Elephant Swarm Water Search Algorithm (ESWSA) to infer Gene Regulatory Network (GRN). This algorithm is mainly based on the water search strategy of intelligent and social elephants during drought, utilizing the different types of communication techniques. Initially, the algorithm is tested against benchmark small and medium scale artificial genetic networks without and with presence of different noise levels and the efficiency was observed in term of parametric error, minimum fitness value, execution time, accuracy of prediction of true regulation, etc. Next, the proposed algorithm is tested against the real time gene expression data of Escherichia Coli SOS Network and results were also compared with others state of the art optimization methods. The experimental results suggest that ESWSA is very efficient for GRN inference problem and performs better than other methods in many ways.
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Decision generation tools and Bayesian inference
NASA Astrophysics Data System (ADS)
Jannson, Tomasz; Wang, Wenjian; Forrester, Thomas; Kostrzewski, Andrew; Veeris, Christian; Nielsen, Thomas
2014-05-01
Digital Decision Generation (DDG) tools are important software sub-systems of Command and Control (C2) systems and technologies. In this paper, we present a special type of DDGs based on Bayesian Inference, related to adverse (hostile) networks, including such important applications as terrorism-related networks and organized crime ones.
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-02-22
...., Core Network Engineering (Deployment Engineering) Division Including Workers in the Core Network Engineering (Deployment Engineering) Division in Alpharetta, GA, Hunt Valley, MD, Naperville, IL, and St... Reconsideration applicable to workers and former workers of Goodman Networks, Inc., Core Network Engineering...
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Gerhard, Felipe; Kispersky, Tilman; Gutierrez, Gabrielle J.; Marder, Eve; Kramer, Mark; Eden, Uri
2013-01-01
Identifying the structure and dynamics of synaptic interactions between neurons is the first step to understanding neural network dynamics. The presence of synaptic connections is traditionally inferred through the use of targeted stimulation and paired recordings or by post-hoc histology. More recently, causal network inference algorithms have been proposed to deduce connectivity directly from electrophysiological signals, such as extracellularly recorded spiking activity. Usually, these algorithms have not been validated on a neurophysiological data set for which the actual circuitry is known. Recent work has shown that traditional network inference algorithms based on linear models typically fail to identify the correct coupling of a small central pattern generating circuit in the stomatogastric ganglion of the crab Cancer borealis. In this work, we show that point process models of observed spike trains can guide inference of relative connectivity estimates that match the known physiological connectivity of the central pattern generator up to a choice of threshold. We elucidate the necessary steps to derive faithful connectivity estimates from a model that incorporates the spike train nature of the data. We then apply the model to measure changes in the effective connectivity pattern in response to two pharmacological interventions, which affect both intrinsic neural dynamics and synaptic transmission. Our results provide the first successful application of a network inference algorithm to a circuit for which the actual physiological synapses between neurons are known. The point process methodology presented here generalizes well to larger networks and can describe the statistics of neural populations. In general we show that advanced statistical models allow for the characterization of effective network structure, deciphering underlying network dynamics and estimating information-processing capabilities. PMID:23874181
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Inferring metabolic networks using the Bayesian adaptive graphical lasso with informative priors.
Peterson, Christine; Vannucci, Marina; Karakas, Cemal; Choi, William; Ma, Lihua; Maletić-Savatić, Mirjana
2013-10-01
Metabolic processes are essential for cellular function and survival. We are interested in inferring a metabolic network in activated microglia, a major neuroimmune cell in the brain responsible for the neuroinflammation associated with neurological diseases, based on a set of quantified metabolites. To achieve this, we apply the Bayesian adaptive graphical lasso with informative priors that incorporate known relationships between covariates. To encourage sparsity, the Bayesian graphical lasso places double exponential priors on the off-diagonal entries of the precision matrix. The Bayesian adaptive graphical lasso allows each double exponential prior to have a unique shrinkage parameter. These shrinkage parameters share a common gamma hyperprior. We extend this model to create an informative prior structure by formulating tailored hyperpriors on the shrinkage parameters. By choosing parameter values for each hyperprior that shift probability mass toward zero for nodes that are close together in a reference network, we encourage edges between covariates with known relationships. This approach can improve the reliability of network inference when the sample size is small relative to the number of parameters to be estimated. When applied to the data on activated microglia, the inferred network includes both known relationships and associations of potential interest for further investigation.
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Inferring metabolic networks using the Bayesian adaptive graphical lasso with informative priors
PETERSON, CHRISTINE; VANNUCCI, MARINA; KARAKAS, CEMAL; CHOI, WILLIAM; MA, LIHUA; MALETIĆ-SAVATIĆ, MIRJANA
2014-01-01
Metabolic processes are essential for cellular function and survival. We are interested in inferring a metabolic network in activated microglia, a major neuroimmune cell in the brain responsible for the neuroinflammation associated with neurological diseases, based on a set of quantified metabolites. To achieve this, we apply the Bayesian adaptive graphical lasso with informative priors that incorporate known relationships between covariates. To encourage sparsity, the Bayesian graphical lasso places double exponential priors on the off-diagonal entries of the precision matrix. The Bayesian adaptive graphical lasso allows each double exponential prior to have a unique shrinkage parameter. These shrinkage parameters share a common gamma hyperprior. We extend this model to create an informative prior structure by formulating tailored hyperpriors on the shrinkage parameters. By choosing parameter values for each hyperprior that shift probability mass toward zero for nodes that are close together in a reference network, we encourage edges between covariates with known relationships. This approach can improve the reliability of network inference when the sample size is small relative to the number of parameters to be estimated. When applied to the data on activated microglia, the inferred network includes both known relationships and associations of potential interest for further investigation. PMID:24533172
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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.
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Learning Probabilistic Inference through Spike-Timing-Dependent Plasticity.
Pecevski, Dejan; Maass, Wolfgang
2016-01-01
Numerous experimental data show that the brain is able to extract information from complex, uncertain, and often ambiguous experiences. Furthermore, it can use such learnt information for decision making through probabilistic inference. Several models have been proposed that aim at explaining how probabilistic inference could be performed by networks of neurons in the brain. We propose here a model that can also explain how such neural network could acquire the necessary information for that from examples. We show that spike-timing-dependent plasticity in combination with intrinsic plasticity generates in ensembles of pyramidal cells with lateral inhibition a fundamental building block for that: probabilistic associations between neurons that represent through their firing current values of random variables. Furthermore, by combining such adaptive network motifs in a recursive manner the resulting network is enabled to extract statistical information from complex input streams, and to build an internal model for the distribution p (*) that generates the examples it receives. This holds even if p (*) contains higher-order moments. The analysis of this learning process is supported by a rigorous theoretical foundation. Furthermore, we show that the network can use the learnt internal model immediately for prediction, decision making, and other types of probabilistic inference.
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Learning Probabilistic Inference through Spike-Timing-Dependent Plasticity123
Pecevski, Dejan
2016-01-01
Abstract Numerous experimental data show that the brain is able to extract information from complex, uncertain, and often ambiguous experiences. Furthermore, it can use such learnt information for decision making through probabilistic inference. Several models have been proposed that aim at explaining how probabilistic inference could be performed by networks of neurons in the brain. We propose here a model that can also explain how such neural network could acquire the necessary information for that from examples. We show that spike-timing-dependent plasticity in combination with intrinsic plasticity generates in ensembles of pyramidal cells with lateral inhibition a fundamental building block for that: probabilistic associations between neurons that represent through their firing current values of random variables. Furthermore, by combining such adaptive network motifs in a recursive manner the resulting network is enabled to extract statistical information from complex input streams, and to build an internal model for the distribution p* that generates the examples it receives. This holds even if p* contains higher-order moments. The analysis of this learning process is supported by a rigorous theoretical foundation. Furthermore, we show that the network can use the learnt internal model immediately for prediction, decision making, and other types of probabilistic inference. PMID:27419214
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Inferring network structure from cascades.
Ghonge, Sushrut; Vural, Dervis Can
2017-07-01
Many physical, biological, and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we offer three topological methods to infer the structure of any directed network given a set of cascade arrival times. Our formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for several different cascade models.
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Inferring network structure from cascades
NASA Astrophysics Data System (ADS)
Ghonge, Sushrut; Vural, Dervis Can
2017-07-01
Many physical, biological, and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we offer three topological methods to infer the structure of any directed network given a set of cascade arrival times. Our formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for several different cascade models.
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Witoonchart, Peerajak; Chongstitvatana, Prabhas
2017-08-01
In this study, for the first time, we show how to formulate a structured support vector machine (SSVM) as two layers in a convolutional neural network, where the top layer is a loss augmented inference layer and the bottom layer is the normal convolutional layer. We show that a deformable part model can be learned with the proposed structured SVM neural network by backpropagating the error of the deformable part model to the convolutional neural network. The forward propagation calculates the loss augmented inference and the backpropagation calculates the gradient from the loss augmented inference layer to the convolutional layer. Thus, we obtain a new type of convolutional neural network called an Structured SVM convolutional neural network, which we applied to the human pose estimation problem. This new neural network can be used as the final layers in deep learning. Our method jointly learns the structural model parameters and the appearance model parameters. We implemented our method as a new layer in the existing Caffe library. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Metabolic Network Modeling of Microbial Interactions in Natural and Engineered Environmental Systems
Perez-Garcia, Octavio; Lear, Gavin; Singhal, Naresh
2016-01-01
We review approaches to characterize metabolic interactions within microbial communities using Stoichiometric Metabolic Network (SMN) models for applications in environmental and industrial biotechnology. SMN models are computational tools used to evaluate the metabolic engineering potential of various organisms. They have successfully been applied to design and optimize the microbial production of antibiotics, alcohols and amino acids by single strains. To date however, such models have been rarely applied to analyze and control the metabolism of more complex microbial communities. This is largely attributed to the diversity of microbial community functions, metabolisms, and interactions. Here, we firstly review different types of microbial interaction and describe their relevance for natural and engineered environmental processes. Next, we provide a general description of the essential methods of the SMN modeling workflow including the steps of network reconstruction, simulation through Flux Balance Analysis (FBA), experimental data gathering, and model calibration. Then we broadly describe and compare four approaches to model microbial interactions using metabolic networks, i.e., (i) lumped networks, (ii) compartment per guild networks, (iii) bi-level optimization simulations, and (iv) dynamic-SMN methods. These approaches can be used to integrate and analyze diverse microbial physiology, ecology and molecular community data. All of them (except the lumped approach) are suitable for incorporating species abundance data but so far they have been used only to model simple communities of two to eight different species. Interactions based on substrate exchange and competition can be directly modeled using the above approaches. However, interactions based on metabolic feedbacks, such as product inhibition and synthropy require extensions to current models, incorporating gene regulation and compounding accumulation mechanisms. SMN models of microbial interactions can be used to analyze complex “omics” data and to infer and optimize metabolic processes. Thereby, SMN models are suitable to capitalize on advances in high-throughput molecular and metabolic data generation. SMN models are starting to be applied to describe microbial interactions during wastewater treatment, in-situ bioremediation, microalgae blooms methanogenic fermentation, and bioplastic production. Despite their current challenges, we envisage that SMN models have future potential for the design and development of novel growth media, biochemical pathways and synthetic microbial associations. PMID:27242701
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Harnessing Diversity towards the Reconstructing of Large Scale Gene Regulatory Networks
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
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Network Model-Assisted Inference from Respondent-Driven Sampling Data
Gile, Krista J.; Handcock, Mark S.
2015-01-01
Summary Respondent-Driven Sampling is a widely-used method for sampling hard-to-reach human populations by link-tracing over their social networks. Inference from such data requires specialized techniques because the sampling process is both partially beyond the control of the researcher, and partially implicitly defined. Therefore, it is not generally possible to directly compute the sampling weights for traditional design-based inference, and likelihood inference requires modeling the complex sampling process. As an alternative, we introduce a model-assisted approach, resulting in a design-based estimator leveraging a working network model. We derive a new class of estimators for population means and a corresponding bootstrap standard error estimator. We demonstrate improved performance compared to existing estimators, including adjustment for an initial convenience sample. We also apply the method and an extension to the estimation of HIV prevalence in a high-risk population. PMID:26640328
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Network Model-Assisted Inference from Respondent-Driven Sampling Data.
Gile, Krista J; Handcock, Mark S
2015-06-01
Respondent-Driven Sampling is a widely-used method for sampling hard-to-reach human populations by link-tracing over their social networks. Inference from such data requires specialized techniques because the sampling process is both partially beyond the control of the researcher, and partially implicitly defined. Therefore, it is not generally possible to directly compute the sampling weights for traditional design-based inference, and likelihood inference requires modeling the complex sampling process. As an alternative, we introduce a model-assisted approach, resulting in a design-based estimator leveraging a working network model. We derive a new class of estimators for population means and a corresponding bootstrap standard error estimator. We demonstrate improved performance compared to existing estimators, including adjustment for an initial convenience sample. We also apply the method and an extension to the estimation of HIV prevalence in a high-risk population.
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Metabolic PathFinding: inferring relevant pathways in biochemical networks.
Croes, Didier; Couche, Fabian; Wodak, Shoshana J; van Helden, Jacques
2005-07-01
Our knowledge of metabolism can be represented as a network comprising several thousands of nodes (compounds and reactions). Several groups applied graph theory to analyse the topological properties of this network and to infer metabolic pathways by path finding. This is, however, not straightforward, with a major problem caused by traversing irrelevant shortcuts through highly connected nodes, which correspond to pool metabolites and co-factors (e.g. H2O, NADP and H+). In this study, we present a web server implementing two simple approaches, which circumvent this problem, thereby improving the relevance of the inferred pathways. In the simplest approach, the shortest path is computed, while filtering out the selection of highly connected compounds. In the second approach, the shortest path is computed on the weighted metabolic graph where each compound is assigned a weight equal to its connectivity in the network. This approach significantly increases the accuracy of the inferred pathways, enabling the correct inference of relatively long pathways (e.g. with as many as eight intermediate reactions). Available options include the calculation of the k-shortest paths between two specified seed nodes (either compounds or reactions). Multiple requests can be submitted in a queue. Results are returned by email, in textual as well as graphical formats (available in http://www.scmbb.ulb.ac.be/pathfinding/).
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INfORM: Inference of NetwOrk Response Modules.
Marwah, Veer Singh; Kinaret, Pia Anneli Sofia; Serra, Angela; Scala, Giovanni; Lauerma, Antti; Fortino, Vittorio; Greco, Dario
2018-06-15
Detecting and interpreting responsive modules from gene expression data by using network-based approaches is a common but laborious task. It often requires the application of several computational methods implemented in different software packages, forcing biologists to compile complex analytical pipelines. Here we introduce INfORM (Inference of NetwOrk Response Modules), an R shiny application that enables non-expert users to detect, evaluate and select gene modules with high statistical and biological significance. INfORM is a comprehensive tool for the identification of biologically meaningful response modules from consensus gene networks inferred by using multiple algorithms. It is accessible through an intuitive graphical user interface allowing for a level of abstraction from the computational steps. INfORM is freely available for academic use at https://github.com/Greco-Lab/INfORM. Supplementary data are available at Bioinformatics online.
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Prophetic Granger Causality to infer gene regulatory networks.
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.
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Prophetic Granger Causality to infer gene regulatory networks
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
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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
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Probabilistic inference in discrete spaces can be implemented into networks of LIF neurons.
Probst, Dimitri; Petrovici, Mihai A; Bytschok, Ilja; Bill, Johannes; Pecevski, Dejan; Schemmel, Johannes; Meier, Karlheinz
2015-01-01
The means by which cortical neural networks are able to efficiently solve inference problems remains an open question in computational neuroscience. Recently, abstract models of Bayesian computation in neural circuits have been proposed, but they lack a mechanistic interpretation at the single-cell level. In this article, we describe a complete theoretical framework for building networks of leaky integrate-and-fire neurons that can sample from arbitrary probability distributions over binary random variables. We test our framework for a model inference task based on a psychophysical phenomenon (the Knill-Kersten optical illusion) and further assess its performance when applied to randomly generated distributions. As the local computations performed by the network strongly depend on the interaction between neurons, we compare several types of couplings mediated by either single synapses or interneuron chains. Due to its robustness to substrate imperfections such as parameter noise and background noise correlations, our model is particularly interesting for implementation on novel, neuro-inspired computing architectures, which can thereby serve as a fast, low-power substrate for solving real-world inference problems.
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Probabilistic inference in discrete spaces can be implemented into networks of LIF neurons
Probst, Dimitri; Petrovici, Mihai A.; Bytschok, Ilja; Bill, Johannes; Pecevski, Dejan; Schemmel, Johannes; Meier, Karlheinz
2015-01-01
The means by which cortical neural networks are able to efficiently solve inference problems remains an open question in computational neuroscience. Recently, abstract models of Bayesian computation in neural circuits have been proposed, but they lack a mechanistic interpretation at the single-cell level. In this article, we describe a complete theoretical framework for building networks of leaky integrate-and-fire neurons that can sample from arbitrary probability distributions over binary random variables. We test our framework for a model inference task based on a psychophysical phenomenon (the Knill-Kersten optical illusion) and further assess its performance when applied to randomly generated distributions. As the local computations performed by the network strongly depend on the interaction between neurons, we compare several types of couplings mediated by either single synapses or interneuron chains. Due to its robustness to substrate imperfections such as parameter noise and background noise correlations, our model is particularly interesting for implementation on novel, neuro-inspired computing architectures, which can thereby serve as a fast, low-power substrate for solving real-world inference problems. PMID:25729361
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Process-driven inference of biological network structure: feasibility, minimality, and multiplicity
NASA Astrophysics Data System (ADS)
Zeng, Chen
2012-02-01
For a given dynamic process, identifying the putative interaction networks to achieve it is the inference problem. In this talk, we address the computational complexity of inference problem in the context of Boolean networks under dominant inhibition condition. The first is a proof that the feasibility problem (is there a network that explains the dynamics?) can be solved in polynomial-time. Second, while the minimality problem (what is the smallest network that explains the dynamics?) is shown to be NP-hard, a simple polynomial-time heuristic is shown to produce near-minimal solutions, as demonstrated by simulation. Third, the theoretical framework also leads to a fast polynomial-time heuristic to estimate the number of network solutions with reasonable accuracy. We will apply these approaches to two simplified Boolean network models for the cell cycle process of budding yeast (Li 2004) and fission yeast (Davidich 2008). Our results demonstrate that each of these networks contains a giant backbone motif spanning all the network nodes that provides the desired main functionality, while the remaining edges in the network form smaller motifs whose role is to confer stability properties rather than provide function. Moreover, we show that the bioprocesses of these two cell cycle models differ considerably from a typically generated process and are intrinsically cascade-like.
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Reservoir characterization using core, well log, and seismic data and intelligent software
NASA Astrophysics Data System (ADS)
Soto Becerra, Rodolfo
We have developed intelligent software, Oilfield Intelligence (OI), as an engineering tool to improve the characterization of oil and gas reservoirs. OI integrates neural networks and multivariate statistical analysis. It is composed of five main subsystems: data input, preprocessing, architecture design, graphics design, and inference engine modules. More than 1,200 lines of programming code as M-files using the language MATLAB been written. The degree of success of many oil and gas drilling, completion, and production activities depends upon the accuracy of the models used in a reservoir description. Neural networks have been applied for identification of nonlinear systems in almost all scientific fields of humankind. Solving reservoir characterization problems is no exception. Neural networks have a number of attractive features that can help to extract and recognize underlying patterns, structures, and relationships among data. However, before developing a neural network model, we must solve the problem of dimensionality such as determining dominant and irrelevant variables. We can apply principal components and factor analysis to reduce the dimensionality and help the neural networks formulate more realistic models. We validated OI by obtaining confident models in three different oil field problems: (1) A neural network in-situ stress model using lithology and gamma ray logs for the Travis Peak formation of east Texas, (2) A neural network permeability model using porosity and gamma ray and a neural network pseudo-gamma ray log model using 3D seismic attributes for the reservoir VLE 196 Lamar field located in Block V of south-central Lake Maracaibo (Venezuela), and (3) Neural network primary ultimate oil recovery (PRUR), initial waterflooding ultimate oil recovery (IWUR), and infill drilling ultimate oil recovery (IDUR) models using reservoir parameters for San Andres and Clearfork carbonate formations in west Texas. In all cases, we compared the results from the neural network models with the results from regression statistical and non-parametric approach models. The results show that it is possible to obtain the highest cross-correlation coefficient between predicted and actual target variables, and the lowest average absolute errors using the integrated techniques of multivariate statistical analysis and neural networks in our intelligent software.
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Protein Inference from the Integration of Tandem MS Data and Interactome Networks.
Zhong, Jiancheng; Wang, Jianxing; Ding, Xiaojun; Zhang, Zhen; Li, Min; Wu, Fang-Xiang; Pan, Yi
2017-01-01
Since proteins are digested into a mixture of peptides in the preprocessing step of tandem mass spectrometry (MS), it is difficult to determine which specific protein a shared peptide belongs to. In recent studies, besides tandem MS data and peptide identification information, some other information is exploited to infer proteins. Different from the methods which first use only tandem MS data to infer proteins and then use network information to refine them, this study proposes a protein inference method named TMSIN, which uses interactome networks directly. As two interacting proteins should co-exist, it is reasonable to assume that if one of the interacting proteins is confidently inferred in a sample, its interacting partners should have a high probability in the same sample, too. Therefore, we can use the neighborhood information of a protein in an interactome network to adjust the probability that the shared peptide belongs to the protein. In TMSIN, a multi-weighted graph is constructed by incorporating the bipartite graph with interactome network information, where the bipartite graph is built with the peptide identification information. Based on multi-weighted graphs, TMSIN adopts an iterative workflow to infer proteins. At each iterative step, the probability that a shared peptide belongs to a specific protein is calculated by using the Bayes' law based on the neighbor protein support scores of each protein which are mapped by the shared peptides. We carried out experiments on yeast data and human data to evaluate the performance of TMSIN in terms of ROC, q-value, and accuracy. The experimental results show that AUC scores yielded by TMSIN are 0.742 and 0.874 in yeast dataset and human dataset, respectively, and TMSIN yields the maximum number of true positives when q-value less than or equal to 0.05. The overlap analysis shows that TMSIN is an effective complementary approach for protein inference.
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Kim, Dongchul; Kang, Mingon; Biswas, Ashis; Liu, Chunyu; Gao, Jean
2016-08-10
Inferring gene regulatory networks is one of the most interesting research areas in the systems biology. Many inference methods have been developed by using a variety of computational models and approaches. However, there are two issues to solve. First, depending on the structural or computational model of inference method, the results tend to be inconsistent due to innately different advantages and limitations of the methods. Therefore the combination of dissimilar approaches is demanded as an alternative way in order to overcome the limitations of standalone methods through complementary integration. Second, sparse linear regression that is penalized by the regularization parameter (lasso) and bootstrapping-based sparse linear regression methods were suggested in state of the art methods for network inference but they are not effective for a small sample size data and also a true regulator could be missed if the target gene is strongly affected by an indirect regulator with high correlation or another true regulator. We present two novel network inference methods based on the integration of three different criteria, (i) z-score to measure the variation of gene expression from knockout data, (ii) mutual information for the dependency between two genes, and (iii) linear regression-based feature selection. Based on these criterion, we propose a lasso-based random feature selection algorithm (LARF) to achieve better performance overcoming the limitations of bootstrapping as mentioned above. In this work, there are three main contributions. First, our z score-based method to measure gene expression variations from knockout data is more effective than similar criteria of related works. Second, we confirmed that the true regulator selection can be effectively improved by LARF. Lastly, we verified that an integrative approach can clearly outperform a single method when two different methods are effectively jointed. In the experiments, our methods were validated by outperforming the state of the art methods on DREAM challenge data, and then LARF was applied to inferences of gene regulatory network associated with psychiatric disorders.
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Personalized microbial network inference via co-regularized spectral clustering.
Imangaliyev, Sultan; Keijser, Bart; Crielaard, Wim; Tsivtsivadze, Evgeni
2015-07-15
We use Human Microbiome Project (HMP) cohort (Peterson et al., 2009) to infer personalized oral microbial networks of healthy individuals. To determine clustering of individuals with similar microbial profiles, co-regularized spectral clustering algorithm is applied to the dataset. For each cluster we discovered, we compute co-occurrence relationships among the microbial species that determine microbial network per cluster of individuals. The results of our study suggest that there are several differences in microbial interactions on personalized network level in healthy oral samples acquired from various niches. Based on the results of co-regularized spectral clustering we discover two groups of individuals with different topology of their microbial interaction network. The results of microbial network inference suggest that niche-wise interactions are different in these two groups. Our study shows that healthy individuals have different microbial clusters according to their oral microbiota. Such personalized microbial networks open a better understanding of the microbial ecology of healthy oral cavities and new possibilities for future targeted medication. The scripts written in scientific Python and in Matlab, which were used for network visualization, are provided for download on the website http://learning-machines.com/. Copyright © 2015 Elsevier Inc. All rights reserved.
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Active learning of cortical connectivity from two-photon imaging data.
Bertrán, Martín A; Martínez, Natalia L; Wang, Ye; Dunson, David; Sapiro, Guillermo; Ringach, Dario
2018-01-01
Understanding how groups of neurons interact within a network is a fundamental question in system neuroscience. Instead of passively observing the ongoing activity of a network, we can typically perturb its activity, either by external sensory stimulation or directly via techniques such as two-photon optogenetics. A natural question is how to use such perturbations to identify the connectivity of the network efficiently. Here we introduce a method to infer sparse connectivity graphs from in-vivo, two-photon imaging of population activity in response to external stimuli. A novel aspect of the work is the introduction of a recommended distribution, incrementally learned from the data, to optimally refine the inferred network. Unlike existing system identification techniques, this "active learning" method automatically focuses its attention on key undiscovered areas of the network, instead of targeting global uncertainty indicators like parameter variance. We show how active learning leads to faster inference while, at the same time, provides confidence intervals for the network parameters. We present simulations on artificial small-world networks to validate the methods and apply the method to real data. Analysis of frequency of motifs recovered show that cortical networks are consistent with a small-world topology model.
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Active learning of cortical connectivity from two-photon imaging data
Wang, Ye; Dunson, David; Sapiro, Guillermo; Ringach, Dario
2018-01-01
Understanding how groups of neurons interact within a network is a fundamental question in system neuroscience. Instead of passively observing the ongoing activity of a network, we can typically perturb its activity, either by external sensory stimulation or directly via techniques such as two-photon optogenetics. A natural question is how to use such perturbations to identify the connectivity of the network efficiently. Here we introduce a method to infer sparse connectivity graphs from in-vivo, two-photon imaging of population activity in response to external stimuli. A novel aspect of the work is the introduction of a recommended distribution, incrementally learned from the data, to optimally refine the inferred network. Unlike existing system identification techniques, this “active learning” method automatically focuses its attention on key undiscovered areas of the network, instead of targeting global uncertainty indicators like parameter variance. We show how active learning leads to faster inference while, at the same time, provides confidence intervals for the network parameters. We present simulations on artificial small-world networks to validate the methods and apply the method to real data. Analysis of frequency of motifs recovered show that cortical networks are consistent with a small-world topology model. PMID:29718955
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Spiking neuron network Helmholtz machine.
Sountsov, Pavel; Miller, Paul
2015-01-01
An increasing amount of behavioral and neurophysiological data suggests that the brain performs optimal (or near-optimal) probabilistic inference and learning during perception and other tasks. Although many machine learning algorithms exist that perform inference and learning in an optimal way, the complete description of how one of those algorithms (or a novel algorithm) can be implemented in the brain is currently incomplete. There have been many proposed solutions that address how neurons can perform optimal inference but the question of how synaptic plasticity can implement optimal learning is rarely addressed. This paper aims to unify the two fields of probabilistic inference and synaptic plasticity by using a neuronal network of realistic model spiking neurons to implement a well-studied computational model called the Helmholtz Machine. The Helmholtz Machine is amenable to neural implementation as the algorithm it uses to learn its parameters, called the wake-sleep algorithm, uses a local delta learning rule. Our spiking-neuron network implements both the delta rule and a small example of a Helmholtz machine. This neuronal network can learn an internal model of continuous-valued training data sets without supervision. The network can also perform inference on the learned internal models. We show how various biophysical features of the neural implementation constrain the parameters of the wake-sleep algorithm, such as the duration of the wake and sleep phases of learning and the minimal sample duration. We examine the deviations from optimal performance and tie them to the properties of the synaptic plasticity rule.
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Spiking neuron network Helmholtz machine
Sountsov, Pavel; Miller, Paul
2015-01-01
An increasing amount of behavioral and neurophysiological data suggests that the brain performs optimal (or near-optimal) probabilistic inference and learning during perception and other tasks. Although many machine learning algorithms exist that perform inference and learning in an optimal way, the complete description of how one of those algorithms (or a novel algorithm) can be implemented in the brain is currently incomplete. There have been many proposed solutions that address how neurons can perform optimal inference but the question of how synaptic plasticity can implement optimal learning is rarely addressed. This paper aims to unify the two fields of probabilistic inference and synaptic plasticity by using a neuronal network of realistic model spiking neurons to implement a well-studied computational model called the Helmholtz Machine. The Helmholtz Machine is amenable to neural implementation as the algorithm it uses to learn its parameters, called the wake-sleep algorithm, uses a local delta learning rule. Our spiking-neuron network implements both the delta rule and a small example of a Helmholtz machine. This neuronal network can learn an internal model of continuous-valued training data sets without supervision. The network can also perform inference on the learned internal models. We show how various biophysical features of the neural implementation constrain the parameters of the wake-sleep algorithm, such as the duration of the wake and sleep phases of learning and the minimal sample duration. We examine the deviations from optimal performance and tie them to the properties of the synaptic plasticity rule. PMID:25954191
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NASA Astrophysics Data System (ADS)
Cabral, Mariza Castanheira De Moura Da Costa
In the fifty-two years since Robert Horton's 1945 pioneering quantitative description of channel network planform (or plan view morphology), no conclusive findings have been presented that permit inference of geomorphological processes from any measures of network planform. All measures of network planform studied exhibit limited geographic variability across different environments. Horton (1945), Langbein et al. (1947), Schumm (1956), Hack (1957), Melton (1958), and Gray (1961) established various "laws" of network planform, that is, statistical relationships between different variables which have limited variability. A wide variety of models which have been proposed to simulate the growth of channel networks in time over a landsurface are generally also in agreement with the above planform laws. An explanation is proposed for the generality of the channel network planform laws. Channel networks must be space filling, that is, they must extend over the landscape to drain every hillslope, leaving no large undrained areas, and with no crossing of channels, often achieving a roughly uniform drainage density in a given environment. It is shown that the space-filling constraint can reduce the sensitivity of planform variables to different network growth models, and it is proposed that this constraint may determine the planform laws. The "Q model" of network growth of Van Pelt and Verwer (1985) is used to generate samples of networks. Sensitivity to the model parameter Q is markedly reduced when the networks generated are required to be space filling. For a wide variety of Q values, the space-filling networks are in approximate agreement with the various channel network planform laws. Additional constraints, including of energy efficiency, were not studied but may further reduce the variability of planform laws. Inference of model parameter Q from network topology is successful only in networks not subject to spatial constraints. In space-filling networks, for a wide range of Q values, the maximal-likelihood Q parameter value is generally in the vicinity of 1/2, which yields topological randomness. It is proposed that space filling originates the appearance of randomness in channel network topology, and may cause difficulties to geomorphological inference from network planform.
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Optimal design of gene knockout experiments for gene regulatory network inference
Ud-Dean, S. M. Minhaz; Gunawan, Rudiyanto
2016-01-01
Motivation: We addressed the problem of inferring gene regulatory network (GRN) from gene expression data of knockout (KO) experiments. This inference is known to be underdetermined and the GRN is not identifiable from data. Past studies have shown that suboptimal design of experiments (DOE) contributes significantly to the identifiability issue of biological networks, including GRNs. However, optimizing DOE has received much less attention than developing methods for GRN inference. Results: We developed REDuction of UnCertain Edges (REDUCE) algorithm for finding the optimal gene KO experiment for inferring directed graphs (digraphs) of GRNs. REDUCE employed ensemble inference to define uncertain gene interactions that could not be verified by prior data. The optimal experiment corresponds to the maximum number of uncertain interactions that could be verified by the resulting data. For this purpose, we introduced the concept of edge separatoid which gave a list of nodes (genes) that upon their removal would allow the verification of a particular gene interaction. Finally, we proposed a procedure that iterates over performing KO experiments, ensemble update and optimal DOE. The case studies including the inference of Escherichia coli GRN and DREAM 4 100-gene GRNs, demonstrated the efficacy of the iterative GRN inference. In comparison to systematic KOs, REDUCE could provide much higher information return per gene KO experiment and consequently more accurate GRN estimates. Conclusions: REDUCE represents an enabling tool for tackling the underdetermined GRN inference. Along with advances in gene deletion and automation technology, the iterative procedure brings an efficient and fully automated GRN inference closer to reality. Availability and implementation: MATLAB and Python scripts of REDUCE are available on www.cabsel.ethz.ch/tools/REDUCE. Contact: rudi.gunawan@chem.ethz.ch Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26568633
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A Machine Learning Approach to Predict Gene Regulatory Networks in Seed Development in Arabidopsis
Ni, Ying; Aghamirzaie, Delasa; Elmarakeby, Haitham; Collakova, Eva; Li, Song; Grene, Ruth; Heath, Lenwood S.
2016-01-01
Gene regulatory networks (GRNs) provide a representation of relationships between regulators and their target genes. Several methods for GRN inference, both unsupervised and supervised, have been developed to date. Because regulatory relationships consistently reprogram in diverse tissues or under different conditions, GRNs inferred without specific biological contexts are of limited applicability. In this report, a machine learning approach is presented to predict GRNs specific to developing Arabidopsis thaliana embryos. We developed the Beacon GRN inference tool to predict GRNs occurring during seed development in Arabidopsis based on a support vector machine (SVM) model. We developed both global and local inference models and compared their performance, demonstrating that local models are generally superior for our application. Using both the expression levels of the genes expressed in developing embryos and prior known regulatory relationships, GRNs were predicted for specific embryonic developmental stages. The targets that are strongly positively correlated with their regulators are mostly expressed at the beginning of seed development. Potential direct targets were identified based on a match between the promoter regions of these inferred targets and the cis elements recognized by specific regulators. Our analysis also provides evidence for previously unknown inhibitory effects of three positive regulators of gene expression. The Beacon GRN inference tool provides a valuable model system for context-specific GRN inference and is freely available at https://github.com/BeaconProjectAtVirginiaTech/beacon_network_inference.git. PMID:28066488
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Gene expression complex networks: synthesis, identification, and analysis.
Lopes, Fabrício M; Cesar, Roberto M; Costa, Luciano Da F
2011-10-01
Thanks to recent advances in molecular biology, allied to an ever increasing amount of experimental data, the functional state of thousands of genes can now be extracted simultaneously by using methods such as cDNA microarrays and RNA-Seq. Particularly important related investigations are the modeling and identification of gene regulatory networks from expression data sets. Such a knowledge is fundamental for many applications, such as disease treatment, therapeutic intervention strategies and drugs design, as well as for planning high-throughput new experiments. Methods have been developed for gene networks modeling and identification from expression profiles. However, an important open problem regards how to validate such approaches and its results. This work presents an objective approach for validation of gene network modeling and identification which comprises the following three main aspects: (1) Artificial Gene Networks (AGNs) model generation through theoretical models of complex networks, which is used to simulate temporal expression data; (2) a computational method for gene network identification from the simulated data, which is founded on a feature selection approach where a target gene is fixed and the expression profile is observed for all other genes in order to identify a relevant subset of predictors; and (3) validation of the identified AGN-based network through comparison with the original network. The proposed framework allows several types of AGNs to be generated and used in order to simulate temporal expression data. The results of the network identification method can then be compared to the original network in order to estimate its properties and accuracy. Some of the most important theoretical models of complex networks have been assessed: the uniformly-random Erdös-Rényi (ER), the small-world Watts-Strogatz (WS), the scale-free Barabási-Albert (BA), and geographical networks (GG). The experimental results indicate that the inference method was sensitive to average degree
variation, decreasing its network recovery rate with the increase of . The signal size was important for the inference method to get better accuracy in the network identification rate, presenting very good results with small expression profiles. However, the adopted inference method was not sensible to recognize distinct structures of interaction among genes, presenting a similar behavior when applied to different network topologies. In summary, the proposed framework, though simple, was adequate for the validation of the inferred networks by identifying some properties of the evaluated method, which can be extended to other inference methods. -
Zarrabi, Narges; Prosperi, Mattia; Belleman, Robert G; Colafigli, Manuela; De Luca, Andrea; Sloot, Peter M A
2012-01-01
Inferring disease transmission networks is important in epidemiology in order to understand and prevent the spread of infectious diseases. Reconstruction of the infection transmission networks requires insight into viral genome data as well as social interactions. For the HIV-1 epidemic, current research either uses genetic information of patients' virus to infer the past infection events or uses statistics of sexual interactions to model the network structure of viral spreading. Methods for a reliable reconstruction of HIV-1 transmission dynamics, taking into account both molecular and societal data are still lacking. The aim of this study is to combine information from both genetic and epidemiological scales to characterize and analyse a transmission network of the HIV-1 epidemic in central Italy.We introduce a novel filter-reduction method to build a network of HIV infected patients based on their social and treatment information. The network is then combined with a genetic network, to infer a hypothetical infection transmission network. We apply this method to a cohort study of HIV-1 infected patients in central Italy and find that patients who are highly connected in the network have longer untreated infection periods. We also find that the network structures for homosexual males and heterosexual populations are heterogeneous, consisting of a majority of 'peripheral nodes' that have only a few sexual interactions and a minority of 'hub nodes' that have many sexual interactions. Inferring HIV-1 transmission networks using this novel combined approach reveals remarkable correlations between high out-degree individuals and longer untreated infection periods. These findings signify the importance of early treatment and support the potential benefit of wide population screening, management of early diagnoses and anticipated antiretroviral treatment to prevent viral transmission and spread. The approach presented here for reconstructing HIV-1 transmission networks can have important repercussions in the design of intervention strategies for disease control.
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Macrostructure from Microstructure: Generating Whole Systems from Ego Networks
Smith, Jeffrey A.
2014-01-01
This paper presents a new simulation method to make global network inference from sampled data. The proposed simulation method takes sampled ego network data and uses Exponential Random Graph Models (ERGM) to reconstruct the features of the true, unknown network. After describing the method, the paper presents two validity checks of the approach: the first uses the 20 largest Add Health networks while the second uses the Sociology Coauthorship network in the 1990's. For each test, I take random ego network samples from the known networks and use my method to make global network inference. I find that my method successfully reproduces the properties of the networks, such as distance and main component size. The results also suggest that simpler, baseline models provide considerably worse estimates for most network properties. I end the paper by discussing the bounds/limitations of ego network sampling. I also discuss possible extensions to the proposed approach. PMID:25339783
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NASA Technical Reports Server (NTRS)
Hayashi, Isao; Nomura, Hiroyoshi; Wakami, Noboru
1991-01-01
Whereas conventional fuzzy reasonings are associated with tuning problems, which are lack of membership functions and inference rule designs, a neural network driven fuzzy reasoning (NDF) capable of determining membership functions by neural network is formulated. In the antecedent parts of the neural network driven fuzzy reasoning, the optimum membership function is determined by a neural network, while in the consequent parts, an amount of control for each rule is determined by other plural neural networks. By introducing an algorithm of neural network driven fuzzy reasoning, inference rules for making a pendulum stand up from its lowest suspended point are determined for verifying the usefulness of the algorithm.
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Automatic physical inference with information maximizing neural networks
NASA Astrophysics Data System (ADS)
Charnock, Tom; Lavaux, Guilhem; Wandelt, Benjamin D.
2018-04-01
Compressing large data sets to a manageable number of summaries that are informative about the underlying parameters vastly simplifies both frequentist and Bayesian inference. When only simulations are available, these summaries are typically chosen heuristically, so they may inadvertently miss important information. We introduce a simulation-based machine learning technique that trains artificial neural networks to find nonlinear functionals of data that maximize Fisher information: information maximizing neural networks (IMNNs). In test cases where the posterior can be derived exactly, likelihood-free inference based on automatically derived IMNN summaries produces nearly exact posteriors, showing that these summaries are good approximations to sufficient statistics. In a series of numerical examples of increasing complexity and astrophysical relevance we show that IMNNs are robustly capable of automatically finding optimal, nonlinear summaries of the data even in cases where linear compression fails: inferring the variance of Gaussian signal in the presence of noise, inferring cosmological parameters from mock simulations of the Lyman-α forest in quasar spectra, and inferring frequency-domain parameters from LISA-like detections of gravitational waveforms. In this final case, the IMNN summary outperforms linear data compression by avoiding the introduction of spurious likelihood maxima. We anticipate that the automatic physical inference method described in this paper will be essential to obtain both accurate and precise cosmological parameter estimates from complex and large astronomical data sets, including those from LSST and Euclid.
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NASA Technical Reports Server (NTRS)
Wu, Cathy; Taylor, Pam; Whitson, George; Smith, Cathy
1990-01-01
This paper describes the building of a corn disease diagnostic expert system using CLIPS, and the development of a neural expert system using the fact representation method of CLIPS for automated knowledge acquisition. The CLIPS corn expert system diagnoses 21 diseases from 52 symptoms and signs with certainty factors. CLIPS has several unique features. It allows the facts in rules to be broken down to object-attribute-value (OAV) triples, allows rule-grouping, and fires rules based on pattern-matching. These features combined with the chained inference engine result to a natural user query system and speedy execution. In order to develop a method for automated knowledge acquisition, an Artificial Neural Expert System (ANES) is developed by a direct mapping from the CLIPS system. The ANES corn expert system uses the same OAV triples in the CLIPS system for its facts. The LHS and RHS facts of the CLIPS rules are mapped into the input and output layers of the ANES, respectively; and the inference engine of the rules is imbedded in the hidden layer. The fact representation by OAC triples gives a natural grouping of the rules. These features allow the ANES system to automate rule-generation, and make it efficient to execute and easy to expand for a large and complex domain.
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Hosseini, Seyed Abolfazl; Esmaili Paeen Afrakoti, Iman
2018-01-17
The purpose of the present study was to reconstruct the energy spectrum of a poly-energetic neutron source using an algorithm developed based on an Adaptive Neuro-Fuzzy Inference System (ANFIS). ANFIS is a kind of artificial neural network based on the Takagi-Sugeno fuzzy inference system. The ANFIS algorithm uses the advantages of both fuzzy inference systems and artificial neural networks to improve the effectiveness of algorithms in various applications such as modeling, control and classification. The neutron pulse height distributions used as input data in the training procedure for the ANFIS algorithm were obtained from the simulations performed by MCNPX-ESUT computational code (MCNPX-Energy engineering of Sharif University of Technology). Taking into account the normalization condition of each energy spectrum, 4300 neutron energy spectra were generated randomly. (The value in each bin was generated randomly, and finally a normalization of each generated energy spectrum was performed). The randomly generated neutron energy spectra were considered as output data of the developed ANFIS computational code in the training step. To calculate the neutron energy spectrum using conventional methods, an inverse problem with an approximately singular response matrix (with the determinant of the matrix close to zero) should be solved. The solution of the inverse problem using the conventional methods unfold neutron energy spectrum with low accuracy. Application of the iterative algorithms in the solution of such a problem, or utilizing the intelligent algorithms (in which there is no need to solve the problem), is usually preferred for unfolding of the energy spectrum. Therefore, the main reason for development of intelligent algorithms like ANFIS for unfolding of neutron energy spectra is to avoid solving the inverse problem. In the present study, the unfolded neutron energy spectra of 252Cf and 241Am-9Be neutron sources using the developed computational code were found to have excellent agreement with the reference data. Also, the unfolded energy spectra of the neutron sources as obtained using ANFIS were more accurate than the results reported from calculations performed using artificial neural networks in previously published papers. © The Author(s) 2018. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.
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Hybrid regulatory models: a statistically tractable approach to model regulatory network dynamics.
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.
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Quantum Enhanced Inference in Markov Logic Networks
NASA Astrophysics Data System (ADS)
Wittek, Peter; Gogolin, Christian
2017-04-01
Markov logic networks (MLNs) reconcile two opposing schools in machine learning and artificial intelligence: causal networks, which account for uncertainty extremely well, and first-order logic, which allows for formal deduction. An MLN is essentially a first-order logic template to generate Markov networks. Inference in MLNs is probabilistic and it is often performed by approximate methods such as Markov chain Monte Carlo (MCMC) Gibbs sampling. An MLN has many regular, symmetric structures that can be exploited at both first-order level and in the generated Markov network. We analyze the graph structures that are produced by various lifting methods and investigate the extent to which quantum protocols can be used to speed up Gibbs sampling with state preparation and measurement schemes. We review different such approaches, discuss their advantages, theoretical limitations, and their appeal to implementations. We find that a straightforward application of a recent result yields exponential speedup compared to classical heuristics in approximate probabilistic inference, thereby demonstrating another example where advanced quantum resources can potentially prove useful in machine learning.
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Development of neural network techniques for finger-vein pattern classification
NASA Astrophysics Data System (ADS)
Wu, Jian-Da; Liu, Chiung-Tsiung; Tsai, Yi-Jang; Liu, Jun-Ching; Chang, Ya-Wen
2010-02-01
A personal identification system using finger-vein patterns and neural network techniques is proposed in the present study. In the proposed system, the finger-vein patterns are captured by a device that can transmit near infrared through the finger and record the patterns for signal analysis and classification. The biometric system for verification consists of a combination of feature extraction using principal component analysis and pattern classification using both back-propagation network and adaptive neuro-fuzzy inference systems. Finger-vein features are first extracted by principal component analysis method to reduce the computational burden and removes noise residing in the discarded dimensions. The features are then used in pattern classification and identification. To verify the effect of the proposed adaptive neuro-fuzzy inference system in the pattern classification, the back-propagation network is compared with the proposed system. The experimental results indicated the proposed system using adaptive neuro-fuzzy inference system demonstrated a better performance than the back-propagation network for personal identification using the finger-vein patterns.
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Quantum Enhanced Inference in Markov Logic Networks.
Wittek, Peter; Gogolin, Christian
2017-04-19
Markov logic networks (MLNs) reconcile two opposing schools in machine learning and artificial intelligence: causal networks, which account for uncertainty extremely well, and first-order logic, which allows for formal deduction. An MLN is essentially a first-order logic template to generate Markov networks. Inference in MLNs is probabilistic and it is often performed by approximate methods such as Markov chain Monte Carlo (MCMC) Gibbs sampling. An MLN has many regular, symmetric structures that can be exploited at both first-order level and in the generated Markov network. We analyze the graph structures that are produced by various lifting methods and investigate the extent to which quantum protocols can be used to speed up Gibbs sampling with state preparation and measurement schemes. We review different such approaches, discuss their advantages, theoretical limitations, and their appeal to implementations. We find that a straightforward application of a recent result yields exponential speedup compared to classical heuristics in approximate probabilistic inference, thereby demonstrating another example where advanced quantum resources can potentially prove useful in machine learning.
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Quantum Enhanced Inference in Markov Logic Networks
Wittek, Peter; Gogolin, Christian
2017-01-01
Markov logic networks (MLNs) reconcile two opposing schools in machine learning and artificial intelligence: causal networks, which account for uncertainty extremely well, and first-order logic, which allows for formal deduction. An MLN is essentially a first-order logic template to generate Markov networks. Inference in MLNs is probabilistic and it is often performed by approximate methods such as Markov chain Monte Carlo (MCMC) Gibbs sampling. An MLN has many regular, symmetric structures that can be exploited at both first-order level and in the generated Markov network. We analyze the graph structures that are produced by various lifting methods and investigate the extent to which quantum protocols can be used to speed up Gibbs sampling with state preparation and measurement schemes. We review different such approaches, discuss their advantages, theoretical limitations, and their appeal to implementations. We find that a straightforward application of a recent result yields exponential speedup compared to classical heuristics in approximate probabilistic inference, thereby demonstrating another example where advanced quantum resources can potentially prove useful in machine learning. PMID:28422093
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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.
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Reverse engineering the gap gene network of Drosophila melanogaster.
Perkins, Theodore J; Jaeger, Johannes; Reinitz, John; Glass, Leon
2006-05-01
A fundamental problem in functional genomics is to determine the structure and dynamics of genetic networks based on expression data. We describe a new strategy for solving this problem and apply it to recently published data on early Drosophila melanogaster development. Our method is orders of magnitude faster than current fitting methods and allows us to fit different types of rules for expressing regulatory relationships. Specifically, we use our approach to fit models using a smooth nonlinear formalism for modeling gene regulation (gene circuits) as well as models using logical rules based on activation and repression thresholds for transcription factors. Our technique also allows us to infer regulatory relationships de novo or to test network structures suggested by the literature. We fit a series of models to test several outstanding questions about gap gene regulation, including regulation of and by hunchback and the role of autoactivation. Based on our modeling results and validation against the experimental literature, we propose a revised network structure for the gap gene system. Interestingly, some relationships in standard textbook models of gap gene regulation appear to be unnecessary for or even inconsistent with the details of gap gene expression during wild-type development.
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Sass, Steffen; Pitea, Adriana; Unger, Kristian; Hess, Julia; Mueller, Nikola S.; Theis, Fabian J.
2015-01-01
MicroRNAs represent ~22 nt long endogenous small RNA molecules that have been experimentally shown to regulate gene expression post-transcriptionally. One main interest in miRNA research is the investigation of their functional roles, which can typically be accomplished by identification of mi-/mRNA interactions and functional annotation of target gene sets. We here present a novel method “miRlastic”, which infers miRNA-target interactions using transcriptomic data as well as prior knowledge and performs functional annotation of target genes by exploiting the local structure of the inferred network. For the network inference, we applied linear regression modeling with elastic net regularization on matched microRNA and messenger RNA expression profiling data to perform feature selection on prior knowledge from sequence-based target prediction resources. The novelty of miRlastic inference originates in predicting data-driven intra-transcriptome regulatory relationships through feature selection. With synthetic data, we showed that miRlastic outperformed commonly used methods and was suitable even for low sample sizes. To gain insight into the functional role of miRNAs and to determine joint functional properties of miRNA clusters, we introduced a local enrichment analysis procedure. The principle of this procedure lies in identifying regions of high functional similarity by evaluating the shortest paths between genes in the network. We can finally assign functional roles to the miRNAs by taking their regulatory relationships into account. We thoroughly evaluated miRlastic on a cohort of head and neck cancer (HNSCC) patients provided by The Cancer Genome Atlas. We inferred an mi-/mRNA regulatory network for human papilloma virus (HPV)-associated miRNAs in HNSCC. The resulting network best enriched for experimentally validated miRNA-target interaction, when compared to common methods. Finally, the local enrichment step identified two functional clusters of miRNAs that were predicted to mediate HPV-associated dysregulation in HNSCC. Our novel approach was able to characterize distinct pathway regulations from matched miRNA and mRNA data. An R package of miRlastic was made available through: http://icb.helmholtz-muenchen.de/mirlastic. PMID:26694379
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Sass, Steffen; Pitea, Adriana; Unger, Kristian; Hess, Julia; Mueller, Nikola S; Theis, Fabian J
2015-12-18
MicroRNAs represent ~22 nt long endogenous small RNA molecules that have been experimentally shown to regulate gene expression post-transcriptionally. One main interest in miRNA research is the investigation of their functional roles, which can typically be accomplished by identification of mi-/mRNA interactions and functional annotation of target gene sets. We here present a novel method "miRlastic", which infers miRNA-target interactions using transcriptomic data as well as prior knowledge and performs functional annotation of target genes by exploiting the local structure of the inferred network. For the network inference, we applied linear regression modeling with elastic net regularization on matched microRNA and messenger RNA expression profiling data to perform feature selection on prior knowledge from sequence-based target prediction resources. The novelty of miRlastic inference originates in predicting data-driven intra-transcriptome regulatory relationships through feature selection. With synthetic data, we showed that miRlastic outperformed commonly used methods and was suitable even for low sample sizes. To gain insight into the functional role of miRNAs and to determine joint functional properties of miRNA clusters, we introduced a local enrichment analysis procedure. The principle of this procedure lies in identifying regions of high functional similarity by evaluating the shortest paths between genes in the network. We can finally assign functional roles to the miRNAs by taking their regulatory relationships into account. We thoroughly evaluated miRlastic on a cohort of head and neck cancer (HNSCC) patients provided by The Cancer Genome Atlas. We inferred an mi-/mRNA regulatory network for human papilloma virus (HPV)-associated miRNAs in HNSCC. The resulting network best enriched for experimentally validated miRNA-target interaction, when compared to common methods. Finally, the local enrichment step identified two functional clusters of miRNAs that were predicted to mediate HPV-associated dysregulation in HNSCC. Our novel approach was able to characterize distinct pathway regulations from matched miRNA and mRNA data. An R package of miRlastic was made available through: http://icb.helmholtz-muenchen.de/mirlastic.
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Assessing dynamics, spatial scale, and uncertainty in task-related brain network analyses
Stephen, Emily P.; Lepage, Kyle Q.; Eden, Uri T.; Brunner, Peter; Schalk, Gerwin; Brumberg, Jonathan S.; Guenther, Frank H.; Kramer, Mark A.
2014-01-01
The brain is a complex network of interconnected elements, whose interactions evolve dynamically in time to cooperatively perform specific functions. A common technique to probe these interactions involves multi-sensor recordings of brain activity during a repeated task. Many techniques exist to characterize the resulting task-related activity, including establishing functional networks, which represent the statistical associations between brain areas. Although functional network inference is commonly employed to analyze neural time series data, techniques to assess the uncertainty—both in the functional network edges and the corresponding aggregate measures of network topology—are lacking. To address this, we describe a statistically principled approach for computing uncertainty in functional networks and aggregate network measures in task-related data. The approach is based on a resampling procedure that utilizes the trial structure common in experimental recordings. We show in simulations that this approach successfully identifies functional networks and associated measures of confidence emergent during a task in a variety of scenarios, including dynamically evolving networks. In addition, we describe a principled technique for establishing functional networks based on predetermined regions of interest using canonical correlation. Doing so provides additional robustness to the functional network inference. Finally, we illustrate the use of these methods on example invasive brain voltage recordings collected during an overt speech task. The general strategy described here—appropriate for static and dynamic network inference and different statistical measures of coupling—permits the evaluation of confidence in network measures in a variety of settings common to neuroscience. PMID:24678295
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Assessing dynamics, spatial scale, and uncertainty in task-related brain network analyses.
Stephen, Emily P; Lepage, Kyle Q; Eden, Uri T; Brunner, Peter; Schalk, Gerwin; Brumberg, Jonathan S; Guenther, Frank H; Kramer, Mark A
2014-01-01
The brain is a complex network of interconnected elements, whose interactions evolve dynamically in time to cooperatively perform specific functions. A common technique to probe these interactions involves multi-sensor recordings of brain activity during a repeated task. Many techniques exist to characterize the resulting task-related activity, including establishing functional networks, which represent the statistical associations between brain areas. Although functional network inference is commonly employed to analyze neural time series data, techniques to assess the uncertainty-both in the functional network edges and the corresponding aggregate measures of network topology-are lacking. To address this, we describe a statistically principled approach for computing uncertainty in functional networks and aggregate network measures in task-related data. The approach is based on a resampling procedure that utilizes the trial structure common in experimental recordings. We show in simulations that this approach successfully identifies functional networks and associated measures of confidence emergent during a task in a variety of scenarios, including dynamically evolving networks. In addition, we describe a principled technique for establishing functional networks based on predetermined regions of interest using canonical correlation. Doing so provides additional robustness to the functional network inference. Finally, we illustrate the use of these methods on example invasive brain voltage recordings collected during an overt speech task. The general strategy described here-appropriate for static and dynamic network inference and different statistical measures of coupling-permits the evaluation of confidence in network measures in a variety of settings common to neuroscience.
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Network portal: a database for storage, analysis and visualization of biological networks
Turkarslan, Serdar; Wurtmann, Elisabeth J.; Wu, Wei-Ju; Jiang, Ning; Bare, J. Christopher; Foley, Karen; Reiss, David J.; Novichkov, Pavel; Baliga, Nitin S.
2014-01-01
The ease of generating high-throughput data has enabled investigations into organismal complexity at the systems level through the inference of networks of interactions among the various cellular components (genes, RNAs, proteins and metabolites). The wider scientific community, however, currently has limited access to tools for network inference, visualization and analysis because these tasks often require advanced computational knowledge and expensive computing resources. We have designed the network portal (http://networks.systemsbiology.net) to serve as a modular database for the integration of user uploaded and public data, with inference algorithms and tools for the storage, visualization and analysis of biological networks. The portal is fully integrated into the Gaggle framework to seamlessly exchange data with desktop and web applications and to allow the user to create, save and modify workspaces, and it includes social networking capabilities for collaborative projects. While the current release of the database contains networks for 13 prokaryotic organisms from diverse phylogenetic clades (4678 co-regulated gene modules, 3466 regulators and 9291 cis-regulatory motifs), it will be rapidly populated with prokaryotic and eukaryotic organisms as relevant data become available in public repositories and through user input. The modular architecture, simple data formats and open API support community development of the portal. PMID:24271392
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Cytoprophet: a Cytoscape plug-in for protein and domain interaction networks inference.
Morcos, Faruck; Lamanna, Charles; Sikora, Marcin; Izaguirre, Jesús
2008-10-01
Cytoprophet is a software tool that allows prediction and visualization of protein and domain interaction networks. It is implemented as a plug-in of Cytoscape, an open source software framework for analysis and visualization of molecular networks. Cytoprophet implements three algorithms that predict new potential physical interactions using the domain composition of proteins and experimental assays. The algorithms for protein and domain interaction inference include maximum likelihood estimation (MLE) using expectation maximization (EM); the set cover approach maximum specificity set cover (MSSC) and the sum-product algorithm (SPA). After accepting an input set of proteins with Uniprot ID/Accession numbers and a selected prediction algorithm, Cytoprophet draws a network of potential interactions with probability scores and GO distances as edge attributes. A network of domain interactions between the domains of the initial protein list can also be generated. Cytoprophet was designed to take advantage of the visual capabilities of Cytoscape and be simple to use. An example of inference in a signaling network of myxobacterium Myxococcus xanthus is presented and available at Cytoprophet's website. http://cytoprophet.cse.nd.edu.
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Monteiro, Antónia
2012-03-01
Co-option of the eye developmental gene regulatory network may have led to the appearance of novel functional traits on the wings of flies and butterflies. The first trait is a recently described wing organ in a species of extinct midge resembling the outer layers of the midge's own compound eye. The second trait is red pigment patches on Heliconius butterfly wings connected to the expression of an eye selector gene, optix. These examples, as well as others, are discussed regarding the type of empirical evidence and burden of proof that have been used to infer gene network co-option underlying the origin of novel traits. A conceptual framework describing increasing confidence in inference of network co-option is proposed. Novel research directions to facilitate inference of network co-option are also highlighted, especially in cases where the pre-existent and novel traits do not resemble each other. Copyright © 2012 WILEY Periodicals, Inc.
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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.
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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.
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Reinforce: An Ensemble Approach for Inferring PPI Network from AP-MS Data.
Tian, Bo; Duan, Qiong; Zhao, Can; Teng, Ben; He, Zengyou
2017-05-17
Affinity Purification-Mass Spectrometry (AP-MS) is one of the most important technologies for constructing protein-protein interaction (PPI) networks. In this paper, we propose an ensemble method, Reinforce, for inferring PPI network from AP-MS data set. The new algorithm named Reinforce is based on rank aggregation and false discovery rate control. Under the null hypothesis that the interaction scores from different scoring methods are randomly generated, Reinforce follows three steps to integrate multiple ranking results from different algorithms or different data sets. The experimental results show that Reinforce can get more stable and accurate inference results than existing algorithms. The source codes of Reinforce and data sets used in the experiments are available at: https://sourceforge.net/projects/reinforce/.
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Memristor-Based Analog Computation and Neural Network Classification with a Dot Product Engine.
Hu, Miao; Graves, Catherine E; Li, Can; Li, Yunning; Ge, Ning; Montgomery, Eric; Davila, Noraica; Jiang, Hao; Williams, R Stanley; Yang, J Joshua; Xia, Qiangfei; Strachan, John Paul
2018-03-01
Using memristor crossbar arrays to accelerate computations is a promising approach to efficiently implement algorithms in deep neural networks. Early demonstrations, however, are limited to simulations or small-scale problems primarily due to materials and device challenges that limit the size of the memristor crossbar arrays that can be reliably programmed to stable and analog values, which is the focus of the current work. High-precision analog tuning and control of memristor cells across a 128 × 64 array is demonstrated, and the resulting vector matrix multiplication (VMM) computing precision is evaluated. Single-layer neural network inference is performed in these arrays, and the performance compared to a digital approach is assessed. Memristor computing system used here reaches a VMM accuracy equivalent of 6 bits, and an 89.9% recognition accuracy is achieved for the 10k MNIST handwritten digit test set. Forecasts show that with integrated (on chip) and scaled memristors, a computational efficiency greater than 100 trillion operations per second per Watt is possible. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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D-score: a search engine independent MD-score.
Vaudel, Marc; Breiter, Daniela; Beck, Florian; Rahnenführer, Jörg; Martens, Lennart; Zahedi, René P
2013-03-01
While peptides carrying PTMs are routinely identified in gel-free MS, the localization of the PTMs onto the peptide sequences remains challenging. Search engine scores of secondary peptide matches have been used in different approaches in order to infer the quality of site inference, by penalizing the localization whenever the search engine similarly scored two candidate peptides with different site assignments. In the present work, we show how the estimation of posterior error probabilities for peptide candidates allows the estimation of a PTM score called the D-score, for multiple search engine studies. We demonstrate the applicability of this score to three popular search engines: Mascot, OMSSA, and X!Tandem, and evaluate its performance using an already published high resolution data set of synthetic phosphopeptides. For those peptides with phosphorylation site inference uncertainty, the number of spectrum matches with correctly localized phosphorylation increased by up to 25.7% when compared to using Mascot alone, although the actual increase depended on the fragmentation method used. Since this method relies only on search engine scores, it can be readily applied to the scoring of the localization of virtually any modification at no additional experimental or in silico cost. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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NASA Astrophysics Data System (ADS)
Guruprasad, R.; Behera, B. K.
2015-10-01
Quantitative prediction of fabric mechanical properties is an essential requirement for design engineering of textile and apparel products. In this work, the possibility of prediction of bending rigidity of cotton woven fabrics has been explored with the application of Artificial Neural Network (ANN) and two hybrid methodologies, namely Neuro-genetic modeling and Adaptive Neuro-Fuzzy Inference System (ANFIS) modeling. For this purpose, a set of cotton woven grey fabrics was desized, scoured and relaxed. The fabrics were then conditioned and tested for bending properties. With the database thus created, a neural network model was first developed using back propagation as the learning algorithm. The second model was developed by applying a hybrid learning strategy, in which genetic algorithm was first used as a learning algorithm to optimize the number of neurons and connection weights of the neural network. The Genetic algorithm optimized network structure was further allowed to learn using back propagation algorithm. In the third model, an ANFIS modeling approach was attempted to map the input-output data. The prediction performances of the models were compared and a sensitivity analysis was reported. The results show that the prediction by neuro-genetic and ANFIS models were better in comparison with that of back propagation neural network model.
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A Legal Negotiatiton Support System Based on A Diagram
NASA Astrophysics Data System (ADS)
Nitta, Katsumi; Shibasaki, Masato; Yasumura, Yoshiaki; Hasegawa, Ryuzo; Fujita, Hiroshi; Koshimura, Miyuki; Inoue, Katsumi; Shirai, Yasuyuki; Komatsu, Hiroshi
We present an overview of a legal negotiation support system, ANS (Argumentation based Negotiation support System). ANS consists of a user interface, three inference engines, a database of old cases, and two decision support modules. The ANS users negotiates or disputes with others via a computer network. The negotiation status is managed in the form of the negotiation diagram. The negotiation diagram is an extension of Toulmin’s argument diagram, and it contains all arguments insisted by participants. The negotiation protocols are defined as operations to the negotiation diagram. By exchanging counter arguments each other, the negotiation diagram grows up. Nonmonotonic reasoning using rule priorities are applied to the negotiation diagram.
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Strain engineering of the silicon-vacancy center in diamond
NASA Astrophysics Data System (ADS)
Meesala, Srujan; Sohn, Young-Ik; Pingault, Benjamin; Shao, Linbo; Atikian, Haig A.; Holzgrafe, Jeffrey; Gündoǧan, Mustafa; Stavrakas, Camille; Sipahigil, Alp; Chia, Cleaven; Evans, Ruffin; Burek, Michael J.; Zhang, Mian; Wu, Lue; Pacheco, Jose L.; Abraham, John; Bielejec, Edward; Lukin, Mikhail D.; Atatüre, Mete; Lončar, Marko
2018-05-01
We control the electronic structure of the silicon-vacancy (SiV) color-center in diamond by changing its static strain environment with a nano-electro-mechanical system. This allows deterministic and local tuning of SiV optical and spin transition frequencies over a wide range, an essential step towards multiqubit networks. In the process, we infer the strain Hamiltonian of the SiV revealing large strain susceptibilities of order 1 PHz/strain for the electronic orbital states. We identify regimes where the spin-orbit interaction results in a large strain susceptibility of order 100 THz/strain for spin transitions, and propose an experiment where the SiV spin is strongly coupled to a nanomechanical resonator.
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Effective network inference through multivariate information transfer estimation
NASA Astrophysics Data System (ADS)
Dahlqvist, Carl-Henrik; Gnabo, Jean-Yves
2018-06-01
Network representation has steadily gained in popularity over the past decades. In many disciplines such as finance, genetics, neuroscience or human travel to cite a few, the network may not directly be observable and needs to be inferred from time-series data, leading to the issue of separating direct interactions between two entities forming the network from indirect interactions coming through its remaining part. Drawing on recent contributions proposing strategies to deal with this problem such as the so-called "global silencing" approach of Barzel and Barabasi or "network deconvolution" of Feizi et al. (2013), we propose a novel methodology to infer an effective network structure from multivariate conditional information transfers. Its core principal is to test the information transfer between two nodes through a step-wise approach by conditioning the transfer for each pair on a specific set of relevant nodes as identified by our algorithm from the rest of the network. The methodology is model free and can be applied to high-dimensional networks with both inter-lag and intra-lag relationships. It outperforms state-of-the-art approaches for eliminating the redundancies and more generally retrieving simulated artificial networks in our Monte-Carlo experiments. We apply the method to stock market data at different frequencies (15 min, 1 h, 1 day) to retrieve the network of US largest financial institutions and then document how bank's centrality measurements relate to bank's systemic vulnerability.
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Schmidt, Helmut; Petkov, George; Richardson, Mark P; Terry, John R
2014-11-01
Graph theory has evolved into a useful tool for studying complex brain networks inferred from a variety of measures of neural activity, including fMRI, DTI, MEG and EEG. In the study of neurological disorders, recent work has discovered differences in the structure of graphs inferred from patient and control cohorts. However, most of these studies pursue a purely observational approach; identifying correlations between properties of graphs and the cohort which they describe, without consideration of the underlying mechanisms. To move beyond this necessitates the development of computational modeling approaches to appropriately interpret network interactions and the alterations in brain dynamics they permit, which in the field of complexity sciences is known as dynamics on networks. In this study we describe the development and application of this framework using modular networks of Kuramoto oscillators. We use this framework to understand functional networks inferred from resting state EEG recordings of a cohort of 35 adults with heterogeneous idiopathic generalized epilepsies and 40 healthy adult controls. Taking emergent synchrony across the global network as a proxy for seizures, our study finds that the critical strength of coupling required to synchronize the global network is significantly decreased for the epilepsy cohort for functional networks inferred from both theta (3-6 Hz) and low-alpha (6-9 Hz) bands. We further identify left frontal regions as a potential driver of seizure activity within these networks. We also explore the ability of our method to identify individuals with epilepsy, observing up to 80% predictive power through use of receiver operating characteristic analysis. Collectively these findings demonstrate that a computer model based analysis of routine clinical EEG provides significant additional information beyond standard clinical interpretation, which should ultimately enable a more appropriate mechanistic stratification of people with epilepsy leading to improved diagnostics and therapeutics.
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Gene Regulatory Network Inferences Using a Maximum-Relevance and Maximum-Significance Strategy
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
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On the inherent competition between valid and spurious inductive inferences in Boolean data
NASA Astrophysics Data System (ADS)
Andrecut, M.
Inductive inference is the process of extracting general rules from specific observations. This problem also arises in the analysis of biological networks, such as genetic regulatory networks, where the interactions are complex and the observations are incomplete. A typical task in these problems is to extract general interaction rules as combinations of Boolean covariates, that explain a measured response variable. The inductive inference process can be considered as an incompletely specified Boolean function synthesis problem. This incompleteness of the problem will also generate spurious inferences, which are a serious threat to valid inductive inference rules. Using random Boolean data as a null model, here we attempt to measure the competition between valid and spurious inductive inference rules from a given data set. We formulate two greedy search algorithms, which synthesize a given Boolean response variable in a sparse disjunct normal form, and respectively a sparse generalized algebraic normal form of the variables from the observation data, and we evaluate numerically their performance.
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Data-driven reconstruction of directed networks
NASA Astrophysics Data System (ADS)
Hempel, Sabrina; Koseska, Aneta; Nikoloski, Zoran
2013-06-01
We investigate the properties of a recently introduced asymmetric association measure, called inner composition alignment (IOTA), aimed at inferring regulatory links (couplings). We show that the measure can be used to determine the direction of coupling, detect superfluous links, and to account for autoregulation. In addition, the measure can be extended to infer the type of regulation (positive or negative). The capabilities of IOTA to correctly infer couplings together with their directionality are compared against Kendall's rank correlation for time series of different lengths, particularly focussing on biological examples. We demonstrate that an extended version of the measure, bidirectional inner composition alignment (biIOTA), increases the accuracy of the network reconstruction for short time series. Finally, we discuss the applicability of the measure to infer couplings in chaotic systems.
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Emissions of methane in Europe inferred by total column measurements
NASA Astrophysics Data System (ADS)
Wunch, D.; Deutscher, N. M.; Hase, F.; Notholt, J.; Sussmann, R.; Toon, G. C.; Warneke, T.
2017-12-01
Atmospheric total column measurements have been used to infer emissions of methane in urban centres around the world. These measurements have been shown to be useful for verifying city-scale bottom-up inventories, and they can provide both timely and sub-annual emission information. We will present our analysis of atmospheric total column measurements of methane and carbon monoxide to infer annual and seasonal regional emissions of methane within Europe using five long-running atmospheric observatories. These observatories are part of the Total Carbon Column Observing Network, part of a global network that has been carefully designed to measure these gases on a consistent scale. Our inferred emissions will then be used to evaluate gridded emissions inventories in the region.
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Reconstruction of the temporal signaling network in Salmonella-infected human cells.
Budak, Gungor; Eren Ozsoy, Oyku; Aydin Son, Yesim; Can, Tolga; Tuncbag, Nurcan
2015-01-01
Salmonella enterica is a bacterial pathogen that usually infects its host through food sources. Translocation of the pathogen proteins into the host cells leads to changes in the signaling mechanism either by activating or inhibiting the host proteins. Given that the bacterial infection modifies the response network of the host, a more coherent view of the underlying biological processes and the signaling networks can be obtained by using a network modeling approach based on the reverse engineering principles. In this work, we have used a published temporal phosphoproteomic dataset of Salmonella-infected human cells and reconstructed the temporal signaling network of the human host by integrating the interactome and the phosphoproteomic dataset. We have combined two well-established network modeling frameworks, the Prize-collecting Steiner Forest (PCSF) approach and the Integer Linear Programming (ILP) based edge inference approach. The resulting network conserves the information on temporality, direction of interactions, while revealing hidden entities in the signaling, such as the SNARE binding, mTOR signaling, immune response, cytoskeleton organization, and apoptosis pathways. Targets of the Salmonella effectors in the host cells such as CDC42, RHOA, 14-3-3δ, Syntaxin family, Oxysterol-binding proteins were included in the reconstructed signaling network although they were not present in the initial phosphoproteomic data. We believe that integrated approaches, such as the one presented here, have a high potential for the identification of clinical targets in infectious diseases, especially in the Salmonella infections.
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Ensemble stacking mitigates biases in inference of synaptic connectivity.
Chambers, Brendan; Levy, Maayan; Dechery, Joseph B; MacLean, Jason N
2018-01-01
A promising alternative to directly measuring the anatomical connections in a neuronal population is inferring the connections from the activity. We employ simulated spiking neuronal networks to compare and contrast commonly used inference methods that identify likely excitatory synaptic connections using statistical regularities in spike timing. We find that simple adjustments to standard algorithms improve inference accuracy: A signing procedure improves the power of unsigned mutual-information-based approaches and a correction that accounts for differences in mean and variance of background timing relationships, such as those expected to be induced by heterogeneous firing rates, increases the sensitivity of frequency-based methods. We also find that different inference methods reveal distinct subsets of the synaptic network and each method exhibits different biases in the accurate detection of reciprocity and local clustering. To correct for errors and biases specific to single inference algorithms, we combine methods into an ensemble. Ensemble predictions, generated as a linear combination of multiple inference algorithms, are more sensitive than the best individual measures alone, and are more faithful to ground-truth statistics of connectivity, mitigating biases specific to single inference methods. These weightings generalize across simulated datasets, emphasizing the potential for the broad utility of ensemble-based approaches.
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Wu, Shuang; Liu, Zhi-Ping; Qiu, Xing; Wu, Hulin
2014-01-01
The immune response to viral infection is regulated by an intricate network of many genes and their products. The reverse engineering of gene regulatory networks (GRNs) using mathematical models from time course gene expression data collected after influenza infection is key to our understanding of the mechanisms involved in controlling influenza infection within a host. A five-step pipeline: detection of temporally differentially expressed genes, clustering genes into co-expressed modules, identification of network structure, parameter estimate refinement, and functional enrichment analysis, is developed for reconstructing high-dimensional dynamic GRNs from genome-wide time course gene expression data. Applying the pipeline to the time course gene expression data from influenza-infected mouse lungs, we have identified 20 distinct temporal expression patterns in the differentially expressed genes and constructed a module-based dynamic network using a linear ODE model. Both intra-module and inter-module annotations and regulatory relationships of our inferred network show some interesting findings and are highly consistent with existing knowledge about the immune response in mice after influenza infection. The proposed method is a computationally efficient, data-driven pipeline bridging experimental data, mathematical modeling, and statistical analysis. The application to the influenza infection data elucidates the potentials of our pipeline in providing valuable insights into systematic modeling of complicated biological processes.
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Fine-granularity inference and estimations to network traffic for SDN.
Jiang, Dingde; Huo, Liuwei; Li, Ya
2018-01-01
An end-to-end network traffic matrix is significantly helpful for network management and for Software Defined Networks (SDN). However, the end-to-end network traffic matrix's inferences and estimations are a challenging problem. Moreover, attaining the traffic matrix in high-speed networks for SDN is a prohibitive challenge. This paper investigates how to estimate and recover the end-to-end network traffic matrix in fine time granularity from the sampled traffic traces, which is a hard inverse problem. Different from previous methods, the fractal interpolation is used to reconstruct the finer-granularity network traffic. Then, the cubic spline interpolation method is used to obtain the smooth reconstruction values. To attain an accurate the end-to-end network traffic in fine time granularity, we perform a weighted-geometric-average process for two interpolation results that are obtained. The simulation results show that our approaches are feasible and effective.
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Fine-granularity inference and estimations to network traffic for SDN
Huo, Liuwei; Li, Ya
2018-01-01
An end-to-end network traffic matrix is significantly helpful for network management and for Software Defined Networks (SDN). However, the end-to-end network traffic matrix's inferences and estimations are a challenging problem. Moreover, attaining the traffic matrix in high-speed networks for SDN is a prohibitive challenge. This paper investigates how to estimate and recover the end-to-end network traffic matrix in fine time granularity from the sampled traffic traces, which is a hard inverse problem. Different from previous methods, the fractal interpolation is used to reconstruct the finer-granularity network traffic. Then, the cubic spline interpolation method is used to obtain the smooth reconstruction values. To attain an accurate the end-to-end network traffic in fine time granularity, we perform a weighted-geometric-average process for two interpolation results that are obtained. The simulation results show that our approaches are feasible and effective. PMID:29718913
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NASA Astrophysics Data System (ADS)
Chang, Hsien-Cheng
Two novel synergistic systems consisting of artificial neural networks and fuzzy inference systems are developed to determine geophysical properties by using well log data. These systems are employed to improve the determination accuracy in carbonate rocks, which are generally more complex than siliciclastic rocks. One system, consisting of a single adaptive resonance theory (ART) neural network and three fuzzy inference systems (FISs), is used to determine the permeability category. The other system, which is composed of three ART neural networks and a single FIS, is employed to determine the lithofacies. The geophysical properties studied in this research, permeability category and lithofacies, are treated as categorical data. The permeability values are transformed into a "permeability category" to account for the effects of scale differences between core analyses and well logs, and heterogeneity in the carbonate rocks. The ART neural networks dynamically cluster the input data sets into different groups. The FIS is used to incorporate geologic experts' knowledge, which is usually in linguistic forms, into systems. These synergistic systems thus provide viable alternative solutions to overcome the effects of heterogeneity, the uncertainties of carbonate rock depositional environments, and the scarcity of well log data. The results obtained in this research show promising improvements over backpropagation neural networks. For the permeability category, the prediction accuracies are 68.4% and 62.8% for the multiple-single ART neural network-FIS and a single backpropagation neural network, respectively. For lithofacies, the prediction accuracies are 87.6%, 79%, and 62.8% for the single-multiple ART neural network-FIS, a single ART neural network, and a single backpropagation neural network, respectively. The sensitivity analysis results show that the multiple-single ART neural networks-FIS and a single ART neural network possess the same matching trends in determining lithofacies. This research shows that the adaptive resonance theory neural networks enable decision-makers to clearly distinguish the importance of different pieces of data which are useful in three-dimensional subsurface modeling. Geologic experts' knowledge can be easily applied and maintained by using the fuzzy inference systems.
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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 the underlying cause of emergent properties and are needed if we are to identify target genes other than those constituting the "low hanging fruit" of genomic analysis. PMID:21232107
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DMirNet: Inferring direct microRNA-mRNA association networks.
Lee, Minsu; Lee, HyungJune
2016-12-05
MicroRNAs (miRNAs) play important regulatory roles in the wide range of biological processes by inducing target mRNA degradation or translational repression. Based on the correlation between expression profiles of a miRNA and its target mRNA, various computational methods have previously been proposed to identify miRNA-mRNA association networks by incorporating the matched miRNA and mRNA expression profiles. However, there remain three major issues to be resolved in the conventional computation approaches for inferring miRNA-mRNA association networks from expression profiles. 1) Inferred correlations from the observed expression profiles using conventional correlation-based methods include numerous erroneous links or over-estimated edge weight due to the transitive information flow among direct associations. 2) Due to the high-dimension-low-sample-size problem on the microarray dataset, it is difficult to obtain an accurate and reliable estimate of the empirical correlations between all pairs of expression profiles. 3) Because the previously proposed computational methods usually suffer from varying performance across different datasets, a more reliable model that guarantees optimal or suboptimal performance across different datasets is highly needed. In this paper, we present DMirNet, a new framework for identifying direct miRNA-mRNA association networks. To tackle the aforementioned issues, DMirNet incorporates 1) three direct correlation estimation methods (namely Corpcor, SPACE, Network deconvolution) to infer direct miRNA-mRNA association networks, 2) the bootstrapping method to fully utilize insufficient training expression profiles, and 3) a rank-based Ensemble aggregation to build a reliable and robust model across different datasets. Our empirical experiments on three datasets demonstrate the combinatorial effects of necessary components in DMirNet. Additional performance comparison experiments show that DMirNet outperforms the state-of-the-art Ensemble-based model [1] which has shown the best performance across the same three datasets, with a factor of up to 1.29. Further, we identify 43 putative novel multi-cancer-related miRNA-mRNA association relationships from an inferred Top 1000 direct miRNA-mRNA association network. We believe that DMirNet is a promising method to identify novel direct miRNA-mRNA relations and to elucidate the direct miRNA-mRNA association networks. Since DMirNet infers direct relationships from the observed data, DMirNet can contribute to reconstructing various direct regulatory pathways, including, but not limited to, the direct miRNA-mRNA association networks.
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IMAGINE: Interstellar MAGnetic field INference Engine
NASA Astrophysics Data System (ADS)
Steininger, Theo
2018-03-01
IMAGINE (Interstellar MAGnetic field INference Engine) performs inference on generic parametric models of the Galaxy. The modular open source framework uses highly optimized tools and technology such as the MultiNest sampler (ascl:1109.006) and the information field theory framework NIFTy (ascl:1302.013) to create an instance of the Milky Way based on a set of parameters for physical observables, using Bayesian statistics to judge the mismatch between measured data and model prediction. The flexibility of the IMAGINE framework allows for simple refitting for newly available data sets and makes state-of-the-art Bayesian methods easily accessible particularly for random components of the Galactic magnetic field.
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Wang, Junbai; Wu, Qianqian; Hu, Xiaohua Tony; Tian, Tianhai
2016-11-01
Investigating the dynamics of genetic regulatory networks through high throughput experimental data, such as microarray gene expression profiles, is a very important but challenging task. One of the major hindrances in building detailed mathematical models for genetic regulation is the large number of unknown model parameters. To tackle this challenge, a new integrated method is proposed by combining a top-down approach and a bottom-up approach. First, the top-down approach uses probabilistic graphical models to predict the network structure of DNA repair pathway that is regulated by the p53 protein. Two networks are predicted, namely a network of eight genes with eight inferred interactions and an extended network of 21 genes with 17 interactions. Then, the bottom-up approach using differential equation models is developed to study the detailed genetic regulations based on either a fully connected regulatory network or a gene network obtained by the top-down approach. Model simulation error, parameter identifiability and robustness property are used as criteria to select the optimal network. Simulation results together with permutation tests of input gene network structures indicate that the prediction accuracy and robustness property of the two predicted networks using the top-down approach are better than those of the corresponding fully connected networks. In particular, the proposed approach reduces computational cost significantly for inferring model parameters. Overall, the new integrated method is a promising approach for investigating the dynamics of genetic regulation. Copyright © 2016 Elsevier Inc. All rights reserved.
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Dynamic Network-Based Epistasis Analysis: Boolean Examples
Azpeitia, Eugenio; Benítez, Mariana; Padilla-Longoria, Pablo; Espinosa-Soto, Carlos; Alvarez-Buylla, Elena R.
2011-01-01
In this article we focus on how the hierarchical and single-path assumptions of epistasis analysis can bias the inference of gene regulatory networks. Here we emphasize the critical importance of dynamic analyses, and specifically illustrate the use of Boolean network models. Epistasis in a broad sense refers to gene interactions, however, as originally proposed by Bateson, epistasis is defined as the blocking of a particular allelic effect due to the effect of another allele at a different locus (herein, classical epistasis). Classical epistasis analysis has proven powerful and useful, allowing researchers to infer and assign directionality to gene interactions. As larger data sets are becoming available, the analysis of classical epistasis is being complemented with computer science tools and system biology approaches. We show that when the hierarchical and single-path assumptions are not met in classical epistasis analysis, the access to relevant information and the correct inference of gene interaction topologies is hindered, and it becomes necessary to consider the temporal dynamics of gene interactions. The use of dynamical networks can overcome these limitations. We particularly focus on the use of Boolean networks that, like classical epistasis analysis, relies on logical formalisms, and hence can complement classical epistasis analysis and relax its assumptions. We develop a couple of theoretical examples and analyze them from a dynamic Boolean network model perspective. Boolean networks could help to guide additional experiments and discern among alternative regulatory schemes that would be impossible or difficult to infer without the elimination of these assumption from the classical epistasis analysis. We also use examples from the literature to show how a Boolean network-based approach has resolved ambiguities and guided epistasis analysis. Our article complements previous accounts, not only by focusing on the implications of the hierarchical and single-path assumption, but also by demonstrating the importance of considering temporal dynamics, and specifically introducing the usefulness of Boolean network models and also reviewing some key properties of network approaches. PMID:22645556
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The Importance of Statistical Modeling in Data Analysis and Inference
ERIC Educational Resources Information Center
Rollins, Derrick, Sr.
2017-01-01
Statistical inference simply means to draw a conclusion based on information that comes from data. Error bars are the most commonly used tool for data analysis and inference in chemical engineering data studies. This work demonstrates, using common types of data collection studies, the importance of specifying the statistical model for sound…
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A Coalitional Game for Distributed Inference in Sensor Networks With Dependent Observations
NASA Astrophysics Data System (ADS)
He, Hao; Varshney, Pramod K.
2016-04-01
We consider the problem of collaborative inference in a sensor network with heterogeneous and statistically dependent sensor observations. Each sensor aims to maximize its inference performance by forming a coalition with other sensors and sharing information within the coalition. It is proved that the inference performance is a nondecreasing function of the coalition size. However, in an energy constrained network, the energy consumption of inter-sensor communication also increases with increasing coalition size, which discourages the formation of the grand coalition (the set of all sensors). In this paper, the formation of non-overlapping coalitions with statistically dependent sensors is investigated under a specific communication constraint. We apply a game theoretical approach to fully explore and utilize the information contained in the spatial dependence among sensors to maximize individual sensor performance. Before formulating the distributed inference problem as a coalition formation game, we first quantify the gain and loss in forming a coalition by introducing the concepts of diversity gain and redundancy loss for both estimation and detection problems. These definitions, enabled by the statistical theory of copulas, allow us to characterize the influence of statistical dependence among sensor observations on inference performance. An iterative algorithm based on merge-and-split operations is proposed for the solution and the stability of the proposed algorithm is analyzed. Numerical results are provided to demonstrate the superiority of our proposed game theoretical approach.
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de Luis Balaguer, Maria Angels; Fisher, Adam P.; Clark, Natalie M.; Fernandez-Espinosa, Maria Guadalupe; Möller, Barbara K.; Weijers, Dolf; Williams, Cranos; Lorenzo, Oscar; Sozzani, Rosangela
2017-01-01
Identifying the transcription factors (TFs) and associated networks involved in stem cell regulation is essential for understanding the initiation and growth of plant tissues and organs. Although many TFs have been shown to have a role in the Arabidopsis root stem cells, a comprehensive view of the transcriptional signature of the stem cells is lacking. In this work, we used spatial and temporal transcriptomic data to predict interactions among the genes involved in stem cell regulation. To accomplish this, we transcriptionally profiled several stem cell populations and developed a gene regulatory network inference algorithm that combines clustering with dynamic Bayesian network inference. We leveraged the topology of our networks to infer potential major regulators. Specifically, through mathematical modeling and experimental validation, we identified PERIANTHIA (PAN) as an important molecular regulator of quiescent center function. The results presented in this work show that our combination of molecular biology, computational biology, and mathematical modeling is an efficient approach to identify candidate factors that function in the stem cells. PMID:28827319
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Model-based redesign of global transcription regulation
Carrera, Javier; Rodrigo, Guillermo; Jaramillo, Alfonso
2009-01-01
Synthetic biology aims to the design or redesign of biological systems. In particular, one possible goal could be the rewiring of the transcription regulation network by exchanging the endogenous promoters. To achieve this objective, we have adapted current methods to the inference of a model based on ordinary differential equations that is able to predict the network response after a major change in its topology. Our procedure utilizes microarray data for training. We have experimentally validated our inferred global regulatory model in Escherichia coli by predicting transcriptomic profiles under new perturbations. We have also tested our methodology in silico by providing accurate predictions of the underlying networks from expression data generated with artificial genomes. In addition, we have shown the predictive power of our methodology by obtaining the gene profile in experimental redesigns of the E. coli genome, where rewiring the transcriptional network by means of knockouts of master regulators or by upregulating transcription factors controlled by different promoters. Our approach is compatible with most network inference methods, allowing to explore computationally future genome-wide redesign experiments in synthetic biology. PMID:19188257
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Takemoto, Kazuhiro; Aie, Kazuki
2017-05-25
Host-pathogen interactions are important in a wide range of research fields. Given the importance of metabolic crosstalk between hosts and pathogens, a metabolic network-based reverse ecology method was proposed to infer these interactions. However, the validity of this method remains unclear because of the various explanations presented and the influence of potentially confounding factors that have thus far been neglected. We re-evaluated the importance of the reverse ecology method for evaluating host-pathogen interactions while statistically controlling for confounding effects using oxygen requirement, genome, metabolic network, and phylogeny data. Our data analyses showed that host-pathogen interactions were more strongly influenced by genome size, primary network parameters (e.g., number of edges), oxygen requirement, and phylogeny than the reserve ecology-based measures. These results indicate the limitations of the reverse ecology method; however, they do not discount the importance of adopting reverse ecology approaches altogether. Rather, we highlight the need for developing more suitable methods for inferring host-pathogen interactions and conducting more careful examinations of the relationships between metabolic networks and host-pathogen interactions.
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Gene regulatory network inference using fused LASSO on multiple data sets
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
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Mental Models of Invisible Logical Networks
NASA Technical Reports Server (NTRS)
Sanderson, P.
1984-01-01
Subjects were required to discover the structure of a logical network whose links were invisible. Network structure had to be inferred from the behavior of the components after a failure. It was hypothesized that since such failure diagnosis tasks often draw on spatial processes, a good deal of spatial complexity in the network should affect network discovery. Results show that the ability to discover the linkages in the network is directly related to the spatial complexity of the pathway described by the linkages. This effect was generally independent of the amount of evidence available to subjects about the existence of the link. These results raise the question of whether inferences about spatially complex pathways were simply not made, or whether they were made but not retained because of a high load on memory resources.
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Gogoshin, Grigoriy; Boerwinkle, Eric
2017-01-01
Abstract Bayesian network (BN) reconstruction is a prototypical systems biology data analysis approach that has been successfully used to reverse engineer and model networks reflecting different layers of biological organization (ranging from genetic to epigenetic to cellular pathway to metabolomic). It is especially relevant in the context of modern (ongoing and prospective) studies that generate heterogeneous high-throughput omics datasets. However, there are both theoretical and practical obstacles to the seamless application of BN modeling to such big data, including computational inefficiency of optimal BN structure search algorithms, ambiguity in data discretization, mixing data types, imputation and validation, and, in general, limited scalability in both reconstruction and visualization of BNs. To overcome these and other obstacles, we present BNOmics, an improved algorithm and software toolkit for inferring and analyzing BNs from omics datasets. BNOmics aims at comprehensive systems biology—type data exploration, including both generating new biological hypothesis and testing and validating the existing ones. Novel aspects of the algorithm center around increasing scalability and applicability to varying data types (with different explicit and implicit distributional assumptions) within the same analysis framework. An output and visualization interface to widely available graph-rendering software is also included. Three diverse applications are detailed. BNOmics was originally developed in the context of genetic epidemiology data and is being continuously optimized to keep pace with the ever-increasing inflow of available large-scale omics datasets. As such, the software scalability and usability on the less than exotic computer hardware are a priority, as well as the applicability of the algorithm and software to the heterogeneous datasets containing many data types—single-nucleotide polymorphisms and other genetic/epigenetic/transcriptome variables, metabolite levels, epidemiological variables, endpoints, and phenotypes, etc. PMID:27681505
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Lidar detection of underwater objects using a neuro-SVM-based architecture.
Mitra, Vikramjit; Wang, Chia-Jiu; Banerjee, Satarupa
2006-05-01
This paper presents a neural network architecture using a support vector machine (SVM) as an inference engine (IE) for classification of light detection and ranging (Lidar) data. Lidar data gives a sequence of laser backscatter intensities obtained from laser shots generated from an airborne object at various altitudes above the earth surface. Lidar data is pre-filtered to remove high frequency noise. As the Lidar shots are taken from above the earth surface, it has some air backscatter information, which is of no importance for detecting underwater objects. Because of these, the air backscatter information is eliminated from the data and a segment of this data is subsequently selected to extract features for classification. This is then encoded using linear predictive coding (LPC) and polynomial approximation. The coefficients thus generated are used as inputs to the two branches of a parallel neural architecture. The decisions obtained from the two branches are vector multiplied and the result is fed to an SVM-based IE that presents the final inference. Two parallel neural architectures using multilayer perception (MLP) and hybrid radial basis function (HRBF) are considered in this paper. The proposed structure fits the Lidar data classification task well due to the inherent classification efficiency of neural networks and accurate decision-making capability of SVM. A Bayesian classifier and a quadratic classifier were considered for the Lidar data classification task but they failed to offer high prediction accuracy. Furthermore, a single-layered artificial neural network (ANN) classifier was also considered and it failed to offer good accuracy. The parallel ANN architecture proposed in this paper offers high prediction accuracy (98.9%) and is found to be the most suitable architecture for the proposed task of Lidar data classification.
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Gogoshin, Grigoriy; Boerwinkle, Eric; Rodin, Andrei S
2017-04-01
Bayesian network (BN) reconstruction is a prototypical systems biology data analysis approach that has been successfully used to reverse engineer and model networks reflecting different layers of biological organization (ranging from genetic to epigenetic to cellular pathway to metabolomic). It is especially relevant in the context of modern (ongoing and prospective) studies that generate heterogeneous high-throughput omics datasets. However, there are both theoretical and practical obstacles to the seamless application of BN modeling to such big data, including computational inefficiency of optimal BN structure search algorithms, ambiguity in data discretization, mixing data types, imputation and validation, and, in general, limited scalability in both reconstruction and visualization of BNs. To overcome these and other obstacles, we present BNOmics, an improved algorithm and software toolkit for inferring and analyzing BNs from omics datasets. BNOmics aims at comprehensive systems biology-type data exploration, including both generating new biological hypothesis and testing and validating the existing ones. Novel aspects of the algorithm center around increasing scalability and applicability to varying data types (with different explicit and implicit distributional assumptions) within the same analysis framework. An output and visualization interface to widely available graph-rendering software is also included. Three diverse applications are detailed. BNOmics was originally developed in the context of genetic epidemiology data and is being continuously optimized to keep pace with the ever-increasing inflow of available large-scale omics datasets. As such, the software scalability and usability on the less than exotic computer hardware are a priority, as well as the applicability of the algorithm and software to the heterogeneous datasets containing many data types-single-nucleotide polymorphisms and other genetic/epigenetic/transcriptome variables, metabolite levels, epidemiological variables, endpoints, and phenotypes, etc.
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Inferring global network properties from egocentric data with applications to epidemics.
Britton, Tom; Trapman, Pieter
2015-03-01
Social networks are often only partly observed, and it is sometimes desirable to infer global properties of the network from 'egocentric' data. In the current paper, we study different types of egocentric data, and show which global network properties are consistent with data. Two global network properties are considered: the size of the largest connected component (the giant) and the size of an epidemic outbreak taking place on the network. The main conclusion is that, in most cases, egocentric data allow for a large range of possible sizes of the giant and the outbreak, implying that egocentric data carry very little information about these global properties. The asymptotic size of the giant and the outbreak is also characterized, assuming the network is selected uniformly among networks with prescribed egocentric data. © The Authors 2013. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.
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NASA Astrophysics Data System (ADS)
Nguyen, Emmanuel; Antoni, Jerome; Grondin, Olivier
2009-12-01
In the automotive industry, the necessary reduction of pollutant emission for new Diesel engines requires the control of combustion events. This control is efficient provided combustion parameters such as combustion occurrence and combustion energy are relevant. Combustion parameters are traditionally measured from cylinder pressure sensors. However this kind of sensor is expensive and has a limited lifetime. Thus this paper proposes to use only one cylinder pressure on a multi-cylinder engine and to extract combustion parameters from the other cylinders with low cost knock sensors. Knock sensors measure the vibration circulating on the engine block, hence they do not all contain the information on the combustion processes, but they are also contaminated by other mechanical noises that disorder the signal. The question is how to combine the information coming from one cylinder pressure and knock sensors to obtain the most relevant combustion parameters in all engine cylinders. In this paper, the issue is addressed trough the Bayesian inference formalism. In that cylinder where a cylinder pressure sensor is mounted, combustion parameters will be measured directly. In the other cylinders, they will be measured indirectly from Bayesian inference. Experimental results obtained on a four cylinder Diesel engine demonstrate the effectiveness of the proposed algorithm toward that purpose.
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2014-01-01
Background Network inference of gene expression data is an important challenge in systems biology. Novel algorithms may provide more detailed gene regulatory networks (GRN) for complex, chronic inflammatory diseases such as rheumatoid arthritis (RA), in which activated synovial fibroblasts (SFBs) play a major role. Since the detailed mechanisms underlying this activation are still unclear, simultaneous investigation of multi-stimuli activation of SFBs offers the possibility to elucidate the regulatory effects of multiple mediators and to gain new insights into disease pathogenesis. Methods A GRN was therefore inferred from RA-SFBs treated with 4 different stimuli (IL-1 β, TNF- α, TGF- β, and PDGF-D). Data from time series microarray experiments (0, 1, 2, 4, 12 h; Affymetrix HG-U133 Plus 2.0) were batch-corrected applying ‘ComBat’, analyzed for differentially expressed genes over time with ‘Limma’, and used for the inference of a robust GRN with NetGenerator V2.0, a heuristic ordinary differential equation-based method with soft integration of prior knowledge. Results Using all genes differentially expressed over time in RA-SFBs for any stimulus, and selecting the genes belonging to the most significant gene ontology (GO) term, i.e., ‘cartilage development’, a dynamic, robust, moderately complex multi-stimuli GRN was generated with 24 genes and 57 edges in total, 31 of which were gene-to-gene edges. Prior literature-based knowledge derived from Pathway Studio or manual searches was reflected in the final network by 25/57 confirmed edges (44%). The model contained known network motifs crucial for dynamic cellular behavior, e.g., cross-talk among pathways, positive feed-back loops, and positive feed-forward motifs (including suppression of the transcriptional repressor OSR2 by all 4 stimuli. Conclusion A multi-stimuli GRN highly concordant with literature data was successfully generated by network inference from the gene expression of stimulated RA-SFBs. The GRN showed high reliability, since 10 predicted edges were independently validated by literature findings post network inference. The selected GO term ‘cartilage development’ contained a number of differentiation markers, growth factors, and transcription factors with potential relevance for RA. Finally, the model provided new insight into the response of RA-SFBs to multiple stimuli implicated in the pathogenesis of RA, in particular to the ‘novel’ potent growth factor PDGF-D. PMID:24989895
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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
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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/ .
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Inferring multi-scale neural mechanisms with brain network modelling
Schirner, Michael; McIntosh, Anthony Randal; Jirsa, Viktor; Deco, Gustavo
2018-01-01
The neurophysiological processes underlying non-invasive brain activity measurements are incompletely understood. Here, we developed a connectome-based brain network model that integrates individual structural and functional data with neural population dynamics to support multi-scale neurophysiological inference. Simulated populations were linked by structural connectivity and, as a novelty, driven by electroencephalography (EEG) source activity. Simulations not only predicted subjects' individual resting-state functional magnetic resonance imaging (fMRI) time series and spatial network topologies over 20 minutes of activity, but more importantly, they also revealed precise neurophysiological mechanisms that underlie and link six empirical observations from different scales and modalities: (1) resting-state fMRI oscillations, (2) functional connectivity networks, (3) excitation-inhibition balance, (4, 5) inverse relationships between α-rhythms, spike-firing and fMRI on short and long time scales, and (6) fMRI power-law scaling. These findings underscore the potential of this new modelling framework for general inference and integration of neurophysiological knowledge to complement empirical studies. PMID:29308767
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Kashyap, Vipul; Morales, Alfredo; Hongsermeier, Tonya
2006-01-01
We present an approach and architecture for implementing scalable and maintainable clinical decision support at the Partners HealthCare System. The architecture integrates a business rules engine that executes declarative if-then rules stored in a rule-base referencing objects and methods in a business object model. The rules engine executes object methods by invoking services implemented on the clinical data repository. Specialized inferences that support classification of data and instances into classes are identified and an approach to implement these inferences using an OWL based ontology engine is presented. Alternative representations of these specialized inferences as if-then rules or OWL axioms are explored and their impact on the scalability and maintenance of the system is presented. Architectural alternatives for integration of clinical decision support functionality with the invoking application and the underlying clinical data repository; and their associated trade-offs are discussed and presented.
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A decision network account of reasoning about other people's choices
Jern, Alan; Kemp, Charles
2015-01-01
The ability to predict and reason about other people's choices is fundamental to social interaction. We propose that people reason about other people's choices using mental models that are similar to decision networks. Decision networks are extensions of Bayesian networks that incorporate the idea that choices are made in order to achieve goals. In our first experiment, we explore how people predict the choices of others. Our remaining three experiments explore how people infer the goals and knowledge of others by observing the choices that they make. We show that decision networks account for our data better than alternative computational accounts that do not incorporate the notion of goal-directed choice or that do not rely on probabilistic inference. PMID:26010559
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Duggento, Andrea; Stankovski, Tomislav; McClintock, Peter V E; Stefanovska, Aneta
2012-12-01
Living systems have time-evolving interactions that, until recently, could not be identified accurately from recorded time series in the presence of noise. Stankovski et al. [Phys. Rev. Lett. 109, 024101 (2012)] introduced a method based on dynamical Bayesian inference that facilitates the simultaneous detection of time-varying synchronization, directionality of influence, and coupling functions. It can distinguish unsynchronized dynamics from noise-induced phase slips. The method is based on phase dynamics, with Bayesian inference of the time-evolving parameters being achieved by shaping the prior densities to incorporate knowledge of previous samples. We now present the method in detail using numerically generated data, data from an analog electronic circuit, and cardiorespiratory data. We also generalize the method to encompass networks of interacting oscillators and thus demonstrate its applicability to small-scale networks.
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Inference of Transmission Network Structure from HIV Phylogenetic Trees
Giardina, Federica; Romero-Severson, Ethan Obie; Albert, Jan; ...
2017-01-13
Phylogenetic inference is an attractive means to reconstruct transmission histories and epidemics. However, there is not a perfect correspondence between transmission history and virus phylogeny. Both node height and topological differences may occur, depending on the interaction between within-host evolutionary dynamics and between-host transmission patterns. To investigate these interactions, we added a within-host evolutionary model in epidemiological simulations and examined if the resulting phylogeny could recover different types of contact networks. To further improve realism, we also introduced patient-specific differences in infectivity across disease stages, and on the epidemic level we considered incomplete sampling and the age of the epidemic.more » Second, we implemented an inference method based on approximate Bayesian computation (ABC) to discriminate among three well-studied network models and jointly estimate both network parameters and key epidemiological quantities such as the infection rate. Our ABC framework used both topological and distance-based tree statistics for comparison between simulated and observed trees. Overall, our simulations showed that a virus time-scaled phylogeny (genealogy) may be substantially different from the between-host transmission tree. This has important implications for the interpretation of what a phylogeny reveals about the underlying epidemic contact network. In particular, we found that while the within-host evolutionary process obscures the transmission tree, the diversification process and infectivity dynamics also add discriminatory power to differentiate between different types of contact networks. We also found that the possibility to differentiate contact networks depends on how far an epidemic has progressed, where distance-based tree statistics have more power early in an epidemic. Finally, we applied our ABC inference on two different outbreaks from the Swedish HIV-1 epidemic.« less
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Inference of Transmission Network Structure from HIV Phylogenetic Trees
DOE Office of Scientific and Technical Information (OSTI.GOV)
Giardina, Federica; Romero-Severson, Ethan Obie; Albert, Jan
Phylogenetic inference is an attractive means to reconstruct transmission histories and epidemics. However, there is not a perfect correspondence between transmission history and virus phylogeny. Both node height and topological differences may occur, depending on the interaction between within-host evolutionary dynamics and between-host transmission patterns. To investigate these interactions, we added a within-host evolutionary model in epidemiological simulations and examined if the resulting phylogeny could recover different types of contact networks. To further improve realism, we also introduced patient-specific differences in infectivity across disease stages, and on the epidemic level we considered incomplete sampling and the age of the epidemic.more » Second, we implemented an inference method based on approximate Bayesian computation (ABC) to discriminate among three well-studied network models and jointly estimate both network parameters and key epidemiological quantities such as the infection rate. Our ABC framework used both topological and distance-based tree statistics for comparison between simulated and observed trees. Overall, our simulations showed that a virus time-scaled phylogeny (genealogy) may be substantially different from the between-host transmission tree. This has important implications for the interpretation of what a phylogeny reveals about the underlying epidemic contact network. In particular, we found that while the within-host evolutionary process obscures the transmission tree, the diversification process and infectivity dynamics also add discriminatory power to differentiate between different types of contact networks. We also found that the possibility to differentiate contact networks depends on how far an epidemic has progressed, where distance-based tree statistics have more power early in an epidemic. Finally, we applied our ABC inference on two different outbreaks from the Swedish HIV-1 epidemic.« less
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Fuzzy regression modeling for tool performance prediction and degradation detection.
Li, X; Er, M J; Lim, B S; Zhou, J H; Gan, O P; Rutkowski, L
2010-10-01
In this paper, the viability of using Fuzzy-Rule-Based Regression Modeling (FRM) algorithm for tool performance and degradation detection is investigated. The FRM is developed based on a multi-layered fuzzy-rule-based hybrid system with Multiple Regression Models (MRM) embedded into a fuzzy logic inference engine that employs Self Organizing Maps (SOM) for clustering. The FRM converts a complex nonlinear problem to a simplified linear format in order to further increase the accuracy in prediction and rate of convergence. The efficacy of the proposed FRM is tested through a case study - namely to predict the remaining useful life of a ball nose milling cutter during a dry machining process of hardened tool steel with a hardness of 52-54 HRc. A comparative study is further made between four predictive models using the same set of experimental data. It is shown that the FRM is superior as compared with conventional MRM, Back Propagation Neural Networks (BPNN) and Radial Basis Function Networks (RBFN) in terms of prediction accuracy and learning speed.
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Deng, Zhimin; Tian, Tianhai
2014-07-29
The advances of systems biology have raised a large number of sophisticated mathematical models for describing the dynamic property of complex biological systems. One of the major steps in developing mathematical models is to estimate unknown parameters of the model based on experimentally measured quantities. However, experimental conditions limit the amount of data that is available for mathematical modelling. The number of unknown parameters in mathematical models may be larger than the number of observation data. The imbalance between the number of experimental data and number of unknown parameters makes reverse-engineering problems particularly challenging. To address the issue of inadequate experimental data, we propose a continuous optimization approach for making reliable inference of model parameters. This approach first uses a spline interpolation to generate continuous functions of system dynamics as well as the first and second order derivatives of continuous functions. The expanded dataset is the basis to infer unknown model parameters using various continuous optimization criteria, including the error of simulation only, error of both simulation and the first derivative, or error of simulation as well as the first and second derivatives. We use three case studies to demonstrate the accuracy and reliability of the proposed new approach. Compared with the corresponding discrete criteria using experimental data at the measurement time points only, numerical results of the ERK kinase activation module show that the continuous absolute-error criteria using both function and high order derivatives generate estimates with better accuracy. This result is also supported by the second and third case studies for the G1/S transition network and the MAP kinase pathway, respectively. This suggests that the continuous absolute-error criteria lead to more accurate estimates than the corresponding discrete criteria. We also study the robustness property of these three models to examine the reliability of estimates. Simulation results show that the models with estimated parameters using continuous fitness functions have better robustness properties than those using the corresponding discrete fitness functions. The inference studies and robustness analysis suggest that the proposed continuous optimization criteria are effective and robust for estimating unknown parameters in mathematical models.
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Social brain volume is associated with in-degree social network size among older adults
2018-01-01
The social brain hypothesis proposes that large neocortex size evolved to support cognitively demanding social interactions. Accordingly, previous studies have observed that larger orbitofrontal and amygdala structures predict the size of an individual's social network. However, it remains uncertain how an individual's social connectedness reported by other people is associated with the social brain volume. In this study, we found that a greater in-degree network size, a measure of social ties identified by a subject's social connections rather than by the subject, significantly correlated with a larger regional volume of the orbitofrontal cortex, dorsomedial prefrontal cortex and lingual gyrus. By contrast, out-degree size, which is based on an individual's self-perceived connectedness, showed no associations. Meta-analytic reverse inference further revealed that regional volume pattern of in-degree size was specifically involved in social inference ability. These findings were possible because our dataset contained the social networks of an entire village, i.e. a global network. The results suggest that the in-degree aspect of social network size not only confirms the previously reported brain correlates of the social network but also shows an association in brain regions involved in the ability to infer other people's minds. This study provides insight into understanding how the social brain is uniquely associated with sociocentric measures derived from a global network. PMID:29367402
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Algorithms for database-dependent search of MS/MS data.
Matthiesen, Rune
2013-01-01
The frequent used bottom-up strategy for identification of proteins and their associated modifications generate nowadays typically thousands of MS/MS spectra that normally are matched automatically against a protein sequence database. Search engines that take as input MS/MS spectra and a protein sequence database are referred as database-dependent search engines. Many programs both commercial and freely available exist for database-dependent search of MS/MS spectra and most of the programs have excellent user documentation. The aim here is therefore to outline the algorithm strategy behind different search engines rather than providing software user manuals. The process of database-dependent search can be divided into search strategy, peptide scoring, protein scoring, and finally protein inference. Most efforts in the literature have been put in to comparing results from different software rather than discussing the underlining algorithms. Such practical comparisons can be cluttered by suboptimal implementation and the observed differences are frequently caused by software parameters settings which have not been set proper to allow even comparison. In other words an algorithmic idea can still be worth considering even if the software implementation has been demonstrated to be suboptimal. The aim in this chapter is therefore to split the algorithms for database-dependent searching of MS/MS data into the above steps so that the different algorithmic ideas become more transparent and comparable. Most search engines provide good implementations of the first three data analysis steps mentioned above, whereas the final step of protein inference are much less developed for most search engines and is in many cases performed by an external software. The final part of this chapter illustrates how protein inference is built into the VEMS search engine and discusses a stand-alone program SIR for protein inference that can import a Mascot search result.
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Jang, Sumin; Choubey, Sandeep; Furchtgott, Leon; Zou, Ling-Nan; Doyle, Adele; Menon, Vilas; Loew, Ethan B; Krostag, Anne-Rachel; Martinez, Refugio A; Madisen, Linda; Levi, Boaz P; Ramanathan, Sharad
2017-01-01
The complexity of gene regulatory networks that lead multipotent cells to acquire different cell fates makes a quantitative understanding of differentiation challenging. Using a statistical framework to analyze single-cell transcriptomics data, we infer the gene expression dynamics of early mouse embryonic stem (mES) cell differentiation, uncovering discrete transitions across nine cell states. We validate the predicted transitions across discrete states using flow cytometry. Moreover, using live-cell microscopy, we show that individual cells undergo abrupt transitions from a naïve to primed pluripotent state. Using the inferred discrete cell states to build a probabilistic model for the underlying gene regulatory network, we further predict and experimentally verify that these states have unique response to perturbations, thus defining them functionally. Our study provides a framework to infer the dynamics of differentiation from single cell transcriptomics data and to build predictive models of the gene regulatory networks that drive the sequence of cell fate decisions during development. DOI: http://dx.doi.org/10.7554/eLife.20487.001 PMID:28296635
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Gong, Wuming; Koyano-Nakagawa, Naoko; Li, Tongbin; Garry, Daniel J
2015-03-07
Decoding the temporal control of gene expression patterns is key to the understanding of the complex mechanisms that govern developmental decisions during heart development. High-throughput methods have been employed to systematically study the dynamic and coordinated nature of cardiac differentiation at the global level with multiple dimensions. Therefore, there is a pressing need to develop a systems approach to integrate these data from individual studies and infer the dynamic regulatory networks in an unbiased fashion. We developed a two-step strategy to integrate data from (1) temporal RNA-seq, (2) temporal histone modification ChIP-seq, (3) transcription factor (TF) ChIP-seq and (4) gene perturbation experiments to reconstruct the dynamic network during heart development. First, we trained a logistic regression model to predict the probability (LR score) of any base being bound by 543 TFs with known positional weight matrices. Second, four dimensions of data were combined using a time-varying dynamic Bayesian network model to infer the dynamic networks at four developmental stages in the mouse [mouse embryonic stem cells (ESCs), mesoderm (MES), cardiac progenitors (CP) and cardiomyocytes (CM)]. Our method not only infers the time-varying networks between different stages of heart development, but it also identifies the TF binding sites associated with promoter or enhancers of downstream genes. The LR scores of experimentally verified ESCs and heart enhancers were significantly higher than random regions (p <10(-100)), suggesting that a high LR score is a reliable indicator for functional TF binding sites. Our network inference model identified a region with an elevated LR score approximately -9400 bp upstream of the transcriptional start site of Nkx2-5, which overlapped with a previously reported enhancer region (-9435 to -8922 bp). TFs such as Tead1, Gata4, Msx2, and Tgif1 were predicted to bind to this region and participate in the regulation of Nkx2-5 gene expression. Our model also predicted the key regulatory networks for the ESC-MES, MES-CP and CP-CM transitions. We report a novel method to systematically integrate multi-dimensional -omics data and reconstruct the gene regulatory networks. This method will allow one to rapidly determine the cis-modules that regulate key genes during cardiac differentiation.
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Reconstruction of stochastic temporal networks through diffusive arrival times
NASA Astrophysics Data System (ADS)
Li, Xun; Li, Xiang
2017-06-01
Temporal networks have opened a new dimension in defining and quantification of complex interacting systems. Our ability to identify and reproduce time-resolved interaction patterns is, however, limited by the restricted access to empirical individual-level data. Here we propose an inverse modelling method based on first-arrival observations of the diffusion process taking place on temporal networks. We describe an efficient coordinate-ascent implementation for inferring stochastic temporal networks that builds in particular but not exclusively on the null model assumption of mutually independent interaction sequences at the dyadic level. The results of benchmark tests applied on both synthesized and empirical network data sets confirm the validity of our algorithm, showing the feasibility of statistically accurate inference of temporal networks only from moderate-sized samples of diffusion cascades. Our approach provides an effective and flexible scheme for the temporally augmented inverse problems of network reconstruction and has potential in a broad variety of applications.
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F-MAP: A Bayesian approach to infer the gene regulatory network using external hints
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
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Reconstruction of stochastic temporal networks through diffusive arrival times
Li, Xun; Li, Xiang
2017-01-01
Temporal networks have opened a new dimension in defining and quantification of complex interacting systems. Our ability to identify and reproduce time-resolved interaction patterns is, however, limited by the restricted access to empirical individual-level data. Here we propose an inverse modelling method based on first-arrival observations of the diffusion process taking place on temporal networks. We describe an efficient coordinate-ascent implementation for inferring stochastic temporal networks that builds in particular but not exclusively on the null model assumption of mutually independent interaction sequences at the dyadic level. The results of benchmark tests applied on both synthesized and empirical network data sets confirm the validity of our algorithm, showing the feasibility of statistically accurate inference of temporal networks only from moderate-sized samples of diffusion cascades. Our approach provides an effective and flexible scheme for the temporally augmented inverse problems of network reconstruction and has potential in a broad variety of applications. PMID:28604687
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Vallat, Laurent; Kemper, Corey A; Jung, Nicolas; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Meyer, Nicolas; Pocheville, Arnaud; Fisher, John W; Gribben, John G; Bahram, Seiamak
2013-01-08
Cellular behavior is sustained by genetic programs that are progressively disrupted in pathological conditions--notably, cancer. High-throughput gene expression profiling has been used to infer statistical models describing these cellular programs, and development is now needed to guide orientated modulation of these systems. Here we develop a regression-based model to reverse-engineer a temporal genetic program, based on relevant patterns of gene expression after cell stimulation. This method integrates the temporal dimension of biological rewiring of genetic programs and enables the prediction of the effect of targeted gene disruption at the system level. We tested the performance accuracy of this model on synthetic data before reverse-engineering the response of primary cancer cells to a proliferative (protumorigenic) stimulation in a multistate leukemia biological model (i.e., chronic lymphocytic leukemia). To validate the ability of our method to predict the effects of gene modulation on the global program, we performed an intervention experiment on a targeted gene. Comparison of the predicted and observed gene expression changes demonstrates the possibility of predicting the effects of a perturbation in a gene regulatory network, a first step toward an orientated intervention in a cancer cell genetic program.
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Differential C3NET reveals disease networks of direct physical interactions
2011-01-01
Background Genes might have different gene interactions in different cell conditions, which might be mapped into different networks. Differential analysis of gene networks allows spotting condition-specific interactions that, for instance, form disease networks if the conditions are a disease, such as cancer, and normal. This could potentially allow developing better and subtly targeted drugs to cure cancer. Differential network analysis with direct physical gene interactions needs to be explored in this endeavour. Results C3NET is a recently introduced information theory based gene network inference algorithm that infers direct physical gene interactions from expression data, which was shown to give consistently higher inference performances over various networks than its competitors. In this paper, we present, DC3net, an approach to employ C3NET in inferring disease networks. We apply DC3net on a synthetic and real prostate cancer datasets, which show promising results. With loose cutoffs, we predicted 18583 interactions from tumor and normal samples in total. Although there are no reference interactions databases for the specific conditions of our samples in the literature, we found verifications for 54 of our predicted direct physical interactions from only four of the biological interaction databases. As an example, we predicted that RAD50 with TRF2 have prostate cancer specific interaction that turned out to be having validation from the literature. It is known that RAD50 complex associates with TRF2 in the S phase of cell cycle, which suggests that this predicted interaction may promote telomere maintenance in tumor cells in order to allow tumor cells to divide indefinitely. Our enrichment analysis suggests that the identified tumor specific gene interactions may be potentially important in driving the growth in prostate cancer. Additionally, we found that the highest connected subnetwork of our predicted tumor specific network is enriched for all proliferation genes, which further suggests that the genes in this network may serve in the process of oncogenesis. Conclusions Our approach reveals disease specific interactions. It may help to make experimental follow-up studies more cost and time efficient by prioritizing disease relevant parts of the global gene network. PMID:21777411
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Single board system for fuzzy inference
NASA Technical Reports Server (NTRS)
Symon, James R.; Watanabe, Hiroyuki
1991-01-01
The very large scale integration (VLSI) implementation of a fuzzy logic inference mechanism allows the use of rule-based control and decision making in demanding real-time applications. Researchers designed a full custom VLSI inference engine. The chip was fabricated using CMOS technology. The chip consists of 688,000 transistors of which 476,000 are used for RAM memory. The fuzzy logic inference engine board system incorporates the custom designed integrated circuit into a standard VMEbus environment. The Fuzzy Logic system uses Transistor-Transistor Logic (TTL) parts to provide the interface between the Fuzzy chip and a standard, double height VMEbus backplane, allowing the chip to perform application process control through the VMEbus host. High level C language functions hide details of the hardware system interface from the applications level programmer. The first version of the board was installed on a robot at Oak Ridge National Laboratory in January of 1990.
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An inference method from multi-layered structure of biomedical data.
Kim, Myungjun; Nam, Yonghyun; Shin, Hyunjung
2017-05-18
Biological system is a multi-layered structure of omics with genome, epigenome, transcriptome, metabolome, proteome, etc., and can be further stretched to clinical/medical layers such as diseasome, drugs, and symptoms. One advantage of omics is that we can figure out an unknown component or its trait by inferring from known omics components. The component can be inferred by the ones in the same level of omics or the ones in different levels. To implement the inference process, an algorithm that can be applied to the multi-layered complex system is required. In this study, we develop a semi-supervised learning algorithm that can be applied to the multi-layered complex system. In order to verify the validity of the inference, it was applied to the prediction problem of disease co-occurrence with a two-layered network composed of symptom-layer and disease-layer. The symptom-disease layered network obtained a fairly high value of AUC, 0.74, which is regarded as noticeable improvement when comparing 0.59 AUC of single-layered disease network. If further stretched to whole layered structure of omics, the proposed method is expected to produce more promising results. This research has novelty in that it is a new integrative algorithm that incorporates the vertical structure of omics data, on contrary to other existing methods that integrate the data in parallel fashion. The results can provide enhanced guideline for disease co-occurrence prediction, thereby serve as a valuable tool for inference process of multi-layered biological system.
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Deconvolution of mixing time series on a graph
Blocker, Alexander W.; Airoldi, Edoardo M.
2013-01-01
In many applications we are interested in making inference on latent time series from indirect measurements, which are often low-dimensional projections resulting from mixing or aggregation. Positron emission tomography, super-resolution, and network traffic monitoring are some examples. Inference in such settings requires solving a sequence of ill-posed inverse problems, yt = Axt, where the projection mechanism provides information on A. We consider problems in which A specifies mixing on a graph of times series that are bursty and sparse. We develop a multilevel state-space model for mixing times series and an efficient approach to inference. A simple model is used to calibrate regularization parameters that lead to efficient inference in the multilevel state-space model. We apply this method to the problem of estimating point-to-point traffic flows on a network from aggregate measurements. Our solution outperforms existing methods for this problem, and our two-stage approach suggests an efficient inference strategy for multilevel models of multivariate time series. PMID:25309135
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A decision network account of reasoning about other people's choices.
Jern, Alan; Kemp, Charles
2015-09-01
The ability to predict and reason about other people's choices is fundamental to social interaction. We propose that people reason about other people's choices using mental models that are similar to decision networks. Decision networks are extensions of Bayesian networks that incorporate the idea that choices are made in order to achieve goals. In our first experiment, we explore how people predict the choices of others. Our remaining three experiments explore how people infer the goals and knowledge of others by observing the choices that they make. We show that decision networks account for our data better than alternative computational accounts that do not incorporate the notion of goal-directed choice or that do not rely on probabilistic inference. Copyright © 2015 Elsevier B.V. All rights reserved.
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Knapp, Bettina; Kaderali, Lars
2013-01-01
Perturbation experiments for example using RNA interference (RNAi) offer an attractive way to elucidate gene function in a high throughput fashion. The placement of hit genes in their functional context and the inference of underlying networks from such data, however, are challenging tasks. One of the problems in network inference is the exponential number of possible network topologies for a given number of genes. Here, we introduce a novel mathematical approach to address this question. We formulate network inference as a linear optimization problem, which can be solved efficiently even for large-scale systems. We use simulated data to evaluate our approach, and show improved performance in particular on larger networks over state-of-the art methods. We achieve increased sensitivity and specificity, as well as a significant reduction in computing time. Furthermore, we show superior performance on noisy data. We then apply our approach to study the intracellular signaling of human primary nave CD4(+) T-cells, as well as ErbB signaling in trastuzumab resistant breast cancer cells. In both cases, our approach recovers known interactions and points to additional relevant processes. In ErbB signaling, our results predict an important role of negative and positive feedback in controlling the cell cycle progression.
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Discriminative Relational Topic Models.
Chen, Ning; Zhu, Jun; Xia, Fei; Zhang, Bo
2015-05-01
Relational topic models (RTMs) provide a probabilistic generative process to describe both the link structure and document contents for document networks, and they have shown promise on predicting network structures and discovering latent topic representations. However, existing RTMs have limitations in both the restricted model expressiveness and incapability of dealing with imbalanced network data. To expand the scope and improve the inference accuracy of RTMs, this paper presents three extensions: 1) unlike the common link likelihood with a diagonal weight matrix that allows the-same-topic interactions only, we generalize it to use a full weight matrix that captures all pairwise topic interactions and is applicable to asymmetric networks; 2) instead of doing standard Bayesian inference, we perform regularized Bayesian inference (RegBayes) with a regularization parameter to deal with the imbalanced link structure issue in real networks and improve the discriminative ability of learned latent representations; and 3) instead of doing variational approximation with strict mean-field assumptions, we present collapsed Gibbs sampling algorithms for the generalized relational topic models by exploring data augmentation without making restricting assumptions. Under the generic RegBayes framework, we carefully investigate two popular discriminative loss functions, namely, the logistic log-loss and the max-margin hinge loss. Experimental results on several real network datasets demonstrate the significance of these extensions on improving prediction performance.
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Wu, Chia-Chou; Chen, Bor-Sen
2016-01-01
Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host–pathogen dynamic interaction networks. The consideration of host–pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host–pathogen molecular interaction networks, and consequent inferences of the host–pathogen relationship could be translated into biomedical applications. PMID:26881892
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Wu, Chia-Chou; Chen, Bor-Sen
2016-01-01
Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host-pathogen dynamic interaction networks. The consideration of host-pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host-pathogen molecular interaction networks, and consequent inferences of the host-pathogen relationship could be translated into biomedical applications.
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An Algebraic Approach to Inference in Complex Networked Structures
2015-07-09
44], [45],[46] where the shift is the elementary non-trivial filter that generates, under an appropriate notion of shift invariance, all linear ... elementary filter, and its output is a graph signal with the value at vertex n of the graph given approximately by a weighted linear combination of...AFRL-AFOSR-VA-TR-2015-0265 An Algebraic Approach to Inference in Complex Networked Structures Jose Moura CARNEGIE MELLON UNIVERSITY Final Report 07
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Model-free inference of direct network interactions from nonlinear collective dynamics.
Casadiego, Jose; Nitzan, Mor; Hallerberg, Sarah; Timme, Marc
2017-12-19
The topology of interactions in network dynamical systems fundamentally underlies their function. Accelerating technological progress creates massively available data about collective nonlinear dynamics in physical, biological, and technological systems. Detecting direct interaction patterns from those dynamics still constitutes a major open problem. In particular, current nonlinear dynamics approaches mostly require to know a priori a model of the (often high dimensional) system dynamics. Here we develop a model-independent framework for inferring direct interactions solely from recording the nonlinear collective dynamics generated. Introducing an explicit dependency matrix in combination with a block-orthogonal regression algorithm, the approach works reliably across many dynamical regimes, including transient dynamics toward steady states, periodic and non-periodic dynamics, and chaos. Together with its capabilities to reveal network (two point) as well as hypernetwork (e.g., three point) interactions, this framework may thus open up nonlinear dynamics options of inferring direct interaction patterns across systems where no model is known.
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NASA Astrophysics Data System (ADS)
Duggento, Andrea; Stankovski, Tomislav; McClintock, Peter V. E.; Stefanovska, Aneta
2012-12-01
Living systems have time-evolving interactions that, until recently, could not be identified accurately from recorded time series in the presence of noise. Stankovski [Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.109.024101 109, 024101 (2012)] introduced a method based on dynamical Bayesian inference that facilitates the simultaneous detection of time-varying synchronization, directionality of influence, and coupling functions. It can distinguish unsynchronized dynamics from noise-induced phase slips. The method is based on phase dynamics, with Bayesian inference of the time-evolving parameters being achieved by shaping the prior densities to incorporate knowledge of previous samples. We now present the method in detail using numerically generated data, data from an analog electronic circuit, and cardiorespiratory data. We also generalize the method to encompass networks of interacting oscillators and thus demonstrate its applicability to small-scale networks.
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Review of Medical Image Classification using the Adaptive Neuro-Fuzzy Inference System
Hosseini, Monireh Sheikh; Zekri, Maryam
2012-01-01
Image classification is an issue that utilizes image processing, pattern recognition and classification methods. Automatic medical image classification is a progressive area in image classification, and it is expected to be more developed in the future. Because of this fact, automatic diagnosis can assist pathologists by providing second opinions and reducing their workload. This paper reviews the application of the adaptive neuro-fuzzy inference system (ANFIS) as a classifier in medical image classification during the past 16 years. ANFIS is a fuzzy inference system (FIS) implemented in the framework of an adaptive fuzzy neural network. It combines the explicit knowledge representation of an FIS with the learning power of artificial neural networks. The objective of ANFIS is to integrate the best features of fuzzy systems and neural networks. A brief comparison with other classifiers, main advantages and drawbacks of this classifier are investigated. PMID:23493054
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Mapping the ecological networks of microbial communities.
Xiao, Yandong; Angulo, Marco Tulio; Friedman, Jonathan; Waldor, Matthew K; Weiss, Scott T; Liu, Yang-Yu
2017-12-11
Mapping the ecological networks of microbial communities is a necessary step toward understanding their assembly rules and predicting their temporal behavior. However, existing methods require assuming a particular population dynamics model, which is not known a priori. Moreover, those methods require fitting longitudinal abundance data, which are often not informative enough for reliable inference. To overcome these limitations, here we develop a new method based on steady-state abundance data. Our method can infer the network topology and inter-taxa interaction types without assuming any particular population dynamics model. Additionally, when the population dynamics is assumed to follow the classic Generalized Lotka-Volterra model, our method can infer the inter-taxa interaction strengths and intrinsic growth rates. We systematically validate our method using simulated data, and then apply it to four experimental data sets. Our method represents a key step towards reliable modeling of complex, real-world microbial communities, such as the human gut microbiota.
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Multichannel Convolutional Neural Network for Biological Relation Extraction.
Quan, Chanqin; Hua, Lei; Sun, Xiao; Bai, Wenjun
2016-01-01
The plethora of biomedical relations which are embedded in medical logs (records) demands researchers' attention. Previous theoretical and practical focuses were restricted on traditional machine learning techniques. However, these methods are susceptible to the issues of "vocabulary gap" and data sparseness and the unattainable automation process in feature extraction. To address aforementioned issues, in this work, we propose a multichannel convolutional neural network (MCCNN) for automated biomedical relation extraction. The proposed model has the following two contributions: (1) it enables the fusion of multiple (e.g., five) versions in word embeddings; (2) the need for manual feature engineering can be obviated by automated feature learning with convolutional neural network (CNN). We evaluated our model on two biomedical relation extraction tasks: drug-drug interaction (DDI) extraction and protein-protein interaction (PPI) extraction. For DDI task, our system achieved an overall f -score of 70.2% compared to the standard linear SVM based system (e.g., 67.0%) on DDIExtraction 2013 challenge dataset. And for PPI task, we evaluated our system on Aimed and BioInfer PPI corpus; our system exceeded the state-of-art ensemble SVM system by 2.7% and 5.6% on f -scores.
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Clustering network layers with the strata multilayer stochastic block model.
Stanley, Natalie; Shai, Saray; Taylor, Dane; Mucha, Peter J
2016-01-01
Multilayer networks are a useful data structure for simultaneously capturing multiple types of relationships between a set of nodes. In such networks, each relational definition gives rise to a layer. While each layer provides its own set of information, community structure across layers can be collectively utilized to discover and quantify underlying relational patterns between nodes. To concisely extract information from a multilayer network, we propose to identify and combine sets of layers with meaningful similarities in community structure. In this paper, we describe the "strata multilayer stochastic block model" (sMLSBM), a probabilistic model for multilayer community structure. The central extension of the model is that there exist groups of layers, called "strata", which are defined such that all layers in a given stratum have community structure described by a common stochastic block model (SBM). That is, layers in a stratum exhibit similar node-to-community assignments and SBM probability parameters. Fitting the sMLSBM to a multilayer network provides a joint clustering that yields node-to-community and layer-to-stratum assignments, which cooperatively aid one another during inference. We describe an algorithm for separating layers into their appropriate strata and an inference technique for estimating the SBM parameters for each stratum. We demonstrate our method using synthetic networks and a multilayer network inferred from data collected in the Human Microbiome Project.
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Bayesian Networks Improve Causal Environmental Assessments for Evidence-Based Policy.
Carriger, John F; Barron, Mace G; Newman, Michael C
2016-12-20
Rule-based weight of evidence approaches to ecological risk assessment may not account for uncertainties and generally lack probabilistic integration of lines of evidence. Bayesian networks allow causal inferences to be made from evidence by including causal knowledge about the problem, using this knowledge with probabilistic calculus to combine multiple lines of evidence, and minimizing biases in predicting or diagnosing causal relationships. Too often, sources of uncertainty in conventional weight of evidence approaches are ignored that can be accounted for with Bayesian networks. Specifying and propagating uncertainties improve the ability of models to incorporate strength of the evidence in the risk management phase of an assessment. Probabilistic inference from a Bayesian network allows evaluation of changes in uncertainty for variables from the evidence. The network structure and probabilistic framework of a Bayesian approach provide advantages over qualitative approaches in weight of evidence for capturing the impacts of multiple sources of quantifiable uncertainty on predictions of ecological risk. Bayesian networks can facilitate the development of evidence-based policy under conditions of uncertainty by incorporating analytical inaccuracies or the implications of imperfect information, structuring and communicating causal issues through qualitative directed graph formulations, and quantitatively comparing the causal power of multiple stressors on valued ecological resources. These aspects are demonstrated through hypothetical problem scenarios that explore some major benefits of using Bayesian networks for reasoning and making inferences in evidence-based policy.
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Clustering network layers with the strata multilayer stochastic block model
Stanley, Natalie; Shai, Saray; Taylor, Dane; Mucha, Peter J.
2016-01-01
Multilayer networks are a useful data structure for simultaneously capturing multiple types of relationships between a set of nodes. In such networks, each relational definition gives rise to a layer. While each layer provides its own set of information, community structure across layers can be collectively utilized to discover and quantify underlying relational patterns between nodes. To concisely extract information from a multilayer network, we propose to identify and combine sets of layers with meaningful similarities in community structure. In this paper, we describe the “strata multilayer stochastic block model” (sMLSBM), a probabilistic model for multilayer community structure. The central extension of the model is that there exist groups of layers, called “strata”, which are defined such that all layers in a given stratum have community structure described by a common stochastic block model (SBM). That is, layers in a stratum exhibit similar node-to-community assignments and SBM probability parameters. Fitting the sMLSBM to a multilayer network provides a joint clustering that yields node-to-community and layer-to-stratum assignments, which cooperatively aid one another during inference. We describe an algorithm for separating layers into their appropriate strata and an inference technique for estimating the SBM parameters for each stratum. We demonstrate our method using synthetic networks and a multilayer network inferred from data collected in the Human Microbiome Project. PMID:28435844
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Noise-induced relations between network connectivity and dynamics
NASA Astrophysics Data System (ADS)
Ching, Emily Sc
Many biological systems of interest can be represented as networks of many nodes that are interacting with one another. Often these systems are subject to external influence or noise. One of the central issues is to understand the relation between dynamics and the interaction pattern of the system or the connectivity structure of the network. In particular, a challenging problem is to infer the network connectivity structure from the dynamics. In this talk, we show that for stochastic dynamical systems subjected to noise, the presence of noise gives rise to mathematical relations between the network connectivity structure and quantities that can be calculated using solely the time-series measurements of the dynamics of the nodes. We present these relations for both undirected networks with bidirectional coupling and directed networks with directional coupling and discuss how such relations can be utilized to infer the network connectivity structure of the systems. Work supported by the Hong Kong Research Grants Council under Grant No. CUHK 14300914.
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Functional network inference of the suprachiasmatic nucleus
Abel, John H.; Meeker, Kirsten; Granados-Fuentes, Daniel; St. John, Peter C.; Wang, Thomas J.; Bales, Benjamin B.; Doyle, Francis J.; Herzog, Erik D.; Petzold, Linda R.
2016-01-01
In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators communicate within a neuronal network to generate precise system-wide circadian rhythms. Although the intracellular genetic oscillator and intercellular biochemical coupling mechanisms have been examined previously, the network topology driving synchronization of the SCN has not been elucidated. This network has been particularly challenging to probe, due to its oscillatory components and slow coupling timescale. In this work, we investigated the SCN network at a single-cell resolution through a chemically induced desynchronization. We then inferred functional connections in the SCN by applying the maximal information coefficient statistic to bioluminescence reporter data from individual neurons while they resynchronized their circadian cycling. Our results demonstrate that the functional network of circadian cells associated with resynchronization has small-world characteristics, with a node degree distribution that is exponential. We show that hubs of this small-world network are preferentially located in the central SCN, with sparsely connected shells surrounding these cores. Finally, we used two computational models of circadian neurons to validate our predictions of network structure. PMID:27044085
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Estimation of the proteomic cancer co-expression sub networks by using association estimators.
Erdoğan, Cihat; Kurt, Zeyneb; Diri, Banu
2017-01-01
In this study, the association estimators, which have significant influences on the gene network inference methods and used for determining the molecular interactions, were examined within the co-expression network inference concept. By using the proteomic data from five different cancer types, the hub genes/proteins within the disease-associated gene-gene/protein-protein interaction sub networks were identified. Proteomic data from various cancer types is collected from The Cancer Proteome Atlas (TCPA). Correlation and mutual information (MI) based nine association estimators that are commonly used in the literature, were compared in this study. As the gold standard to measure the association estimators' performance, a multi-layer data integration platform on gene-disease associations (DisGeNET) and the Molecular Signatures Database (MSigDB) was used. Fisher's exact test was used to evaluate the performance of the association estimators by comparing the created co-expression networks with the disease-associated pathways. It was observed that the MI based estimators provided more successful results than the Pearson and Spearman correlation approaches, which are used in the estimation of biological networks in the weighted correlation network analysis (WGCNA) package. In correlation-based methods, the best average success rate for five cancer types was 60%, while in MI-based methods the average success ratio was 71% for James-Stein Shrinkage (Shrink) and 64% for Schurmann-Grassberger (SG) association estimator, respectively. Moreover, the hub genes and the inferred sub networks are presented for the consideration of researchers and experimentalists.
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MacGilvray, Matthew E; Shishkova, Evgenia; Chasman, Deborah; Place, Michael; Gitter, Anthony; Coon, Joshua J; Gasch, Audrey P
2018-05-01
Cells respond to stressful conditions by coordinating a complex, multi-faceted response that spans many levels of physiology. Much of the response is coordinated by changes in protein phosphorylation. Although the regulators of transcriptome changes during stress are well characterized in Saccharomyces cerevisiae, the upstream regulatory network controlling protein phosphorylation is less well dissected. Here, we developed a computational approach to infer the signaling network that regulates phosphorylation changes in response to salt stress. We developed an approach to link predicted regulators to groups of likely co-regulated phospho-peptides responding to stress, thereby creating new edges in a background protein interaction network. We then use integer linear programming (ILP) to integrate wild type and mutant phospho-proteomic data and predict the network controlling stress-activated phospho-proteomic changes. The network we inferred predicted new regulatory connections between stress-activated and growth-regulating pathways and suggested mechanisms coordinating metabolism, cell-cycle progression, and growth during stress. We confirmed several network predictions with co-immunoprecipitations coupled with mass-spectrometry protein identification and mutant phospho-proteomic analysis. Results show that the cAMP-phosphodiesterase Pde2 physically interacts with many stress-regulated transcription factors targeted by PKA, and that reduced phosphorylation of those factors during stress requires the Rck2 kinase that we show physically interacts with Pde2. Together, our work shows how a high-quality computational network model can facilitate discovery of new pathway interactions during osmotic stress.
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Estimation of the proteomic cancer co-expression sub networks by using association estimators
Kurt, Zeyneb; Diri, Banu
2017-01-01
In this study, the association estimators, which have significant influences on the gene network inference methods and used for determining the molecular interactions, were examined within the co-expression network inference concept. By using the proteomic data from five different cancer types, the hub genes/proteins within the disease-associated gene-gene/protein-protein interaction sub networks were identified. Proteomic data from various cancer types is collected from The Cancer Proteome Atlas (TCPA). Correlation and mutual information (MI) based nine association estimators that are commonly used in the literature, were compared in this study. As the gold standard to measure the association estimators’ performance, a multi-layer data integration platform on gene-disease associations (DisGeNET) and the Molecular Signatures Database (MSigDB) was used. Fisher's exact test was used to evaluate the performance of the association estimators by comparing the created co-expression networks with the disease-associated pathways. It was observed that the MI based estimators provided more successful results than the Pearson and Spearman correlation approaches, which are used in the estimation of biological networks in the weighted correlation network analysis (WGCNA) package. In correlation-based methods, the best average success rate for five cancer types was 60%, while in MI-based methods the average success ratio was 71% for James-Stein Shrinkage (Shrink) and 64% for Schurmann-Grassberger (SG) association estimator, respectively. Moreover, the hub genes and the inferred sub networks are presented for the consideration of researchers and experimentalists. PMID:29145449
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Reconstructing directed gene regulatory network by only gene expression data.
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 related to Alzheimer's disease; 2. ZNF329 and RB1 significantly regulate those 'mesenchymal' gene expression signature genes for brain tumors. By merely leveraging gene expression data, CBDN can efficiently infer the existence of gene-gene interactions as well as their regulatory directions. The constructed networks are helpful in the identification of important regulators for complex diseases.
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Implicit and explicit social mentalizing: dual processes driven by a shared neural network
Van Overwalle, Frank; Vandekerckhove, Marie
2013-01-01
Recent social neuroscientific evidence indicates that implicit and explicit inferences on the mind of another person (i.e., intentions, attributions or traits), are subserved by a shared mentalizing network. Under both implicit and explicit instructions, ERP studies reveal that early inferences occur at about the same time, and fMRI studies demonstrate an overlap in core mentalizing areas, including the temporo-parietal junction (TPJ) and the medial prefrontal cortex (mPFC). These results suggest a rapid shared implicit intuition followed by a slower explicit verification processes (as revealed by additional brain activation during explicit vs. implicit inferences). These data provide support for a default-adjustment dual-process framework of social mentalizing. PMID:24062663
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Inferring personal economic status from social network location
NASA Astrophysics Data System (ADS)
Luo, Shaojun; Morone, Flaviano; Sarraute, Carlos; Travizano, Matías; Makse, Hernán A.
2017-05-01
It is commonly believed that patterns of social ties affect individuals' economic status. Here we translate this concept into an operational definition at the network level, which allows us to infer the economic well-being of individuals through a measure of their location and influence in the social network. We analyse two large-scale sources: telecommunications and financial data of a whole country's population. Our results show that an individual's location, measured as the optimal collective influence to the structural integrity of the social network, is highly correlated with personal economic status. The observed social network patterns of influence mimic the patterns of economic inequality. For pragmatic use and validation, we carry out a marketing campaign that shows a threefold increase in response rate by targeting individuals identified by our social network metrics as compared to random targeting. Our strategy can also be useful in maximizing the effects of large-scale economic stimulus policies.
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Inferring personal economic status from social network location.
Luo, Shaojun; Morone, Flaviano; Sarraute, Carlos; Travizano, Matías; Makse, Hernán A
2017-05-16
It is commonly believed that patterns of social ties affect individuals' economic status. Here we translate this concept into an operational definition at the network level, which allows us to infer the economic well-being of individuals through a measure of their location and influence in the social network. We analyse two large-scale sources: telecommunications and financial data of a whole country's population. Our results show that an individual's location, measured as the optimal collective influence to the structural integrity of the social network, is highly correlated with personal economic status. The observed social network patterns of influence mimic the patterns of economic inequality. For pragmatic use and validation, we carry out a marketing campaign that shows a threefold increase in response rate by targeting individuals identified by our social network metrics as compared to random targeting. Our strategy can also be useful in maximizing the effects of large-scale economic stimulus policies.
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Inference of quantitative models of bacterial promoters from time-series reporter gene data.
Stefan, Diana; Pinel, Corinne; Pinhal, Stéphane; Cinquemani, Eugenio; Geiselmann, Johannes; de Jong, Hidde
2015-01-01
The inference of regulatory interactions and quantitative models of gene regulation from time-series transcriptomics data has been extensively studied and applied to a range of problems in drug discovery, cancer research, and biotechnology. The application of existing methods is commonly based on implicit assumptions on the biological processes under study. First, the measurements of mRNA abundance obtained in transcriptomics experiments are taken to be representative of protein concentrations. Second, the observed changes in gene expression are assumed to be solely due to transcription factors and other specific regulators, while changes in the activity of the gene expression machinery and other global physiological effects are neglected. While convenient in practice, these assumptions are often not valid and bias the reverse engineering process. Here we systematically investigate, using a combination of models and experiments, the importance of this bias and possible corrections. We measure in real time and in vivo the activity of genes involved in the FliA-FlgM module of the E. coli motility network. From these data, we estimate protein concentrations and global physiological effects by means of kinetic models of gene expression. Our results indicate that correcting for the bias of commonly-made assumptions improves the quality of the models inferred from the data. Moreover, we show by simulation that these improvements are expected to be even stronger for systems in which protein concentrations have longer half-lives and the activity of the gene expression machinery varies more strongly across conditions than in the FliA-FlgM module. The approach proposed in this study is broadly applicable when using time-series transcriptome data to learn about the structure and dynamics of regulatory networks. In the case of the FliA-FlgM module, our results demonstrate the importance of global physiological effects and the active regulation of FliA and FlgM half-lives for the dynamics of FliA-dependent promoters.
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Statistics for nuclear engineers and scientists. Part 1. Basic statistical inference
DOE Office of Scientific and Technical Information (OSTI.GOV)
Beggs, W.J.
1981-02-01
This report is intended for the use of engineers and scientists working in the nuclear industry, especially at the Bettis Atomic Power Laboratory. It serves as the basis for several Bettis in-house statistics courses. The objectives of the report are to introduce the reader to the language and concepts of statistics and to provide a basic set of techniques to apply to problems of the collection and analysis of data. Part 1 covers subjects of basic inference. The subjects include: descriptive statistics; probability; simple inference for normally distributed populations, and for non-normal populations as well; comparison of two populations; themore » analysis of variance; quality control procedures; and linear regression analysis.« less
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Suratanee, Apichat; Plaimas, Kitiporn
2017-01-01
The associations between proteins and diseases are crucial information for investigating pathological mechanisms. However, the number of known and reliable protein-disease associations is quite small. In this study, an analysis framework to infer associations between proteins and diseases was developed based on a large data set of a human protein-protein interaction network integrating an effective network search, namely, the reverse k -nearest neighbor (R k NN) search. The R k NN search was used to identify an impact of a protein on other proteins. Then, associations between proteins and diseases were inferred statistically. The method using the R k NN search yielded a much higher precision than a random selection, standard nearest neighbor search, or when applying the method to a random protein-protein interaction network. All protein-disease pair candidates were verified by a literature search. Supporting evidence for 596 pairs was identified. In addition, cluster analysis of these candidates revealed 10 promising groups of diseases to be further investigated experimentally. This method can be used to identify novel associations to better understand complex relationships between proteins and diseases.
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Network Inference via the Time-Varying Graphical Lasso
Hallac, David; Park, Youngsuk; Boyd, Stephen; Leskovec, Jure
2018-01-01
Many important problems can be modeled as a system of interconnected entities, where each entity is recording time-dependent observations or measurements. In order to spot trends, detect anomalies, and interpret the temporal dynamics of such data, it is essential to understand the relationships between the different entities and how these relationships evolve over time. In this paper, we introduce the time-varying graphical lasso (TVGL), a method of inferring time-varying networks from raw time series data. We cast the problem in terms of estimating a sparse time-varying inverse covariance matrix, which reveals a dynamic network of interdependencies between the entities. Since dynamic network inference is a computationally expensive task, we derive a scalable message-passing algorithm based on the Alternating Direction Method of Multipliers (ADMM) to solve this problem in an efficient way. We also discuss several extensions, including a streaming algorithm to update the model and incorporate new observations in real time. Finally, we evaluate our TVGL algorithm on both real and synthetic datasets, obtaining interpretable results and outperforming state-of-the-art baselines in terms of both accuracy and scalability. PMID:29770256
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Constructing an integrated gene similarity network for the identification of disease genes.
Tian, Zhen; Guo, Maozu; Wang, Chunyu; Xing, LinLin; Wang, Lei; Zhang, Yin
2017-09-20
Discovering novel genes that are involved human diseases is a challenging task in biomedical research. In recent years, several computational approaches have been proposed to prioritize candidate disease genes. Most of these methods are mainly based on protein-protein interaction (PPI) networks. However, since these PPI networks contain false positives and only cover less half of known human genes, their reliability and coverage are very low. Therefore, it is highly necessary to fuse multiple genomic data to construct a credible gene similarity network and then infer disease genes on the whole genomic scale. We proposed a novel method, named RWRB, to infer causal genes of interested diseases. First, we construct five individual gene (protein) similarity networks based on multiple genomic data of human genes. Then, an integrated gene similarity network (IGSN) is reconstructed based on similarity network fusion (SNF) method. Finally, we employee the random walk with restart algorithm on the phenotype-gene bilayer network, which combines phenotype similarity network, IGSN as well as phenotype-gene association network, to prioritize candidate disease genes. We investigate the effectiveness of RWRB through leave-one-out cross-validation methods in inferring phenotype-gene relationships. Results show that RWRB is more accurate than state-of-the-art methods on most evaluation metrics. Further analysis shows that the success of RWRB is benefited from IGSN which has a wider coverage and higher reliability comparing with current PPI networks. Moreover, we conduct a comprehensive case study for Alzheimer's disease and predict some novel disease genes that supported by literature. RWRB is an effective and reliable algorithm in prioritizing candidate disease genes on the genomic scale. Software and supplementary information are available at http://nclab.hit.edu.cn/~tianzhen/RWRB/ .
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Electronic Communication in Engineering Work.
ERIC Educational Resources Information Center
Bishop, Ann P.
1992-01-01
Discusses the role of electronic networks in engineering work; reviews selected literature on engineering work, knowledge, and communication; describes current uses of electronic networks; and presents results from a study of the use of networks by engineers in the aerospace industry, including their perceptions of networks. (67 references) (LRW)
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Generative models for discovering sparse distributed representations.
Hinton, G E; Ghahramani, Z
1997-01-01
We describe a hierarchical, generative model that can be viewed as a nonlinear generalization of factor analysis and can be implemented in a neural network. The model uses bottom-up, top-down and lateral connections to perform Bayesian perceptual inference correctly. Once perceptual inference has been performed the connection strengths can be updated using a very simple learning rule that only requires locally available information. We demonstrate that the network learns to extract sparse, distributed, hierarchical representations. PMID:9304685
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Chertkov, Michael
2012-07-24
The goal of the DTRA project is to develop a mathematical framework that will provide the fundamental understanding of network survivability, algorithms for detecting/inferring pre-cursors of abnormal network behaviors, and methods for network adaptability and self-healing from cascading failures.
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TRACING CO-REGULATORY NETWORK DYNAMICS IN NOISY, SINGLE-CELL TRANSCRIPTOME TRAJECTORIES.
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.
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Golightly, Andrew; Wilkinson, Darren J.
2011-01-01
Computational systems biology is concerned with the development of detailed mechanistic models of biological processes. Such models are often stochastic and analytically intractable, containing uncertain parameters that must be estimated from time course data. In this article, we consider the task of inferring the parameters of a stochastic kinetic model defined as a Markov (jump) process. Inference for the parameters of complex nonlinear multivariate stochastic process models is a challenging problem, but we find here that algorithms based on particle Markov chain Monte Carlo turn out to be a very effective computationally intensive approach to the problem. Approximations to the inferential model based on stochastic differential equations (SDEs) are considered, as well as improvements to the inference scheme that exploit the SDE structure. We apply the methodology to a Lotka–Volterra system and a prokaryotic auto-regulatory network. PMID:23226583
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An Ada inference engine for expert systems
NASA Technical Reports Server (NTRS)
Lavallee, David B.
1986-01-01
The purpose is to investigate the feasibility of using Ada for rule-based expert systems with real-time performance requirements. This includes exploring the Ada features which give improved performance to expert systems as well as optimizing the tradeoffs or workarounds that the use of Ada may require. A prototype inference engine was built using Ada, and rule firing rates in excess of 500 per second were demonstrated on a single MC68000 processor. The knowledge base uses a directed acyclic graph to represent production lines. The graph allows the use of AND, OR, and NOT logical operators. The inference engine uses a combination of both forward and backward chaining in order to reach goals as quickly as possible. Future efforts will include additional investigation of multiprocessing to improve performance and creating a user interface allowing rule input in an Ada-like syntax. Investigation of multitasking and alternate knowledge base representations will help to analyze some of the performance issues as they relate to larger problems.
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fastBMA: scalable network inference and transitive reduction.
Hung, Ling-Hong; Shi, Kaiyuan; Wu, Migao; Young, William Chad; Raftery, Adrian E; Yeung, Ka Yee
2017-10-01
Inferring genetic networks from genome-wide expression data is extremely demanding computationally. We have developed fastBMA, a distributed, parallel, and scalable implementation of Bayesian model averaging (BMA) for this purpose. fastBMA also includes a computationally efficient module for eliminating redundant indirect edges in the network by mapping the transitive reduction to an easily solved shortest-path problem. We evaluated the performance of fastBMA on synthetic data and experimental genome-wide time series yeast and human datasets. When using a single CPU core, fastBMA is up to 100 times faster than the next fastest method, LASSO, with increased accuracy. It is a memory-efficient, parallel, and distributed application that scales to human genome-wide expression data. A 10 000-gene regulation network can be obtained in a matter of hours using a 32-core cloud cluster (2 nodes of 16 cores). fastBMA is a significant improvement over its predecessor ScanBMA. It is more accurate and orders of magnitude faster than other fast network inference methods such as the 1 based on LASSO. The improved scalability allows it to calculate networks from genome scale data in a reasonable time frame. The transitive reduction method can improve accuracy in denser networks. fastBMA is available as code (M.I.T. license) from GitHub (https://github.com/lhhunghimself/fastBMA), as part of the updated networkBMA Bioconductor package (https://www.bioconductor.org/packages/release/bioc/html/networkBMA.html) and as ready-to-deploy Docker images (https://hub.docker.com/r/biodepot/fastbma/). © The Authors 2017. Published by Oxford University Press.
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Mineral and Geochemical Classification From Spectroscopy/Diffraction Through Neural Networks
NASA Astrophysics Data System (ADS)
Ferralis, N.; Grossman, J.; Summons, R. E.
2017-12-01
Spectroscopy and diffraction techniques are essential for understanding structural, chemical and functional properties of geological materials for Earth and Planetary Sciences. Beyond data collection, quantitative insight relies on experimentally assembled, or computationally derived spectra. Inference on the geochemical or geophysical properties (such as crystallographic order, chemical functionality, elemental composition, etc.) of a particular geological material (mineral, organic matter, etc.) is based on fitting unknown spectra and comparing the fit with consolidated databases. The complexity of fitting highly convoluted spectra, often limits the ability to infer geochemical characteristics, and limits the throughput for extensive datasets. With the emergence of heuristic approaches to pattern recognitions though machine learning, in this work we investigate the possibility and potential of using supervised neural networks trained on available public spectroscopic database to directly infer geochemical parameters from unknown spectra. Using Raman, infrared spectroscopy and powder x-ray diffraction from the publicly available RRUFF database, we train neural network models to classify mineral and organic compounds (pure or mixtures) based on crystallographic structure from diffraction, chemical functionality, elemental composition and bonding from spectroscopy. As expected, the accuracy of the inference is strongly dependent on the quality and extent of the training data. We will identify a series of requirements and guidelines for the training dataset needed to achieve consistent high accuracy inference, along with methods to compensate for limited of data.
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Deep Unfolding for Topic Models.
Chien, Jen-Tzung; Lee, Chao-Hsi
2018-02-01
Deep unfolding provides an approach to integrate the probabilistic generative models and the deterministic neural networks. Such an approach is benefited by deep representation, easy interpretation, flexible learning and stochastic modeling. This study develops the unsupervised and supervised learning of deep unfolded topic models for document representation and classification. Conventionally, the unsupervised and supervised topic models are inferred via the variational inference algorithm where the model parameters are estimated by maximizing the lower bound of logarithm of marginal likelihood using input documents without and with class labels, respectively. The representation capability or classification accuracy is constrained by the variational lower bound and the tied model parameters across inference procedure. This paper aims to relax these constraints by directly maximizing the end performance criterion and continuously untying the parameters in learning process via deep unfolding inference (DUI). The inference procedure is treated as the layer-wise learning in a deep neural network. The end performance is iteratively improved by using the estimated topic parameters according to the exponentiated updates. Deep learning of topic models is therefore implemented through a back-propagation procedure. Experimental results show the merits of DUI with increasing number of layers compared with variational inference in unsupervised as well as supervised topic models.
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False belief and counterfactual reasoning in a social environment.
Van Hoeck, Nicole; Begtas, Elizabet; Steen, Johan; Kestemont, Jenny; Vandekerckhove, Marie; Van Overwalle, Frank
2014-04-15
Behavioral studies indicate that theory of mind and counterfactual reasoning are strongly related cognitive processes. In a neuroimaging study, we explored the common and distinct regions underlying these inference processes. We directly compared false belief reasoning (inferring an agent's false belief about an object's location or content) and counterfactual reasoning (inferring what the object's location or content would be if an agent had acted differently), both in contrast with a baseline condition of conditional reasoning (inferring what the true location or content of an object is). Results indicate that these three types of reasoning about social scenarios are supported by activations in the mentalizing network (left temporo-parietal junction and precuneus) and the executive control network (bilateral prefrontal cortex [PFC] and right inferior parietal lobule). In addition, representing a false belief or counterfactual state (both not directly observable in the external world) recruits additional activity in the executive control network (left dorsolateral PFC and parietal lobe). The results further suggest that counterfactual reasoning is a more complex cognitive process than false belief reasoning, showing stronger activation of the dorsomedial, left dorsolateral PFC, cerebellum and left temporal cortex. Copyright © 2013 Elsevier Inc. All rights reserved.
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Genome-wide inference of regulatory networks in Streptomyces coelicolor.
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.
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The Art of Artificial Intelligence. 1. Themes and Case Studies of Knowledge Engineering
1977-08-01
in scientific and medical inference illuminate the art of knowledge engineering and its parent science , Artificial Intelligence....The knowledge engineer practices the art of bringing the principles and tools of AI research to bear on difficult applications problems requiring
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Misra, Sudip; Singh, Ranjit; Rohith Mohan, S. V.
2010-01-01
The proposed mechanism for jamming attack detection for wireless sensor networks is novel in three respects: firstly, it upgrades the jammer to include versatile military jammers; secondly, it graduates from the existing node-centric detection system to the network-centric system making it robust and economical at the nodes, and thirdly, it tackles the problem through fuzzy inference system, as the decision regarding intensity of jamming is seldom crisp. The system with its high robustness, ability to grade nodes with jamming indices, and its true-detection rate as high as 99.8%, is worthy of consideration for information warfare defense purposes. PMID:22319307
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NASA Astrophysics Data System (ADS)
Lian, Jie; Liu, Yun; Zhang, Zhen-jiang; Gui, Chang-ni
2013-10-01
Bipartite network based recommendations have attracted extensive attentions in recent years. Differing from traditional object-oriented recommendations, the recommendation in a Microblog network has two crucial differences. One is high authority users or one’s special friends usually play a very active role in tweet-oriented recommendation. The other is that the object in a Microblog network corresponds to a set of tweets on same topic instead of an actual and single entity, e.g. goods or movies in traditional networks. Thus repeat recommendations of the tweets in one’s collected topics are indispensable. Therefore, this paper improves network based inference (NBI) algorithm by original link matrix and link weight on resource allocation processes. This paper finally proposes the Microblog recommendation model based on the factors of improved network based inference and user influence model. Adjusting the weights of these two factors could generate the best recommendation results in algorithm accuracy and recommendation personalization.
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Cerebellarlike corrective model inference engine for manipulation tasks.
Luque, Niceto Rafael; Garrido, Jesús Alberto; Carrillo, Richard Rafael; Coenen, Olivier J-M D; Ros, Eduardo
2011-10-01
This paper presents how a simple cerebellumlike architecture can infer corrective models in the framework of a control task when manipulating objects that significantly affect the dynamics model of the system. The main motivation of this paper is to evaluate a simplified bio-mimetic approach in the framework of a manipulation task. More concretely, the paper focuses on how the model inference process takes place within a feedforward control loop based on the cerebellar structure and on how these internal models are built up by means of biologically plausible synaptic adaptation mechanisms. This kind of investigation may provide clues on how biology achieves accurate control of non-stiff-joint robot with low-power actuators which involve controlling systems with high inertial components. This paper studies how a basic temporal-correlation kernel including long-term depression (LTD) and a constant long-term potentiation (LTP) at parallel fiber-Purkinje cell synapses can effectively infer corrective models. We evaluate how this spike-timing-dependent plasticity correlates sensorimotor activity arriving through the parallel fibers with teaching signals (dependent on error estimates) arriving through the climbing fibers from the inferior olive. This paper addresses the study of how these LTD and LTP components need to be well balanced with each other to achieve accurate learning. This is of interest to evaluate the relevant role of homeostatic mechanisms in biological systems where adaptation occurs in a distributed manner. Furthermore, we illustrate how the temporal-correlation kernel can also work in the presence of transmission delays in sensorimotor pathways. We use a cerebellumlike spiking neural network which stores the corrective models as well-structured weight patterns distributed among the parallel fibers to Purkinje cell connections.
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Koda, Satoru; Onda, Yoshihiko; Matsui, Hidetoshi; Takahagi, Kotaro; Yamaguchi-Uehara, Yukiko; Shimizu, Minami; Inoue, Komaki; Yoshida, Takuhiro; Sakurai, Tetsuya; Honda, Hiroshi; Eguchi, Shinto; Nishii, Ryuei; Mochida, Keiichi
2017-01-01
We report the comprehensive identification of periodic genes and their network inference, based on a gene co-expression analysis and an Auto-Regressive eXogenous (ARX) model with a group smoothly clipped absolute deviation (SCAD) method using a time-series transcriptome dataset in a model grass, Brachypodium distachyon . To reveal the diurnal changes in the transcriptome in B. distachyon , we performed RNA-seq analysis of its leaves sampled through a diurnal cycle of over 48 h at 4 h intervals using three biological replications, and identified 3,621 periodic genes through our wavelet analysis. The expression data are feasible to infer network sparsity based on ARX models. We found that genes involved in biological processes such as transcriptional regulation, protein degradation, and post-transcriptional modification and photosynthesis are significantly enriched in the periodic genes, suggesting that these processes might be regulated by circadian rhythm in B. distachyon . On the basis of the time-series expression patterns of the periodic genes, we constructed a chronological gene co-expression network and identified putative transcription factors encoding genes that might be involved in the time-specific regulatory transcriptional network. Moreover, we inferred a transcriptional network composed of the periodic genes in B. distachyon , aiming to identify genes associated with other genes through variable selection by grouping time points for each gene. Based on the ARX model with the group SCAD regularization using our time-series expression datasets of the periodic genes, we constructed gene networks and found that the networks represent typical scale-free structure. Our findings demonstrate that the diurnal changes in the transcriptome in B. distachyon leaves have a sparse network structure, demonstrating the spatiotemporal gene regulatory network over the cyclic phase transitions in B. distachyon diurnal growth.
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2013-01-01
Background In recent years, various types of cellular networks have penetrated biology and are nowadays used omnipresently for studying eukaryote and prokaryote organisms. Still, the relation and the biological overlap among phenomenological and inferential gene networks, e.g., between the protein interaction network and the gene regulatory network inferred from large-scale transcriptomic data, is largely unexplored. Results We provide in this study an in-depth analysis of the structural, functional and chromosomal relationship between a protein-protein network, a transcriptional regulatory network and an inferred gene regulatory network, for S. cerevisiae and E. coli. Further, we study global and local aspects of these networks and their biological information overlap by comparing, e.g., the functional co-occurrence of Gene Ontology terms by exploiting the available interaction structure among the genes. Conclusions Although the individual networks represent different levels of cellular interactions with global structural and functional dissimilarities, we observe crucial functions of their network interfaces for the assembly of protein complexes, proteolysis, transcription, translation, metabolic and regulatory interactions. Overall, our results shed light on the integrability of these networks and their interfacing biological processes. PMID:23663484
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NASA Astrophysics Data System (ADS)
Gimazov, R.; Shidlovskiy, S.
2018-05-01
In this paper, we consider the architecture of the algorithm for extreme regulation in the photovoltaic system. An algorithm based on an adaptive neural network with fuzzy inference is proposed. The implementation of such an algorithm not only allows solving a number of problems in existing algorithms for extreme power regulation of photovoltaic systems, but also creates a reserve for the creation of a universal control system for a photovoltaic system.
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Lemmens, Karen; De Bie, Tijl; Dhollander, Thomas; De Keersmaecker, Sigrid C; Thijs, Inge M; Schoofs, Geert; De Weerdt, Ami; De Moor, Bart; Vanderleyden, Jos; Collado-Vides, Julio; Engelen, Kristof; Marchal, Kathleen
2009-01-01
We present DISTILLER, a data integration framework for the inference of transcriptional module networks. Experimental validation of predicted targets for the well-studied fumarate nitrate reductase regulator showed the effectiveness of our approach in Escherichia coli. In addition, the condition dependency and modularity of the inferred transcriptional network was studied. Surprisingly, the level of regulatory complexity seemed lower than that which would be expected from RegulonDB, indicating that complex regulatory programs tend to decrease the degree of modularity.
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Probabilistic inference using linear Gaussian importance sampling for hybrid Bayesian networks
NASA Astrophysics Data System (ADS)
Sun, Wei; Chang, K. C.
2005-05-01
Probabilistic inference for Bayesian networks is in general NP-hard using either exact algorithms or approximate methods. However, for very complex networks, only the approximate methods such as stochastic sampling could be used to provide a solution given any time constraint. There are several simulation methods currently available. They include logic sampling (the first proposed stochastic method for Bayesian networks, the likelihood weighting algorithm) the most commonly used simulation method because of its simplicity and efficiency, the Markov blanket scoring method, and the importance sampling algorithm. In this paper, we first briefly review and compare these available simulation methods, then we propose an improved importance sampling algorithm called linear Gaussian importance sampling algorithm for general hybrid model (LGIS). LGIS is aimed for hybrid Bayesian networks consisting of both discrete and continuous random variables with arbitrary distributions. It uses linear function and Gaussian additive noise to approximate the true conditional probability distribution for continuous variable given both its parents and evidence in a Bayesian network. One of the most important features of the newly developed method is that it can adaptively learn the optimal important function from the previous samples. We test the inference performance of LGIS using a 16-node linear Gaussian model and a 6-node general hybrid model. The performance comparison with other well-known methods such as Junction tree (JT) and likelihood weighting (LW) shows that LGIS-GHM is very promising.
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A Multi-Method Approach for Proteomic Network Inference in 11 Human Cancers.
Şenbabaoğlu, Yasin; Sümer, Selçuk Onur; Sánchez-Vega, Francisco; Bemis, Debra; Ciriello, Giovanni; Schultz, Nikolaus; Sander, Chris
2016-02-01
Protein expression and post-translational modification levels are tightly regulated in neoplastic cells to maintain cellular processes known as 'cancer hallmarks'. The first Pan-Cancer initiative of The Cancer Genome Atlas (TCGA) Research Network has aggregated protein expression profiles for 3,467 patient samples from 11 tumor types using the antibody based reverse phase protein array (RPPA) technology. The resultant proteomic data can be utilized to computationally infer protein-protein interaction (PPI) networks and to study the commonalities and differences across tumor types. In this study, we compare the performance of 13 established network inference methods in their capacity to retrieve the curated Pathway Commons interactions from RPPA data. We observe that no single method has the best performance in all tumor types, but a group of six methods, including diverse techniques such as correlation, mutual information, and regression, consistently rank highly among the tested methods. We utilize the high performing methods to obtain a consensus network; and identify four robust and densely connected modules that reveal biological processes as well as suggest antibody-related technical biases. Mapping the consensus network interactions to Reactome gene lists confirms the pan-cancer importance of signal transduction pathways, innate and adaptive immune signaling, cell cycle, metabolism, and DNA repair; and also suggests several biological processes that may be specific to a subset of tumor types. Our results illustrate the utility of the RPPA platform as a tool to study proteomic networks in cancer.
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Hu, Yanzhu; Ai, Xinbo
2016-01-01
Complex network methodology is very useful for complex system explorer. However, the relationships among variables in complex system are usually not clear. Therefore, inferring association networks among variables from their observed data has been a popular research topic. We propose a synthetic method, named small-shuffle partial symbolic transfer entropy spectrum (SSPSTES), for inferring association network from multivariate time series. The method synthesizes surrogate data, partial symbolic transfer entropy (PSTE) and Granger causality. A proper threshold selection is crucial for common correlation identification methods and it is not easy for users. The proposed method can not only identify the strong correlation without selecting a threshold but also has the ability of correlation quantification, direction identification and temporal relation identification. The method can be divided into three layers, i.e. data layer, model layer and network layer. In the model layer, the method identifies all the possible pair-wise correlation. In the network layer, we introduce a filter algorithm to remove the indirect weak correlation and retain strong correlation. Finally, we build a weighted adjacency matrix, the value of each entry representing the correlation level between pair-wise variables, and then get the weighted directed association network. Two numerical simulated data from linear system and nonlinear system are illustrated to show the steps and performance of the proposed approach. The ability of the proposed method is approved by an application finally. PMID:27832153
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Multinomial Bayesian learning for modeling classical and nonclassical receptive field properties.
Hosoya, Haruo
2012-08-01
We study the interplay of Bayesian inference and natural image learning in a hierarchical vision system, in relation to the response properties of early visual cortex. We particularly focus on a Bayesian network with multinomial variables that can represent discrete feature spaces similar to hypercolumns combining minicolumns, enforce sparsity of activation to learn efficient representations, and explain divisive normalization. We demonstrate that maximal-likelihood learning using sampling-based Bayesian inference gives rise to classical receptive field properties similar to V1 simple cells and V2 cells, while inference performed on the trained network yields nonclassical context-dependent response properties such as cross-orientation suppression and filling in. Comparison with known physiological properties reveals some qualitative and quantitative similarities.
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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
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NASA Astrophysics Data System (ADS)
Jeon, Gyuhyeon; Park, Juyong
2017-02-01
In the common jury-contestant competition format, a jury consisting of multiple judges grade contestants on their performances to determine their ranking. Unlike in another common competition format where two contestants play a head-to-head match to produce the winner such as in football or basketball, the objectivity of judges are often called into question, potentially undermining the public's trust in the fairness of the competition. In this work we show, by modeling the jury-contestant competition format as a weighted bipartite network, how one can identify biased scores and how they impact the competition and its structure. Analyzing the prestigious International Chopin Piano Competition of 2015 as an example with a well-publicized scoring controversy, we show that the presence of even a very small fraction of biased edges can gravely distort our inference of the network structure —in the example a single biased edge is shown to lead to an incorrect “solution” that also wrongly appears to be robust exclusively, dominating other reasonable solutions— highlighting the importance of bias detection and elimination in network inference. In the process our work also presents a modified modularity measure for the one-mode projection of weighted complete bipartite networks.
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Autonomous entropy-based intelligent experimental design
NASA Astrophysics Data System (ADS)
Malakar, Nabin Kumar
2011-07-01
The aim of this thesis is to explore the application of probability and information theory in experimental design, and to do so in a way that combines what we know about inference and inquiry in a comprehensive and consistent manner. Present day scientific frontiers involve data collection at an ever-increasing rate. This requires that we find a way to collect the most relevant data in an automated fashion. By following the logic of the scientific method, we couple an inference engine with an inquiry engine to automate the iterative process of scientific learning. The inference engine involves Bayesian machine learning techniques to estimate model parameters based upon both prior information and previously collected data, while the inquiry engine implements data-driven exploration. By choosing an experiment whose distribution of expected results has the maximum entropy, the inquiry engine selects the experiment that maximizes the expected information gain. The coupled inference and inquiry engines constitute an autonomous learning method for scientific exploration. We apply it to a robotic arm to demonstrate the efficacy of the method. Optimizing inquiry involves searching for an experiment that promises, on average, to be maximally informative. If the set of potential experiments is described by many parameters, the search involves a high-dimensional entropy space. In such cases, a brute force search method will be slow and computationally expensive. We develop an entropy-based search algorithm, called nested entropy sampling, to select the most informative experiment. This helps to reduce the number of computations necessary to find the optimal experiment. We also extended the method of maximizing entropy, and developed a method of maximizing joint entropy so that it could be used as a principle of collaboration between two robots. This is a major achievement of this thesis, as it allows the information-based collaboration between two robotic units towards a same goal in an automated fashion.
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Development of a Spacecraft Materials Selector Expert System
NASA Technical Reports Server (NTRS)
Pippin, G.; Kauffman, W. (Technical Monitor)
2002-01-01
This report contains a description of the knowledge base tool and examples of its use. A downloadable version of the Spacecraft Materials Selector (SMS) knowledge base is available through the NASA Space Environments and Effects Program. The "Spacecraft Materials Selector" knowledge base is part of an electronic expert system. The expert system consists of an inference engine that contains the "decision-making" code and the knowledge base that contains the selected body of information. The inference engine is a software package previously developed at Boeing, called the Boeing Expert System Tool (BEST) kit.
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Signal Processing Expert Code (SPEC)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ames, H.S.
1985-12-01
The purpose of this paper is to describe a prototype expert system called SPEC which was developed to demonstrate the utility of providing an intelligent interface for users of SIG, a general purpose signal processing code. The expert system is written in NIL, runs on a VAX 11/750 and consists of a backward chaining inference engine and an English-like parser. The inference engine uses knowledge encoded as rules about the formats of SIG commands and about how to perform frequency analyses using SIG. The system demonstrated that expert system can be used to control existing codes.
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Bayesian Inference of Natural Rankings in Incomplete Competition Networks
Park, Juyong; Yook, Soon-Hyung
2014-01-01
Competition between a complex system's constituents and a corresponding reward mechanism based on it have profound influence on the functioning, stability, and evolution of the system. But determining the dominance hierarchy or ranking among the constituent parts from the strongest to the weakest – essential in determining reward and penalty – is frequently an ambiguous task due to the incomplete (partially filled) nature of competition networks. Here we introduce the “Natural Ranking,” an unambiguous ranking method applicable to a round robin tournament, and formulate an analytical model based on the Bayesian formula for inferring the expected mean and error of the natural ranking of nodes from an incomplete network. We investigate its potential and uses in resolving important issues of ranking by applying it to real-world competition networks. PMID:25163528
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Bayesian Inference of Natural Rankings in Incomplete Competition Networks
NASA Astrophysics Data System (ADS)
Park, Juyong; Yook, Soon-Hyung
2014-08-01
Competition between a complex system's constituents and a corresponding reward mechanism based on it have profound influence on the functioning, stability, and evolution of the system. But determining the dominance hierarchy or ranking among the constituent parts from the strongest to the weakest - essential in determining reward and penalty - is frequently an ambiguous task due to the incomplete (partially filled) nature of competition networks. Here we introduce the ``Natural Ranking,'' an unambiguous ranking method applicable to a round robin tournament, and formulate an analytical model based on the Bayesian formula for inferring the expected mean and error of the natural ranking of nodes from an incomplete network. We investigate its potential and uses in resolving important issues of ranking by applying it to real-world competition networks.
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Personalized recommendation via unbalance full-connectivity inference
NASA Astrophysics Data System (ADS)
Ma, Wenping; Ren, Chen; Wu, Yue; Wang, Shanfeng; Feng, Xiang
2017-10-01
Recommender systems play an important role to help us to find useful information. They are widely used by most e-commerce web sites to push the potential items to individual user according to purchase history. Network-based recommendation algorithms are popular and effective in recommendation, which use two types of elements to represent users and items respectively. In this paper, based on consistence-based inference (CBI) algorithm, we propose a novel network-based algorithm, in which users and items are recognized with no difference. The proposed algorithm also uses information diffusion to find the relationship between users and items. Different from traditional network-based recommendation algorithms, information diffusion initializes from users and items, respectively. Experiments show that the proposed algorithm is effective compared with traditional network-based recommendation algorithms.
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A Neural Network Aero Design System for Advanced Turbo-Engines
NASA Technical Reports Server (NTRS)
Sanz, Jose M.
1999-01-01
An inverse design method calculates the blade shape that produces a prescribed input pressure distribution. By controlling this input pressure distribution the aerodynamic design objectives can easily be met. Because of the intrinsic relationship between pressure distribution and airfoil physical properties, a Neural Network can be trained to choose the optimal pressure distribution that would meet a set of physical requirements. Neural network systems have been attempted in the context of direct design methods. From properties ascribed to a set of blades the neural network is trained to infer the properties of an 'interpolated' blade shape. The problem is that, especially in transonic regimes where we deal with intrinsically non linear and ill posed problems, small perturbations of the blade shape can produce very large variations of the flow parameters. It is very unlikely that, under these circumstances, a neural network will be able to find the proper solution. The unique situation in the present method is that the neural network can be trained to extract the required input pressure distribution from a database of pressure distributions while the inverse method will still compute the exact blade shape that corresponds to this 'interpolated' input pressure distribution. In other words, the interpolation process is transferred to a smoother problem, namely, finding what pressure distribution would produce the required flow conditions and, once this is done, the inverse method will compute the exact solution for this problem. The use of neural network is, in this context, highly related to the use of proper optimization techniques. The optimization is used essentially as an automation procedure to force the input pressure distributions to achieve the required aero and structural design parameters. A multilayered feed forward network with back-propagation is used to train the system for pattern association and classification.
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SPIKE – a database, visualization and analysis tool of cellular signaling pathways
Elkon, Ran; Vesterman, Rita; Amit, Nira; Ulitsky, Igor; Zohar, Idan; Weisz, Mali; Mass, Gilad; Orlev, Nir; Sternberg, Giora; Blekhman, Ran; Assa, Jackie; Shiloh, Yosef; Shamir, Ron
2008-01-01
Background Biological signaling pathways that govern cellular physiology form an intricate web of tightly regulated interlocking processes. Data on these regulatory networks are accumulating at an unprecedented pace. The assimilation, visualization and interpretation of these data have become a major challenge in biological research, and once met, will greatly boost our ability to understand cell functioning on a systems level. Results To cope with this challenge, we are developing the SPIKE knowledge-base of signaling pathways. SPIKE contains three main software components: 1) A database (DB) of biological signaling pathways. Carefully curated information from the literature and data from large public sources constitute distinct tiers of the DB. 2) A visualization package that allows interactive graphic representations of regulatory interactions stored in the DB and superposition of functional genomic and proteomic data on the maps. 3) An algorithmic inference engine that analyzes the networks for novel functional interplays between network components. SPIKE is designed and implemented as a community tool and therefore provides a user-friendly interface that allows registered users to upload data to SPIKE DB. Our vision is that the DB will be populated by a distributed and highly collaborative effort undertaken by multiple groups in the research community, where each group contributes data in its field of expertise. Conclusion The integrated capabilities of SPIKE make it a powerful platform for the analysis of signaling networks and the integration of knowledge on such networks with omics data. PMID:18289391
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Inferring Structure and Forecasting Dynamics on Evolving Networks
2016-01-05
Graphs ........................................................................................................................ 23 7. Sacred Values...5) Team Formation; (6) Games of Graphs; (7) Sacred Values and Legitimacy in Network Interactions; (8) Network processes in Geo-Social Context. 1...Authority, Cooperation and Competition in Religious Networks Key Papers: McBride 2015a [72] and McBride 2015b [73] McBride (2015a) examines
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Functional network inference of the suprachiasmatic nucleus
DOE Office of Scientific and Technical Information (OSTI.GOV)
Abel, John H.; Meeker, Kirsten; Granados-Fuentes, Daniel
2016-04-04
In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators communicate within a neuronal network to generate precise system-wide circadian rhythms. Although the intracellular genetic oscillator and intercellular biochemical coupling mechanisms have been examined previously, the network topology driving synchronization of the SCN has not been elucidated. This network has been particularly challenging to probe, due to its oscillatory components and slow coupling timescale. In this work, we investigated the SCN network at a single-cell resolution through a chemically induced desynchronization. We then inferred functional connections in the SCN by applying the maximal information coefficient statistic to bioluminescence reporter data frommore » individual neurons while they resynchronized their circadian cycling. Our results demonstrate that the functional network of circadian cells associated with resynchronization has small-world characteristics, with a node degree distribution that is exponential. We show that hubs of this small-world network are preferentially located in the central SCN, with sparsely connected shells surrounding these cores. Finally, we used two computational models of circadian neurons to validate our predictions of network structure.« less
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Nir, Oaz; Bakal, Chris; Perrimon, Norbert; Berger, Bonnie
2010-03-01
Biological networks are highly complex systems, consisting largely of enzymes that act as molecular switches to activate/inhibit downstream targets via post-translational modification. Computational techniques have been developed to perform signaling network inference using some high-throughput data sources, such as those generated from transcriptional and proteomic studies, but comparable methods have not been developed to use high-content morphological data, which are emerging principally from large-scale RNAi screens, to these ends. Here, we describe a systematic computational framework based on a classification model for identifying genetic interactions using high-dimensional single-cell morphological data from genetic screens, apply it to RhoGAP/GTPase regulation in Drosophila, and evaluate its efficacy. Augmented by knowledge of the basic structure of RhoGAP/GTPase signaling, namely, that GAPs act directly upstream of GTPases, we apply our framework for identifying genetic interactions to predict signaling relationships between these proteins. We find that our method makes mediocre predictions using only RhoGAP single-knockdown morphological data, yet achieves vastly improved accuracy by including original data from a double-knockdown RhoGAP genetic screen, which likely reflects the redundant network structure of RhoGAP/GTPase signaling. We consider other possible methods for inference and show that our primary model outperforms the alternatives. This work demonstrates the fundamental fact that high-throughput morphological data can be used in a systematic, successful fashion to identify genetic interactions and, using additional elementary knowledge of network structure, to infer signaling relations.
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Scalable Probabilistic Inference for Global Seismic Monitoring
NASA Astrophysics Data System (ADS)
Arora, N. S.; Dear, T.; Russell, S.
2011-12-01
We describe a probabilistic generative model for seismic events, their transmission through the earth, and their detection (or mis-detection) at seismic stations. We also describe an inference algorithm that constructs the most probable event bulletin explaining the observed set of detections. The model and inference are called NET-VISA (network processing vertically integrated seismic analysis) and is designed to replace the current automated network processing at the IDC, the SEL3 bulletin. Our results (attached table) demonstrate that NET-VISA significantly outperforms SEL3 by reducing the missed events from 30.3% down to 12.5%. The difference is even more dramatic for smaller magnitude events. NET-VISA has no difficulty in locating nuclear explosions as well. The attached figure demonstrates the location predicted by NET-VISA versus other bulletins for the second DPRK event. Further evaluation on dense regional networks demonstrates that NET-VISA finds many events missed in the LEB bulletin, which is produced by the human analysts. Large aftershock sequences, as produced by the 2004 December Sumatra earthquake and the 2011 March Tohoku earthquake, can pose a significant load for automated processing, often delaying the IDC bulletins by weeks or months. Indeed these sequences can overload the serial NET-VISA inference as well. We describe an enhancement to NET-VISA to make it multi-threaded, and hence take full advantage of the processing power of multi-core and -cpu machines. Our experiments show that the new inference algorithm is able to achieve 80% efficiency in parallel speedup.
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Cross-Dependency Inference in Multi-Layered Networks: A Collaborative Filtering Perspective.
Chen, Chen; Tong, Hanghang; Xie, Lei; Ying, Lei; He, Qing
2017-08-01
The increasingly connected world has catalyzed the fusion of networks from different domains, which facilitates the emergence of a new network model-multi-layered networks. Examples of such kind of network systems include critical infrastructure networks, biological systems, organization-level collaborations, cross-platform e-commerce, and so forth. One crucial structure that distances multi-layered network from other network models is its cross-layer dependency, which describes the associations between the nodes from different layers. Needless to say, the cross-layer dependency in the network plays an essential role in many data mining applications like system robustness analysis and complex network control. However, it remains a daunting task to know the exact dependency relationships due to noise, limited accessibility, and so forth. In this article, we tackle the cross-layer dependency inference problem by modeling it as a collective collaborative filtering problem. Based on this idea, we propose an effective algorithm Fascinate that can reveal unobserved dependencies with linear complexity. Moreover, we derive Fascinate-ZERO, an online variant of Fascinate that can respond to a newly added node timely by checking its neighborhood dependencies. We perform extensive evaluations on real datasets to substantiate the superiority of our proposed approaches.
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White, H; Racine, J
2001-01-01
We propose tests for individual and joint irrelevance of network inputs. Such tests can be used to determine whether an input or group of inputs "belong" in a particular model, thus permitting valid statistical inference based on estimated feedforward neural-network models. The approaches employ well-known statistical resampling techniques. We conduct a small Monte Carlo experiment showing that our tests have reasonable level and power behavior, and we apply our methods to examine whether there are predictable regularities in foreign exchange rates. We find that exchange rates do appear to contain information that is exploitable for enhanced point prediction, but the nature of the predictive relations evolves through time.
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Inverse Ising problem in continuous time: A latent variable approach
NASA Astrophysics Data System (ADS)
Donner, Christian; Opper, Manfred
2017-12-01
We consider the inverse Ising problem: the inference of network couplings from observed spin trajectories for a model with continuous time Glauber dynamics. By introducing two sets of auxiliary latent random variables we render the likelihood into a form which allows for simple iterative inference algorithms with analytical updates. The variables are (1) Poisson variables to linearize an exponential term which is typical for point process likelihoods and (2) Pólya-Gamma variables, which make the likelihood quadratic in the coupling parameters. Using the augmented likelihood, we derive an expectation-maximization (EM) algorithm to obtain the maximum likelihood estimate of network parameters. Using a third set of latent variables we extend the EM algorithm to sparse couplings via L1 regularization. Finally, we develop an efficient approximate Bayesian inference algorithm using a variational approach. We demonstrate the performance of our algorithms on data simulated from an Ising model. For data which are simulated from a more biologically plausible network with spiking neurons, we show that the Ising model captures well the low order statistics of the data and how the Ising couplings are related to the underlying synaptic structure of the simulated network.
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Discovering time-lagged rules from microarray data using gene profile classifiers
2011-01-01
Background Gene regulatory networks have an essential role in every process of life. In this regard, the amount of genome-wide time series data is becoming increasingly available, providing the opportunity to discover the time-delayed gene regulatory networks that govern the majority of these molecular processes. Results This paper aims at reconstructing gene regulatory networks from multiple genome-wide microarray time series datasets. In this sense, a new model-free algorithm called GRNCOP2 (Gene Regulatory Network inference by Combinatorial OPtimization 2), which is a significant evolution of the GRNCOP algorithm, was developed using combinatorial optimization of gene profile classifiers. The method is capable of inferring potential time-delay relationships with any span of time between genes from various time series datasets given as input. The proposed algorithm was applied to time series data composed of twenty yeast genes that are highly relevant for the cell-cycle study, and the results were compared against several related approaches. The outcomes have shown that GRNCOP2 outperforms the contrasted methods in terms of the proposed metrics, and that the results are consistent with previous biological knowledge. Additionally, a genome-wide study on multiple publicly available time series data was performed. In this case, the experimentation has exhibited the soundness and scalability of the new method which inferred highly-related statistically-significant gene associations. Conclusions A novel method for inferring time-delayed gene regulatory networks from genome-wide time series datasets is proposed in this paper. The method was carefully validated with several publicly available data sets. The results have demonstrated that the algorithm constitutes a usable model-free approach capable of predicting meaningful relationships between genes, revealing the time-trends of gene regulation. PMID:21524308
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2018-01-01
Signaling pathways represent parts of the global biological molecular network which connects them into a seamless whole through complex direct and indirect (hidden) crosstalk whose structure can change during development or in pathological conditions. We suggest a novel methodology, called Googlomics, for the structural analysis of directed biological networks using spectral analysis of their Google matrices, using parallels with quantum scattering theory, developed for nuclear and mesoscopic physics and quantum chaos. We introduce analytical “reduced Google matrix” method for the analysis of biological network structure. The method allows inferring hidden causal relations between the members of a signaling pathway or a functionally related group of genes. We investigate how the structure of hidden causal relations can be reprogrammed as a result of changes in the transcriptional network layer during cancerogenesis. The suggested Googlomics approach rigorously characterizes complex systemic changes in the wiring of large causal biological networks in a computationally efficient way. PMID:29370181
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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
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Statistical inference to advance network models in epidemiology.
Welch, David; Bansal, Shweta; Hunter, David R
2011-03-01
Contact networks are playing an increasingly important role in the study of epidemiology. Most of the existing work in this area has focused on considering the effect of underlying network structure on epidemic dynamics by using tools from probability theory and computer simulation. This work has provided much insight on the role that heterogeneity in host contact patterns plays on infectious disease dynamics. Despite the important understanding afforded by the probability and simulation paradigm, this approach does not directly address important questions about the structure of contact networks such as what is the best network model for a particular mode of disease transmission, how parameter values of a given model should be estimated, or how precisely the data allow us to estimate these parameter values. We argue that these questions are best answered within a statistical framework and discuss the role of statistical inference in estimating contact networks from epidemiological data. Copyright © 2011 Elsevier B.V. All rights reserved.
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NASA Astrophysics Data System (ADS)
Rings, Thorsten; Lehnertz, Klaus
2016-09-01
We investigate the relative merit of phase-based methods for inferring directional couplings in complex networks of weakly interacting dynamical systems from multivariate time-series data. We compare the evolution map approach and its partialized extension to each other with respect to their ability to correctly infer the network topology in the presence of indirect directional couplings for various simulated experimental situations using coupled model systems. In addition, we investigate whether the partialized approach allows for additional or complementary indications of directional interactions in evolving epileptic brain networks using intracranial electroencephalographic recordings from an epilepsy patient. For such networks, both direct and indirect directional couplings can be expected, given the brain's connection structure and effects that may arise from limitations inherent to the recording technique. Our findings indicate that particularly in larger networks (number of nodes ≫10 ), the partialized approach does not provide information about directional couplings extending the information gained with the evolution map approach.
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Mason, Robert A.; Williams, Diane L.; Kana, Rajesh K.; Minshew, Nancy; Just, Marcel Adam
2008-01-01
The intersection of Theory of Mind (ToM) processing and complex narrative comprehension in high functioning autism was examined by comparing cortical activation during the reading of passages that required inferences based on either intentions, emotional states, or physical causality. Right hemisphere activation was substantially greater for all sentences in the autism group than in a matched control group suggesting decreased LH capacity in autism resulting in a spillover of processing to RH homologs. Moreover, the ToM network was disrupted. The autism group showed similar activation for all inference types in the right temporo-parietal component of the ToM network whereas the control participants selectively activated this network only when appropriate. The autism group had lower functional connectivity within the ToM network and also between the ToM and a left hemisphere language network. Furthermore, the within-network functional connectivity in autism was correlated with the size of the anterior portion of the corpus callosum. PMID:17869314
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Mason, Robert A; Williams, Diane L; Kana, Rajesh K; Minshew, Nancy; Just, Marcel Adam
2008-01-15
The intersection of Theory of Mind (ToM) processing and complex narrative comprehension in high functioning autism was examined by comparing cortical activation during the reading of passages that required inferences based on either intentions, emotional states, or physical causality. Right hemisphere activation was substantially greater for all sentences in the autism group than in a matched control group suggesting decreased LH capacity in autism resulting in a spillover of processing to RH homologs. Moreover, the ToM network was disrupted. The autism group showed similar activation for all inference types in the right temporo-parietal component of the ToM network whereas the control participants selectively activated this network only when appropriate. The autism group had lower functional connectivity within the ToM network and also between the ToM and a left hemisphere language network. Furthermore, the within-network functional connectivity in autism was correlated with the size of the anterior portion of the corpus callosum.
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Boolean network inference from time series data incorporating prior biological knowledge.
Haider, Saad; Pal, Ranadip
2012-01-01
Numerous approaches exist for modeling of genetic regulatory networks (GRNs) but the low sampling rates often employed in biological studies prevents the inference of detailed models from experimental data. In this paper, we analyze the issues involved in estimating a model of a GRN from single cell line time series data with limited time points. We present an inference approach for a Boolean Network (BN) model of a GRN from limited transcriptomic or proteomic time series data based on prior biological knowledge of connectivity, constraints on attractor structure and robust design. We applied our inference approach to 6 time point transcriptomic data on Human Mammary Epithelial Cell line (HMEC) after application of Epidermal Growth Factor (EGF) and generated a BN with a plausible biological structure satisfying the data. We further defined and applied a similarity measure to compare synthetic BNs and BNs generated through the proposed approach constructed from transitions of various paths of the synthetic BNs. We have also compared the performance of our algorithm with two existing BN inference algorithms. Through theoretical analysis and simulations, we showed the rarity of arriving at a BN from limited time series data with plausible biological structure using random connectivity and absence of structure in data. The framework when applied to experimental data and data generated from synthetic BNs were able to estimate BNs with high similarity scores. Comparison with existing BN inference algorithms showed the better performance of our proposed algorithm for limited time series data. The proposed framework can also be applied to optimize the connectivity of a GRN from experimental data when the prior biological knowledge on regulators is limited or not unique.
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Learning a Markov Logic network for supervised gene regulatory network inference
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-box model such as a pairwise SVM while providing relevant insights on the predictions. Conclusions The numerical studies show that MLN achieves very good predictive performance while opening the door to some interpretability of the decisions. Besides the ability to suggest new regulations, such an approach allows to cross-validate experimental data with existing knowledge. PMID:24028533
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Learning a Markov Logic network for supervised gene regulatory network inference.
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 pairwise SVM while providing relevant insights on the predictions. The numerical studies show that MLN achieves very good predictive performance while opening the door to some interpretability of the decisions. Besides the ability to suggest new regulations, such an approach allows to cross-validate experimental data with existing knowledge.
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Interests diffusion in social networks
NASA Astrophysics Data System (ADS)
D'Agostino, Gregorio; D'Antonio, Fulvio; De Nicola, Antonio; Tucci, Salvatore
2015-10-01
We provide a model for diffusion of interests in Social Networks (SNs). We demonstrate that the topology of the SN plays a crucial role in the dynamics of the individual interests. Understanding cultural phenomena on SNs and exploiting the implicit knowledge about their members is attracting the interest of different research communities both from the academic and the business side. The community of complexity science is devoting significant efforts to define laws, models, and theories, which, based on acquired knowledge, are able to predict future observations (e.g. success of a product). In the mean time, the semantic web community aims at engineering a new generation of advanced services by defining constructs, models and methods, adding a semantic layer to SNs. In this context, a leapfrog is expected to come from a hybrid approach merging the disciplines above. Along this line, this work focuses on the propagation of individual interests in social networks. The proposed framework consists of the following main components: a method to gather information about the members of the social networks; methods to perform some semantic analysis of the Domain of Interest; a procedure to infer members' interests; and an interests evolution theory to predict how the interests propagate in the network. As a result, one achieves an analytic tool to measure individual features, such as members' susceptibilities and authorities. Although the approach applies to any type of social network, here it is has been tested against the computer science research community. The DBLP (Digital Bibliography and Library Project) database has been elected as test-case since it provides the most comprehensive list of scientific production in this field.
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Real-time earthquake monitoring using a search engine method.
Zhang, Jie; Zhang, Haijiang; Chen, Enhong; Zheng, Yi; Kuang, Wenhuan; Zhang, Xiong
2014-12-04
When an earthquake occurs, seismologists want to use recorded seismograms to infer its location, magnitude and source-focal mechanism as quickly as possible. If such information could be determined immediately, timely evacuations and emergency actions could be undertaken to mitigate earthquake damage. Current advanced methods can report the initial location and magnitude of an earthquake within a few seconds, but estimating the source-focal mechanism may require minutes to hours. Here we present an earthquake search engine, similar to a web search engine, that we developed by applying a computer fast search method to a large seismogram database to find waveforms that best fit the input data. Our method is several thousand times faster than an exact search. For an Mw 5.9 earthquake on 8 March 2012 in Xinjiang, China, the search engine can infer the earthquake's parameters in <1 s after receiving the long-period surface wave data.
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Real-time earthquake monitoring using a search engine method
Zhang, Jie; Zhang, Haijiang; Chen, Enhong; Zheng, Yi; Kuang, Wenhuan; Zhang, Xiong
2014-01-01
When an earthquake occurs, seismologists want to use recorded seismograms to infer its location, magnitude and source-focal mechanism as quickly as possible. If such information could be determined immediately, timely evacuations and emergency actions could be undertaken to mitigate earthquake damage. Current advanced methods can report the initial location and magnitude of an earthquake within a few seconds, but estimating the source-focal mechanism may require minutes to hours. Here we present an earthquake search engine, similar to a web search engine, that we developed by applying a computer fast search method to a large seismogram database to find waveforms that best fit the input data. Our method is several thousand times faster than an exact search. For an Mw 5.9 earthquake on 8 March 2012 in Xinjiang, China, the search engine can infer the earthquake’s parameters in <1 s after receiving the long-period surface wave data. PMID:25472861
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Preparing for a Career as a Network Engineer
ERIC Educational Resources Information Center
Morris, Gerard; Fustos, Janos; Haga, Wayne
2012-01-01
A network engineer is an Information Technology (IT) professional who designs, implements, maintains, and troubleshoots computer networks. While the United States is still experiencing relatively high unemployment, demand for network engineers remains strong. To determine what skills employers are looking for, data was collected and analyzed from…
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Neuronal integration of dynamic sources: Bayesian learning and Bayesian inference.
Siegelmann, Hava T; Holzman, Lars E
2010-09-01
One of the brain's most basic functions is integrating sensory data from diverse sources. This ability causes us to question whether the neural system is computationally capable of intelligently integrating data, not only when sources have known, fixed relative dependencies but also when it must determine such relative weightings based on dynamic conditions, and then use these learned weightings to accurately infer information about the world. We suggest that the brain is, in fact, fully capable of computing this parallel task in a single network and describe a neural inspired circuit with this property. Our implementation suggests the possibility that evidence learning requires a more complex organization of the network than was previously assumed, where neurons have different specialties, whose emergence brings the desired adaptivity seen in human online inference.
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Creative brains: designing in the real world†
Goel, Vinod
2014-01-01
The process of designing artifacts is a creative activity. It is proposed that, at the cognitive level, one key to understanding design creativity is to understand the array of symbol systems designers utilize. These symbol systems range from being vague, imprecise, abstract, ambiguous, and indeterminate (like conceptual sketches), to being very precise, concrete, unambiguous, and determinate (like contract documents). The former types of symbol systems support associative processes that facilitate lateral (or divergent) transformations that broaden the problem space, while the latter types of symbol systems support inference processes facilitating vertical (or convergent) transformations that deepen of the problem space. The process of artifact design requires the judicious application of both lateral and vertical transformations. This leads to a dual mechanism model of design problem-solving comprising of an associative engine and an inference engine. It is further claimed that this dual mechanism model is supported by an interesting hemispheric dissociation in human prefrontal cortex. The associative engine and neural structures that support imprecise, ambiguous, abstract, indeterminate representations are lateralized in the right prefrontal cortex, while the inference engine and neural structures that support precise, unambiguous, determinant representations are lateralized in the left prefrontal cortex. At the brain level, successful design of artifacts requires a delicate balance between the two hemispheres of prefrontal cortex. PMID:24817846
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Use of Network Inference to Elucidate Common and Chemical-specific Effects on Steoidogenesis
Microarray data is a key source for modeling gene regulatory interactions. Regulatory network models based on multiple datasets are potentially more robust and can provide greater confidence. In this study, we used network modeling on microarray data generated by exposing the fat...
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The objective of this work is to elucidate biological networks underlying cellular tipping points using time-course data. We discretized the high-content imaging (HCI) data and inferred Boolean networks (BNs) that could accurately predict dynamic cellular trajectories. We found t...
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A generative model of whole-brain effective connectivity.
Frässle, Stefan; Lomakina, Ekaterina I; Kasper, Lars; Manjaly, Zina M; Leff, Alex; Pruessmann, Klaas P; Buhmann, Joachim M; Stephan, Klaas E
2018-05-25
The development of whole-brain models that can infer effective (directed) connection strengths from fMRI data represents a central challenge for computational neuroimaging. A recently introduced generative model of fMRI data, regression dynamic causal modeling (rDCM), moves towards this goal as it scales gracefully to very large networks. However, large-scale networks with thousands of connections are difficult to interpret; additionally, one typically lacks information (data points per free parameter) for precise estimation of all model parameters. This paper introduces sparsity constraints to the variational Bayesian framework of rDCM as a solution to these problems in the domain of task-based fMRI. This sparse rDCM approach enables highly efficient effective connectivity analyses in whole-brain networks and does not require a priori assumptions about the network's connectivity structure but prunes fully (all-to-all) connected networks as part of model inversion. Following the derivation of the variational Bayesian update equations for sparse rDCM, we use both simulated and empirical data to assess the face validity of the model. In particular, we show that it is feasible to infer effective connection strengths from fMRI data using a network with more than 100 regions and 10,000 connections. This demonstrates the feasibility of whole-brain inference on effective connectivity from fMRI data - in single subjects and with a run-time below 1 min when using parallelized code. We anticipate that sparse rDCM may find useful application in connectomics and clinical neuromodeling - for example, for phenotyping individual patients in terms of whole-brain network structure. Copyright © 2018. Published by Elsevier Inc.
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A recurrent self-organizing neural fuzzy inference network.
Juang, C F; Lin, C T
1999-01-01
A recurrent self-organizing neural fuzzy inference network (RSONFIN) is proposed in this paper. The RSONFIN is inherently a recurrent multilayered connectionist network for realizing the basic elements and functions of dynamic fuzzy inference, and may be considered to be constructed from a series of dynamic fuzzy rules. The temporal relations embedded in the network are built by adding some feedback connections representing the memory elements to a feedforward neural fuzzy network. Each weight as well as node in the RSONFIN has its own meaning and represents a special element in a fuzzy rule. There are no hidden nodes (i.e., no membership functions and fuzzy rules) initially in the RSONFIN. They are created on-line via concurrent structure identification (the construction of dynamic fuzzy if-then rules) and parameter identification (the tuning of the free parameters of membership functions). The structure learning together with the parameter learning forms a fast learning algorithm for building a small, yet powerful, dynamic neural fuzzy network. Two major characteristics of the RSONFIN can thus be seen: 1) the recurrent property of the RSONFIN makes it suitable for dealing with temporal problems and 2) no predetermination, like the number of hidden nodes, must be given, since the RSONFIN can find its optimal structure and parameters automatically and quickly. Moreover, to reduce the number of fuzzy rules generated, a flexible input partition method, the aligned clustering-based algorithm, is proposed. Various simulations on temporal problems are done and performance comparisons with some existing recurrent networks are also made. Efficiency of the RSONFIN is verified from these results.
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Lemmens, Karen; De Bie, Tijl; Dhollander, Thomas; De Keersmaecker, Sigrid C; Thijs, Inge M; Schoofs, Geert; De Weerdt, Ami; De Moor, Bart; Vanderleyden, Jos; Collado-Vides, Julio; Engelen, Kristof; Marchal, Kathleen
2009-01-01
We present DISTILLER, a data integration framework for the inference of transcriptional module networks. Experimental validation of predicted targets for the well-studied fumarate nitrate reductase regulator showed the effectiveness of our approach in Escherichia coli. In addition, the condition dependency and modularity of the inferred transcriptional network was studied. Surprisingly, the level of regulatory complexity seemed lower than that which would be expected from RegulonDB, indicating that complex regulatory programs tend to decrease the degree of modularity. PMID:19265557
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Griffin: A Tool for Symbolic Inference of Synchronous Boolean Molecular Networks.
Muñoz, Stalin; Carrillo, Miguel; Azpeitia, Eugenio; Rosenblueth, David A
2018-01-01
Boolean networks are important models of biochemical systems, located at the high end of the abstraction spectrum. A number of Boolean gene networks have been inferred following essentially the same method. Such a method first considers experimental data for a typically underdetermined "regulation" graph. Next, Boolean networks are inferred by using biological constraints to narrow the search space, such as a desired set of (fixed-point or cyclic) attractors. We describe Griffin , a computer tool enhancing this method. Griffin incorporates a number of well-established algorithms, such as Dubrova and Teslenko's algorithm for finding attractors in synchronous Boolean networks. In addition, a formal definition of regulation allows Griffin to employ "symbolic" techniques, able to represent both large sets of network states and Boolean constraints. We observe that when the set of attractors is required to be an exact set, prohibiting additional attractors, a naive Boolean coding of this constraint may be unfeasible. Such cases may be intractable even with symbolic methods, as the number of Boolean constraints may be astronomically large. To overcome this problem, we employ an Artificial Intelligence technique known as "clause learning" considerably increasing Griffin 's scalability. Without clause learning only toy examples prohibiting additional attractors are solvable: only one out of seven queries reported here is answered. With clause learning, by contrast, all seven queries are answered. We illustrate Griffin with three case studies drawn from the Arabidopsis thaliana literature. Griffin is available at: http://turing.iimas.unam.mx/griffin.
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Emad, Amin; Milenkovic, Olgica
2014-01-01
We introduce a novel algorithm for inference of causal gene interactions, termed CaSPIAN (Causal Subspace Pursuit for Inference and Analysis of Networks), which is based on coupling compressive sensing and Granger causality techniques. The core of the approach is to discover sparse linear dependencies between shifted time series of gene expressions using a sequential list-version of the subspace pursuit reconstruction algorithm and to estimate the direction of gene interactions via Granger-type elimination. The method is conceptually simple and computationally efficient, and it allows for dealing with noisy measurements. Its performance as a stand-alone platform without biological side-information was tested on simulated networks, on the synthetic IRMA network in Saccharomyces cerevisiae, and on data pertaining to the human HeLa cell network and the SOS network in E. coli. The results produced by CaSPIAN are compared to the results of several related algorithms, demonstrating significant improvements in inference accuracy of documented interactions. These findings highlight the importance of Granger causality techniques for reducing the number of false-positives, as well as the influence of noise and sampling period on the accuracy of the estimates. In addition, the performance of the method was tested in conjunction with biological side information of the form of sparse “scaffold networks”, to which new edges were added using available RNA-seq or microarray data. These biological priors aid in increasing the sensitivity and precision of the algorithm in the small sample regime. PMID:24622336
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ERIC Educational Resources Information Center
Zhang, Jingjing; Skryabin, Maxim; Song, Xiongwei
2016-01-01
This study attempts to make inferences about the mechanisms that drive network change over time. It adopts simulation investigation for empirical network analysis to examine the patterns and evolution of relationships formed in the context of a massive open online course (MOOC) discussion forum. Four network effects--"homophily,"…
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Inference and Analysis of Population Structure Using Genetic Data and Network Theory
Greenbaum, Gili; Templeton, Alan R.; Bar-David, Shirli
2016-01-01
Clustering individuals to subpopulations based on genetic data has become commonplace in many genetic studies. Inference about population structure is most often done by applying model-based approaches, aided by visualization using distance-based approaches such as multidimensional scaling. While existing distance-based approaches suffer from a lack of statistical rigor, model-based approaches entail assumptions of prior conditions such as that the subpopulations are at Hardy-Weinberg equilibria. Here we present a distance-based approach for inference about population structure using genetic data by defining population structure using network theory terminology and methods. A network is constructed from a pairwise genetic-similarity matrix of all sampled individuals. The community partition, a partition of a network to dense subgraphs, is equated with population structure, a partition of the population to genetically related groups. Community-detection algorithms are used to partition the network into communities, interpreted as a partition of the population to subpopulations. The statistical significance of the structure can be estimated by using permutation tests to evaluate the significance of the partition’s modularity, a network theory measure indicating the quality of community partitions. To further characterize population structure, a new measure of the strength of association (SA) for an individual to its assigned community is presented. The strength of association distribution (SAD) of the communities is analyzed to provide additional population structure characteristics, such as the relative amount of gene flow experienced by the different subpopulations and identification of hybrid individuals. Human genetic data and simulations are used to demonstrate the applicability of the analyses. The approach presented here provides a novel, computationally efficient model-free method for inference about population structure that does not entail assumption of prior conditions. The method is implemented in the software NetStruct (available at https://giligreenbaum.wordpress.com/software/). PMID:26888080
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Inference and Analysis of Population Structure Using Genetic Data and Network Theory.
Greenbaum, Gili; Templeton, Alan R; Bar-David, Shirli
2016-04-01
Clustering individuals to subpopulations based on genetic data has become commonplace in many genetic studies. Inference about population structure is most often done by applying model-based approaches, aided by visualization using distance-based approaches such as multidimensional scaling. While existing distance-based approaches suffer from a lack of statistical rigor, model-based approaches entail assumptions of prior conditions such as that the subpopulations are at Hardy-Weinberg equilibria. Here we present a distance-based approach for inference about population structure using genetic data by defining population structure using network theory terminology and methods. A network is constructed from a pairwise genetic-similarity matrix of all sampled individuals. The community partition, a partition of a network to dense subgraphs, is equated with population structure, a partition of the population to genetically related groups. Community-detection algorithms are used to partition the network into communities, interpreted as a partition of the population to subpopulations. The statistical significance of the structure can be estimated by using permutation tests to evaluate the significance of the partition's modularity, a network theory measure indicating the quality of community partitions. To further characterize population structure, a new measure of the strength of association (SA) for an individual to its assigned community is presented. The strength of association distribution (SAD) of the communities is analyzed to provide additional population structure characteristics, such as the relative amount of gene flow experienced by the different subpopulations and identification of hybrid individuals. Human genetic data and simulations are used to demonstrate the applicability of the analyses. The approach presented here provides a novel, computationally efficient model-free method for inference about population structure that does not entail assumption of prior conditions. The method is implemented in the software NetStruct (available at https://giligreenbaum.wordpress.com/software/). Copyright © 2016 by the Genetics Society of America.
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Random graph models for dynamic networks
NASA Astrophysics Data System (ADS)
Zhang, Xiao; Moore, Cristopher; Newman, Mark E. J.
2017-10-01
Recent theoretical work on the modeling of network structure has focused primarily on networks that are static and unchanging, but many real-world networks change their structure over time. There exist natural generalizations to the dynamic case of many static network models, including the classic random graph, the configuration model, and the stochastic block model, where one assumes that the appearance and disappearance of edges are governed by continuous-time Markov processes with rate parameters that can depend on properties of the nodes. Here we give an introduction to this class of models, showing for instance how one can compute their equilibrium properties. We also demonstrate their use in data analysis and statistical inference, giving efficient algorithms for fitting them to observed network data using the method of maximum likelihood. This allows us, for example, to estimate the time constants of network evolution or infer community structure from temporal network data using cues embedded both in the probabilities over time that node pairs are connected by edges and in the characteristic dynamics of edge appearance and disappearance. We illustrate these methods with a selection of applications, both to computer-generated test networks and real-world examples.
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2001-02-16
New Center Network Deployment ribbon Cutting: from left to right: Maryland Edwards, Code JT upgrade project deputy task manager; Ed Murphy, foundry networks systems engineer; Bohdan Cmaylo, Code JT upgrade project task manager, Scott Santiago, Division Chief, Code JT; Greg Miller, Raytheon Network engineer and Frank Daras, Raytheon network engineering manager.
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NASA Astrophysics Data System (ADS)
Rehfeld, Kira; Goswami, Bedartha; Marwan, Norbert; Breitenbach, Sebastian; Kurths, Jürgen
2013-04-01
Statistical analysis of dependencies amongst paleoclimate data helps to infer on the climatic processes they reflect. Three key challenges have to be addressed, however: the datasets are heterogeneous in time (i) and space (ii), and furthermore time itself is a variable that needs to be reconstructed, which (iii) introduces additional uncertainties. To address these issues in a flexible way we developed the paleoclimate network framework, inspired by the increasing application of complex networks in climate research. Nodes in the paleoclimate network represent a paleoclimate archive, and an associated time series. Links between these nodes are assigned, if these time series are significantly similar. Therefore, the base of the paleoclimate network is formed by linear and nonlinear estimators for Pearson correlation, mutual information and event synchronization, which quantify similarity from irregularly sampled time series. Age uncertainties are propagated into the final network analysis using time series ensembles which reflect the uncertainty. We discuss how spatial heterogeneity influences the results obtained from network measures, and demonstrate the power of the approach by inferring teleconnection variability of the Asian summer monsoon for the past 1000 years.
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Van Landeghem, Sofie; Van Parys, Thomas; Dubois, Marieke; Inzé, Dirk; Van de Peer, Yves
2016-01-05
Differential networks have recently been introduced as a powerful way to study the dynamic rewiring capabilities of an interactome in response to changing environmental conditions or stimuli. Currently, such differential networks are generated and visualised using ad hoc methods, and are often limited to the analysis of only one condition-specific response or one interaction type at a time. In this work, we present a generic, ontology-driven framework to infer, visualise and analyse an arbitrary set of condition-specific responses against one reference network. To this end, we have implemented novel ontology-based algorithms that can process highly heterogeneous networks, accounting for both physical interactions and regulatory associations, symmetric and directed edges, edge weights and negation. We propose this integrative framework as a standardised methodology that allows a unified view on differential networks and promotes comparability between differential network studies. As an illustrative application, we demonstrate its usefulness on a plant abiotic stress study and we experimentally confirmed a predicted regulator. Diffany is freely available as open-source java library and Cytoscape plugin from http://bioinformatics.psb.ugent.be/supplementary_data/solan/diffany/.
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Inference Engine in an Intelligent Ship Course-Keeping System
2017-01-01
The article presents an original design of an expert system, whose function is to automatically stabilize ship's course. The focus is put on the inference engine, a mechanism that consists of two functional components. One is responsible for the construction of state space regions, implemented on the basis of properly processed signals recorded by sensors from the input and output of an object. The other component is responsible for generating a control decision based on the knowledge obtained in the first module. The computing experiments described herein prove the effective and correct operation of the proposed system. PMID:29317859
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Weiss, Scott T.
2014-01-01
Bayesian Networks (BN) have been a popular predictive modeling formalism in bioinformatics, but their application in modern genomics has been slowed by an inability to cleanly handle domains with mixed discrete and continuous variables. Existing free BN software packages either discretize continuous variables, which can lead to information loss, or do not include inference routines, which makes prediction with the BN impossible. We present CGBayesNets, a BN package focused around prediction of a clinical phenotype from mixed discrete and continuous variables, which fills these gaps. CGBayesNets implements Bayesian likelihood and inference algorithms for the conditional Gaussian Bayesian network (CGBNs) formalism, one appropriate for predicting an outcome of interest from, e.g., multimodal genomic data. We provide four different network learning algorithms, each making a different tradeoff between computational cost and network likelihood. CGBayesNets provides a full suite of functions for model exploration and verification, including cross validation, bootstrapping, and AUC manipulation. We highlight several results obtained previously with CGBayesNets, including predictive models of wood properties from tree genomics, leukemia subtype classification from mixed genomic data, and robust prediction of intensive care unit mortality outcomes from metabolomic profiles. We also provide detailed example analysis on public metabolomic and gene expression datasets. CGBayesNets is implemented in MATLAB and available as MATLAB source code, under an Open Source license and anonymous download at http://www.cgbayesnets.com. PMID:24922310
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McGeachie, Michael J; Chang, Hsun-Hsien; Weiss, Scott T
2014-06-01
Bayesian Networks (BN) have been a popular predictive modeling formalism in bioinformatics, but their application in modern genomics has been slowed by an inability to cleanly handle domains with mixed discrete and continuous variables. Existing free BN software packages either discretize continuous variables, which can lead to information loss, or do not include inference routines, which makes prediction with the BN impossible. We present CGBayesNets, a BN package focused around prediction of a clinical phenotype from mixed discrete and continuous variables, which fills these gaps. CGBayesNets implements Bayesian likelihood and inference algorithms for the conditional Gaussian Bayesian network (CGBNs) formalism, one appropriate for predicting an outcome of interest from, e.g., multimodal genomic data. We provide four different network learning algorithms, each making a different tradeoff between computational cost and network likelihood. CGBayesNets provides a full suite of functions for model exploration and verification, including cross validation, bootstrapping, and AUC manipulation. We highlight several results obtained previously with CGBayesNets, including predictive models of wood properties from tree genomics, leukemia subtype classification from mixed genomic data, and robust prediction of intensive care unit mortality outcomes from metabolomic profiles. We also provide detailed example analysis on public metabolomic and gene expression datasets. CGBayesNets is implemented in MATLAB and available as MATLAB source code, under an Open Source license and anonymous download at http://www.cgbayesnets.com.
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Statistical Inference for Cultural Consensus Theory
2014-02-24
Social Network Conference XXXII , Redondo Beach, California, March 2012. Agrawal, K. (Presenter), and Batchelder, W. H. Cultural Consensus Theory...Aggregating Complete Signed Graphs Under a Balance Constraint -- Part 2. International Sunbelt Social Network Conference XXXII , Redondo Beach
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Modeling complexity in engineered infrastructure system: Water distribution network as an example
NASA Astrophysics Data System (ADS)
Zeng, Fang; Li, Xiang; Li, Ke
2017-02-01
The complex topology and adaptive behavior of infrastructure systems are driven by both self-organization of the demand and rigid engineering solutions. Therefore, engineering complex systems requires a method balancing holism and reductionism. To model the growth of water distribution networks, a complex network model was developed following the combination of local optimization rules and engineering considerations. The demand node generation is dynamic and follows the scaling law of urban growth. The proposed model can generate a water distribution network (WDN) similar to reported real-world WDNs on some structural properties. Comparison with different modeling approaches indicates that a realistic demand node distribution and co-evolvement of demand node and network are important for the simulation of real complex networks. The simulation results indicate that the efficiency of water distribution networks is exponentially affected by the urban growth pattern. On the contrary, the improvement of efficiency by engineering optimization is limited and relatively insignificant. The redundancy and robustness, on another aspect, can be significantly improved through engineering methods.
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-08-23
... First Public Meeting of the Crash Injury Research and Engineering Network (CIREN) AGENCY: National... announces the Twenty First Public Meeting of members of the Crash Injury Research and Engineering Network... of centers, medical and engineering. Medical centers are based at Level I Trauma Centers that admit...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-08-02
... Nineteenth Public Meeting of the Crash Injury Research and Engineering Network (CIREN) AGENCY: National... announces the Nineteenth Public Meeting of members of the Crash Injury Research and Engineering Network... of centers, medical and engineering. Medical centers are based at Level I Trauma Centers that admit...
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-02
... Twentieth Public Meeting of the Crash Injury Research and Engineering Network (CIREN) AGENCY: National... announces the Twentieth Public Meeting of members of the Crash Injury Research and Engineering Network... of centers, medical and engineering. Medical centers are based at Level I Trauma Centers that admit...
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Knowledge Engineering Aspects of Affective Bi-Modal Educational Applications
NASA Astrophysics Data System (ADS)
Alepis, Efthymios; Virvou, Maria; Kabassi, Katerina
This paper analyses the knowledge and software engineering aspects of educational applications that provide affective bi-modal human-computer interaction. For this purpose, a system that provides affective interaction based on evidence from two different modes has been developed. More specifically, the system's inferences about students' emotions are based on user input evidence from the keyboard and the microphone. Evidence from these two modes is combined by a user modelling component that incorporates user stereotypes as well as a multi criteria decision making theory. The mechanism that integrates the inferences from the two modes has been based on the results of two empirical studies that were conducted in the context of knowledge engineering of the system. The evaluation of the developed system showed significant improvements in the recognition of the emotional states of users.
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Thompson, Steven K
2006-12-01
A flexible class of adaptive sampling designs is introduced for sampling in network and spatial settings. In the designs, selections are made sequentially with a mixture distribution based on an active set that changes as the sampling progresses, using network or spatial relationships as well as sample values. The new designs have certain advantages compared with previously existing adaptive and link-tracing designs, including control over sample sizes and of the proportion of effort allocated to adaptive selections. Efficient inference involves averaging over sample paths consistent with the minimal sufficient statistic. A Markov chain resampling method makes the inference computationally feasible. The designs are evaluated in network and spatial settings using two empirical populations: a hidden human population at high risk for HIV/AIDS and an unevenly distributed bird population.
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Nonparametric weighted stochastic block models
NASA Astrophysics Data System (ADS)
Peixoto, Tiago P.
2018-01-01
We present a Bayesian formulation of weighted stochastic block models that can be used to infer the large-scale modular structure of weighted networks, including their hierarchical organization. Our method is nonparametric, and thus does not require the prior knowledge of the number of groups or other dimensions of the model, which are instead inferred from data. We give a comprehensive treatment of different kinds of edge weights (i.e., continuous or discrete, signed or unsigned, bounded or unbounded), as well as arbitrary weight transformations, and describe an unsupervised model selection approach to choose the best network description. We illustrate the application of our method to a variety of empirical weighted networks, such as global migrations, voting patterns in congress, and neural connections in the human brain.
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Distributed Sensing and Processing for Multi-Camera Networks
NASA Astrophysics Data System (ADS)
Sankaranarayanan, Aswin C.; Chellappa, Rama; Baraniuk, Richard G.
Sensor networks with large numbers of cameras are becoming increasingly prevalent in a wide range of applications, including video conferencing, motion capture, surveillance, and clinical diagnostics. In this chapter, we identify some of the fundamental challenges in designing such systems: robust statistical inference, computationally efficiency, and opportunistic and parsimonious sensing. We show that the geometric constraints induced by the imaging process are extremely useful for identifying and designing optimal estimators for object detection and tracking tasks. We also derive pipelined and parallelized implementations of popular tools used for statistical inference in non-linear systems, of which multi-camera systems are examples. Finally, we highlight the use of the emerging theory of compressive sensing in reducing the amount of data sensed and communicated by a camera network.
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NASA Technical Reports Server (NTRS)
Carvalho, Robert F.; Williams, James; Keller, Richard; Sturken, Ian; Panontin, Tina
2004-01-01
InvestigationOrganizer (IO) is a collaborative web-based system designed to support the conduct of mishap investigations. IO provides a common repository for a wide range of mishap related information, and allows investigators to make explicit, shared, and meaningful links between evidence, causal models, findings and recommendations. It integrates the functionality of a database, a common document repository, a semantic knowledge network, a rule-based inference engine, and causal modeling and visualization. Thus far, IO has been used to support four mishap investigations within NASA, ranging from a small property damage case to the loss of the Space Shuttle Columbia. This paper describes how the functionality of IO supports mishap investigations and the lessons learned from the experience of supporting two of the NASA mishap investigations: the Columbia Accident Investigation and the CONTOUR Loss Investigation.
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NASA Astrophysics Data System (ADS)
Hayati, M.; Rashidi, A. M.; Rezaei, A.
2012-10-01
In this paper, the applicability of ANFIS as an accurate model for the prediction of the mass gain during high temperature oxidation using experimental data obtained for aluminized nanostructured (NS) nickel is presented. For developing the model, exposure time and temperature are taken as input and the mass gain as output. A hybrid learning algorithm consists of back-propagation and least-squares estimation is used for training the network. We have compared the proposed ANFIS model with experimental data. The predicted data are found to be in good agreement with the experimental data with mean relative error less than 1.1%. Therefore, we can use ANFIS model to predict the performances of thermal systems in engineering applications, such as modeling the mass gain for NS materials.
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Perspectives of Probabilistic Inferences: Reinforcement Learning and an Adaptive Network Compared
ERIC Educational Resources Information Center
Rieskamp, Jorg
2006-01-01
The assumption that people possess a strategy repertoire for inferences has been raised repeatedly. The strategy selection learning theory specifies how people select strategies from this repertoire. The theory assumes that individuals select strategies proportional to their subjective expectations of how well the strategies solve particular…
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Xu, Yungang; Guo, Maozu; Zou, Quan; Liu, Xiaoyan; Wang, Chunyu; Liu, Yang
2014-01-01
Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN), a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max), due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs), in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional interactome at the genome and microRNome levels. Additionally, a web tool for information retrieval and analysis of SoyFGNs can be accessed at SoyFN: http://nclab.hit.edu.cn/SoyFN.
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Xu, Yungang; Guo, Maozu; Zou, Quan; Liu, Xiaoyan; Wang, Chunyu; Liu, Yang
2014-01-01
Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN), a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max), due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs), in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional interactome at the genome and microRNome levels. Additionally, a web tool for information retrieval and analysis of SoyFGNs can be accessed at SoyFN: http://nclab.hit.edu.cn/SoyFN. PMID:25423109
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On imputing function to structure from the behavioural effects of brain lesions.
Young, M P; Hilgetag, C C; Scannell, J W
2000-01-29
What is the link, if any, between the patterns of connections in the brain and the behavioural effects of localized brain lesions? We explored this question in four related ways. First, we investigated the distribution of activity decrements that followed simulated damage to elements of the thalamocortical network, using integrative mechanisms that have recently been used to successfully relate connection data to information on the spread of activation, and to account simultaneously for a variety of lesion effects. Second, we examined the consequences of the patterns of decrement seen in the simulation for each type of inference that has been employed to impute function to structure on the basis of the effects of brain lesions. Every variety of conventional inference, including double dissociation, readily misattributed function to structure. Third, we tried to derive a more reliable framework of inference for imputing function to structure, by clarifying concepts of function, and exploring a more formal framework, in which knowledge of connectivity is necessary but insufficient, based on concepts capable of mathematical specification. Fourth, we applied this framework to inferences about function relating to a simple network that reproduces intact, lesioned and paradoxically restored orientating behaviour. Lesion effects could be used to recover detailed and reliable information on which structures contributed to particular functions in this simple network. Finally, we explored how the effects of brain lesions and this formal approach could be used in conjunction with information from multiple neuroscience methodologies to develop a practical and reliable approach to inferring the functional roles of brain structures.
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NASA Technical Reports Server (NTRS)
Bishop, Ann P.; Pinelli, Thomas E.
1994-01-01
This paper presents selected results from an empirical investigation into the use of computer networks in aerospace engineering. Such networks allow aerospace engineers to communicate with people and access remote resources through electronic mail, file transfer, and remote log-in. The study drew its subjects from private sector, government and academic organizations in the U.S. aerospace industry. Data presented here were gathered in a mail survey, conducted in Spring 1993, that was distributed to aerospace engineers performing a wide variety of jobs. Results from the mail survey provide a snapshot of the current use of computer networks in the aerospace industry, suggest factors associated with the use of networks, and identify perceived impacts of networks on aerospace engineering work and communication.
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Uncertainty quantification of measured quantities for a HCCI engine: composition or temperatures
DOE Office of Scientific and Technical Information (OSTI.GOV)
Petitpas, Guillaume; Whitesides, Russell
UQHCCI_1 computes the measurement uncertainties of a HCCI engine test bench using the pressure trace and the estimated uncertainties of the measured quantities as inputs, then propagating them through Bayesian inference and a mixing model.
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Iwata, Hiroaki; Mizutani, Sayaka; Tabei, Yasuo; Kotera, Masaaki; Goto, Susumu; Yamanishi, Yoshihiro
2013-01-01
Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains.
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Inference of topology and the nature of synapses, and the flow of information in neuronal networks
NASA Astrophysics Data System (ADS)
Borges, F. S.; Lameu, E. L.; Iarosz, K. C.; Protachevicz, P. R.; Caldas, I. L.; Viana, R. L.; Macau, E. E. N.; Batista, A. M.; Baptista, M. S.
2018-02-01
The characterization of neuronal connectivity is one of the most important matters in neuroscience. In this work, we show that a recently proposed informational quantity, the causal mutual information, employed with an appropriate methodology, can be used not only to correctly infer the direction of the underlying physical synapses, but also to identify their excitatory or inhibitory nature, considering easy to handle and measure bivariate time series. The success of our approach relies on a surprising property found in neuronal networks by which nonadjacent neurons do "understand" each other (positive mutual information), however, this exchange of information is not capable of causing effect (zero transfer entropy). Remarkably, inhibitory connections, responsible for enhancing synchronization, transfer more information than excitatory connections, known to enhance entropy in the network. We also demonstrate that our methodology can be used to correctly infer directionality of synapses even in the presence of dynamic and observational Gaussian noise, and is also successful in providing the effective directionality of intermodular connectivity, when only mean fields can be measured.
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Inferring general relations between network characteristics from specific network ensembles.
Cardanobile, Stefano; Pernice, Volker; Deger, Moritz; Rotter, Stefan
2012-01-01
Different network models have been suggested for the topology underlying complex interactions in natural systems. These models are aimed at replicating specific statistical features encountered in real-world networks. However, it is rarely considered to which degree the results obtained for one particular network class can be extrapolated to real-world networks. We address this issue by comparing different classical and more recently developed network models with respect to their ability to generate networks with large structural variability. In particular, we consider the statistical constraints which the respective construction scheme imposes on the generated networks. After having identified the most variable networks, we address the issue of which constraints are common to all network classes and are thus suitable candidates for being generic statistical laws of complex networks. In fact, we find that generic, not model-related dependencies between different network characteristics do exist. This makes it possible to infer global features from local ones using regression models trained on networks with high generalization power. Our results confirm and extend previous findings regarding the synchronization properties of neural networks. Our method seems especially relevant for large networks, which are difficult to map completely, like the neural networks in the brain. The structure of such large networks cannot be fully sampled with the present technology. Our approach provides a method to estimate global properties of under-sampled networks in good approximation. Finally, we demonstrate on three different data sets (C. elegans neuronal network, R. prowazekii metabolic network, and a network of synonyms extracted from Roget's Thesaurus) that real-world networks have statistical relations compatible with those obtained using regression models.
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Gálvez, Jorge A; Pappas, Janine M; Ahumada, Luis; Martin, John N; Simpao, Allan F; Rehman, Mohamed A; Witmer, Char
2017-10-01
Venous thromboembolism (VTE) is a potentially life-threatening condition that includes both deep vein thrombosis (DVT) and pulmonary embolism. We sought to improve detection and reporting of children with a new diagnosis of VTE by applying natural language processing (NLP) tools to radiologists' reports. We validated an NLP tool, Reveal NLP (Health Fidelity Inc, San Mateo, CA) and inference rules engine's performance in identifying reports with deep venous thrombosis using a curated set of ultrasound reports. We then configured the NLP tool to scan all available radiology reports on a daily basis for studies that met criteria for VTE between July 1, 2015, and March 31, 2016. The NLP tool and inference rules engine correctly identified 140 out of 144 reports with positive DVT findings and 98 out of 106 negative reports in the validation set. The tool's sensitivity was 97.2% (95% CI 93-99.2%), specificity was 92.5% (95% CI 85.7-96.7%). Subsequently, the NLP tool and inference rules engine processed 6373 radiology reports from 3371 hospital encounters. The NLP tool and inference rules engine identified 178 positive reports and 3193 negative reports with a sensitivity of 82.9% (95% CI 74.8-89.2) and specificity of 97.5% (95% CI 96.9-98). The system functions well as a safety net to screen patients for HA-VTE on a daily basis and offers value as an automated, redundant system. To our knowledge, this is the first pediatric study to apply NLP technology in a prospective manner for HA-VTE identification.
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Pathway connectivity and signaling coordination in the yeast stress-activated signaling network
Chasman, Deborah; Ho, Yi-Hsuan; Berry, David B; Nemec, Corey M; MacGilvray, Matthew E; Hose, James; Merrill, Anna E; Lee, M Violet; Will, Jessica L; Coon, Joshua J; Ansari, Aseem Z; Craven, Mark; Gasch, Audrey P
2014-01-01
Stressed cells coordinate a multi-faceted response spanning many levels of physiology. Yet knowledge of the complete stress-activated regulatory network as well as design principles for signal integration remains incomplete. We developed an experimental and computational approach to integrate available protein interaction data with gene fitness contributions, mutant transcriptome profiles, and phospho-proteome changes in cells responding to salt stress, to infer the salt-responsive signaling network in yeast. The inferred subnetwork presented many novel predictions by implicating new regulators, uncovering unrecognized crosstalk between known pathways, and pointing to previously unknown ‘hubs’ of signal integration. We exploited these predictions to show that Cdc14 phosphatase is a central hub in the network and that modification of RNA polymerase II coordinates induction of stress-defense genes with reduction of growth-related transcripts. We find that the orthologous human network is enriched for cancer-causing genes, underscoring the importance of the subnetwork's predictions in understanding stress biology. PMID:25411400
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ramirez Aviles, Camila A.; Rao, Nageswara S.
We consider the problem of inferring the operational state of a reactor facility by using measurements from a radiation sensor network, which is deployed around the facility’s ventilation stack. The radiation emissions from the stack decay with distance, and the corresponding measurements are inherently random with parameters determined by radiation intensity levels at the sensor locations. We fuse measurements from network sensors to estimate the intensity at the stack, and use this estimate in a one-sided Sequential Probability Ratio Test (SPRT) to infer the on/off state of the reactor facility. We demonstrate the superior performance of this method over conventionalmore » majority vote fusers and individual sensors using (i) test measurements from a network of NaI sensors, and (ii) emulated measurements using radioactive effluents collected at a reactor facility stack. We analytically quantify the performance improvements of individual sensors and their networks with adaptive thresholds over those with fixed ones, by using the packing number of the radiation intensity space.« less
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Reconstruction of a Real World Social Network using the Potts Model and Loopy Belief Propagation.
Bisconti, Cristian; Corallo, Angelo; Fortunato, Laura; Gentile, Antonio A; Massafra, Andrea; Pellè, Piergiuseppe
2015-01-01
The scope of this paper is to test the adoption of a statistical model derived from Condensed Matter Physics, for the reconstruction of the structure of a social network. The inverse Potts model, traditionally applied to recursive observations of quantum states in an ensemble of particles, is here addressed to observations of the members' states in an organization and their (anti)correlations, thus inferring interactions as links among the members. Adopting proper (Bethe) approximations, such an inverse problem is showed to be tractable. Within an operational framework, this network-reconstruction method is tested for a small real-world social network, the Italian parliament. In this study case, it is easy to track statuses of the parliament members, using (co)sponsorships of law proposals as the initial dataset. In previous studies of similar activity-based networks, the graph structure was inferred directly from activity co-occurrences: here we compare our statistical reconstruction with such standard methods, outlining discrepancies and advantages.
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Reconstruction of a Real World Social Network using the Potts Model and Loopy Belief Propagation
Bisconti, Cristian; Corallo, Angelo; Fortunato, Laura; Gentile, Antonio A.; Massafra, Andrea; Pellè, Piergiuseppe
2015-01-01
The scope of this paper is to test the adoption of a statistical model derived from Condensed Matter Physics, for the reconstruction of the structure of a social network. The inverse Potts model, traditionally applied to recursive observations of quantum states in an ensemble of particles, is here addressed to observations of the members' states in an organization and their (anti)correlations, thus inferring interactions as links among the members. Adopting proper (Bethe) approximations, such an inverse problem is showed to be tractable. Within an operational framework, this network-reconstruction method is tested for a small real-world social network, the Italian parliament. In this study case, it is easy to track statuses of the parliament members, using (co)sponsorships of law proposals as the initial dataset. In previous studies of similar activity-based networks, the graph structure was inferred directly from activity co-occurrences: here we compare our statistical reconstruction with such standard methods, outlining discrepancies and advantages. PMID:26617539
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78 FR 7464 - Large Scale Networking (LSN) ; Joint Engineering Team (JET)
Federal Register 2010, 2011, 2012, 2013, 2014
2013-02-01
... NATIONAL SCIENCE FOUNDATION Large Scale Networking (LSN) ; Joint Engineering Team (JET) AGENCY: The Networking and Information Technology Research and Development (NITRD) National Coordination...://www.nitrd.gov/nitrdgroups/index.php?title=Joint_Engineering_Team_ (JET)#title. SUMMARY: The JET...
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In silico prediction of protein-protein interactions in human macrophages
2014-01-01
Background Protein-protein interaction (PPI) network analyses are highly valuable in deciphering and understanding the intricate organisation of cellular functions. Nevertheless, the majority of available protein-protein interaction networks are context-less, i.e. without any reference to the spatial, temporal or physiological conditions in which the interactions may occur. In this work, we are proposing a protocol to infer the most likely protein-protein interaction (PPI) network in human macrophages. Results We integrated the PPI dataset from the Agile Protein Interaction DataAnalyzer (APID) with different meta-data to infer a contextualized macrophage-specific interactome using a combination of statistical methods. The obtained interactome is enriched in experimentally verified interactions and in proteins involved in macrophage-related biological processes (i.e. immune response activation, regulation of apoptosis). As a case study, we used the contextualized interactome to highlight the cellular processes induced upon Mycobacterium tuberculosis infection. Conclusion Our work confirms that contextualizing interactomes improves the biological significance of bioinformatic analyses. More specifically, studying such inferred network rather than focusing at the gene expression level only, is informative on the processes involved in the host response. Indeed, important immune features such as apoptosis are solely highlighted when the spotlight is on the protein interaction level. PMID:24636261
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Knowledge-guided fuzzy logic modeling to infer cellular signaling networks from proteomic data
Liu, Hui; Zhang, Fan; Mishra, Shital Kumar; Zhou, Shuigeng; Zheng, Jie
2016-01-01
Modeling of signaling pathways is crucial for understanding and predicting cellular responses to drug treatments. However, canonical signaling pathways curated from literature are seldom context-specific and thus can hardly predict cell type-specific response to external perturbations; purely data-driven methods also have drawbacks such as limited biological interpretability. Therefore, hybrid methods that can integrate prior knowledge and real data for network inference are highly desirable. In this paper, we propose a knowledge-guided fuzzy logic network model to infer signaling pathways by exploiting both prior knowledge and time-series data. In particular, the dynamic time warping algorithm is employed to measure the goodness of fit between experimental and predicted data, so that our method can model temporally-ordered experimental observations. We evaluated the proposed method on a synthetic dataset and two real phosphoproteomic datasets. The experimental results demonstrate that our model can uncover drug-induced alterations in signaling pathways in cancer cells. Compared with existing hybrid models, our method can model feedback loops so that the dynamical mechanisms of signaling networks can be uncovered from time-series data. By calibrating generic models of signaling pathways against real data, our method supports precise predictions of context-specific anticancer drug effects, which is an important step towards precision medicine. PMID:27774993
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Lo, Benjamin W. Y.; Macdonald, R. Loch; Baker, Andrew; Levine, Mitchell A. H.
2013-01-01
Objective. The novel clinical prediction approach of Bayesian neural networks with fuzzy logic inferences is created and applied to derive prognostic decision rules in cerebral aneurysmal subarachnoid hemorrhage (aSAH). Methods. The approach of Bayesian neural networks with fuzzy logic inferences was applied to data from five trials of Tirilazad for aneurysmal subarachnoid hemorrhage (3551 patients). Results. Bayesian meta-analyses of observational studies on aSAH prognostic factors gave generalizable posterior distributions of population mean log odd ratios (ORs). Similar trends were noted in Bayesian and linear regression ORs. Significant outcome predictors include normal motor response, cerebral infarction, history of myocardial infarction, cerebral edema, history of diabetes mellitus, fever on day 8, prior subarachnoid hemorrhage, admission angiographic vasospasm, neurological grade, intraventricular hemorrhage, ruptured aneurysm size, history of hypertension, vasospasm day, age and mean arterial pressure. Heteroscedasticity was present in the nontransformed dataset. Artificial neural networks found nonlinear relationships with 11 hidden variables in 1 layer, using the multilayer perceptron model. Fuzzy logic decision rules (centroid defuzzification technique) denoted cut-off points for poor prognosis at greater than 2.5 clusters. Discussion. This aSAH prognostic system makes use of existing knowledge, recognizes unknown areas, incorporates one's clinical reasoning, and compensates for uncertainty in prognostication. PMID:23690884
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Transmission network of the 2014-2015 Ebola epidemic in Sierra Leone.
Yang, Wan; Zhang, Wenyi; Kargbo, David; Yang, Ruifu; Chen, Yong; Chen, Zeliang; Kamara, Abdul; Kargbo, Brima; Kandula, Sasikiran; Karspeck, Alicia; Liu, Chao; Shaman, Jeffrey
2015-11-06
Understanding the growth and spatial expansion of (re)emerging infectious disease outbreaks, such as Ebola and avian influenza, is critical for the effective planning of control measures; however, such efforts are often compromised by data insufficiencies and observational errors. Here, we develop a spatial-temporal inference methodology using a modified network model in conjunction with the ensemble adjustment Kalman filter, a Bayesian inference method equipped to handle observational errors. The combined method is capable of revealing the spatial-temporal progression of infectious disease, while requiring only limited, readily compiled data. We use this method to reconstruct the transmission network of the 2014-2015 Ebola epidemic in Sierra Leone and identify source and sink regions. Our inference suggests that, in Sierra Leone, transmission within the network introduced Ebola to neighbouring districts and initiated self-sustaining local epidemics; two of the more populous and connected districts, Kenema and Port Loko, facilitated two independent transmission pathways. Epidemic intensity differed by district, was highly correlated with population size (r = 0.76, p = 0.0015) and a critical window of opportunity for containing local Ebola epidemics at the source (ca one month) existed. This novel methodology can be used to help identify and contain the spatial expansion of future (re)emerging infectious disease outbreaks. © 2015 The Author(s).
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Forecasting of natural gas consumption with neural network and neuro fuzzy system
NASA Astrophysics Data System (ADS)
Kaynar, Oguz; Yilmaz, Isik; Demirkoparan, Ferhan
2010-05-01
The prediction of natural gas consumption is crucial for Turkey which follows foreign-dependent policy in point of providing natural gas and whose stock capacity is only 5% of internal total consumption. Prediction accuracy of demand is one of the elements which has an influence on sectored investments and agreements about obtaining natural gas, so on development of sector. In recent years, new techniques, such as artificial neural networks and fuzzy inference systems, have been widely used in natural gas consumption prediction in addition to classical time series analysis. In this study, weekly natural gas consumption of Turkey has been predicted by means of three different approaches. The first one is Autoregressive Integrated Moving Average (ARIMA), which is classical time series analysis method. The second approach is the Artificial Neural Network. Two different ANN models, which are Multi Layer Perceptron (MLP) and Radial Basis Function Network (RBFN), are employed to predict natural gas consumption. The last is Adaptive Neuro Fuzzy Inference System (ANFIS), which combines ANN and Fuzzy Inference System. Different prediction models have been constructed and one model, which has the best forecasting performance, is determined for each method. Then predictions are made by using these models and results are compared. Keywords: ANN, ANFIS, ARIMA, Natural Gas, Forecasting
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Robust Inference of Genetic Exchange Communities from Microbial Genomes Using TF-IDF.
Cong, Yingnan; Chan, Yao-Ban; Phillips, Charles A; Langston, Michael A; Ragan, Mark A
2017-01-01
Bacteria and archaea can exchange genetic material across lineages through processes of lateral genetic transfer (LGT). Collectively, these exchange relationships can be modeled as a network and analyzed using concepts from graph theory. In particular, densely connected regions within an LGT network have been defined as genetic exchange communities (GECs). However, it has been problematic to construct networks in which edges solely represent LGT. Here we apply term frequency-inverse document frequency (TF-IDF), an alignment-free method originating from document analysis, to infer regions of lateral origin in bacterial genomes. We examine four empirical datasets of different size (number of genomes) and phyletic breadth, varying a key parameter (word length k ) within bounds established in previous work. We map the inferred lateral regions to genes in recipient genomes, and construct networks in which the nodes are groups of genomes, and the edges natively represent LGT. We then extract maximum and maximal cliques (i.e., GECs) from these graphs, and identify nodes that belong to GECs across a wide range of k . Most surviving lateral transfer has happened within these GECs. Using Gene Ontology enrichment tests we demonstrate that biological processes associated with metabolism, regulation and transport are often over-represented among the genes affected by LGT within these communities. These enrichments are largely robust to change of k .
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Analysis of the GRNs Inference by Using Tsallis Entropy and a Feature Selection Approach
NASA Astrophysics Data System (ADS)
Lopes, Fabrício M.; de Oliveira, Evaldo A.; Cesar, Roberto M.
An important problem in the bioinformatics field is to understand how genes are regulated and interact through gene networks. This knowledge can be helpful for many applications, such as disease treatment design and drugs creation purposes. For this reason, it is very important to uncover the functional relationship among genes and then to construct the gene regulatory network (GRN) from temporal expression data. However, this task usually involves data with a large number of variables and small number of observations. In this way, there is a strong motivation to use pattern recognition and dimensionality reduction approaches. In particular, feature selection is specially important in order to select the most important predictor genes that can explain some phenomena associated with the target genes. This work presents a first study about the sensibility of entropy methods regarding the entropy functional form, applied to the problem of topology recovery of GRNs. The generalized entropy proposed by Tsallis is used to study this sensibility. The inference process is based on a feature selection approach, which is applied to simulated temporal expression data generated by an artificial gene network (AGN) model. The inferred GRNs are validated in terms of global network measures. Some interesting conclusions can be drawn from the experimental results, as reported for the first time in the present paper.
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NASA Astrophysics Data System (ADS)
Ndu, Obibobi Kamtochukwu
To ensure that estimates of risk and reliability inform design and resource allocation decisions in the development of complex engineering systems, early engagement in the design life cycle is necessary. An unfortunate constraint on the accuracy of such estimates at this stage of concept development is the limited amount of high fidelity design and failure information available on the actual system under development. Applying the human ability to learn from experience and augment our state of knowledge to evolve better solutions mitigates this limitation. However, the challenge lies in formalizing a methodology that takes this highly abstract, but fundamentally human cognitive, ability and extending it to the field of risk analysis while maintaining the tenets of generalization, Bayesian inference, and probabilistic risk analysis. We introduce an integrated framework for inferring the reliability, or other probabilistic measures of interest, of a new system or a conceptual variant of an existing system. Abstractly, our framework is based on learning from the performance of precedent designs and then applying the acquired knowledge, appropriately adjusted based on degree of relevance, to the inference process. This dissertation presents a method for inferring properties of the conceptual variant using a pseudo-spatial model that describes the spatial configuration of the family of systems to which the concept belongs. Through non-metric multidimensional scaling, we formulate the pseudo-spatial model based on rank-ordered subjective expert perception of design similarity between systems that elucidate the psychological space of the family. By a novel extension of Kriging methods for analysis of geospatial data to our "pseudo-space of comparable engineered systems", we develop a Bayesian inference model that allows prediction of the probabilistic measure of interest.
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Usefulness of Neuro-Fuzzy Models' Application for Tobacco Control
NASA Astrophysics Data System (ADS)
Petrovic-Lazarevic, Sonja; Zhang, Jian Ying
2007-12-01
The paper presents neuro-fuzzy models' application appropriate for tobacco control: the fuzzy control model, Adaptive Network Based Fuzzy Inference System, Evolving Fuzzy Neural Network models, and EVOlving POLicies. We propose further the use of Fuzzy Casual Networks to help tobacco control decision makers develop policies and measure their impact on social regulation.
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Lin, Chin-Teng; Wu, Rui-Cheng; Chang, Jyh-Yeong; Liang, Sheng-Fu
2004-02-01
In this paper, a new technique for the Chinese text-to-speech (TTS) system is proposed. Our major effort focuses on the prosodic information generation. New methodologies for constructing fuzzy rules in a prosodic model simulating human's pronouncing rules are developed. The proposed Recurrent Fuzzy Neural Network (RFNN) is a multilayer recurrent neural network (RNN) which integrates a Self-cOnstructing Neural Fuzzy Inference Network (SONFIN) into a recurrent connectionist structure. The RFNN can be functionally divided into two parts. The first part adopts the SONFIN as a prosodic model to explore the relationship between high-level linguistic features and prosodic information based on fuzzy inference rules. As compared to conventional neural networks, the SONFIN can always construct itself with an economic network size in high learning speed. The second part employs a five-layer network to generate all prosodic parameters by directly using the prosodic fuzzy rules inferred from the first part as well as other important features of syllables. The TTS system combined with the proposed method can behave not only sandhi rules but also the other prosodic phenomena existing in the traditional TTS systems. Moreover, the proposed scheme can even find out some new rules about prosodic phrase structure. The performance of the proposed RFNN-based prosodic model is verified by imbedding it into a Chinese TTS system with a Chinese monosyllable database based on the time-domain pitch synchronous overlap add (TD-PSOLA) method. Our experimental results show that the proposed RFNN can generate proper prosodic parameters including pitch means, pitch shapes, maximum energy levels, syllable duration, and pause duration. Some synthetic sounds are online available for demonstration.
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Kim, Jongrae; Bates, Declan G; Postlethwaite, Ian; Heslop-Harrison, Pat; Cho, Kwang-Hyun
2008-05-15
Inherent non-linearities in biomolecular interactions make the identification of network interactions difficult. One of the principal problems is that all methods based on the use of linear time-invariant models will have fundamental limitations in their capability to infer certain non-linear network interactions. Another difficulty is the multiplicity of possible solutions, since, for a given dataset, there may be many different possible networks which generate the same time-series expression profiles. A novel algorithm for the inference of biomolecular interaction networks from temporal expression data is presented. Linear time-varying models, which can represent a much wider class of time-series data than linear time-invariant models, are employed in the algorithm. From time-series expression profiles, the model parameters are identified by solving a non-linear optimization problem. In order to systematically reduce the set of possible solutions for the optimization problem, a filtering process is performed using a phase-portrait analysis with random numerical perturbations. The proposed approach has the advantages of not requiring the system to be in a stable steady state, of using time-series profiles which have been generated by a single experiment, and of allowing non-linear network interactions to be identified. The ability of the proposed algorithm to correctly infer network interactions is illustrated by its application to three examples: a non-linear model for cAMP oscillations in Dictyostelium discoideum, the cell-cycle data for Saccharomyces cerevisiae and a large-scale non-linear model of a group of synchronized Dictyostelium cells. The software used in this article is available from http://sbie.kaist.ac.kr/software
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Integrating Genetic and Functional Genomic Data to Elucidate Common Disease Tra
NASA Astrophysics Data System (ADS)
Schadt, Eric
2005-03-01
The reconstruction of genetic networks in mammalian systems is one of the primary goals in biological research, especially as such reconstructions relate to elucidating not only common, polygenic human diseases, but living systems more generally. Here I present a statistical procedure for inferring causal relationships between gene expression traits and more classic clinical traits, including complex disease traits. This procedure has been generalized to the gene network reconstruction problem, where naturally occurring genetic variations in segregating mouse populations are used as a source of perturbations to elucidate tissue-specific gene networks. Differences in the extent of genetic control between genders and among four different tissues are highlighted. I also demonstrate that the networks derived from expression data in segregating mouse populations using the novel network reconstruction algorithm are able to capture causal associations between genes that result in increased predictive power, compared to more classically reconstructed networks derived from the same data. This approach to causal inference in large segregating mouse populations over multiple tissues not only elucidates fundamental aspects of transcriptional control, it also allows for the objective identification of key drivers of common human diseases.
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From molecular noise to behavioural variability in a single bacterium
NASA Astrophysics Data System (ADS)
Korobkova, Ekaterina; Emonet, Thierry; Vilar, Jose M. G.; Shimizu, Thomas S.; Cluzel, Philippe
2004-04-01
The chemotaxis network that governs the motion of Escherichia coli has long been studied to gain a general understanding of signal transduction. Although this pathway is composed of just a few components, it exhibits some essential characteristics of biological complexity, such as adaptation and response to environmental signals. In studying intracellular networks, most experiments and mathematical models have assumed that network properties can be inferred from population measurements. However, this approach masks underlying temporal fluctuations of intracellular signalling events. We have inferred fundamental properties of the chemotaxis network from a noise analysis of behavioural variations in individual bacteria. Here we show that certain properties established by population measurements, such as adapted states, are not conserved at the single-cell level: for timescales ranging from seconds to several minutes, the behaviour of non-stimulated cells exhibit temporal variations much larger than the expected statistical fluctuations. We find that the signalling network itself causes this noise and identify the molecular events that produce it. Small changes in the concentration of one key network component suppress temporal behavioural variability, suggesting that such variability is a selected property of this adaptive system.
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Dynamic social networks based on movement
Scharf, Henry; Hooten, Mevin B.; Fosdick, Bailey K.; Johnson, Devin S.; London, Joshua M.; Durban, John W.
2016-01-01
Network modeling techniques provide a means for quantifying social structure in populations of individuals. Data used to define social connectivity are often expensive to collect and based on case-specific, ad hoc criteria. Moreover, in applications involving animal social networks, collection of these data is often opportunistic and can be invasive. Frequently, the social network of interest for a given population is closely related to the way individuals move. Thus, telemetry data, which are minimally invasive and relatively inexpensive to collect, present an alternative source of information. We develop a framework for using telemetry data to infer social relationships among animals. To achieve this, we propose a Bayesian hierarchical model with an underlying dynamic social network controlling movement of individuals via two mechanisms: an attractive effect and an aligning effect. We demonstrate the model and its ability to accurately identify complex social behavior in simulation, and apply our model to telemetry data arising from killer whales. Using auxiliary information about the study population, we investigate model validity and find the inferred dynamic social network is consistent with killer whale ecology and expert knowledge.
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77 FR 58415 - Large Scale Networking (LSN); Joint Engineering Team (JET)
Federal Register 2010, 2011, 2012, 2013, 2014
2012-09-20
... NATIONAL SCIENCE FOUNDATION Large Scale Networking (LSN); Joint Engineering Team (JET) AGENCY: The Networking and Information Technology Research and Development (NITRD) National Coordination Office (NCO..._Engineering_Team_ (JET). SUMMARY: The JET, established in 1997, provides for information sharing among Federal...
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78 FR 70076 - Large Scale Networking (LSN)-Joint Engineering Team (JET)
Federal Register 2010, 2011, 2012, 2013, 2014
2013-11-22
... NATIONAL SCIENCE FOUNDATION Large Scale Networking (LSN)--Joint Engineering Team (JET) AGENCY: The Networking and Information Technology Research and Development (NITRD) National Coordination Office (NCO..._Engineering_Team_ (JET)#title. SUMMARY: The JET, established in 1997, provides for information sharing among...
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An expert system environment for the Generic VHSIC Spaceborne Computer (GVSC)
NASA Astrophysics Data System (ADS)
Cockerham, Ann; Labhart, Jay; Rowe, Michael; Skinner, James
The authors describe a Phase II Phillips Laboratory Small Business Innovative Research (SBIR) program being performed to implement a flexible and general-purpose inference environment for embedded space and avionics applications. This inference environment is being developed in Ada and takes special advantage of the target architecture, the GVSC. The GVSC implements the MIL-STD-1750A ISA and contains enhancements to allow access of up to 8 MBytes of memory. The inference environment makes use of the Merit Enhanced Traversal Engine (METE) algorithm, which employs the latest inference and knowledge representation strategies to optimize both run-time speed and memory utilization.
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Towards Breaking the Histone Code – Bayesian Graphical Models for Histone Modifications
Mitra, Riten; Müller, Peter; Liang, Shoudan; Xu, Yanxun; Ji, Yuan
2013-01-01
Background Histones are proteins that wrap DNA around in small spherical structures called nucleosomes. Histone modifications (HMs) refer to the post-translational modifications to the histone tails. At a particular genomic locus, each of these HMs can either be present or absent, and the combinatory patterns of the presence or absence of multiple HMs, or the ‘histone codes,’ are believed to co-regulate important biological processes. We aim to use raw data on HM markers at different genomic loci to (1) decode the complex biological network of HMs in a single region and (2) demonstrate how the HM networks differ in different regulatory regions. We suggest that these differences in network attributes form a significant link between histones and genomic functions. Methods and Results We develop a powerful graphical model under Bayesian paradigm. Posterior inference is fully probabilistic, allowing us to compute the probabilities of distinct dependence patterns of the HMs using graphs. Furthermore, our model-based framework allows for easy but important extensions for inference on differential networks under various conditions, such as the different annotations of the genomic locations (e.g., promoters versus insulators). We applied these models to ChIP-Seq data based on CD4+ T lymphocytes. The results confirmed many existing findings and provided a unified tool to generate various promising hypotheses. Differential network analyses revealed new insights on co-regulation of HMs of transcriptional activities in different genomic regions. Conclusions The use of Bayesian graphical models and borrowing strength across different conditions provide high power to infer histone networks and their differences. PMID:23748248
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Applying dynamic Bayesian networks to perturbed gene expression data.
Dojer, Norbert; Gambin, Anna; Mizera, Andrzej; Wilczyński, Bartek; Tiuryn, Jerzy
2006-05-08
A central goal of molecular biology is to understand the regulatory mechanisms of gene transcription and protein synthesis. Because of their solid basis in statistics, allowing to deal with the stochastic aspects of gene expressions and noisy measurements in a natural way, Bayesian networks appear attractive in the field of inferring gene interactions structure from microarray experiments data. However, the basic formalism has some disadvantages, e.g. it is sometimes hard to distinguish between the origin and the target of an interaction. Two kinds of microarray experiments yield data particularly rich in information regarding the direction of interactions: time series and perturbation experiments. In order to correctly handle them, the basic formalism must be modified. For example, dynamic Bayesian networks (DBN) apply to time series microarray data. To our knowledge the DBN technique has not been applied in the context of perturbation experiments. We extend the framework of dynamic Bayesian networks in order to incorporate perturbations. Moreover, an exact algorithm for inferring an optimal network is proposed and a discretization method specialized for time series data from perturbation experiments is introduced. We apply our procedure to realistic simulations data. The results are compared with those obtained by standard DBN learning techniques. Moreover, the advantages of using exact learning algorithm instead of heuristic methods are analyzed. We show that the quality of inferred networks dramatically improves when using data from perturbation experiments. We also conclude that the exact algorithm should be used when it is possible, i.e. when considered set of genes is small enough.
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Automated quantification of neuronal networks and single-cell calcium dynamics using calcium imaging
Patel, Tapan P.; Man, Karen; Firestein, Bonnie L.; Meaney, David F.
2017-01-01
Background Recent advances in genetically engineered calcium and membrane potential indicators provide the potential to estimate the activation dynamics of individual neurons within larger, mesoscale networks (100s–1000 +neurons). However, a fully integrated automated workflow for the analysis and visualization of neural microcircuits from high speed fluorescence imaging data is lacking. New method Here we introduce FluoroSNNAP, Fluorescence Single Neuron and Network Analysis Package. FluoroSNNAP is an open-source, interactive software developed in MATLAB for automated quantification of numerous biologically relevant features of both the calcium dynamics of single-cells and network activity patterns. FluoroSNNAP integrates and improves upon existing tools for spike detection, synchronization analysis, and inference of functional connectivity, making it most useful to experimentalists with little or no programming knowledge. Results We apply FluoroSNNAP to characterize the activity patterns of neuronal microcircuits undergoing developmental maturation in vitro. Separately, we highlight the utility of single-cell analysis for phenotyping a mixed population of neurons expressing a human mutant variant of the microtubule associated protein tau and wild-type tau. Comparison with existing method(s) We show the performance of semi-automated cell segmentation using spatiotemporal independent component analysis and significant improvement in detecting calcium transients using a template-based algorithm in comparison to peak-based or wavelet-based detection methods. Our software further enables automated analysis of microcircuits, which is an improvement over existing methods. Conclusions We expect the dissemination of this software will facilitate a comprehensive analysis of neuronal networks, promoting the rapid interrogation of circuits in health and disease. PMID:25629800
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Principles of Biomimetic Vascular Network Design Applied to a Tissue-Engineered Liver Scaffold
Hoganson, David M.; Pryor, Howard I.; Spool, Ira D.; Burns, Owen H.; Gilmore, J. Randall
2010-01-01
Branched vascular networks are a central component of scaffold architecture for solid organ tissue engineering. In this work, seven biomimetic principles were established as the major guiding technical design considerations of a branched vascular network for a tissue-engineered scaffold. These biomimetic design principles were applied to a branched radial architecture to develop a liver-specific vascular network. Iterative design changes and computational fluid dynamic analysis were used to optimize the network before mold manufacturing. The vascular network mold was created using a new mold technique that achieves a 1:1 aspect ratio for all channels. In vitro blood flow testing confirmed the physiologic hemodynamics of the network as predicted by computational fluid dynamic analysis. These results indicate that this biomimetic liver vascular network design will provide a foundation for developing complex vascular networks for solid organ tissue engineering that achieve physiologic blood flow. PMID:20001254
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Principles of biomimetic vascular network design applied to a tissue-engineered liver scaffold.
Hoganson, David M; Pryor, Howard I; Spool, Ira D; Burns, Owen H; Gilmore, J Randall; Vacanti, Joseph P
2010-05-01
Branched vascular networks are a central component of scaffold architecture for solid organ tissue engineering. In this work, seven biomimetic principles were established as the major guiding technical design considerations of a branched vascular network for a tissue-engineered scaffold. These biomimetic design principles were applied to a branched radial architecture to develop a liver-specific vascular network. Iterative design changes and computational fluid dynamic analysis were used to optimize the network before mold manufacturing. The vascular network mold was created using a new mold technique that achieves a 1:1 aspect ratio for all channels. In vitro blood flow testing confirmed the physiologic hemodynamics of the network as predicted by computational fluid dynamic analysis. These results indicate that this biomimetic liver vascular network design will provide a foundation for developing complex vascular networks for solid organ tissue engineering that achieve physiologic blood flow.
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Spontaneous Trait Inferences on Social Media.
Levordashka, Ana; Utz, Sonja
2017-01-01
The present research investigates whether spontaneous trait inferences occur under conditions characteristic of social media and networking sites: nonextreme, ostensibly self-generated content, simultaneous presentation of multiple cues, and self-paced browsing. We used an established measure of trait inferences (false recognition paradigm) and a direct assessment of impressions. Without being asked to do so, participants spontaneously formed impressions of people whose status updates they saw. Our results suggest that trait inferences occurred from nonextreme self-generated content, which is commonly found in social media updates (Experiment 1) and when nine status updates from different people were presented in parallel (Experiment 2). Although inferences did occur during free browsing, the results suggest that participants did not necessarily associate the traits with the corresponding status update authors (Experiment 3). Overall, the findings suggest that spontaneous trait inferences occur on social media. We discuss implications for online communication and research on spontaneous trait inferences.
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1988-06-27
de olf nessse end Id e ;-tl Sb ieeI smleo) ,Optical Artificial Intellegence ; Optical inference engines; Optical logic; Optical informationprocessing...common. They arise in areas such as expert systems and other artificial intelligence systems. In recent years, the computer science language PROLOG has...cal processors should in principle be well suited for : I artificial intelligence applications. In recent years, symbolic logic processing. , the
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Computational statistics using the Bayesian Inference Engine
NASA Astrophysics Data System (ADS)
Weinberg, Martin D.
2013-09-01
This paper introduces the Bayesian Inference Engine (BIE), a general parallel, optimized software package for parameter inference and model selection. This package is motivated by the analysis needs of modern astronomical surveys and the need to organize and reuse expensive derived data. The BIE is the first platform for computational statistics designed explicitly to enable Bayesian update and model comparison for astronomical problems. Bayesian update is based on the representation of high-dimensional posterior distributions using metric-ball-tree based kernel density estimation. Among its algorithmic offerings, the BIE emphasizes hybrid tempered Markov chain Monte Carlo schemes that robustly sample multimodal posterior distributions in high-dimensional parameter spaces. Moreover, the BIE implements a full persistence or serialization system that stores the full byte-level image of the running inference and previously characterized posterior distributions for later use. Two new algorithms to compute the marginal likelihood from the posterior distribution, developed for and implemented in the BIE, enable model comparison for complex models and data sets. Finally, the BIE was designed to be a collaborative platform for applying Bayesian methodology to astronomy. It includes an extensible object-oriented and easily extended framework that implements every aspect of the Bayesian inference. By providing a variety of statistical algorithms for all phases of the inference problem, a scientist may explore a variety of approaches with a single model and data implementation. Additional technical details and download details are available from http://www.astro.umass.edu/bie. The BIE is distributed under the GNU General Public License.
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From Blickets to Synapses: Inferring Temporal Causal Networks by Observation
ERIC Educational Resources Information Center
Fernando, Chrisantha
2013-01-01
How do human infants learn the causal dependencies between events? Evidence suggests that this remarkable feat can be achieved by observation of only a handful of examples. Many computational models have been produced to explain how infants perform causal inference without explicit teaching about statistics or the scientific method. Here, we…
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On the Structure of Cortical Microcircuits Inferred from Small Sample Sizes.
Vegué, Marina; Perin, Rodrigo; Roxin, Alex
2017-08-30
The structure in cortical microcircuits deviates from what would be expected in a purely random network, which has been seen as evidence of clustering. To address this issue, we sought to reproduce the nonrandom features of cortical circuits by considering several distinct classes of network topology, including clustered networks, networks with distance-dependent connectivity, and those with broad degree distributions. To our surprise, we found that all of these qualitatively distinct topologies could account equally well for all reported nonrandom features despite being easily distinguishable from one another at the network level. This apparent paradox was a consequence of estimating network properties given only small sample sizes. In other words, networks that differ markedly in their global structure can look quite similar locally. This makes inferring network structure from small sample sizes, a necessity given the technical difficulty inherent in simultaneous intracellular recordings, problematic. We found that a network statistic called the sample degree correlation (SDC) overcomes this difficulty. The SDC depends only on parameters that can be estimated reliably given small sample sizes and is an accurate fingerprint of every topological family. We applied the SDC criterion to data from rat visual and somatosensory cortex and discovered that the connectivity was not consistent with any of these main topological classes. However, we were able to fit the experimental data with a more general network class, of which all previous topologies were special cases. The resulting network topology could be interpreted as a combination of physical spatial dependence and nonspatial, hierarchical clustering. SIGNIFICANCE STATEMENT The connectivity of cortical microcircuits exhibits features that are inconsistent with a simple random network. Here, we show that several classes of network models can account for this nonrandom structure despite qualitative differences in their global properties. This apparent paradox is a consequence of the small numbers of simultaneously recorded neurons in experiment: when inferred via small sample sizes, many networks may be indistinguishable despite being globally distinct. We develop a connectivity measure that successfully classifies networks even when estimated locally with a few neurons at a time. We show that data from rat cortex is consistent with a network in which the likelihood of a connection between neurons depends on spatial distance and on nonspatial, asymmetric clustering. Copyright © 2017 the authors 0270-6474/17/378498-13$15.00/0.
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Hiratani, Naoki; Fukai, Tomoki
2016-01-01
In the adult mammalian cortex, a small fraction of spines are created and eliminated every day, and the resultant synaptic connection structure is highly nonrandom, even in local circuits. However, it remains unknown whether a particular synaptic connection structure is functionally advantageous in local circuits, and why creation and elimination of synaptic connections is necessary in addition to rich synaptic weight plasticity. To answer these questions, we studied an inference task model through theoretical and numerical analyses. We demonstrate that a robustly beneficial network structure naturally emerges by combining Hebbian-type synaptic weight plasticity and wiring plasticity. Especially in a sparsely connected network, wiring plasticity achieves reliable computation by enabling efficient information transmission. Furthermore, the proposed rule reproduces experimental observed correlation between spine dynamics and task performance. PMID:27303271
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Modeling of a 5-cell direct methanol fuel cell using adaptive-network-based fuzzy inference systems
NASA Astrophysics Data System (ADS)
Wang, Rongrong; Qi, Liang; Xie, Xiaofeng; Ding, Qingqing; Li, Chunwen; Ma, ChenChi M.
The methanol concentrations, temperature and current were considered as inputs, the cell voltage was taken as output, and the performance of a direct methanol fuel cell (DMFC) was modeled by adaptive-network-based fuzzy inference systems (ANFIS). The artificial neural network (ANN) and polynomial-based models were selected to be compared with the ANFIS in respect of quality and accuracy. Based on the ANFIS model obtained, the characteristics of the DMFC were studied. The results show that temperature and methanol concentration greatly affect the performance of the DMFC. Within a restricted current range, the methanol concentration does not greatly affect the stack voltage. In order to obtain higher fuel utilization efficiency, the methanol concentrations and temperatures should be adjusted according to the load on the system.
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Spectral Entropies as Information-Theoretic Tools for Complex Network Comparison
NASA Astrophysics Data System (ADS)
De Domenico, Manlio; Biamonte, Jacob
2016-10-01
Any physical system can be viewed from the perspective that information is implicitly represented in its state. However, the quantification of this information when it comes to complex networks has remained largely elusive. In this work, we use techniques inspired by quantum statistical mechanics to define an entropy measure for complex networks and to develop a set of information-theoretic tools, based on network spectral properties, such as Rényi q entropy, generalized Kullback-Leibler and Jensen-Shannon divergences, the latter allowing us to define a natural distance measure between complex networks. First, we show that by minimizing the Kullback-Leibler divergence between an observed network and a parametric network model, inference of model parameter(s) by means of maximum-likelihood estimation can be achieved and model selection can be performed with appropriate information criteria. Second, we show that the information-theoretic metric quantifies the distance between pairs of networks and we can use it, for instance, to cluster the layers of a multilayer system. By applying this framework to networks corresponding to sites of the human microbiome, we perform hierarchical cluster analysis and recover with high accuracy existing community-based associations. Our results imply that spectral-based statistical inference in complex networks results in demonstrably superior performance as well as a conceptual backbone, filling a gap towards a network information theory.
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Displayed Trees Do Not Determine Distinguishability Under the Network Multispecies Coalescent
Zhu, Sha; Degnan, James H.
2017-01-01
Abstract Recent work in estimating species relationships from gene trees has included inferring networks assuming that past hybridization has occurred between species. Probabilistic models using the multispecies coalescent can be used in this framework for likelihood-based inference of both network topologies and parameters, including branch lengths and hybridization parameters. A difficulty for such methods is that it is not always clear whether, or to what extent, networks are identifiable—that is whether there could be two distinct networks that lead to the same distribution of gene trees. For cases in which incomplete lineage sorting occurs in addition to hybridization, we demonstrate a new representation of the species network likelihood that expresses the probability distribution of the gene tree topologies as a linear combination of gene tree distributions given a set of species trees. This representation makes it clear that in some cases in which two distinct networks give the same distribution of gene trees when sampling one allele per species, the two networks can be distinguished theoretically when multiple individuals are sampled per species. This result means that network identifiability is not only a function of the trees displayed by the networks but also depends on allele sampling within species. We additionally give an example in which two networks that display exactly the same trees can be distinguished from their gene trees even when there is only one lineage sampled per species. PMID:27780899
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Network geometry inference using common neighbors
NASA Astrophysics Data System (ADS)
Papadopoulos, Fragkiskos; Aldecoa, Rodrigo; Krioukov, Dmitri
2015-08-01
We introduce and explore a method for inferring hidden geometric coordinates of nodes in complex networks based on the number of common neighbors between the nodes. We compare this approach to the HyperMap method, which is based only on the connections (and disconnections) between the nodes, i.e., on the links that the nodes have (or do not have). We find that for high degree nodes, the common-neighbors approach yields a more accurate inference than the link-based method, unless heuristic periodic adjustments (or "correction steps") are used in the latter. The common-neighbors approach is computationally intensive, requiring O (t4) running time to map a network of t nodes, versus O (t3) in the link-based method. But we also develop a hybrid method with O (t3) running time, which combines the common-neighbors and link-based approaches, and we explore a heuristic that reduces its running time further to O (t2) , without significant reduction in the mapping accuracy. We apply this method to the autonomous systems (ASs) Internet, and we reveal how soft communities of ASs evolve over time in the similarity space. We further demonstrate the method's predictive power by forecasting future links between ASs. Taken altogether, our results advance our understanding of how to efficiently and accurately map real networks to their latent geometric spaces, which is an important necessary step toward understanding the laws that govern the dynamics of nodes in these spaces, and the fine-grained dynamics of network connections.
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Defining and Exposing Privacy Issues with Social Media
2012-06-11
Twitter, and Linked In[ I 0). VI. SEARCH ENGINES In addition to social networking sites, search engines pose new issues to privacy. As...networking, search engines , and storing personal information online in general have been accepted worldwide due to the benefits they provide. Social...networking provides even more communication in an information-demanding age, allowing users to interact across great distances. Search engines allow
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NASA Astrophysics Data System (ADS)
Lee, K. David; Wiesenfeld, Eric; Gelfand, Andrew
2007-04-01
One of the greatest challenges in modern combat is maintaining a high level of timely Situational Awareness (SA). In many situations, computational complexity and accuracy considerations make the development and deployment of real-time, high-level inference tools very difficult. An innovative hybrid framework that combines Bayesian inference, in the form of Bayesian Networks, and Possibility Theory, in the form of Fuzzy Logic systems, has recently been introduced to provide a rigorous framework for high-level inference. In previous research, the theoretical basis and benefits of the hybrid approach have been developed. However, lacking is a concrete experimental comparison of the hybrid framework with traditional fusion methods, to demonstrate and quantify this benefit. The goal of this research, therefore, is to provide a statistical analysis on the comparison of the accuracy and performance of hybrid network theory, with pure Bayesian and Fuzzy systems and an inexact Bayesian system approximated using Particle Filtering. To accomplish this task, domain specific models will be developed under these different theoretical approaches and then evaluated, via Monte Carlo Simulation, in comparison to situational ground truth to measure accuracy and fidelity. Following this, a rigorous statistical analysis of the performance results will be performed, to quantify the benefit of hybrid inference to other fusion tools.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Dana L. Kelly; Albert Malkhasyan
2010-06-01
There is a nearly ubiquitous assumption in PSA that parameter values are at least piecewise-constant in time. As a result, Bayesian inference tends to incorporate many years of plant operation, over which there have been significant changes in plant operational and maintenance practices, plant management, etc. These changes can cause significant changes in parameter values over time; however, failure to perform Bayesian inference in the proper time-dependent framework can mask these changes. Failure to question the assumption of constant parameter values, and failure to perform Bayesian inference in the proper time-dependent framework were noted as important issues in NUREG/CR-6813, performedmore » for the U. S. Nuclear Regulatory Commission’s Advisory Committee on Reactor Safeguards in 2003. That report noted that “industry lacks tools to perform time-trend analysis with Bayesian updating.” This paper describes an application of time-dependent Bayesian inference methods developed for the European Commission Ageing PSA Network. These methods utilize open-source software, implementing Markov chain Monte Carlo sampling. The paper also illustrates the development of a generic prior distribution, which incorporates multiple sources of generic data via weighting factors that address differences in key influences, such as vendor, component boundaries, conditions of the operating environment, etc.« less
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NASA Technical Reports Server (NTRS)
Kobayashi, Takahisa; Simon, Donald L.
2002-01-01
As part of the NASA Aviation Safety Program, a unique model-based diagnostics method that employs neural networks and genetic algorithms for aircraft engine performance diagnostics has been developed and demonstrated at the NASA Glenn Research Center against a nonlinear gas turbine engine model. Neural networks are applied to estimate the internal health condition of the engine, and genetic algorithms are used for sensor fault detection, isolation, and quantification. This hybrid architecture combines the excellent nonlinear estimation capabilities of neural networks with the capability to rank the likelihood of various faults given a specific sensor suite signature. The method requires a significantly smaller data training set than a neural network approach alone does, and it performs the combined engine health monitoring objectives of performance diagnostics and sensor fault detection and isolation in the presence of nominal and degraded engine health conditions.
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Floares, Alexandru George
2008-01-01
Modeling neural networks with ordinary differential equations systems is a sensible approach, but also very difficult. This paper describes a new algorithm based on linear genetic programming which can be used to reverse engineer neural networks. The RODES algorithm automatically discovers the structure of the network, including neural connections, their signs and strengths, estimates its parameters, and can even be used to identify the biophysical mechanisms involved. The algorithm is tested on simulated time series data, generated using a realistic model of the subthalamopallidal network of basal ganglia. The resulting ODE system is highly accurate, and results are obtained in a matter of minutes. This is because the problem of reverse engineering a system of coupled differential equations is reduced to one of reverse engineering individual algebraic equations. The algorithm allows the incorporation of common domain knowledge to restrict the solution space. To our knowledge, this is the first time a realistic reverse engineering algorithm based on linear genetic programming has been applied to neural networks.