Learning and coding in biological neural networks

NASA Astrophysics Data System (ADS)

Fiete, Ila Rani

How can large groups of neurons that locally modify their activities learn to collectively perform a desired task? Do studies of learning in small networks tell us anything about learning in the fantastically large collection of neurons that make up a vertebrate brain? What factors do neurons optimize by encoding sensory inputs or motor commands in the way they do? In this thesis I present a collection of four theoretical works: each of the projects was motivated by specific constraints and complexities of biological neural networks, as revealed by experimental studies; together, they aim to partially address some of the central questions of neuroscience posed above. We first study the role of sparse neural activity, as seen in the coding of sequential commands in a premotor area responsible for birdsong. We show that the sparse coding of temporal sequences in the songbird brain can, in a network where the feedforward plastic weights must translate the sparse sequential code into a time-varying muscle code, facilitate learning by minimizing synaptic interference. Next, we propose a biologically plausible synaptic plasticity rule that can perform goal-directed learning in recurrent networks of voltage-based spiking neurons that interact through conductances. Learning is based on the correlation of noisy local activity with a global reward signal; we prove that this rule performs stochastic gradient ascent on the reward. Thus, if the reward signal quantifies network performance on some desired task, the plasticity rule provably drives goal-directed learning in the network. To assess the convergence properties of the learning rule, we compare it with a known example of learning in the brain. Song-learning in finches is a clear example of a learned behavior, with detailed available neurophysiological data. With our learning rule, we train an anatomically accurate model birdsong network that drives a sound source to mimic an actual zebrafinch song. Simulation and theoretical results on the scalability of this rule show that learning with stochastic gradient ascent may be adequately fast to explain learning in the bird. Finally, we address the more general issue of the scalability of stochastic gradient learning on quadratic cost surfaces in linear systems, as a function of system size and task characteristics, by deriving analytical expressions for the learning curves.

Learning Biological Networks via Bootstrapping with Optimized GO-based Gene Similarity

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

Taylor, Ronald C.; Sanfilippo, Antonio P.; McDermott, Jason E.

2010-08-02

Microarray gene expression data provide a unique information resource for learning biological networks using "reverse engineering" methods. However, there are a variety of cases in which we know which genes are involved in a given pathology of interest, but we do not have enough experimental evidence to support the use of fully-supervised/reverse-engineering learning methods. In this paper, we explore a novel semi-supervised approach in which biological networks are learned from a reference list of genes and a partial set of links for these genes extracted automatically from PubMed abstracts, using a knowledge-driven bootstrapping algorithm. We show how new relevant linksmore » across 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. We describe an application of this approach to the TGFB pathway as a case study and show how the ensuing results prove the feasibility of the approach as an alternate or complementary technique to fully supervised methods.« less

Robust Learning of High-dimensional Biological Networks with Bayesian Networks

NASA Astrophysics Data System (ADS)

Nägele, Andreas; Dejori, Mathäus; Stetter, Martin

Structure learning of Bayesian networks applied to gene expression data has become a potentially useful method to estimate interactions between genes. However, the NP-hardness of Bayesian network structure learning renders the reconstruction of the full genetic network with thousands of genes unfeasible. Consequently, the maximal network size is usually restricted dramatically to a small set of genes (corresponding with variables in the Bayesian network). Although this feature reduction step makes structure learning computationally tractable, on the downside, the learned structure might be adversely affected due to the introduction of missing genes. Additionally, gene expression data are usually very sparse with respect to the number of samples, i.e., the number of genes is much greater than the number of different observations. Given these problems, learning robust network features from microarray data is a challenging task. This chapter presents several approaches tackling the robustness issue in order to obtain a more reliable estimation of learned network features.

A review on machine learning principles for multi-view biological data integration.

PubMed

Li, Yifeng; Wu, Fang-Xiang; Ngom, Alioune

2018-03-01

Driven by high-throughput sequencing techniques, modern genomic and clinical studies are in a strong need of integrative machine learning models for better use of vast volumes of heterogeneous information in the deep understanding of biological systems and the development of predictive models. How data from multiple sources (called multi-view data) are incorporated in a learning system is a key step for successful analysis. In this article, we provide a comprehensive review on omics and clinical data integration techniques, from a machine learning perspective, for various analyses such as prediction, clustering, dimension reduction and association. We shall show that Bayesian models are able to use prior information and model measurements with various distributions; tree-based methods can either build a tree with all features or collectively make a final decision based on trees learned from each view; kernel methods fuse the similarity matrices learned from individual views together for a final similarity matrix or learning model; network-based fusion methods are capable of inferring direct and indirect associations in a heterogeneous network; matrix factorization models have potential to learn interactions among features from different views; and a range of deep neural networks can be integrated in multi-modal learning for capturing the complex mechanism of biological systems.

Functional model of biological neural networks.

PubMed

Lo, James Ting-Ho

2010-12-01

A functional model of biological neural networks, called temporal hierarchical probabilistic associative memory (THPAM), is proposed in this paper. THPAM comprises functional models of dendritic trees for encoding inputs to neurons, a first type of neuron for generating spike trains, a second type of neuron for generating graded signals to modulate neurons of the first type, supervised and unsupervised Hebbian learning mechanisms for easy learning and retrieving, an arrangement of dendritic trees for maximizing generalization, hardwiring for rotation-translation-scaling invariance, and feedback connections with different delay durations for neurons to make full use of present and past informations generated by neurons in the same and higher layers. These functional models and their processing operations have many functions of biological neural networks that have not been achieved by other models in the open literature and provide logically coherent answers to many long-standing neuroscientific questions. However, biological justifications of these functional models and their processing operations are required for THPAM to qualify as a macroscopic model (or low-order approximate) of biological neural networks.

An introduction to deep learning on biological sequence data: examples and solutions.

PubMed

Jurtz, Vanessa Isabell; Johansen, Alexander Rosenberg; Nielsen, Morten; Almagro Armenteros, Jose Juan; Nielsen, Henrik; Sønderby, Casper Kaae; Winther, Ole; Sønderby, Søren Kaae

2017-11-15

Deep neural network architectures such as convolutional and long short-term memory networks have become increasingly popular as machine learning tools during the recent years. The availability of greater computational resources, more data, new algorithms for training deep models and easy to use libraries for implementation and training of neural networks are the drivers of this development. The use of deep learning has been especially successful in image recognition; and the development of tools, applications and code examples are in most cases centered within this field rather than within biology. Here, we aim to further the development of deep learning methods within biology by providing application examples and ready to apply and adapt code templates. Given such examples, we illustrate how architectures consisting of convolutional and long short-term memory neural networks can relatively easily be designed and trained to state-of-the-art performance on three biological sequence problems: prediction of subcellular localization, protein secondary structure and the binding of peptides to MHC Class II molecules. All implementations and datasets are available online to the scientific community at https://github.com/vanessajurtz/lasagne4bio. skaaesonderby@gmail.com. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Synthetic biology: exploring and exploiting genetic modularity through the design of novel biological networks.

PubMed

Agapakis, Christina M; Silver, Pamela A

2009-07-01

Synthetic biology has been used to describe many biological endeavors over the past thirty years--from designing enzymes and in vitro systems, to manipulating existing metabolisms and gene expression, to creating entirely synthetic replicating life forms. What separates the current incarnation of synthetic biology from the recombinant DNA technology or metabolic engineering of the past is an emphasis on principles from engineering such as modularity, standardization, and rigorously predictive models. As such, synthetic biology represents a new paradigm for learning about and using biological molecules and data, with applications in basic science, biotechnology, and medicine. This review covers the canonical examples as well as some recent advances in synthetic biology in terms of what we know and what we can learn about the networks underlying biology, and how this endeavor may shape our understanding of living systems.

Bayesian network prior: network analysis of biological data using external knowledge

PubMed Central

Isci, Senol; Dogan, Haluk; Ozturk, Cengizhan; Otu, Hasan H.

2014-01-01

Motivation: Reverse engineering GI networks from experimental data is a challenging task due to the complex nature of the networks and the noise inherent in the data. One way to overcome these hurdles would be incorporating the vast amounts of external biological knowledge when building interaction networks. We propose a framework where GI networks are learned from experimental data using Bayesian networks (BNs) and the incorporation of external knowledge is also done via a BN that we call Bayesian Network Prior (BNP). BNP depicts the relation between various evidence types that contribute to the event ‘gene interaction’ and is used to calculate the probability of a candidate graph (G) in the structure learning process. Results: Our simulation results on synthetic, simulated and real biological data show that the proposed approach can identify the underlying interaction network with high accuracy even when the prior information is distorted and outperforms existing methods. Availability: Accompanying BNP software package is freely available for academic use at http://bioe.bilgi.edu.tr/BNP. Contact: hasan.otu@bilgi.edu.tr Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:24215027

Commentary: Biochemistry and Molecular Biology Educators Launch National Network

ERIC Educational Resources Information Center

Bailey, Cheryl; Bell, Ellis; Johnson, Margaret; Mattos, Carla; Sears, Duane; White, Harold B.

2010-01-01

The American Society of Biochemistry and Molecular Biology (ASBMB) has launched an National Science Foundation (NSF)-funded 5 year project to support biochemistry and molecular biology educators learning what and how students learn. As a part of this initiative, hundreds of life scientists will plan and develop a rich central resource for…

Understanding the neural basis of cognitive bias modification as a clinical treatment for depression.

PubMed

Eguchi, Akihiro; Walters, Daniel; Peerenboom, Nele; Dury, Hannah; Fox, Elaine; Stringer, Simon

2017-03-01

[Correction Notice: An Erratum for this article was reported in Vol 85(3) of Journal of Consulting and Clinical Psychology (see record 2017-07144-002). In the article, there was an error in the Discussion section's first paragraph for Implications and Future Work. The in-text reference citation for Penton-Voak et al. (2013) was incorrectly listed as "Blumenfeld, Preminger, Sagi, and Tsodyks (2006)". All versions of this article have been corrected.] Objective: Cognitive bias modification (CBM) eliminates cognitive biases toward negative information and is efficacious in reducing depression recurrence, but the mechanisms behind the bias elimination are not fully understood. The present study investigated, through computer simulation of neural network models, the neural dynamics underlying the use of CBM in eliminating the negative biases in the way that depressed patients evaluate facial expressions. We investigated 2 new CBM methodologies using biologically plausible synaptic learning mechanisms-continuous transformation learning and trace learning-which guide learning by exploiting either the spatial or temporal continuity between visual stimuli presented during training. We first describe simulations with a simplified 1-layer neural network, and then we describe simulations in a biologically detailed multilayer neural network model of the ventral visual pathway. After training with either the continuous transformation learning rule or the trace learning rule, the 1-layer neural network eliminated biases in interpreting neutral stimuli as sad. The multilayer neural network trained with realistic face stimuli was also shown to be able to use continuous transformation learning or trace learning to reduce biases in the interpretation of neutral stimuli. The simulation results suggest 2 biologically plausible synaptic learning mechanisms, continuous transformation learning and trace learning, that may subserve CBM. The results are highly informative for the development of experimental protocols to produce optimal CBM training methodologies with human participants. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Representational Distance Learning for Deep Neural Networks

PubMed Central

McClure, Patrick; Kriegeskorte, Nikolaus

2016-01-01

Deep neural networks (DNNs) provide useful models of visual representational transformations. We present a method that enables a DNN (student) to learn from the internal representational spaces of a reference model (teacher), which could be another DNN or, in the future, a biological brain. Representational spaces of the student and the teacher are characterized by representational distance matrices (RDMs). We propose representational distance learning (RDL), a stochastic gradient descent method that drives the RDMs of the student to approximate the RDMs of the teacher. We demonstrate that RDL is competitive with other transfer learning techniques for two publicly available benchmark computer vision datasets (MNIST and CIFAR-100), while allowing for architectural differences between student and teacher. By pulling the student's RDMs toward those of the teacher, RDL significantly improved visual classification performance when compared to baseline networks that did not use transfer learning. In the future, RDL may enable combined supervised training of deep neural networks using task constraints (e.g., images and category labels) and constraints from brain-activity measurements, so as to build models that replicate the internal representational spaces of biological brains. PMID:28082889

Representational Distance Learning for Deep Neural Networks.

PubMed

McClure, Patrick; Kriegeskorte, Nikolaus

2016-01-01

Deep neural networks (DNNs) provide useful models of visual representational transformations. We present a method that enables a DNN (student) to learn from the internal representational spaces of a reference model (teacher), which could be another DNN or, in the future, a biological brain. Representational spaces of the student and the teacher are characterized by representational distance matrices (RDMs). We propose representational distance learning (RDL), a stochastic gradient descent method that drives the RDMs of the student to approximate the RDMs of the teacher. We demonstrate that RDL is competitive with other transfer learning techniques for two publicly available benchmark computer vision datasets (MNIST and CIFAR-100), while allowing for architectural differences between student and teacher. By pulling the student's RDMs toward those of the teacher, RDL significantly improved visual classification performance when compared to baseline networks that did not use transfer learning. In the future, RDL may enable combined supervised training of deep neural networks using task constraints (e.g., images and category labels) and constraints from brain-activity measurements, so as to build models that replicate the internal representational spaces of biological brains.

Thermodynamic efficiency of learning a rule in neural networks

NASA Astrophysics Data System (ADS)

Goldt, Sebastian; Seifert, Udo

2017-11-01

Biological systems have to build models from their sensory input data that allow them to efficiently process previously unseen inputs. Here, we study a neural network learning a binary classification rule for these inputs from examples provided by a teacher. We analyse the ability of the network to apply the rule to new inputs, that is to generalise from past experience. Using stochastic thermodynamics, we show that the thermodynamic costs of the learning process provide an upper bound on the amount of information that the network is able to learn from its teacher for both batch and online learning. This allows us to introduce a thermodynamic efficiency of learning. We analytically compute the dynamics and the efficiency of a noisy neural network performing online learning in the thermodynamic limit. In particular, we analyse three popular learning algorithms, namely Hebbian, Perceptron and AdaTron learning. Our work extends the methods of stochastic thermodynamics to a new type of learning problem and might form a suitable basis for investigating the thermodynamics of decision-making.

Puzzles in modern biology. V. Why are genomes overwired?

PubMed

Frank, Steven A

2017-01-01

Many factors affect eukaryotic gene expression. Transcription factors, histone codes, DNA folding, and noncoding RNA modulate expression. Those factors interact in large, broadly connected regulatory control networks. An engineer following classical principles of control theory would design a simpler regulatory network. Why are genomes overwired? Neutrality or enhanced robustness may lead to the accumulation of additional factors that complicate network architecture. Dynamics progresses like a ratchet. New factors get added. Genomes adapt to the additional complexity. The newly added factors can no longer be removed without significant loss of fitness. Alternatively, highly wired genomes may be more malleable. In large networks, most genomic variants tend to have a relatively small effect on gene expression and trait values. Many small effects lead to a smooth gradient, in which traits may change steadily with respect to underlying regulatory changes. A smooth gradient may provide a continuous path from a starting point up to the highest peak of performance. A potential path of increasing performance promotes adaptability and learning. Genomes gain by the inductive process of natural selection, a trial and error learning algorithm that discovers general solutions for adapting to environmental challenge. Similarly, deeply and densely connected computational networks gain by various inductive trial and error learning procedures, in which the networks learn to reduce the errors in sequential trials. Overwiring alters the geometry of induction by smoothing the gradient along the inductive pathways of improving performance. Those overwiring benefits for induction apply to both natural biological networks and artificial deep learning networks.

Teaching Triple Science: GCSE Biology

ERIC Educational Resources Information Center

Learning and Skills Network (NJ3), 2007

2007-01-01

The Department for Children, Schools and Families (DCSF) has contracted with the Learning and Skills Network to support awareness and take-up of Triple Science GCSEs through the Triple Science Support Programme. This publication provides an introduction to teaching and learning approaches for the extension topics within GCSE Biology. It highlights…

From biological and social network metaphors to coupled bio-social wireless networks

PubMed Central

Barrett, Christopher L.; Eubank, Stephen; Anil Kumar, V.S.; Marathe, Madhav V.

2010-01-01

Biological and social analogies have been long applied to complex systems. Inspiration has been drawn from biological solutions to solve problems in engineering products and systems, ranging from Velcro to camouflage to robotics to adaptive and learning computing methods. In this paper, we present an overview of recent advances in understanding biological systems as networks and use this understanding to design and analyse wireless communication networks. We expand on two applications, namely cognitive sensing and control and wireless epidemiology. We discuss how our work in these two applications is motivated by biological metaphors. We believe that recent advances in computing and communications coupled with advances in health and social sciences raise the possibility of studying coupled bio-social communication networks. We argue that we can better utilise the advances in our understanding of one class of networks to better our understanding of the other. PMID:21643462

Deep Learning and Its Applications in Biomedicine.

PubMed

Cao, Chensi; Liu, Feng; Tan, Hai; Song, Deshou; Shu, Wenjie; Li, Weizhong; Zhou, Yiming; Bo, Xiaochen; Xie, Zhi

2018-02-01

Advances in biological and medical technologies have been providing us explosive volumes of biological and physiological data, such as medical images, electroencephalography, genomic and protein sequences. Learning from these data facilitates the understanding of human health and disease. Developed from artificial neural networks, deep learning-based algorithms show great promise in extracting features and learning patterns from complex data. The aim of this paper is to provide an overview of deep learning techniques and some of the state-of-the-art applications in the biomedical field. We first introduce the development of artificial neural network and deep learning. We then describe two main components of deep learning, i.e., deep learning architectures and model optimization. Subsequently, some examples are demonstrated for deep learning applications, including medical image classification, genomic sequence analysis, as well as protein structure classification and prediction. Finally, we offer our perspectives for the future directions in the field of deep learning. Copyright © 2018. Production and hosting by Elsevier B.V.

Protein complexes, big data, machine learning and integrative proteomics: lessons learned over a decade of systematic analysis of protein interaction networks.

PubMed

Havugimana, Pierre C; Hu, Pingzhao; Emili, Andrew

2017-10-01

Elucidation of the networks of physical (functional) interactions present in cells and tissues is fundamental for understanding the molecular organization of biological systems, the mechanistic basis of essential and disease-related processes, and for functional annotation of previously uncharacterized proteins (via guilt-by-association or -correlation). After a decade in the field, we felt it timely to document our own experiences in the systematic analysis of protein interaction networks. Areas covered: Researchers worldwide have contributed innovative experimental and computational approaches that have driven the rapidly evolving field of 'functional proteomics'. These include mass spectrometry-based methods to characterize macromolecular complexes on a global-scale and sophisticated data analysis tools - most notably machine learning - that allow for the generation of high-quality protein association maps. Expert commentary: Here, we recount some key lessons learned, with an emphasis on successful workflows, and challenges, arising from our own and other groups' ongoing efforts to generate, interpret and report proteome-scale interaction networks in increasingly diverse biological contexts.

Model Of Neural Network With Creative Dynamics

NASA Technical Reports Server (NTRS)

Zak, Michail; Barhen, Jacob

1993-01-01

Paper presents analysis of mathematical model of one-neuron/one-synapse neural network featuring coupled activation and learning dynamics and parametrical periodic excitation. Demonstrates self-programming, partly random behavior of suitable designed neural network; believed to be related to spontaneity and creativity of biological neural networks.

Unsupervised learning of digit recognition using spike-timing-dependent plasticity

PubMed Central

Diehl, Peter U.; Cook, Matthew

2015-01-01

In order to understand how the mammalian neocortex is performing computations, two things are necessary; we need to have a good understanding of the available neuronal processing units and mechanisms, and we need to gain a better understanding of how those mechanisms are combined to build functioning systems. Therefore, in recent years there is an increasing interest in how spiking neural networks (SNN) can be used to perform complex computations or solve pattern recognition tasks. However, it remains a challenging task to design SNNs which use biologically plausible mechanisms (especially for learning new patterns), since most such SNN architectures rely on training in a rate-based network and subsequent conversion to a SNN. We present a SNN for digit recognition which is based on mechanisms with increased biological plausibility, i.e., conductance-based instead of current-based synapses, spike-timing-dependent plasticity with time-dependent weight change, lateral inhibition, and an adaptive spiking threshold. Unlike most other systems, we do not use a teaching signal and do not present any class labels to the network. Using this unsupervised learning scheme, our architecture achieves 95% accuracy on the MNIST benchmark, which is better than previous SNN implementations without supervision. The fact that we used no domain-specific knowledge points toward the general applicability of our network design. Also, the performance of our network scales well with the number of neurons used and shows similar performance for four different learning rules, indicating robustness of the full combination of mechanisms, which suggests applicability in heterogeneous biological neural networks. PMID:26941637

Computational modeling of neural plasticity for self-organization of neural networks.

PubMed

Chrol-Cannon, Joseph; Jin, Yaochu

2014-11-01

Self-organization in biological nervous systems during the lifetime is known to largely occur through a process of plasticity that is dependent upon the spike-timing activity in connected neurons. In the field of computational neuroscience, much effort has been dedicated to building up computational models of neural plasticity to replicate experimental data. Most recently, increasing attention has been paid to understanding the role of neural plasticity in functional and structural neural self-organization, as well as its influence on the learning performance of neural networks for accomplishing machine learning tasks such as classification and regression. Although many ideas and hypothesis have been suggested, the relationship between the structure, dynamics and learning performance of neural networks remains elusive. The purpose of this article is to review the most important computational models for neural plasticity and discuss various ideas about neural plasticity's role. Finally, we suggest a few promising research directions, in particular those along the line that combines findings in computational neuroscience and systems biology, and their synergetic roles in understanding learning, memory and cognition, thereby bridging the gap between computational neuroscience, systems biology and computational intelligence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Computational modeling of spiking neural network with learning rules from STDP and intrinsic plasticity

NASA Astrophysics Data System (ADS)

Li, Xiumin; Wang, Wei; Xue, Fangzheng; Song, Yongduan

2018-02-01

Recently there has been continuously increasing interest in building up computational models of spiking neural networks (SNN), such as the Liquid State Machine (LSM). The biologically inspired self-organized neural networks with neural plasticity can enhance the capability of computational performance, with the characteristic features of dynamical memory and recurrent connection cycles which distinguish them from the more widely used feedforward neural networks. Despite a variety of computational models for brain-like learning and information processing have been proposed, the modeling of self-organized neural networks with multi-neural plasticity is still an important open challenge. The main difficulties lie in the interplay among different forms of neural plasticity rules and understanding how structures and dynamics of neural networks shape the computational performance. In this paper, we propose a novel approach to develop the models of LSM with a biologically inspired self-organizing network based on two neural plasticity learning rules. The connectivity among excitatory neurons is adapted by spike-timing-dependent plasticity (STDP) learning; meanwhile, the degrees of neuronal excitability are regulated to maintain a moderate average activity level by another learning rule: intrinsic plasticity (IP). Our study shows that LSM with STDP+IP performs better than LSM with a random SNN or SNN obtained by STDP alone. The noticeable improvement with the proposed method is due to the better reflected competition among different neurons in the developed SNN model, as well as the more effectively encoded and processed relevant dynamic information with its learning and self-organizing mechanism. This result gives insights to the optimization of computational models of spiking neural networks with neural plasticity.

Convolutional Deep Belief Networks for Single-Cell/Object Tracking in Computational Biology and Computer Vision.

PubMed

Zhong, Bineng; Pan, Shengnan; Zhang, Hongbo; Wang, Tian; Du, Jixiang; Chen, Duansheng; Cao, Liujuan

2016-01-01

In this paper, we propose deep architecture to dynamically learn the most discriminative features from data for both single-cell and object tracking in computational biology and computer vision. Firstly, the discriminative features are automatically learned via a convolutional deep belief network (CDBN). Secondly, we design a simple yet effective method to transfer features learned from CDBNs on the source tasks for generic purpose to the object tracking tasks using only limited amount of training data. Finally, to alleviate the tracker drifting problem caused by model updating, we jointly consider three different types of positive samples. Extensive experiments validate the robustness and effectiveness of the proposed method.

Convolutional Deep Belief Networks for Single-Cell/Object Tracking in Computational Biology and Computer Vision

PubMed Central

Pan, Shengnan; Zhang, Hongbo; Wang, Tian; Du, Jixiang; Chen, Duansheng; Cao, Liujuan

2016-01-01

In this paper, we propose deep architecture to dynamically learn the most discriminative features from data for both single-cell and object tracking in computational biology and computer vision. Firstly, the discriminative features are automatically learned via a convolutional deep belief network (CDBN). Secondly, we design a simple yet effective method to transfer features learned from CDBNs on the source tasks for generic purpose to the object tracking tasks using only limited amount of training data. Finally, to alleviate the tracker drifting problem caused by model updating, we jointly consider three different types of positive samples. Extensive experiments validate the robustness and effectiveness of the proposed method. PMID:27847827

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

PubMed

Carré, Clément; Mas, André; Krouk, Gabriel

2017-01-01

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

Competitive STDP Learning of Overlapping Spatial Patterns.

PubMed

Krunglevicius, Dalius

2015-08-01

Spike-timing-dependent plasticity (STDP) is a set of Hebbian learning rules firmly based on biological evidence. It has been demonstrated that one of the STDP learning rules is suited for learning spatiotemporal patterns. When multiple neurons are organized in a simple competitive spiking neural network, this network is capable of learning multiple distinct patterns. If patterns overlap significantly (i.e., patterns are mutually inclusive), however, competition would not preclude trained neuron's responding to a new pattern and adjusting synaptic weights accordingly. This letter presents a simple neural network that combines vertical inhibition and Euclidean distance-dependent synaptic strength factor. This approach helps to solve the problem of pattern size-dependent parameter optimality and significantly reduces the probability of a neuron's forgetting an already learned pattern. For demonstration purposes, the network was trained for the first ten letters of the Braille alphabet.

GENIUS: web server to predict local gene networks and key genes for biological functions.

PubMed

Puelma, Tomas; Araus, Viviana; Canales, Javier; Vidal, Elena A; Cabello, Juan M; Soto, Alvaro; Gutiérrez, Rodrigo A

2017-03-01

GENIUS is a user-friendly web server that uses a novel machine learning algorithm to infer functional gene networks focused on specific genes and experimental conditions that are relevant to biological functions of interest. These functions may have different levels of complexity, from specific biological processes to complex traits that involve several interacting processes. GENIUS also enriches the network with new genes related to the biological function of interest, with accuracies comparable to highly discriminative Support Vector Machine methods. GENIUS currently supports eight model organisms and is freely available for public use at http://networks.bio.puc.cl/genius . genius.psbl@gmail.com. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Synaptic plasticity and memory functions achieved in a WO3-x-based nanoionics device by using the principle of atomic switch operation

NASA Astrophysics Data System (ADS)

Yang, Rui; Terabe, Kazuya; Yao, Yiping; Tsuruoka, Tohru; Hasegawa, Tsuyoshi; Gimzewski, James K.; Aono, Masakazu

2013-09-01

A compact neuromorphic nanodevice with inherent learning and memory properties emulating those of biological synapses is the key to developing artificial neural networks rivaling their biological counterparts. Experimental results showed that memorization with a wide time scale from volatile to permanent can be achieved in a WO3-x-based nanoionics device and can be precisely and cumulatively controlled by adjusting the device’s resistance state and input pulse parameters such as the amplitude, interval, and number. This control is analogous to biological synaptic plasticity including short-term plasticity, long-term potentiation, transition from short-term memory to long-term memory, forgetting processes for short- and long-term memory, learning speed, and learning history. A compact WO3-x-based nanoionics device with a simple stacked layer structure should thus be a promising candidate for use as an inorganic synapse in artificial neural networks due to its striking resemblance to the biological synapse.

Perception Evolution Network Based on Cognition Deepening Model--Adapting to the Emergence of New Sensory Receptor.

PubMed

Xing, Youlu; Shen, Furao; Zhao, Jinxi

2016-03-01

The proposed perception evolution network (PEN) is a biologically inspired neural network model for unsupervised learning and online incremental learning. It is able to automatically learn suitable prototypes from learning data in an incremental way, and it does not require the predefined prototype number or the predefined similarity threshold. Meanwhile, being more advanced than the existing unsupervised neural network model, PEN permits the emergence of a new dimension of perception in the perception field of the network. When a new dimension of perception is introduced, PEN is able to integrate the new dimensional sensory inputs with the learned prototypes, i.e., the prototypes are mapped to a high-dimensional space, which consists of both the original dimension and the new dimension of the sensory inputs. In the experiment, artificial data and real-world data are used to test the proposed PEN, and the results show that PEN can work effectively.

Molecular heterogeneity at the network level: high-dimensional testing, clustering and a TCGA case study.

PubMed

Städler, Nicolas; Dondelinger, Frank; Hill, Steven M; Akbani, Rehan; Lu, Yiling; Mills, Gordon B; Mukherjee, Sach

2017-09-15

Molecular pathways and networks play a key role in basic and disease biology. An emerging notion is that networks encoding patterns of molecular interplay may themselves differ between contexts, such as cell type, tissue or disease (sub)type. However, while statistical testing of differences in mean expression levels has been extensively studied, testing of network differences remains challenging. Furthermore, since network differences could provide important and biologically interpretable information to identify molecular subgroups, there is a need to consider the unsupervised task of learning subgroups and networks that define them. This is a nontrivial clustering problem, with neither subgroups nor subgroup-specific networks known at the outset. We leverage recent ideas from high-dimensional statistics for testing and clustering in the network biology setting. The methods we describe can be applied directly to most continuous molecular measurements and networks do not need to be specified beforehand. We illustrate the ideas and methods in a case study using protein data from The Cancer Genome Atlas (TCGA). This provides evidence that patterns of interplay between signalling proteins differ significantly between cancer types. Furthermore, we show how the proposed approaches can be used to learn subtypes and the molecular networks that define them. As the Bioconductor package nethet. staedler.n@gmail.com or sach.mukherjee@dzne.de. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Sparse Regression Based Structure Learning of Stochastic Reaction Networks from Single Cell Snapshot Time Series.

PubMed

Klimovskaia, Anna; Ganscha, Stefan; Claassen, Manfred

2016-12-01

Stochastic chemical reaction networks constitute a model class to quantitatively describe dynamics and cell-to-cell variability in biological systems. The topology of these networks typically is only partially characterized due to experimental limitations. Current approaches for refining network topology are based on the explicit enumeration of alternative topologies and are therefore restricted to small problem instances with almost complete knowledge. We propose the reactionet lasso, a computational procedure that derives a stepwise sparse regression approach on the basis of the Chemical Master Equation, enabling large-scale structure learning for reaction networks by implicitly accounting for billions of topology variants. We have assessed the structure learning capabilities of the reactionet lasso on synthetic data for the complete TRAIL induced apoptosis signaling cascade comprising 70 reactions. We find that the reactionet lasso is able to efficiently recover the structure of these reaction systems, ab initio, with high sensitivity and specificity. With only < 1% false discoveries, the reactionet lasso is able to recover 45% of all true reactions ab initio among > 6000 possible reactions and over 102000 network topologies. In conjunction with information rich single cell technologies such as single cell RNA sequencing or mass cytometry, the reactionet lasso will enable large-scale structure learning, particularly in areas with partial network structure knowledge, such as cancer biology, and thereby enable the detection of pathological alterations of reaction networks. We provide software to allow for wide applicability of the reactionet lasso.

Hebbian based learning with winner-take-all for spiking neural networks

NASA Astrophysics Data System (ADS)

Gupta, Ankur; Long, Lyle

2009-03-01

Learning methods for spiking neural networks are not as well developed as the traditional neural networks that widely use back-propagation training. We propose and implement a Hebbian based learning method with winner-take-all competition for spiking neural networks. This approach is spike time dependent which makes it naturally well suited for a network of spiking neurons. Homeostasis with Hebbian learning is implemented which ensures stability and quicker learning. Homeostasis implies that the net sum of incoming weights associated with a neuron remains the same. Winner-take-all is also implemented for competitive learning between output neurons. We implemented this learning rule on a biologically based vision processing system that we are developing, and use layers of leaky integrate and fire neurons. The network when presented with 4 bars (or Gabor filters) of different orientation learns to recognize the bar orientations (or Gabor filters). After training, each output neuron learns to recognize a bar at specific orientation and responds by firing more vigorously to that bar and less vigorously to others. These neurons are found to have bell shaped tuning curves and are similar to the simple cells experimentally observed by Hubel and Wiesel in the striate cortex of cat and monkey.

A tree-like Bayesian structure learning algorithm for small-sample datasets from complex biological model systems.

PubMed

Yin, Weiwei; Garimalla, Swetha; Moreno, Alberto; Galinski, Mary R; Styczynski, Mark P

2015-08-28

There are increasing efforts to bring high-throughput systems biology techniques to bear on complex animal model systems, often with a goal of learning about underlying regulatory network structures (e.g., gene regulatory networks). However, complex animal model systems typically have significant limitations on cohort sizes, number of samples, and the ability to perform follow-up and validation experiments. These constraints are particularly problematic for many current network learning approaches, which require large numbers of samples and may predict many more regulatory relationships than actually exist. Here, we test the idea that by leveraging the accuracy and efficiency of classifiers, we can construct high-quality networks that capture important interactions between variables in datasets with few samples. We start from a previously-developed tree-like Bayesian classifier and generalize its network learning approach to allow for arbitrary depth and complexity of tree-like networks. Using four diverse sample networks, we demonstrate that this approach performs consistently better at low sample sizes than the Sparse Candidate Algorithm, a representative approach for comparison because it is known to generate Bayesian networks with high positive predictive value. We develop and demonstrate a resampling-based approach to enable the identification of a viable root for the learned tree-like network, important for cases where the root of a network is not known a priori. We also develop and demonstrate an integrated resampling-based approach to the reduction of variable space for the learning of the network. Finally, we demonstrate the utility of this approach via the analysis of a transcriptional dataset of a malaria challenge in a non-human primate model system, Macaca mulatta, suggesting the potential to capture indicators of the earliest stages of cellular differentiation during leukopoiesis. We demonstrate that by starting from effective and efficient approaches for creating classifiers, we can identify interesting tree-like network structures with significant ability to capture the relationships in the training data. This approach represents a promising strategy for inferring networks with high positive predictive value under the constraint of small numbers of samples, meeting a need that will only continue to grow as more high-throughput studies are applied to complex model systems.

Toxicological Tipping Points: Learning Boolean Networks from High-Content Imaging Data. (BOSC meeting)

EPA Science Inventory

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...

Discover mouse gene coexpression landscapes using dictionary learning and sparse coding.

PubMed

Li, Yujie; Chen, Hanbo; Jiang, Xi; Li, Xiang; Lv, Jinglei; Peng, Hanchuan; Tsien, Joe Z; Liu, Tianming

2017-12-01

Gene coexpression patterns carry rich information regarding enormously complex brain structures and functions. Characterization of these patterns in an unbiased, integrated, and anatomically comprehensive manner will illuminate the higher-order transcriptome organization and offer genetic foundations of functional circuitry. Here using dictionary learning and sparse coding, we derived coexpression networks from the space-resolved anatomical comprehensive in situ hybridization data from Allen Mouse Brain Atlas dataset. The key idea is that if two genes use the same dictionary to represent their original signals, then their gene expressions must share similar patterns, thereby considering them as "coexpressed." For each network, we have simultaneous knowledge of spatial distributions, the genes in the network and the extent a particular gene conforms to the coexpression pattern. Gene ontologies and the comparisons with published gene lists reveal biologically identified coexpression networks, some of which correspond to major cell types, biological pathways, and/or anatomical regions.

Adaptive Neurons For Artificial Neural Networks

NASA Technical Reports Server (NTRS)

Tawel, Raoul

1990-01-01

Training time decreases dramatically. In improved mathematical model of neural-network processor, temperature of neurons (in addition to connection strengths, also called weights, of synapses) varied during supervised-learning phase of operation according to mathematical formalism and not heuristic rule. Evidence that biological neural networks also process information at neuronal level.

Prototype-Incorporated Emotional Neural Network.

PubMed

Oyedotun, Oyebade K; Khashman, Adnan

2017-08-15

Artificial neural networks (ANNs) aim to simulate the biological neural activities. Interestingly, many ''engineering'' prospects in ANN have relied on motivations from cognition and psychology studies. So far, two important learning theories that have been subject of active research are the prototype and adaptive learning theories. The learning rules employed for ANNs can be related to adaptive learning theory, where several examples of the different classes in a task are supplied to the network for adjusting internal parameters. Conversely, the prototype-learning theory uses prototypes (representative examples); usually, one prototype per class of the different classes contained in the task. These prototypes are supplied for systematic matching with new examples so that class association can be achieved. In this paper, we propose and implement a novel neural network algorithm based on modifying the emotional neural network (EmNN) model to unify the prototype- and adaptive-learning theories. We refer to our new model as ``prototype-incorporated EmNN''. Furthermore, we apply the proposed model to two real-life challenging tasks, namely, static hand-gesture recognition and face recognition, and compare the result to those obtained using the popular back-propagation neural network (BPNN), emotional BPNN (EmNN), deep networks, an exemplar classification model, and k-nearest neighbor.

Discriminative graph embedding for label propagation.

PubMed

Nguyen, Canh Hao; Mamitsuka, Hiroshi

2011-09-01

In many applications, the available information is encoded in graph structures. This is a common problem in biological networks, social networks, web communities and document citations. We investigate the problem of classifying nodes' labels on a similarity graph given only a graph structure on the nodes. Conventional machine learning methods usually require data to reside in some Euclidean spaces or to have a kernel representation. Applying these methods to nodes on graphs would require embedding the graphs into these spaces. By embedding and then learning the nodes on graphs, most methods are either flexible with different learning objectives or efficient enough for large scale applications. We propose a method to embed a graph into a feature space for a discriminative purpose. Our idea is to include label information into the embedding process, making the space representation tailored to the task. We design embedding objective functions that the following learning formulations become spectral transforms. We then reformulate these spectral transforms into multiple kernel learning problems. Our method, while being tailored to the discriminative tasks, is efficient and can scale to massive data sets. We show the need of discriminative embedding on some simulations. Applying to biological network problems, our method is shown to outperform baselines.

Sampling from complex networks using distributed learning automata

NASA Astrophysics Data System (ADS)

Rezvanian, Alireza; Rahmati, Mohammad; Meybodi, Mohammad Reza

2014-02-01

A complex network provides a framework for modeling many real-world phenomena in the form of a network. In general, a complex network is considered as a graph of real world phenomena such as biological networks, ecological networks, technological networks, information networks and particularly social networks. Recently, major studies are reported for the characterization of social networks due to a growing trend in analysis of online social networks as dynamic complex large-scale graphs. Due to the large scale and limited access of real networks, the network model is characterized using an appropriate part of a network by sampling approaches. In this paper, a new sampling algorithm based on distributed learning automata has been proposed for sampling from complex networks. In the proposed algorithm, a set of distributed learning automata cooperate with each other in order to take appropriate samples from the given network. To investigate the performance of the proposed algorithm, several simulation experiments are conducted on well-known complex networks. Experimental results are compared with several sampling methods in terms of different measures. The experimental results demonstrate the superiority of the proposed algorithm over the others.

Rewiring cells: synthetic biology as a tool to interrogate the organizational principles of living systems.

PubMed

Bashor, Caleb J; Horwitz, Andrew A; Peisajovich, Sergio G; Lim, Wendell A

2010-01-01

The living cell is an incredibly complex entity, and the goal of predictively and quantitatively understanding its function is one of the next great challenges in biology. Much of what we know about the cell concerns its constituent parts, but to a great extent we have yet to decode how these parts are organized to yield complex physiological function. Classically, we have learned about the organization of cellular networks by disrupting them through genetic or chemical means. The emerging discipline of synthetic biology offers an additional, powerful approach to study systems. By rearranging the parts that comprise existing networks, we can gain valuable insight into the hierarchical logic of the networks and identify the modular building blocks that evolution uses to generate innovative function. In addition, by building minimal toy networks, one can systematically explore the relationship between network structure and function. Here, we outline recent work that uses synthetic biology approaches to investigate the organization and function of cellular networks, and describe a vision for a synthetic biology toolkit that could be used to interrogate the design principles of diverse systems.

Supervised Learning in Spiking Neural Networks for Precise Temporal Encoding

PubMed Central

Gardner, Brian; Grüning, André

2016-01-01

Precise spike timing as a means to encode information in neural networks is biologically supported, and is advantageous over frequency-based codes by processing input features on a much shorter time-scale. For these reasons, much recent attention has been focused on the development of supervised learning rules for spiking neural networks that utilise a temporal coding scheme. However, despite significant progress in this area, there still lack rules that have a theoretical basis, and yet can be considered biologically relevant. Here we examine the general conditions under which synaptic plasticity most effectively takes place to support the supervised learning of a precise temporal code. As part of our analysis we examine two spike-based learning methods: one of which relies on an instantaneous error signal to modify synaptic weights in a network (INST rule), and the other one relying on a filtered error signal for smoother synaptic weight modifications (FILT rule). We test the accuracy of the solutions provided by each rule with respect to their temporal encoding precision, and then measure the maximum number of input patterns they can learn to memorise using the precise timings of individual spikes as an indication of their storage capacity. Our results demonstrate the high performance of the FILT rule in most cases, underpinned by the rule’s error-filtering mechanism, which is predicted to provide smooth convergence towards a desired solution during learning. We also find the FILT rule to be most efficient at performing input pattern memorisations, and most noticeably when patterns are identified using spikes with sub-millisecond temporal precision. In comparison with existing work, we determine the performance of the FILT rule to be consistent with that of the highly efficient E-learning Chronotron rule, but with the distinct advantage that our FILT rule is also implementable as an online method for increased biological realism. PMID:27532262

Supervised Learning in Spiking Neural Networks for Precise Temporal Encoding.

PubMed

Gardner, Brian; Grüning, André

2016-01-01

Precise spike timing as a means to encode information in neural networks is biologically supported, and is advantageous over frequency-based codes by processing input features on a much shorter time-scale. For these reasons, much recent attention has been focused on the development of supervised learning rules for spiking neural networks that utilise a temporal coding scheme. However, despite significant progress in this area, there still lack rules that have a theoretical basis, and yet can be considered biologically relevant. Here we examine the general conditions under which synaptic plasticity most effectively takes place to support the supervised learning of a precise temporal code. As part of our analysis we examine two spike-based learning methods: one of which relies on an instantaneous error signal to modify synaptic weights in a network (INST rule), and the other one relying on a filtered error signal for smoother synaptic weight modifications (FILT rule). We test the accuracy of the solutions provided by each rule with respect to their temporal encoding precision, and then measure the maximum number of input patterns they can learn to memorise using the precise timings of individual spikes as an indication of their storage capacity. Our results demonstrate the high performance of the FILT rule in most cases, underpinned by the rule's error-filtering mechanism, which is predicted to provide smooth convergence towards a desired solution during learning. We also find the FILT rule to be most efficient at performing input pattern memorisations, and most noticeably when patterns are identified using spikes with sub-millisecond temporal precision. In comparison with existing work, we determine the performance of the FILT rule to be consistent with that of the highly efficient E-learning Chronotron rule, but with the distinct advantage that our FILT rule is also implementable as an online method for increased biological realism.

Scalable training of artificial neural networks with adaptive sparse connectivity inspired by network science.

PubMed

Mocanu, Decebal Constantin; Mocanu, Elena; Stone, Peter; Nguyen, Phuong H; Gibescu, Madeleine; Liotta, Antonio

2018-06-19

Through the success of deep learning in various domains, artificial neural networks are currently among the most used artificial intelligence methods. Taking inspiration from the network properties of biological neural networks (e.g. sparsity, scale-freeness), we argue that (contrary to general practice) artificial neural networks, too, should not have fully-connected layers. Here we propose sparse evolutionary training of artificial neural networks, an algorithm which evolves an initial sparse topology (Erdős-Rényi random graph) of two consecutive layers of neurons into a scale-free topology, during learning. Our method replaces artificial neural networks fully-connected layers with sparse ones before training, reducing quadratically the number of parameters, with no decrease in accuracy. We demonstrate our claims on restricted Boltzmann machines, multi-layer perceptrons, and convolutional neural networks for unsupervised and supervised learning on 15 datasets. Our approach has the potential to enable artificial neural networks to scale up beyond what is currently possible.

A Qualitative Study on Learning and Teaching with Learning Paths in a Learning Management System

ERIC Educational Resources Information Center

De Smet, Cindy; Valcke, Martin; Schellens, Tammy; De Wever, Bram; Vanderlinde, Ruben

2016-01-01

This article presents the findings of a qualitative study (carried out between 2011 and 2013) about the adoption and implementation of learning paths within a Learning Management System (LMS). Sixteen secondary school biology teachers of the GO! Network in Flanders (an urbanized region in Belgium) were involved in the study and questioned via…

Pattern recognition neural-net by spatial mapping of biology visual field

NASA Astrophysics Data System (ADS)

Lin, Xin; Mori, Masahiko

2000-05-01

The method of spatial mapping in biology vision field is applied to artificial neural networks for pattern recognition. By the coordinate transform that is called the complex-logarithm mapping and Fourier transform, the input images are transformed into scale- rotation- and shift- invariant patterns, and then fed into a multilayer neural network for learning and recognition. The results of computer simulation and an optical experimental system are described.

Conduction Delay Learning Model for Unsupervised and Supervised Classification of Spatio-Temporal Spike Patterns

PubMed Central

Matsubara, Takashi

2017-01-01

Precise spike timing is considered to play a fundamental role in communications and signal processing in biological neural networks. Understanding the mechanism of spike timing adjustment would deepen our understanding of biological systems and enable advanced engineering applications such as efficient computational architectures. However, the biological mechanisms that adjust and maintain spike timing remain unclear. Existing algorithms adopt a supervised approach, which adjusts the axonal conduction delay and synaptic efficacy until the spike timings approximate the desired timings. This study proposes a spike timing-dependent learning model that adjusts the axonal conduction delay and synaptic efficacy in both unsupervised and supervised manners. The proposed learning algorithm approximates the Expectation-Maximization algorithm, and classifies the input data encoded into spatio-temporal spike patterns. Even in the supervised classification, the algorithm requires no external spikes indicating the desired spike timings unlike existing algorithms. Furthermore, because the algorithm is consistent with biological models and hypotheses found in existing biological studies, it could capture the mechanism underlying biological delay learning. PMID:29209191

Conduction Delay Learning Model for Unsupervised and Supervised Classification of Spatio-Temporal Spike Patterns.

PubMed

Matsubara, Takashi

2017-01-01

Precise spike timing is considered to play a fundamental role in communications and signal processing in biological neural networks. Understanding the mechanism of spike timing adjustment would deepen our understanding of biological systems and enable advanced engineering applications such as efficient computational architectures. However, the biological mechanisms that adjust and maintain spike timing remain unclear. Existing algorithms adopt a supervised approach, which adjusts the axonal conduction delay and synaptic efficacy until the spike timings approximate the desired timings. This study proposes a spike timing-dependent learning model that adjusts the axonal conduction delay and synaptic efficacy in both unsupervised and supervised manners. The proposed learning algorithm approximates the Expectation-Maximization algorithm, and classifies the input data encoded into spatio-temporal spike patterns. Even in the supervised classification, the algorithm requires no external spikes indicating the desired spike timings unlike existing algorithms. Furthermore, because the algorithm is consistent with biological models and hypotheses found in existing biological studies, it could capture the mechanism underlying biological delay learning.

A Community-Building Framework for Collaborative Research Coordination across the Education and Biology Research Disciplines

ERIC Educational Resources Information Center

Pelaez, Nancy; Anderson, Trevor R.; Gardner, Stephanie M.; Yin, Yue; Abraham, Joel K.; Barlett, Edward L.; Gormally, Cara; Hurney, Carol A.; Long, Tammy M.; Newman, Dina L.; Sirum, Karen; Stevens, Michael T.

2018-01-01

Since 2009, the U.S. National Science Foundation Directorate for Biological Sciences has funded Research Coordination Networks (RCN) aimed at collaborative efforts to improve participation, learning, and assessment in undergraduate biology education (UBE). RCN-UBE projects focus on coordination and communication among scientists and educators who…

Competitive repetition suppression (CoRe) clustering: a biologically inspired learning model with application to robust clustering.

PubMed

Bacciu, Davide; Starita, Antonina

2008-11-01

Determining a compact neural coding for a set of input stimuli is an issue that encompasses several biological memory mechanisms as well as various artificial neural network models. In particular, establishing the optimal network structure is still an open problem when dealing with unsupervised learning models. In this paper, we introduce a novel learning algorithm, named competitive repetition-suppression (CoRe) learning, inspired by a cortical memory mechanism called repetition suppression (RS). We show how such a mechanism is used, at various levels of the cerebral cortex, to generate compact neural representations of the visual stimuli. From the general CoRe learning model, we derive a clustering algorithm, named CoRe clustering, that can automatically estimate the unknown cluster number from the data without using a priori information concerning the input distribution. We illustrate how CoRe clustering, besides its biological plausibility, posses strong theoretical properties in terms of robustness to noise and outliers, and we provide an error function describing CoRe learning dynamics. Such a description is used to analyze CoRe relationships with the state-of-the art clustering models and to highlight CoRe similitude with rival penalized competitive learning (RPCL), showing how CoRe extends such a model by strengthening the rival penalization estimation by means of loss functions from robust statistics.

Bio-inspired spiking neural network for nonlinear systems control.

PubMed

Pérez, Javier; Cabrera, Juan A; Castillo, Juan J; Velasco, Juan M

2018-08-01

Spiking neural networks (SNN) are the third generation of artificial neural networks. SNN are the closest approximation to biological neural networks. SNNs make use of temporal spike trains to command inputs and outputs, allowing a faster and more complex computation. As demonstrated by biological organisms, they are a potentially good approach to designing controllers for highly nonlinear dynamic systems in which the performance of controllers developed by conventional techniques is not satisfactory or difficult to implement. SNN-based controllers exploit their ability for online learning and self-adaptation to evolve when transferred from simulations to the real world. SNN's inherent binary and temporary way of information codification facilitates their hardware implementation compared to analog neurons. Biological neural networks often require a lower number of neurons compared to other controllers based on artificial neural networks. In this work, these neuronal systems are imitated to perform the control of non-linear dynamic systems. For this purpose, a control structure based on spiking neural networks has been designed. Particular attention has been paid to optimizing the structure and size of the neural network. The proposed structure is able to control dynamic systems with a reduced number of neurons and connections. A supervised learning process using evolutionary algorithms has been carried out to perform controller training. The efficiency of the proposed network has been verified in two examples of dynamic systems control. Simulations show that the proposed control based on SNN exhibits superior performance compared to other approaches based on Neural Networks and SNNs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prototype-Distortion Category Learning: A Two-Phase Learning Process across a Distributed Network

ERIC Educational Resources Information Center

Little, Deborah M.; Thulborn, Keith R.

2006-01-01

This paper reviews a body of work conducted in our laboratory that applies functional magnetic resonance imaging (fMRI) to better understand the biological response and change that occurs during prototype-distortion learning. We review results from two experiments (Little, Klein, Shobat, McClure, & Thulborn, 2004; Little & Thulborn, 2005) that…

Back to the biology in systems biology: what can we learn from biomolecular networks?

PubMed

Huang, Sui

2004-02-01

Genome-scale molecular networks, including protein interaction and gene regulatory networks, have taken centre stage in the investigation of the burgeoning disciplines of systems biology and biocomplexity. What do networks tell us? Some see in networks simply the comprehensive, detailed description of all cellular pathways, others seek in networks simple, higher-order qualities that emerge from the collective action of the individual pathways. This paper discusses networks from an encompassing category of thinking that will hopefully help readers to bridge the gap between these polarised viewpoints. Systems biology so far has emphasised the characterisation of large pathway maps. Now one has to ask: where is the actual biology in 'systems biology'? As structures midway between genome and phenome, and by serving as an 'extended genotype' or an 'elementary phenotype', molecular networks open a new window to the study of evolution and gene function in complex living systems. For the study of evolution, features in network topology offer a novel starting point for addressing the old debate on the relative contributions of natural selection versus intrinsic constraints to a particular trait. To study the function of genes, it is necessary not only to see them in the context of gene networks, but also to reach beyond describing network topology and to embrace the global dynamics of networks that will reveal higher-order, collective behaviour of the interacting genes. This will pave the way to understanding how the complexity of genome-wide molecular networks collapses to produce a robust whole-cell behaviour that manifests as tightly-regulated switching between distinct cell fates - the basis for multicellular life.

On the applicability of STDP-based learning mechanisms to spiking neuron network models

NASA Astrophysics Data System (ADS)

Sboev, A.; Vlasov, D.; Serenko, A.; Rybka, R.; Moloshnikov, I.

2016-11-01

The ways to creating practically effective method for spiking neuron networks learning, that would be appropriate for implementing in neuromorphic hardware and at the same time based on the biologically plausible plasticity rules, namely, on STDP, are discussed. The influence of the amount of correlation between input and output spike trains on the learnability by different STDP rules is evaluated. A usability of alternative combined learning schemes, involving artificial and spiking neuron models is demonstrated on the iris benchmark task and on the practical task of gender recognition.

DL-ReSuMe: A Delay Learning-Based Remote Supervised Method for Spiking Neurons.

PubMed

Taherkhani, Aboozar; Belatreche, Ammar; Li, Yuhua; Maguire, Liam P

2015-12-01

Recent research has shown the potential capability of spiking neural networks (SNNs) to model complex information processing in the brain. There is biological evidence to prove the use of the precise timing of spikes for information coding. However, the exact learning mechanism in which the neuron is trained to fire at precise times remains an open problem. The majority of the existing learning methods for SNNs are based on weight adjustment. However, there is also biological evidence that the synaptic delay is not constant. In this paper, a learning method for spiking neurons, called delay learning remote supervised method (DL-ReSuMe), is proposed to merge the delay shift approach and ReSuMe-based weight adjustment to enhance the learning performance. DL-ReSuMe uses more biologically plausible properties, such as delay learning, and needs less weight adjustment than ReSuMe. Simulation results have shown that the proposed DL-ReSuMe approach achieves learning accuracy and learning speed improvements compared with ReSuMe.

Classifying the molecular functions of Rab GTPases in membrane trafficking using deep convolutional neural networks.

PubMed

Le, Nguyen-Quoc-Khanh; Ho, Quang-Thai; Ou, Yu-Yen

2018-06-13

Deep learning has been increasingly used to solve a number of problems with state-of-the-art performance in a wide variety of fields. In biology, deep learning can be applied to reduce feature extraction time and achieve high levels of performance. In our present work, we apply deep learning via two-dimensional convolutional neural networks and position-specific scoring matrices to classify Rab protein molecules, which are main regulators in membrane trafficking for transferring proteins and other macromolecules throughout the cell. The functional loss of specific Rab molecular functions has been implicated in a variety of human diseases, e.g., choroideremia, intellectual disabilities, cancer. Therefore, creating a precise model for classifying Rabs is crucial in helping biologists understand the molecular functions of Rabs and design drug targets according to such specific human disease information. We constructed a robust deep neural network for classifying Rabs that achieved an accuracy of 99%, 99.5%, 96.3%, and 97.6% for each of four specific molecular functions. Our approach demonstrates superior performance to traditional artificial neural networks. Therefore, from our proposed study, we provide both an effective tool for classifying Rab proteins and a basis for further research that can improve the performance of biological modeling using deep neural networks. Copyright © 2018 Elsevier Inc. All rights reserved.

RM-SORN: a reward-modulated self-organizing recurrent neural network.

PubMed

Aswolinskiy, Witali; Pipa, Gordon

2015-01-01

Neural plasticity plays an important role in learning and memory. Reward-modulation of plasticity offers an explanation for the ability of the brain to adapt its neural activity to achieve a rewarded goal. Here, we define a neural network model that learns through the interaction of Intrinsic Plasticity (IP) and reward-modulated Spike-Timing-Dependent Plasticity (STDP). IP enables the network to explore possible output sequences and STDP, modulated by reward, reinforces the creation of the rewarded output sequences. The model is tested on tasks for prediction, recall, non-linear computation, pattern recognition, and sequence generation. It achieves performance comparable to networks trained with supervised learning, while using simple, biologically motivated plasticity rules, and rewarding strategies. The results confirm the importance of investigating the interaction of several plasticity rules in the context of reward-modulated learning and whether reward-modulated self-organization can explain the amazing capabilities of the brain.

Teaching the bioinformatics of signaling networks: an integrated approach to facilitate multi-disciplinary learning.

PubMed

Korcsmaros, Tamas; Dunai, Zsuzsanna A; Vellai, Tibor; Csermely, Peter

2013-09-01

The number of bioinformatics tools and resources that support molecular and cell biology approaches is continuously expanding. Moreover, systems and network biology analyses are accompanied more and more by integrated bioinformatics methods. Traditional information-centered university teaching methods often fail, as (1) it is impossible to cover all existing approaches in the frame of a single course, and (2) a large segment of the current bioinformation can become obsolete in a few years. Signaling network offers an excellent example for teaching bioinformatics resources and tools, as it is both focused and complex at the same time. Here, we present an outline of a university bioinformatics course with four sample practices to demonstrate how signaling network studies can integrate biochemistry, genetics, cell biology and network sciences. We show that several bioinformatics resources and tools, as well as important concepts and current trends, can also be integrated to signaling network studies. The research-type hands-on experiences we show enable the students to improve key competences such as teamworking, creative and critical thinking and problem solving. Our classroom course curriculum can be re-formulated as an e-learning material or applied as a part of a specific training course. The multi-disciplinary approach and the mosaic setup of the course have the additional benefit to support the advanced teaching of talented students.

Computational properties of networks of synchronous groups of spiking neurons.

PubMed

Dayhoff, Judith E

2007-09-01

We demonstrate a model in which synchronously firing ensembles of neurons are networked to produce computational results. Each ensemble is a group of biological integrate-and-fire spiking neurons, with probabilistic interconnections between groups. An analogy is drawn in which each individual processing unit of an artificial neural network corresponds to a neuronal group in a biological model. The activation value of a unit in the artificial neural network corresponds to the fraction of active neurons, synchronously firing, in a biological neuronal group. Weights of the artificial neural network correspond to the product of the interconnection density between groups, the group size of the presynaptic group, and the postsynaptic potential heights in the synchronous group model. All three of these parameters can modulate connection strengths between neuronal groups in the synchronous group models. We give an example of nonlinear classification (XOR) and a function approximation example in which the capability of the artificial neural network can be captured by a neural network model with biological integrate-and-fire neurons configured as a network of synchronously firing ensembles of such neurons. We point out that the general function approximation capability proven for feedforward artificial neural networks appears to be approximated by networks of neuronal groups that fire in synchrony, where the groups comprise integrate-and-fire neurons. We discuss the advantages of this type of model for biological systems, its possible learning mechanisms, and the associated timing relationships.

Models of Acetylcholine and Dopamine Signals Differentially Improve Neural Representations

PubMed Central

Holca-Lamarre, Raphaël; Lücke, Jörg; Obermayer, Klaus

2017-01-01

Biological and artificial neural networks (ANNs) represent input signals as patterns of neural activity. In biology, neuromodulators can trigger important reorganizations of these neural representations. For instance, pairing a stimulus with the release of either acetylcholine (ACh) or dopamine (DA) evokes long lasting increases in the responses of neurons to the paired stimulus. The functional roles of ACh and DA in rearranging representations remain largely unknown. Here, we address this question using a Hebbian-learning neural network model. Our aim is both to gain a functional understanding of ACh and DA transmission in shaping biological representations and to explore neuromodulator-inspired learning rules for ANNs. We model the effects of ACh and DA on synaptic plasticity and confirm that stimuli coinciding with greater neuromodulator activation are over represented in the network. We then simulate the physiological release schedules of ACh and DA. We measure the impact of neuromodulator release on the network's representation and on its performance on a classification task. We find that ACh and DA trigger distinct changes in neural representations that both improve performance. The putative ACh signal redistributes neural preferences so that more neurons encode stimulus classes that are challenging for the network. The putative DA signal adapts synaptic weights so that they better match the classes of the task at hand. Our model thus offers a functional explanation for the effects of ACh and DA on cortical representations. Additionally, our learning algorithm yields performances comparable to those of state-of-the-art optimisation methods in multi-layer perceptrons while requiring weaker supervision signals and interacting with synaptically-local weight updates. PMID:28690509

Biologically plausible learning in neural networks: a lesson from bacterial chemotaxis.

PubMed

Shimansky, Yury P

2009-12-01

Learning processes in the brain are usually associated with plastic changes made to optimize the strength of connections between neurons. Although many details related to biophysical mechanisms of synaptic plasticity have been discovered, it is unclear how the concurrent performance of adaptive modifications in a huge number of spatial locations is organized to minimize a given objective function. Since direct experimental observation of even a relatively small subset of such changes is not feasible, computational modeling is an indispensable investigation tool for solving this problem. However, the conventional method of error back-propagation (EBP) employed for optimizing synaptic weights in artificial neural networks is not biologically plausible. This study based on computational experiments demonstrated that such optimization can be performed rather efficiently using the same general method that bacteria employ for moving closer to an attractant or away from a repellent. With regard to neural network optimization, this method consists of regulating the probability of an abrupt change in the direction of synaptic weight modification according to the temporal gradient of the objective function. Neural networks utilizing this method (regulation of modification probability, RMP) can be viewed as analogous to swimming in the multidimensional space of their parameters in the flow of biochemical agents carrying information about the optimality criterion. The efficiency of RMP is comparable to that of EBP, while RMP has several important advantages. Since the biological plausibility of RMP is beyond a reasonable doubt, the RMP concept provides a constructive framework for the experimental analysis of learning in natural neural networks.

Evolving autonomous learning in cognitive networks.

PubMed

Sheneman, Leigh; Hintze, Arend

2017-12-01

There are two common approaches for optimizing the performance of a machine: genetic algorithms and machine learning. A genetic algorithm is applied over many generations whereas machine learning works by applying feedback until the system meets a performance threshold. These methods have been previously combined, particularly in artificial neural networks using an external objective feedback mechanism. We adapt this approach to Markov Brains, which are evolvable networks of probabilistic and deterministic logic gates. Prior to this work MB could only adapt from one generation to the other, so we introduce feedback gates which augment their ability to learn during their lifetime. We show that Markov Brains can incorporate these feedback gates in such a way that they do not rely on an external objective feedback signal, but instead can generate internal feedback that is then used to learn. This results in a more biologically accurate model of the evolution of learning, which will enable us to study the interplay between evolution and learning and could be another step towards autonomously learning machines.

Biologically inspired intelligent decision making: a commentary on the use of artificial neural networks in bioinformatics.

PubMed

Manning, Timmy; Sleator, Roy D; Walsh, Paul

2014-01-01

Artificial neural networks (ANNs) are a class of powerful machine learning models for classification and function approximation which have analogs in nature. An ANN learns to map stimuli to responses through repeated evaluation of exemplars of the mapping. This learning approach results in networks which are recognized for their noise tolerance and ability to generalize meaningful responses for novel stimuli. It is these properties of ANNs which make them appealing for applications to bioinformatics problems where interpretation of data may not always be obvious, and where the domain knowledge required for deductive techniques is incomplete or can cause a combinatorial explosion of rules. In this paper, we provide an introduction to artificial neural network theory and review some interesting recent applications to bioinformatics problems.

Using i2b2 to Bootstrap Rural Health Analytics and Learning Networks

PubMed Central

Harris, Daniel R.; Baus, Adam D.; Harper, Tamela J.; Jarrett, Traci D.; Pollard, Cecil R.; Talbert, Jeffery C.

2017-01-01

We demonstrate that the open-source i2b2 (Informatics for Integrating Biology and the Bedside) data model can be used to bootstrap rural health analytics and learning networks. These networks promote communication and research initiatives by providing the infrastructure necessary for sharing data and insights across a group of healthcare and research partners. Data integration remains a crucial challenge in connecting rural healthcare sites with a common data sharing and learning network due to the lack of interoperability and standards within electronic health records. The i2b2 data model acts as a point of convergence for disparate data from multiple healthcare sites. A consistent and natural data model for healthcare data is essential for overcoming integration issues, but challenges such as those caused by weak data standardization must still be addressed. We describe our experience in the context of building the West Virginia/Kentucky Health Analytics and Learning Network, a collaborative, multi-state effort connecting rural healthcare sites. PMID:28261006

Using i2b2 to Bootstrap Rural Health Analytics and Learning Networks.

PubMed

Harris, Daniel R; Baus, Adam D; Harper, Tamela J; Jarrett, Traci D; Pollard, Cecil R; Talbert, Jeffery C

2016-08-01

We demonstrate that the open-source i2b2 (Informatics for Integrating Biology and the Bedside) data model can be used to bootstrap rural health analytics and learning networks. These networks promote communication and research initiatives by providing the infrastructure necessary for sharing data and insights across a group of healthcare and research partners. Data integration remains a crucial challenge in connecting rural healthcare sites with a common data sharing and learning network due to the lack of interoperability and standards within electronic health records. The i2b2 data model acts as a point of convergence for disparate data from multiple healthcare sites. A consistent and natural data model for healthcare data is essential for overcoming integration issues, but challenges such as those caused by weak data standardization must still be addressed. We describe our experience in the context of building the West Virginia/Kentucky Health Analytics and Learning Network, a collaborative, multi-state effort connecting rural healthcare sites.

Deep Learning: A Primer for Radiologists.

PubMed

Chartrand, Gabriel; Cheng, Phillip M; Vorontsov, Eugene; Drozdzal, Michal; Turcotte, Simon; Pal, Christopher J; Kadoury, Samuel; Tang, An

2017-01-01

Deep learning is a class of machine learning methods that are gaining success and attracting interest in many domains, including computer vision, speech recognition, natural language processing, and playing games. Deep learning methods produce a mapping from raw inputs to desired outputs (eg, image classes). Unlike traditional machine learning methods, which require hand-engineered feature extraction from inputs, deep learning methods learn these features directly from data. With the advent of large datasets and increased computing power, these methods can produce models with exceptional performance. These models are multilayer artificial neural networks, loosely inspired by biologic neural systems. Weighted connections between nodes (neurons) in the network are iteratively adjusted based on example pairs of inputs and target outputs by back-propagating a corrective error signal through the network. For computer vision tasks, convolutional neural networks (CNNs) have proven to be effective. Recently, several clinical applications of CNNs have been proposed and studied in radiology for classification, detection, and segmentation tasks. This article reviews the key concepts of deep learning for clinical radiologists, discusses technical requirements, describes emerging applications in clinical radiology, and outlines limitations and future directions in this field. Radiologists should become familiar with the principles and potential applications of deep learning in medical imaging. © RSNA, 2017.

A Community-Building Framework for Collaborative Research Coordination across the Education and Biology Research Disciplines.

PubMed

Pelaez, Nancy; Anderson, Trevor R; Gardner, Stephanie M; Yin, Yue; Abraham, Joel K; Bartlett, Edward L; Gormally, Cara; Hurney, Carol A; Long, Tammy M; Newman, Dina L; Sirum, Karen; Stevens, Michael T

2018-06-01

Since 2009, the U.S. National Science Foundation Directorate for Biological Sciences has funded Research Coordination Networks (RCN) aimed at collaborative efforts to improve participation, learning, and assessment in undergraduate biology education (UBE). RCN-UBE projects focus on coordination and communication among scientists and educators who are fostering improved and innovative approaches to biology education. When faculty members collaborate with the overarching goal of advancing undergraduate biology education, there is a need to optimize collaboration between participants in order to deeply integrate the knowledge across disciplinary boundaries. In this essay we propose a novel guiding framework for bringing colleagues together to advance knowledge and its integration across disciplines, the "Five 'C's' of Collaboration: Commitment, Collegiality, Communication, Consensus, and Continuity." This guiding framework for professional network practice is informed by both relevant literature and empirical evidence from community-building experience within the RCN-UBE Advancing Competencies in Experimentation-Biology (ACE-Bio) Network. The framework is presented with practical examples to illustrate how it might be used to enhance collaboration between new and existing participants in the ACE-Bio Network as well as within other interdisciplinary networks.

An artificial neural network model for periodic trajectory generation

NASA Astrophysics Data System (ADS)

Shankar, S.; Gander, R. E.; Wood, H. C.

A neural network model based on biological systems was developed for potential robotic application. The model consists of three interconnected layers of artificial neurons or units: an input layer subdivided into state and plan units, an output layer, and a hidden layer between the two outer layers which serves to implement nonlinear mappings between the input and output activation vectors. Weighted connections are created between the three layers, and learning is effected by modifying these weights. Feedback connections between the output and the input state serve to make the network operate as a finite state machine. The activation vector of the plan units of the input layer emulates the supraspinal commands in biological central pattern generators in that different plan activation vectors correspond to different sequences or trajectories being recalled, even with different frequencies. Three trajectories were chosen for implementation, and learning was accomplished in 10,000 trials. The fault tolerant behavior, adaptiveness, and phase maintenance of the implemented network are discussed.

Unsupervised Learning in an Ensemble of Spiking Neural Networks Mediated by ITDP.

PubMed

Shim, Yoonsik; Philippides, Andrew; Staras, Kevin; Husbands, Phil

2016-10-01

We propose a biologically plausible architecture for unsupervised ensemble learning in a population of spiking neural network classifiers. A mixture of experts type organisation is shown to be effective, with the individual classifier outputs combined via a gating network whose operation is driven by input timing dependent plasticity (ITDP). The ITDP gating mechanism is based on recent experimental findings. An abstract, analytically tractable model of the ITDP driven ensemble architecture is derived from a logical model based on the probabilities of neural firing events. A detailed analysis of this model provides insights that allow it to be extended into a full, biologically plausible, computational implementation of the architecture which is demonstrated on a visual classification task. The extended model makes use of a style of spiking network, first introduced as a model of cortical microcircuits, that is capable of Bayesian inference, effectively performing expectation maximization. The unsupervised ensemble learning mechanism, based around such spiking expectation maximization (SEM) networks whose combined outputs are mediated by ITDP, is shown to perform the visual classification task well and to generalize to unseen data. The combined ensemble performance is significantly better than that of the individual classifiers, validating the ensemble architecture and learning mechanisms. The properties of the full model are analysed in the light of extensive experiments with the classification task, including an investigation into the influence of different input feature selection schemes and a comparison with a hierarchical STDP based ensemble architecture.

Unsupervised Learning in an Ensemble of Spiking Neural Networks Mediated by ITDP

PubMed Central

Staras, Kevin

2016-01-01

We propose a biologically plausible architecture for unsupervised ensemble learning in a population of spiking neural network classifiers. A mixture of experts type organisation is shown to be effective, with the individual classifier outputs combined via a gating network whose operation is driven by input timing dependent plasticity (ITDP). The ITDP gating mechanism is based on recent experimental findings. An abstract, analytically tractable model of the ITDP driven ensemble architecture is derived from a logical model based on the probabilities of neural firing events. A detailed analysis of this model provides insights that allow it to be extended into a full, biologically plausible, computational implementation of the architecture which is demonstrated on a visual classification task. The extended model makes use of a style of spiking network, first introduced as a model of cortical microcircuits, that is capable of Bayesian inference, effectively performing expectation maximization. The unsupervised ensemble learning mechanism, based around such spiking expectation maximization (SEM) networks whose combined outputs are mediated by ITDP, is shown to perform the visual classification task well and to generalize to unseen data. The combined ensemble performance is significantly better than that of the individual classifiers, validating the ensemble architecture and learning mechanisms. The properties of the full model are analysed in the light of extensive experiments with the classification task, including an investigation into the influence of different input feature selection schemes and a comparison with a hierarchical STDP based ensemble architecture. PMID:27760125

Noise in Neural Networks: Thresholds, Hysteresis, and Neuromodulation of Signal-To-Noise

NASA Astrophysics Data System (ADS)

Keeler, James D.; Pichler, Elgar E.; Ross, John

1989-03-01

We study a neural-network model including Gaussian noise, higher-order neuronal interactions, and neuromodulation. For a first-order network, there is a threshold in the noise level (phase transition) above which the network displays only disorganized behavior and critical slowing down near the noise threshold. The network can tolerate more noise if it has higher-order feedback interactions, which also lead to hysteresis and multistability in the network dynamics. The signal-to-noise ratio can be adjusted in a biological neural network by neuromodulators such as norepinephrine. Comparisons are made to experimental results and further investigations are suggested to test the effects of hysteresis and neuromodulation in pattern recognition and learning. We propose that norepinephrine may ``quench'' the neural patterns of activity to enhance the ability to learn details.

Understanding Classrooms through Social Network Analysis: A Primer for Social Network Analysis in Education Research.

PubMed

Grunspan, Daniel Z; Wiggins, Benjamin L; Goodreau, Steven M

2014-01-01

Social interactions between students are a major and underexplored part of undergraduate education. Understanding how learning relationships form in undergraduate classrooms, as well as the impacts these relationships have on learning outcomes, can inform educators in unique ways and improve educational reform. Social network analysis (SNA) provides the necessary tool kit for investigating questions involving relational data. We introduce basic concepts in SNA, along with methods for data collection, data processing, and data analysis, using a previously collected example study on an undergraduate biology classroom as a tutorial. We conduct descriptive analyses of the structure of the network of costudying relationships. We explore generative processes that create observed study networks between students and also test for an association between network position and success on exams. We also cover practical issues, such as the unique aspects of human subjects review for network studies. Our aims are to convince readers that using SNA in classroom environments allows rich and informative analyses to take place and to provide some initial tools for doing so, in the process inspiring future educational studies incorporating relational data. © 2014 D. Z. Grunspan et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

SuperSpike: Supervised Learning in Multilayer Spiking Neural Networks.

PubMed

Zenke, Friedemann; Ganguli, Surya

2018-06-01

A vast majority of computation in the brain is performed by spiking neural networks. Despite the ubiquity of such spiking, we currently lack an understanding of how biological spiking neural circuits learn and compute in vivo, as well as how we can instantiate such capabilities in artificial spiking circuits in silico. Here we revisit the problem of supervised learning in temporally coding multilayer spiking neural networks. First, by using a surrogate gradient approach, we derive SuperSpike, a nonlinear voltage-based three-factor learning rule capable of training multilayer networks of deterministic integrate-and-fire neurons to perform nonlinear computations on spatiotemporal spike patterns. Second, inspired by recent results on feedback alignment, we compare the performance of our learning rule under different credit assignment strategies for propagating output errors to hidden units. Specifically, we test uniform, symmetric, and random feedback, finding that simpler tasks can be solved with any type of feedback, while more complex tasks require symmetric feedback. In summary, our results open the door to obtaining a better scientific understanding of learning and computation in spiking neural networks by advancing our ability to train them to solve nonlinear problems involving transformations between different spatiotemporal spike time patterns.

Deep Learning Accurately Predicts Estrogen Receptor Status in Breast Cancer Metabolomics Data.

PubMed

Alakwaa, Fadhl M; Chaudhary, Kumardeep; Garmire, Lana X

2018-01-05

Metabolomics holds the promise as a new technology to diagnose highly heterogeneous diseases. Conventionally, metabolomics data analysis for diagnosis is done using various statistical and machine learning based classification methods. However, it remains unknown if deep neural network, a class of increasingly popular machine learning methods, is suitable to classify metabolomics data. Here we use a cohort of 271 breast cancer tissues, 204 positive estrogen receptor (ER+), and 67 negative estrogen receptor (ER-) to test the accuracies of feed-forward networks, a deep learning (DL) framework, as well as six widely used machine learning models, namely random forest (RF), support vector machines (SVM), recursive partitioning and regression trees (RPART), linear discriminant analysis (LDA), prediction analysis for microarrays (PAM), and generalized boosted models (GBM). DL framework has the highest area under the curve (AUC) of 0.93 in classifying ER+/ER- patients, compared to the other six machine learning algorithms. Furthermore, the biological interpretation of the first hidden layer reveals eight commonly enriched significant metabolomics pathways (adjusted P-value <0.05) that cannot be discovered by other machine learning methods. Among them, protein digestion and absorption and ATP-binding cassette (ABC) transporters pathways are also confirmed in integrated analysis between metabolomics and gene expression data in these samples. In summary, deep learning method shows advantages for metabolomics based breast cancer ER status classification, with both the highest prediction accuracy (AUC = 0.93) and better revelation of disease biology. We encourage the adoption of feed-forward networks based deep learning method in the metabolomics research community for classification.

Learning may need only a few bits of synaptic precision

NASA Astrophysics Data System (ADS)

Baldassi, Carlo; Gerace, Federica; Lucibello, Carlo; Saglietti, Luca; Zecchina, Riccardo

2016-05-01

Learning in neural networks poses peculiar challenges when using discretized rather then continuous synaptic states. The choice of discrete synapses is motivated by biological reasoning and experiments, and possibly by hardware implementation considerations as well. In this paper we extend a previous large deviations analysis which unveiled the existence of peculiar dense regions in the space of synaptic states which accounts for the possibility of learning efficiently in networks with binary synapses. We extend the analysis to synapses with multiple states and generally more plausible biological features. The results clearly indicate that the overall qualitative picture is unchanged with respect to the binary case, and very robust to variation of the details of the model. We also provide quantitative results which suggest that the advantages of increasing the synaptic precision (i.e., the number of internal synaptic states) rapidly vanish after the first few bits, and therefore that, for practical applications, only few bits may be needed for near-optimal performance, consistent with recent biological findings. Finally, we demonstrate how the theoretical analysis can be exploited to design efficient algorithmic search strategies.

A Checklist for Successful Quantitative Live Cell Imaging in Systems Biology

PubMed Central

Sung, Myong-Hee

2013-01-01

Mathematical modeling of signaling and gene regulatory networks has provided unique insights about systems behaviors for many cell biological problems of medical importance. Quantitative single cell monitoring has a crucial role in advancing systems modeling of molecular networks. However, due to the multidisciplinary techniques that are necessary for adaptation of such systems biology approaches, dissemination to a wide research community has been relatively slow. In this essay, I focus on some technical aspects that are often under-appreciated, yet critical in harnessing live cell imaging methods to achieve single-cell-level understanding and quantitative modeling of molecular networks. The importance of these technical considerations will be elaborated with examples of successes and shortcomings. Future efforts will benefit by avoiding some pitfalls and by utilizing the lessons collectively learned from recent applications of imaging in systems biology. PMID:24709701

Learning disease relationships from clinical drug trials.

PubMed

Haslam, Bryan; Perez-Breva, Luis

2017-01-01

Our objective is to test the limits of the assumption that better learning from data in medicine requires more granular data. We hypothesize that clinical trial metadata contains latent scientific, clinical, and regulatory expert knowledge that can be accessed to draw conclusions about the underlying biology of diseases. We seek to demonstrate that this latent information can be uncovered from the whole body of clinical trials. We extract free-text metadata from 93 654 clinical drug trials and introduce a representation that allows us to compare different trials. We then construct a network of diseases using only the trial metadata. We view each trial as the summation of expert knowledge of biological mechanisms and medical evidence linking a disease to a drug believed to modulate the pathways of that disease. Our network representation allows us to visualize disease relationships based on this underlying information. Our disease network shows surprising agreement with another disease network based on genetic data and on the Medical Subject Headings (MeSH) taxonomy, yet also contains unique disease similarities. The agreement of our results with other sources indicates that our premise regarding latent expert knowledge holds. The disease relationships unique to our network may be used to generate hypotheses for future biological and clinical research as well as drug repurposing and design. Our results provide an example of using experimental data on humans to generate biologically useful information and point to a set of new and promising strategies to link clinical outcomes data back to biological research. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Gene Network Construction from Microarray Data Identifies a Key Network Module and Several Candidate Hub Genes in Age-Associated Spatial Learning Impairment

PubMed Central

Uddin, Raihan; Singh, Shiva M.

2017-01-01

As humans age many suffer from a decrease in normal brain functions including spatial learning impairments. This study aimed to better understand the molecular mechanisms in age-associated spatial learning impairment (ASLI). We used a mathematical modeling approach implemented in Weighted Gene Co-expression Network Analysis (WGCNA) to create and compare gene network models of young (learning unimpaired) and aged (predominantly learning impaired) brains from a set of exploratory datasets in rats in the context of ASLI. The major goal was to overcome some of the limitations previously observed in the traditional meta- and pathway analysis using these data, and identify novel ASLI related genes and their networks based on co-expression relationship of genes. This analysis identified a set of network modules in the young, each of which is highly enriched with genes functioning in broad but distinct GO functional categories or biological pathways. Interestingly, the analysis pointed to a single module that was highly enriched with genes functioning in “learning and memory” related functions and pathways. Subsequent differential network analysis of this “learning and memory” module in the aged (predominantly learning impaired) rats compared to the young learning unimpaired rats allowed us to identify a set of novel ASLI candidate hub genes. Some of these genes show significant repeatability in networks generated from independent young and aged validation datasets. These hub genes are highly co-expressed with other genes in the network, which not only show differential expression but also differential co-expression and differential connectivity across age and learning impairment. The known function of these hub genes indicate that they play key roles in critical pathways, including kinase and phosphatase signaling, in functions related to various ion channels, and in maintaining neuronal integrity relating to synaptic plasticity and memory formation. Taken together, they provide a new insight and generate new hypotheses into the molecular mechanisms responsible for age associated learning impairment, including spatial learning. PMID:29066959

Gene Network Construction from Microarray Data Identifies a Key Network Module and Several Candidate Hub Genes in Age-Associated Spatial Learning Impairment.

PubMed

Uddin, Raihan; Singh, Shiva M

2017-01-01

As humans age many suffer from a decrease in normal brain functions including spatial learning impairments. This study aimed to better understand the molecular mechanisms in age-associated spatial learning impairment (ASLI). We used a mathematical modeling approach implemented in Weighted Gene Co-expression Network Analysis (WGCNA) to create and compare gene network models of young (learning unimpaired) and aged (predominantly learning impaired) brains from a set of exploratory datasets in rats in the context of ASLI. The major goal was to overcome some of the limitations previously observed in the traditional meta- and pathway analysis using these data, and identify novel ASLI related genes and their networks based on co-expression relationship of genes. This analysis identified a set of network modules in the young, each of which is highly enriched with genes functioning in broad but distinct GO functional categories or biological pathways. Interestingly, the analysis pointed to a single module that was highly enriched with genes functioning in "learning and memory" related functions and pathways. Subsequent differential network analysis of this "learning and memory" module in the aged (predominantly learning impaired) rats compared to the young learning unimpaired rats allowed us to identify a set of novel ASLI candidate hub genes. Some of these genes show significant repeatability in networks generated from independent young and aged validation datasets. These hub genes are highly co-expressed with other genes in the network, which not only show differential expression but also differential co-expression and differential connectivity across age and learning impairment. The known function of these hub genes indicate that they play key roles in critical pathways, including kinase and phosphatase signaling, in functions related to various ion channels, and in maintaining neuronal integrity relating to synaptic plasticity and memory formation. Taken together, they provide a new insight and generate new hypotheses into the molecular mechanisms responsible for age associated learning impairment, including spatial learning.

Neural network regulation driven by autonomous neural firings

NASA Astrophysics Data System (ADS)

Cho, Myoung Won

2016-07-01

Biological neurons naturally fire spontaneously due to the existence of a noisy current. Such autonomous firings may provide a driving force for network formation because synaptic connections can be modified due to neural firings. Here, we study the effect of autonomous firings on network formation. For the temporally asymmetric Hebbian learning, bidirectional connections lose their balance easily and become unidirectional ones. Defining the difference between reciprocal connections as new variables, we could express the learning dynamics as if Ising model spins interact with each other in magnetism. We present a theoretical method to estimate the interaction between the new variables in a neural system. We apply the method to some network systems and find some tendencies of autonomous neural network regulation.

Biologically inspired intelligent decision making

PubMed Central

Manning, Timmy; Sleator, Roy D; Walsh, Paul

2014-01-01

Artificial neural networks (ANNs) are a class of powerful machine learning models for classification and function approximation which have analogs in nature. An ANN learns to map stimuli to responses through repeated evaluation of exemplars of the mapping. This learning approach results in networks which are recognized for their noise tolerance and ability to generalize meaningful responses for novel stimuli. It is these properties of ANNs which make them appealing for applications to bioinformatics problems where interpretation of data may not always be obvious, and where the domain knowledge required for deductive techniques is incomplete or can cause a combinatorial explosion of rules. In this paper, we provide an introduction to artificial neural network theory and review some interesting recent applications to bioinformatics problems. PMID:24335433

Biologically inspired computation and learning in Sensorimotor Systems

NASA Astrophysics Data System (ADS)

Lee, Daniel D.; Seung, H. S.

2001-11-01

Networking systems presently lack the ability to intelligently process the rich multimedia content of the data traffic they carry. Endowing artificial systems with the ability to adapt to changing conditions requires algorithms that can rapidly learn from examples. We demonstrate the application of such learning algorithms on an inexpensive quadruped robot constructed to perform simple sensorimotor tasks. The robot learns to track a particular object by discovering the salient visual and auditory cues unique to that object. The system uses a convolutional neural network that automatically combines color, luminance, motion, and auditory information. The weights of the networks are adjusted using feedback from a teacher to reflect the reliability of the various input channels in the surrounding environment. Additionally, the robot is able to compensate for its own motion by adapting the parameters of a vestibular ocular reflex system.

Cell-Type-Specific Predictive Network Yields Novel Insights into Mouse Embryonic Stem Cell Self-Renewal and Cell Fate

PubMed Central

Dowell, Karen G.; Simons, Allen K.; Wang, Zack Z.; Yun, Kyuson; Hibbs, Matthew A.

2013-01-01

Self-renewal, the ability of a stem cell to divide repeatedly while maintaining an undifferentiated state, is a defining characteristic of all stem cells. Here, we clarify the molecular foundations of mouse embryonic stem cell (mESC) self-renewal by applying a proven Bayesian network machine learning approach to integrate high-throughput data for protein function discovery. By focusing on a single stem-cell system, at a specific developmental stage, within the context of well-defined biological processes known to be active in that cell type, we produce a consensus predictive network that reflects biological reality more closely than those made by prior efforts using more generalized, context-independent methods. In addition, we show how machine learning efforts may be misled if the tissue specific role of mammalian proteins is not defined in the training set and circumscribed in the evidential data. For this study, we assembled an extensive compendium of mESC data: ∼2.2 million data points, collected from 60 different studies, under 992 conditions. We then integrated these data into a consensus mESC functional relationship network focused on biological processes associated with embryonic stem cell self-renewal and cell fate determination. Computational evaluations, literature validation, and analyses of predicted functional linkages show that our results are highly accurate and biologically relevant. Our mESC network predicts many novel players involved in self-renewal and serves as the foundation for future pluripotent stem cell studies. This network can be used by stem cell researchers (at http://StemSight.org) to explore hypotheses about gene function in the context of self-renewal and to prioritize genes of interest for experimental validation. PMID:23468881

Automatic Classification Using Supervised Learning in a Medical Document Filtering Application.

ERIC Educational Resources Information Center

Mostafa, J.; Lam, W.

2000-01-01

Presents a multilevel model of the information filtering process that permits document classification. Evaluates a document classification approach based on a supervised learning algorithm, measures the accuracy of the algorithm in a neural network that was trained to classify medical documents on cell biology, and discusses filtering…

Architecture and biological applications of artificial neural networks: a tuberculosis perspective.

PubMed

Darsey, Jerry A; Griffin, William O; Joginipelli, Sravanthi; Melapu, Venkata Kiran

2015-01-01

Advancement of science and technology has prompted researchers to develop new intelligent systems that can solve a variety of problems such as pattern recognition, prediction, and optimization. The ability of the human brain to learn in a fashion that tolerates noise and error has attracted many researchers and provided the starting point for the development of artificial neural networks: the intelligent systems. Intelligent systems can acclimatize to the environment or data and can maximize the chances of success or improve the efficiency of a search. Due to massive parallelism with large numbers of interconnected processers and their ability to learn from the data, neural networks can solve a variety of challenging computational problems. Neural networks have the ability to derive meaning from complicated and imprecise data; they are used in detecting patterns, and trends that are too complex for humans, or other computer systems. Solutions to the toughest problems will not be found through one narrow specialization; therefore we need to combine interdisciplinary approaches to discover the solutions to a variety of problems. Many researchers in different disciplines such as medicine, bioinformatics, molecular biology, and pharmacology have successfully applied artificial neural networks. This chapter helps the reader in understanding the basics of artificial neural networks, their applications, and methodology; it also outlines the network learning process and architecture. We present a brief outline of the application of neural networks to medical diagnosis, drug discovery, gene identification, and protein structure prediction. We conclude with a summary of the results from our study on tuberculosis data using neural networks, in diagnosing active tuberculosis, and predicting chronic vs. infiltrative forms of tuberculosis.

Large-Scale Simulations of Plastic Neural Networks on Neuromorphic Hardware

PubMed Central

Knight, James C.; Tully, Philip J.; Kaplan, Bernhard A.; Lansner, Anders; Furber, Steve B.

2016-01-01

SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Rather than using bespoke analog or digital hardware, the basic computational unit of a SpiNNaker system is a general-purpose ARM processor, allowing it to be programmed to simulate a wide variety of neuron and synapse models. This flexibility is particularly valuable in the study of biological plasticity phenomena. A recently proposed learning rule based on the Bayesian Confidence Propagation Neural Network (BCPNN) paradigm offers a generic framework for modeling the interaction of different plasticity mechanisms using spiking neurons. However, it can be computationally expensive to simulate large networks with BCPNN learning since it requires multiple state variables for each synapse, each of which needs to be updated every simulation time-step. We discuss the trade-offs in efficiency and accuracy involved in developing an event-based BCPNN implementation for SpiNNaker based on an analytical solution to the BCPNN equations, and detail the steps taken to fit this within the limited computational and memory resources of the SpiNNaker architecture. We demonstrate this learning rule by learning temporal sequences of neural activity within a recurrent attractor network which we simulate at scales of up to 2.0 × 104 neurons and 5.1 × 107 plastic synapses: the largest plastic neural network ever to be simulated on neuromorphic hardware. We also run a comparable simulation on a Cray XC-30 supercomputer system and find that, if it is to match the run-time of our SpiNNaker simulation, the super computer system uses approximately 45× more power. This suggests that cheaper, more power efficient neuromorphic systems are becoming useful discovery tools in the study of plasticity in large-scale brain models. PMID:27092061

The Role of Architectural and Learning Constraints in Neural Network Models: A Case Study on Visual Space Coding.

PubMed

Testolin, Alberto; De Filippo De Grazia, Michele; Zorzi, Marco

2017-01-01

The recent "deep learning revolution" in artificial neural networks had strong impact and widespread deployment for engineering applications, but the use of deep learning for neurocomputational modeling has been so far limited. In this article we argue that unsupervised deep learning represents an important step forward for improving neurocomputational models of perception and cognition, because it emphasizes the role of generative learning as opposed to discriminative (supervised) learning. As a case study, we present a series of simulations investigating the emergence of neural coding of visual space for sensorimotor transformations. We compare different network architectures commonly used as building blocks for unsupervised deep learning by systematically testing the type of receptive fields and gain modulation developed by the hidden neurons. In particular, we compare Restricted Boltzmann Machines (RBMs), which are stochastic, generative networks with bidirectional connections trained using contrastive divergence, with autoencoders, which are deterministic networks trained using error backpropagation. For both learning architectures we also explore the role of sparse coding, which has been identified as a fundamental principle of neural computation. The unsupervised models are then compared with supervised, feed-forward networks that learn an explicit mapping between different spatial reference frames. Our simulations show that both architectural and learning constraints strongly influenced the emergent coding of visual space in terms of distribution of tuning functions at the level of single neurons. Unsupervised models, and particularly RBMs, were found to more closely adhere to neurophysiological data from single-cell recordings in the primate parietal cortex. These results provide new insights into how basic properties of artificial neural networks might be relevant for modeling neural information processing in biological systems.

The Role of Architectural and Learning Constraints in Neural Network Models: A Case Study on Visual Space Coding

PubMed Central

Testolin, Alberto; De Filippo De Grazia, Michele; Zorzi, Marco

2017-01-01

The recent “deep learning revolution” in artificial neural networks had strong impact and widespread deployment for engineering applications, but the use of deep learning for neurocomputational modeling has been so far limited. In this article we argue that unsupervised deep learning represents an important step forward for improving neurocomputational models of perception and cognition, because it emphasizes the role of generative learning as opposed to discriminative (supervised) learning. As a case study, we present a series of simulations investigating the emergence of neural coding of visual space for sensorimotor transformations. We compare different network architectures commonly used as building blocks for unsupervised deep learning by systematically testing the type of receptive fields and gain modulation developed by the hidden neurons. In particular, we compare Restricted Boltzmann Machines (RBMs), which are stochastic, generative networks with bidirectional connections trained using contrastive divergence, with autoencoders, which are deterministic networks trained using error backpropagation. For both learning architectures we also explore the role of sparse coding, which has been identified as a fundamental principle of neural computation. The unsupervised models are then compared with supervised, feed-forward networks that learn an explicit mapping between different spatial reference frames. Our simulations show that both architectural and learning constraints strongly influenced the emergent coding of visual space in terms of distribution of tuning functions at the level of single neurons. Unsupervised models, and particularly RBMs, were found to more closely adhere to neurophysiological data from single-cell recordings in the primate parietal cortex. These results provide new insights into how basic properties of artificial neural networks might be relevant for modeling neural information processing in biological systems. PMID:28377709

Heuristic pattern correction scheme using adaptively trained generalized regression neural networks.

PubMed

Hoya, T; Chambers, J A

2001-01-01

In many pattern classification problems, an intelligent neural system is required which can learn the newly encountered but misclassified patterns incrementally, while keeping a good classification performance over the past patterns stored in the network. In the paper, an heuristic pattern correction scheme is proposed using adaptively trained generalized regression neural networks (GRNNs). The scheme is based upon both network growing and dual-stage shrinking mechanisms. In the network growing phase, a subset of the misclassified patterns in each incoming data set is iteratively added into the network until all the patterns in the incoming data set are classified correctly. Then, the redundancy in the growing phase is removed in the dual-stage network shrinking. Both long- and short-term memory models are considered in the network shrinking, which are motivated from biological study of the brain. The learning capability of the proposed scheme is investigated through extensive simulation studies.

Use artificial neural network to align biological ontologies.

PubMed

Huang, Jingshan; Dang, Jiangbo; Huhns, Michael N; Zheng, W Jim

2008-09-16

Being formal, declarative knowledge representation models, ontologies help to address the problem of imprecise terminologies in biological and biomedical research. However, ontologies constructed under the auspices of the Open Biomedical Ontologies (OBO) group have exhibited a great deal of variety, because different parties can design ontologies according to their own conceptual views of the world. It is therefore becoming critical to align ontologies from different parties. During automated/semi-automated alignment across biological ontologies, different semantic aspects, i.e., concept name, concept properties, and concept relationships, contribute in different degrees to alignment results. Therefore, a vector of weights must be assigned to these semantic aspects. It is not trivial to determine what those weights should be, and current methodologies depend a lot on human heuristics. In this paper, we take an artificial neural network approach to learn and adjust these weights, and thereby support a new ontology alignment algorithm, customized for biological ontologies, with the purpose of avoiding some disadvantages in both rule-based and learning-based aligning algorithms. This approach has been evaluated by aligning two real-world biological ontologies, whose features include huge file size, very few instances, concept names in numerical strings, and others. The promising experiment results verify our proposed hypothesis, i.e., three weights for semantic aspects learned from a subset of concepts are representative of all concepts in the same ontology. Therefore, our method represents a large leap forward towards automating biological ontology alignment.

Feature to prototype transition in neural networks

NASA Astrophysics Data System (ADS)

Krotov, Dmitry; Hopfield, John

Models of associative memory with higher order (higher than quadratic) interactions, and their relationship to neural networks used in deep learning are discussed. Associative memory is conventionally described by recurrent neural networks with dynamical convergence to stable points. Deep learning typically uses feedforward neural nets without dynamics. However, a simple duality relates these two different views when applied to problems of pattern classification. From the perspective of associative memory such models deserve attention because they make it possible to store a much larger number of memories, compared to the quadratic case. In the dual description, these models correspond to feedforward neural networks with one hidden layer and unusual activation functions transmitting the activities of the visible neurons to the hidden layer. These activation functions are rectified polynomials of a higher degree rather than the rectified linear functions used in deep learning. The network learns representations of the data in terms of features for rectified linear functions, but as the power in the activation function is increased there is a gradual shift to a prototype-based representation, the two extreme regimes of pattern recognition known in cognitive psychology. Simons Center for Systems Biology.

Neuromorphic implementations of neurobiological learning algorithms for spiking neural networks.

PubMed

Walter, Florian; Röhrbein, Florian; Knoll, Alois

2015-12-01

The application of biologically inspired methods in design and control has a long tradition in robotics. Unlike previous approaches in this direction, the emerging field of neurorobotics not only mimics biological mechanisms at a relatively high level of abstraction but employs highly realistic simulations of actual biological nervous systems. Even today, carrying out these simulations efficiently at appropriate timescales is challenging. Neuromorphic chip designs specially tailored to this task therefore offer an interesting perspective for neurorobotics. Unlike Von Neumann CPUs, these chips cannot be simply programmed with a standard programming language. Like real brains, their functionality is determined by the structure of neural connectivity and synaptic efficacies. Enabling higher cognitive functions for neurorobotics consequently requires the application of neurobiological learning algorithms to adjust synaptic weights in a biologically plausible way. In this paper, we therefore investigate how to program neuromorphic chips by means of learning. First, we provide an overview over selected neuromorphic chip designs and analyze them in terms of neural computation, communication systems and software infrastructure. On the theoretical side, we review neurobiological learning techniques. Based on this overview, we then examine on-die implementations of these learning algorithms on the considered neuromorphic chips. A final discussion puts the findings of this work into context and highlights how neuromorphic hardware can potentially advance the field of autonomous robot systems. The paper thus gives an in-depth overview of neuromorphic implementations of basic mechanisms of synaptic plasticity which are required to realize advanced cognitive capabilities with spiking neural networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pattern Learning, Damage and Repair within Biological Neural Networks

NASA Astrophysics Data System (ADS)

Siu, Theodore; Fitzgerald O'Neill, Kate; Shinbrot, Troy

2015-03-01

Traumatic brain injury (TBI) causes damage to neural networks, potentially leading to disability or even death. Nearly one in ten of these patients die, and most of the remainder suffer from symptoms ranging from headaches and nausea to convulsions and paralysis. In vitro studies to develop treatments for TBI have limited in vivo applicability, and in vitro therapies have even proven to worsen the outcome of TBI patients. We propose that this disconnect between in vitro and in vivo outcomes may be associated with the fact that in vitro tests assess indirect measures of neuronal health, but do not investigate the actual function of neuronal networks. Therefore in this talk, we examine both in vitro and in silico neuronal networks that actually perform a function: pattern identification. We allow the networks to execute genetic, Hebbian, learning, and additionally, we examine the effects of damage and subsequent repair within our networks. We show that the length of repaired connections affects the overall pattern learning performance of the network and we propose therapies that may improve function following TBI in clinical settings.

TopologyNet: Topology based deep convolutional and multi-task neural networks for biomolecular property predictions

PubMed Central

2017-01-01

Although deep learning approaches have had tremendous success in image, video and audio processing, computer vision, and speech recognition, their applications to three-dimensional (3D) biomolecular structural data sets have been hindered by the geometric and biological complexity. To address this problem we introduce the element-specific persistent homology (ESPH) method. ESPH represents 3D complex geometry by one-dimensional (1D) topological invariants and retains important biological information via a multichannel image-like representation. This representation reveals hidden structure-function relationships in biomolecules. We further integrate ESPH and deep convolutional neural networks to construct a multichannel topological neural network (TopologyNet) for the predictions of protein-ligand binding affinities and protein stability changes upon mutation. To overcome the deep learning limitations from small and noisy training sets, we propose a multi-task multichannel topological convolutional neural network (MM-TCNN). We demonstrate that TopologyNet outperforms the latest methods in the prediction of protein-ligand binding affinities, mutation induced globular protein folding free energy changes, and mutation induced membrane protein folding free energy changes. Availability: weilab.math.msu.edu/TDL/ PMID:28749969

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

PubMed

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

2013-04-01

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

Summit of the Research Coordination Networks for Undergraduate Biology Education

PubMed Central

Eaton, Carrie Diaz; Allen, Deborah; Anderson, Laurel J.; Bowser, Gillian; Pauley, Mark A.; Williams, Kathy S.; Uno, Gordon E.

2016-01-01

The first summit of projects funded by the National Science Foundation’s Research Coordination Networks for Undergraduate Biology Education (RCN-UBE) program was held January 14–16, 2016, in Washington, DC. Sixty-five scientists and science educators from 38 of the 41 Incubator and Full RCN-UBE awards discussed the value and contributions of RCNs to the national biology education reform effort. The summit illustrated the progress of this innovative UBE track, first awarded in 2009. Participants shared experiences regarding network development and growth, identified best practices and challenges faced in network management, and discussed work accomplished. We report here on key aspects of network evaluation, characteristics of successful networks, and how to sustain and broaden participation in networks. Evidence from successful networks indicates that 5 years (the length of a Full RCN-UBE) may be insufficient time to produce a cohesive and effective network. While online communication promotes the activities of a network and disseminates effective practices, face-to-face meetings are critical for establishing ties between network participants. Creation of these National Science Foundation–funded networks may be particularly useful for consortia of faculty working to address problems or exchange novel solutions discovered while introducing active-learning methods and/or course-based research into their curricula.

Neural Classifiers for Learning Higher-Order Correlations

NASA Astrophysics Data System (ADS)

Güler, Marifi

1999-01-01

Studies by various authors suggest that higher-order networks can be more powerful and are biologically more plausible with respect to the more traditional multilayer networks. These architectures make explicit use of nonlinear interactions between input variables in the form of higher-order units or product units. If it is known a priori that the problem to be implemented possesses a given set of invariances like in the translation, rotation, and scale invariant pattern recognition problems, those invariances can be encoded, thus eliminating all higher-order terms which are incompatible with the invariances. In general, however, it is a serious set-back that the complexity of learning increases exponentially with the size of inputs. This paper reviews higher-order networks and introduces an implicit representation in which learning complexity is mainly decided by the number of higher-order terms to be learned and increases only linearly with the input size.

Strong systematicity through sensorimotor conceptual grounding: an unsupervised, developmental approach to connectionist sentence processing

NASA Astrophysics Data System (ADS)

Jansen, Peter A.; Watter, Scott

2012-03-01

Connectionist language modelling typically has difficulty with syntactic systematicity, or the ability to generalise language learning to untrained sentences. This work develops an unsupervised connectionist model of infant grammar learning. Following the semantic boostrapping hypothesis, the network distils word category using a developmentally plausible infant-scale database of grounded sensorimotor conceptual representations, as well as a biologically plausible semantic co-occurrence activation function. The network then uses this knowledge to acquire an early benchmark clausal grammar using correlational learning, and further acquires separate conceptual and grammatical category representations. The network displays strongly systematic behaviour indicative of the general acquisition of the combinatorial systematicity present in the grounded infant-scale language stream, outperforms previous contemporary models that contain primarily noun and verb word categories, and successfully generalises broadly to novel untrained sensorimotor grounded sentences composed of unfamiliar nouns and verbs. Limitations as well as implications to later grammar learning are discussed.

Culture and biology in the origins of linguistic structure.

PubMed

Kirby, Simon

2017-02-01

Language is systematically structured at all levels of description, arguably setting it apart from all other instances of communication in nature. In this article, I survey work over the last 20 years that emphasises the contributions of individual learning, cultural transmission, and biological evolution to explaining the structural design features of language. These 3 complex adaptive systems exist in a network of interactions: individual learning biases shape the dynamics of cultural evolution; universal features of linguistic structure arise from this cultural process and form the ultimate linguistic phenotype; the nature of this phenotype affects the fitness landscape for the biological evolution of the language faculty; and in turn this determines individuals' learning bias. Using a combination of computational simulation, laboratory experiments, and comparison with real-world cases of language emergence, I show that linguistic structure emerges as a natural outcome of cultural evolution once certain minimal biological requirements are in place.

Automated cross-modal mapping in robotic eye/hand systems using plastic radial basis function networks

NASA Astrophysics Data System (ADS)

Meng, Qinggang; Lee, M. H.

2007-03-01

Advanced autonomous artificial systems will need incremental learning and adaptive abilities similar to those seen in humans. Knowledge from biology, psychology and neuroscience is now inspiring new approaches for systems that have sensory-motor capabilities and operate in complex environments. Eye/hand coordination is an important cross-modal cognitive function, and is also typical of many of the other coordinations that must be involved in the control and operation of embodied intelligent systems. This paper examines a biologically inspired approach for incrementally constructing compact mapping networks for eye/hand coordination. We present a simplified node-decoupled extended Kalman filter for radial basis function networks, and compare this with other learning algorithms. An experimental system consisting of a robot arm and a pan-and-tilt head with a colour camera is used to produce results and test the algorithms in this paper. We also present three approaches for adapting to structural changes during eye/hand coordination tasks, and the robustness of the algorithms under noise are investigated. The learning and adaptation approaches in this paper have similarities with current ideas about neural growth in the brains of humans and animals during tool-use, and infants during early cognitive development.

Effect of dilution in asymmetric recurrent neural networks.

PubMed

Folli, Viola; Gosti, Giorgio; Leonetti, Marco; Ruocco, Giancarlo

2018-04-16

We study with numerical simulation the possible limit behaviors of synchronous discrete-time deterministic recurrent neural networks composed of N binary neurons as a function of a network's level of dilution and asymmetry. The network dilution measures the fraction of neuron couples that are connected, and the network asymmetry measures to what extent the underlying connectivity matrix is asymmetric. For each given neural network, we study the dynamical evolution of all the different initial conditions, thus characterizing the full dynamical landscape without imposing any learning rule. Because of the deterministic dynamics, each trajectory converges to an attractor, that can be either a fixed point or a limit cycle. These attractors form the set of all the possible limit behaviors of the neural network. For each network we then determine the convergence times, the limit cycles' length, the number of attractors, and the sizes of the attractors' basin. We show that there are two network structures that maximize the number of possible limit behaviors. The first optimal network structure is fully-connected and symmetric. On the contrary, the second optimal network structure is highly sparse and asymmetric. The latter optimal is similar to what observed in different biological neuronal circuits. These observations lead us to hypothesize that independently from any given learning model, an efficient and effective biologic network that stores a number of limit behaviors close to its maximum capacity tends to develop a connectivity structure similar to one of the optimal networks we found. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Nature vs Nurture: Effects of Learning on Evolution

NASA Astrophysics Data System (ADS)

Nagrani, Nagina

In the field of Evolutionary Robotics, the design, development and application of artificial neural networks as controllers have derived their inspiration from biology. Biologists and artificial intelligence researchers are trying to understand the effects of neural network learning during the lifetime of the individuals on evolution of these individuals by qualitative and quantitative analyses. The conclusion of these analyses can help develop optimized artificial neural networks to perform any given task. The purpose of this thesis is to study the effects of learning on evolution. This has been done by applying Temporal Difference Reinforcement Learning methods to the evolution of Artificial Neural Tissue controller. The controller has been assigned the task to collect resources in a designated area in a simulated environment. The performance of the individuals is measured by the amount of resources collected. A comparison has been made between the results obtained by incorporating learning in evolution and evolution alone. The effects of learning parameters: learning rate, training period, discount rate, and policy on evolution have also been studied. It was observed that learning delays the performance of the evolving individuals over the generations. However, the non zero learning rate throughout the evolution process signifies natural selection preferring individuals possessing plasticity.

An argument for mechanism-based statistical inference in cancer

PubMed Central

Ochs, Michael; Price, Nathan D.; Tomasetti, Cristian; Younes, Laurent

2015-01-01

Cancer is perhaps the prototypical systems disease, and as such has been the focus of extensive study in quantitative systems biology. However, translating these programs into personalized clinical care remains elusive and incomplete. In this perspective, we argue that realizing this agenda—in particular, predicting disease phenotypes, progression and treatment response for individuals—requires going well beyond standard computational and bioinformatics tools and algorithms. It entails designing global mathematical models over network-scale configurations of genomic states and molecular concentrations, and learning the model parameters from limited available samples of high-dimensional and integrative omics data. As such, any plausible design should accommodate: biological mechanism, necessary for both feasible learning and interpretable decision making; stochasticity, to deal with uncertainty and observed variation at many scales; and a capacity for statistical inference at the patient level. This program, which requires a close, sustained collaboration between mathematicians and biologists, is illustrated in several contexts, including learning bio-markers, metabolism, cell signaling, network inference and tumorigenesis. PMID:25381197

Integrating Information in Biological Ontologies and Molecular Networks to Infer Novel Terms.

PubMed

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/.

A renaissance of neural networks in drug discovery.

PubMed

Baskin, Igor I; Winkler, David; Tetko, Igor V

2016-08-01

Neural networks are becoming a very popular method for solving machine learning and artificial intelligence problems. The variety of neural network types and their application to drug discovery requires expert knowledge to choose the most appropriate approach. In this review, the authors discuss traditional and newly emerging neural network approaches to drug discovery. Their focus is on backpropagation neural networks and their variants, self-organizing maps and associated methods, and a relatively new technique, deep learning. The most important technical issues are discussed including overfitting and its prevention through regularization, ensemble and multitask modeling, model interpretation, and estimation of applicability domain. Different aspects of using neural networks in drug discovery are considered: building structure-activity models with respect to various targets; predicting drug selectivity, toxicity profiles, ADMET and physicochemical properties; characteristics of drug-delivery systems and virtual screening. Neural networks continue to grow in importance for drug discovery. Recent developments in deep learning suggests further improvements may be gained in the analysis of large chemical data sets. It's anticipated that neural networks will be more widely used in drug discovery in the future, and applied in non-traditional areas such as drug delivery systems, biologically compatible materials, and regenerative medicine.

A Novel Robot System Integrating Biological and Mechanical Intelligence Based on Dissociated Neural Network-Controlled Closed-Loop Environment.

PubMed

Li, Yongcheng; Sun, Rong; Wang, Yuechao; Li, Hongyi; Zheng, Xiongfei

2016-01-01

We propose the architecture of a novel robot system merging biological and artificial intelligence based on a neural controller connected to an external agent. We initially built a framework that connected the dissociated neural network to a mobile robot system to implement a realistic vehicle. The mobile robot system characterized by a camera and two-wheeled robot was designed to execute the target-searching task. We modified a software architecture and developed a home-made stimulation generator to build a bi-directional connection between the biological and the artificial components via simple binomial coding/decoding schemes. In this paper, we utilized a specific hierarchical dissociated neural network for the first time as the neural controller. Based on our work, neural cultures were successfully employed to control an artificial agent resulting in high performance. Surprisingly, under the tetanus stimulus training, the robot performed better and better with the increasement of training cycle because of the short-term plasticity of neural network (a kind of reinforced learning). Comparing to the work previously reported, we adopted an effective experimental proposal (i.e. increasing the training cycle) to make sure of the occurrence of the short-term plasticity, and preliminarily demonstrated that the improvement of the robot's performance could be caused independently by the plasticity development of dissociated neural network. This new framework may provide some possible solutions for the learning abilities of intelligent robots by the engineering application of the plasticity processing of neural networks, also for the development of theoretical inspiration for the next generation neuro-prostheses on the basis of the bi-directional exchange of information within the hierarchical neural networks.

A Novel Robot System Integrating Biological and Mechanical Intelligence Based on Dissociated Neural Network-Controlled Closed-Loop Environment

PubMed Central

Wang, Yuechao; Li, Hongyi; Zheng, Xiongfei

2016-01-01

We propose the architecture of a novel robot system merging biological and artificial intelligence based on a neural controller connected to an external agent. We initially built a framework that connected the dissociated neural network to a mobile robot system to implement a realistic vehicle. The mobile robot system characterized by a camera and two-wheeled robot was designed to execute the target-searching task. We modified a software architecture and developed a home-made stimulation generator to build a bi-directional connection between the biological and the artificial components via simple binomial coding/decoding schemes. In this paper, we utilized a specific hierarchical dissociated neural network for the first time as the neural controller. Based on our work, neural cultures were successfully employed to control an artificial agent resulting in high performance. Surprisingly, under the tetanus stimulus training, the robot performed better and better with the increasement of training cycle because of the short-term plasticity of neural network (a kind of reinforced learning). Comparing to the work previously reported, we adopted an effective experimental proposal (i.e. increasing the training cycle) to make sure of the occurrence of the short-term plasticity, and preliminarily demonstrated that the improvement of the robot’s performance could be caused independently by the plasticity development of dissociated neural network. This new framework may provide some possible solutions for the learning abilities of intelligent robots by the engineering application of the plasticity processing of neural networks, also for the development of theoretical inspiration for the next generation neuro-prostheses on the basis of the bi-directional exchange of information within the hierarchical neural networks. PMID:27806074

Memory and learning behaviors mimicked in nanogranular SiO2-based proton conductor gated oxide-based synaptic transistors

NASA Astrophysics Data System (ADS)

Wan, Chang Jin; Zhu, Li Qiang; Zhou, Ju Mei; Shi, Yi; Wan, Qing

2013-10-01

In neuroscience, signal processing, memory and learning function are established in the brain by modifying ionic fluxes in neurons and synapses. Emulation of memory and learning behaviors of biological systems by nanoscale ionic/electronic devices is highly desirable for building neuromorphic systems or even artificial neural networks. Here, novel artificial synapses based on junctionless oxide-based protonic/electronic hybrid transistors gated by nanogranular phosphorus-doped SiO2-based proton-conducting films are fabricated on glass substrates by a room-temperature process. Short-term memory (STM) and long-term memory (LTM) are mimicked by tuning the pulse gate voltage amplitude. The LTM process in such an artificial synapse is due to the proton-related interfacial electrochemical reaction. Our results are highly desirable for building future neuromorphic systems or even artificial networks via electronic elements.In neuroscience, signal processing, memory and learning function are established in the brain by modifying ionic fluxes in neurons and synapses. Emulation of memory and learning behaviors of biological systems by nanoscale ionic/electronic devices is highly desirable for building neuromorphic systems or even artificial neural networks. Here, novel artificial synapses based on junctionless oxide-based protonic/electronic hybrid transistors gated by nanogranular phosphorus-doped SiO2-based proton-conducting films are fabricated on glass substrates by a room-temperature process. Short-term memory (STM) and long-term memory (LTM) are mimicked by tuning the pulse gate voltage amplitude. The LTM process in such an artificial synapse is due to the proton-related interfacial electrochemical reaction. Our results are highly desirable for building future neuromorphic systems or even artificial networks via electronic elements. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr02987e

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.

Using Facebook Groups to Encourage Science Discussions in a Large-Enrollment Biology Class

ERIC Educational Resources Information Center

Pai, Aditi; McGinnis, Gene; Bryant, Dana; Cole, Megan; Kovacs, Jennifer; Stovall, Kyndra; Lee, Mark

2017-01-01

This case study reports the instructional development, impact, and lessons learned regarding the use of Facebook as an educational tool within a large enrollment Biology class at Spelman College (Atlanta, GA). We describe the use of this social networking site to (a) engage students in active scientific discussions, (b) build community within the…

Functional vs. Structural Modularity: do they imply each other?

NASA Astrophysics Data System (ADS)

Toroczkai, Zoltan

2009-03-01

While many deterministic and stochastic processes have been proposed to produce heterogeneous graphs mimicking real-world networks, only a handful of studies attempt to connect structure and dynamics with the function(s) performed by the network. In this talk I will present an approach built on the premise that structure, dynamics, and their observed heterogeneity, are implementations of various functions and their compositions. After a brief review of real-world networks where this connection can explicitly be made, I will focus on biological networks. Biological networks are known to possess functionally specialized modules, which perform tasks almost independently of each other. While proposals have been made for the evolutionary emergence of modularity, it is far from clear that adaptation on evolutionary timescales is the sole mechanism leading to functional specialization. We show that non-evolutionary learning can also lead to the formation of functionally specialized modules in a system exposed to multiple environmental constraints. A natural example suggesting that this is possible is the cerebral cortex, where there are clearly delineated functional areas in spite of the largely uniform anatomical construction of the cortical tissue. However, as numerous experiments show, when damaged, regions specialized for a certain function can be retrained to perform functions normally attributed to other regions. We use the paradigm of neural networks to represent a multitasking system, and use several non-evolutionary learning algorithms as mechanisms for phenotypic adaptation. We show that for a network learning to perform multiple tasks, the degree of independence between the tasks dictates the degree of functional specialization emerging in the network. To uncover the functional modules, we introduce a method of node knockouts that explicitly rates the contribution of each node to different tasks (differential robustness). Through a concrete example we also demonstrate the potential inability of purely topology-based clustering methods to detect functional modules. The robustness of these results suggests that similar mechanisms might be responsible for the emergence of functional specialization in other multitasking networks, as well, including social networks.

Neuromodulated Synaptic Plasticity on the SpiNNaker Neuromorphic System

PubMed Central

Mikaitis, Mantas; Pineda García, Garibaldi; Knight, James C.; Furber, Steve B.

2018-01-01

SpiNNaker is a digital neuromorphic architecture, designed specifically for the low power simulation of large-scale spiking neural networks at speeds close to biological real-time. Unlike other neuromorphic systems, SpiNNaker allows users to develop their own neuron and synapse models as well as specify arbitrary connectivity. As a result SpiNNaker has proved to be a powerful tool for studying different neuron models as well as synaptic plasticity—believed to be one of the main mechanisms behind learning and memory in the brain. A number of Spike-Timing-Dependent-Plasticity(STDP) rules have already been implemented on SpiNNaker and have been shown to be capable of solving various learning tasks in real-time. However, while STDP is an important biological theory of learning, it is a form of Hebbian or unsupervised learning and therefore does not explain behaviors that depend on feedback from the environment. Instead, learning rules based on neuromodulated STDP (three-factor learning rules) have been shown to be capable of solving reinforcement learning tasks in a biologically plausible manner. In this paper we demonstrate for the first time how a model of three-factor STDP, with the third-factor representing spikes from dopaminergic neurons, can be implemented on the SpiNNaker neuromorphic system. Using this learning rule we first show how reward and punishment signals can be delivered to a single synapse before going on to demonstrate it in a larger network which solves the credit assignment problem in a Pavlovian conditioning experiment. Because of its extra complexity, we find that our three-factor learning rule requires approximately 2× as much processing time as the existing SpiNNaker STDP learning rules. However, we show that it is still possible to run our Pavlovian conditioning model with up to 1 × 104 neurons in real-time, opening up new research opportunities for modeling behavioral learning on SpiNNaker. PMID:29535600

The value of prior knowledge in machine learning of complex network systems.

PubMed

Ferranti, Dana; Krane, David; Craft, David

2017-11-15

Our overall goal is to develop machine-learning approaches based on genomics and other relevant accessible information for use in predicting how a patient will respond to a given proposed drug or treatment. Given the complexity of this problem, we begin by developing, testing and analyzing learning methods using data from simulated systems, which allows us access to a known ground truth. We examine the benefits of using prior system knowledge and investigate how learning accuracy depends on various system parameters as well as the amount of training data available. The simulations are based on Boolean networks-directed graphs with 0/1 node states and logical node update rules-which are the simplest computational systems that can mimic the dynamic behavior of cellular systems. Boolean networks can be generated and simulated at scale, have complex yet cyclical dynamics and as such provide a useful framework for developing machine-learning algorithms for modular and hierarchical networks such as biological systems in general and cancer in particular. We demonstrate that utilizing prior knowledge (in the form of network connectivity information), without detailed state equations, greatly increases the power of machine-learning algorithms to predict network steady-state node values ('phenotypes') and perturbation responses ('drug effects'). Links to codes and datasets here: https://gray.mgh.harvard.edu/people-directory/71-david-craft-phd. dcraft@broadinstitute.org. 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

Boosting compound-protein interaction prediction by deep learning.

PubMed

Tian, Kai; Shao, Mingyu; Wang, Yang; Guan, Jihong; Zhou, Shuigeng

2016-11-01

The identification of interactions between compounds and proteins plays an important role in network pharmacology and drug discovery. However, experimentally identifying compound-protein interactions (CPIs) is generally expensive and time-consuming, computational approaches are thus introduced. Among these, machine-learning based methods have achieved a considerable success. However, due to the nonlinear and imbalanced nature of biological data, many machine learning approaches have their own limitations. Recently, deep learning techniques show advantages over many state-of-the-art machine learning methods in some applications. In this study, we aim at improving the performance of CPI prediction based on deep learning, and propose a method called DL-CPI (the abbreviation of Deep Learning for Compound-Protein Interactions prediction), which employs deep neural network (DNN) to effectively learn the representations of compound-protein pairs. Extensive experiments show that DL-CPI can learn useful features of compound-protein pairs by a layerwise abstraction, and thus achieves better prediction performance than existing methods on both balanced and imbalanced datasets. Copyright © 2016 Elsevier Inc. All rights reserved.

Equilibrium point control of a monkey arm simulator by a fast learning tree structured artificial neural network.

PubMed

Dornay, M; Sanger, T D

1993-01-01

A planar 17 muscle model of the monkey's arm based on realistic biomechanical measurements was simulated on a Symbolics Lisp Machine. The simulator implements the equilibrium point hypothesis for the control of arm movements. Given initial and final desired positions, it generates a minimum-jerk desired trajectory of the hand and uses the backdriving algorithm to determine an appropriate sequence of motor commands to the muscles (Flash 1987; Mussa-Ivaldi et al. 1991; Dornay 1991b). These motor commands specify a temporal sequence of stable (attractive) equilibrium positions which lead to the desired hand movement. A strong disadvantage of the simulator is that it has no memory of previous computations. Determining the desired trajectory using the minimum-jerk model is instantaneous, but the laborious backdriving algorithm is slow, and can take up to one hour for some trajectories. The complexity of the required computations makes it a poor model for biological motor control. We propose a computationally simpler and more biologically plausible method for control which achieves the benefits of the backdriving algorithm. A fast learning, tree-structured network (Sanger 1991c) was trained to remember the knowledge obtained by the backdriving algorithm. The neural network learned the nonlinear mapping from a 2-dimensional cartesian planar hand position (x,y) to a 17-dimensional motor command space (u1, . . ., u17). Learning 20 training trajectories, each composed of 26 sample points [[x,y], [u1, . . ., u17] took only 20 min on a Sun-4 Sparc workstation. After the learning stage, new, untrained test trajectories as well as the original trajectories of the hand were given to the neural network as input. The network calculated the required motor commands for these movements. The resulting movements were close to the desired ones for both the training and test cases.

Spiking neural networks for handwritten digit recognition-Supervised learning and network optimization.

PubMed

Kulkarni, Shruti R; Rajendran, Bipin

2018-07-01

We demonstrate supervised learning in Spiking Neural Networks (SNNs) for the problem of handwritten digit recognition using the spike triggered Normalized Approximate Descent (NormAD) algorithm. Our network that employs neurons operating at sparse biological spike rates below 300Hz achieves a classification accuracy of 98.17% on the MNIST test database with four times fewer parameters compared to the state-of-the-art. We present several insights from extensive numerical experiments regarding optimization of learning parameters and network configuration to improve its accuracy. We also describe a number of strategies to optimize the SNN for implementation in memory and energy constrained hardware, including approximations in computing the neuronal dynamics and reduced precision in storing the synaptic weights. Experiments reveal that even with 3-bit synaptic weights, the classification accuracy of the designed SNN does not degrade beyond 1% as compared to the floating-point baseline. Further, the proposed SNN, which is trained based on the precise spike timing information outperforms an equivalent non-spiking artificial neural network (ANN) trained using back propagation, especially at low bit precision. Thus, our study shows the potential for realizing efficient neuromorphic systems that use spike based information encoding and learning for real-world applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Leaky Integrate and Fire Neuron by Charge-Discharge Dynamics in Floating-Body MOSFET.

PubMed

Dutta, Sangya; Kumar, Vinay; Shukla, Aditya; Mohapatra, Nihar R; Ganguly, Udayan

2017-08-15

Neuro-biology inspired Spiking Neural Network (SNN) enables efficient learning and recognition tasks. To achieve a large scale network akin to biology, a power and area efficient electronic neuron is essential. Earlier, we had demonstrated an LIF neuron by a novel 4-terminal impact ionization based n+/p/n+ with an extended gate (gated-INPN) device by physics simulation. Excellent improvement in area and power compared to conventional analog circuit implementations was observed. In this paper, we propose and experimentally demonstrate a compact conventional 3-terminal partially depleted (PD) SOI- MOSFET (100 nm gate length) to replace the 4-terminal gated-INPN device. Impact ionization (II) induced floating body effect in SOI-MOSFET is used to capture LIF neuron behavior to demonstrate spiking frequency dependence on input. MHz operation enables attractive hardware acceleration compared to biology. Overall, conventional PD-SOI-CMOS technology enables very-large-scale-integration (VLSI) which is essential for biology scale (~10 11 neuron based) large neural networks.

Neural network system for purposeful behavior based on foveal visual preprocessor

NASA Astrophysics Data System (ADS)

Golovan, Alexander V.; Shevtsova, Natalia A.; Klepatch, Arkadi A.

1996-10-01

Biologically plausible model of the system with an adaptive behavior in a priori environment and resistant to impairment has been developed. The system consists of input, learning, and output subsystems. The first subsystems classifies input patterns presented as n-dimensional vectors in accordance with some associative rule. The second one being a neural network determines adaptive responses of the system to input patterns. Arranged neural groups coding possible input patterns and appropriate output responses are formed during learning by means of negative reinforcement. Output subsystem maps a neural network activity into the system behavior in the environment. The system developed has been studied by computer simulation imitating a collision-free motion of a mobile robot. After some learning period the system 'moves' along a road without collisions. It is shown that in spite of impairment of some neural network elements the system functions reliably after relearning. Foveal visual preprocessor model developed earlier has been tested to form a kind of visual input to the system.

Think globally and solve locally: secondary memory-based network learning for automated multi-species function prediction

PubMed Central

2014-01-01

Background Network-based learning algorithms for automated function prediction (AFP) are negatively affected by the limited coverage of experimental data and limited a priori known functional annotations. As a consequence their application to model organisms is often restricted to well characterized biological processes and pathways, and their effectiveness with poorly annotated species is relatively limited. A possible solution to this problem might consist in the construction of big networks including multiple species, but this in turn poses challenging computational problems, due to the scalability limitations of existing algorithms and the main memory requirements induced by the construction of big networks. Distributed computation or the usage of big computers could in principle respond to these issues, but raises further algorithmic problems and require resources not satisfiable with simple off-the-shelf computers. Results We propose a novel framework for scalable network-based learning of multi-species protein functions based on both a local implementation of existing algorithms and the adoption of innovative technologies: we solve “locally” the AFP problem, by designing “vertex-centric” implementations of network-based algorithms, but we do not give up thinking “globally” by exploiting the overall topology of the network. This is made possible by the adoption of secondary memory-based technologies that allow the efficient use of the large memory available on disks, thus overcoming the main memory limitations of modern off-the-shelf computers. This approach has been applied to the analysis of a large multi-species network including more than 300 species of bacteria and to a network with more than 200,000 proteins belonging to 13 Eukaryotic species. To our knowledge this is the first work where secondary-memory based network analysis has been applied to multi-species function prediction using biological networks with hundreds of thousands of proteins. Conclusions The combination of these algorithmic and technological approaches makes feasible the analysis of large multi-species networks using ordinary computers with limited speed and primary memory, and in perspective could enable the analysis of huge networks (e.g. the whole proteomes available in SwissProt), using well-equipped stand-alone machines. PMID:24843788

Training set expansion: an approach to improving the reconstruction of biological networks from limited and uneven reliable interactions

PubMed Central

Yip, Kevin Y.; Gerstein, Mark

2009-01-01

Motivation: An important problem in systems biology is reconstructing complete networks of interactions between biological objects by extrapolating from a few known interactions as examples. While there are many computational techniques proposed for this network reconstruction task, their accuracy is consistently limited by the small number of high-confidence examples, and the uneven distribution of these examples across the potential interaction space, with some objects having many known interactions and others few. Results: To address this issue, we propose two computational methods based on the concept of training set expansion. They work particularly effectively in conjunction with kernel approaches, which are a popular class of approaches for fusing together many disparate types of features. Both our methods are based on semi-supervised learning and involve augmenting the limited number of gold-standard training instances with carefully chosen and highly confident auxiliary examples. The first method, prediction propagation, propagates highly confident predictions of one local model to another as the auxiliary examples, thus learning from information-rich regions of the training network to help predict the information-poor regions. The second method, kernel initialization, takes the most similar and most dissimilar objects of each object in a global kernel as the auxiliary examples. Using several sets of experimentally verified protein–protein interactions from yeast, we show that training set expansion gives a measurable performance gain over a number of representative, state-of-the-art network reconstruction methods, and it can correctly identify some interactions that are ranked low by other methods due to the lack of training examples of the involved proteins. Contact: mark.gerstein@yale.edu Availability: The datasets and additional materials can be found at http://networks.gersteinlab.org/tse. PMID:19015141

Unsupervised segmentation with dynamical units.

PubMed

Rao, A Ravishankar; Cecchi, Guillermo A; Peck, Charles C; Kozloski, James R

2008-01-01

In this paper, we present a novel network to separate mixtures of inputs that have been previously learned. A significant capability of the network is that it segments the components of each input object that most contribute to its classification. The network consists of amplitude-phase units that can synchronize their dynamics, so that separation is determined by the amplitude of units in an output layer, and segmentation by phase similarity between input and output layer units. Learning is unsupervised and based on a Hebbian update, and the architecture is very simple. Moreover, efficient segmentation can be achieved even when there is considerable superposition of the inputs. The network dynamics are derived from an objective function that rewards sparse coding in the generalized amplitude-phase variables. We argue that this objective function can provide a possible formal interpretation of the binding problem and that the implementation of the network architecture and dynamics is biologically plausible.

Holographic deep learning for rapid optical screening of anthrax spores

PubMed Central

Jo, YoungJu; Park, Sangjin; Jung, JaeHwang; Yoon, Jonghee; Joo, Hosung; Kim, Min-hyeok; Kang, Suk-Jo; Choi, Myung Chul; Lee, Sang Yup; Park, YongKeun

2017-01-01

Establishing early warning systems for anthrax attacks is crucial in biodefense. Despite numerous studies for decades, the limited sensitivity of conventional biochemical methods essentially requires preprocessing steps and thus has limitations to be used in realistic settings of biological warfare. We present an optical method for rapid and label-free screening of Bacillus anthracis spores through the synergistic application of holographic microscopy and deep learning. A deep convolutional neural network is designed to classify holographic images of unlabeled living cells. After training, the network outperforms previous techniques in all accuracy measures, achieving single-spore sensitivity and subgenus specificity. The unique “representation learning” capability of deep learning enables direct training from raw images instead of manually extracted features. The method automatically recognizes key biological traits encoded in the images and exploits them as fingerprints. This remarkable learning ability makes the proposed method readily applicable to classifying various single cells in addition to B. anthracis, as demonstrated for the diagnosis of Listeria monocytogenes, without any modification. We believe that our strategy will make holographic microscopy more accessible to medical doctors and biomedical scientists for easy, rapid, and accurate point-of-care diagnosis of pathogens. PMID:28798957

On the design of neuro-controllers for individual and social learning behaviour in autonomous robots: an evolutionary approach

NASA Astrophysics Data System (ADS)

Pini, Giovanni; Tuci, Elio

2008-06-01

In biology/psychology, the capability of natural organisms to learn from the observation/interaction with conspecifics is referred to as social learning. Roboticists have recently developed an interest in social learning, since it might represent an effective strategy to enhance the adaptivity of a team of autonomous robots. In this study, we show that a methodological approach based on artifcial neural networks shaped by evolutionary computation techniques can be successfully employed to synthesise the individual and social learning mechanisms for robots required to learn a desired action (i.e. phototaxis or antiphototaxis).

Integrating Information in Biological Ontologies and Molecular Networks to Infer Novel Terms

PubMed Central

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

A case study of evolutionary computation of biochemical adaptation

NASA Astrophysics Data System (ADS)

François, Paul; Siggia, Eric D.

2008-06-01

Simulations of evolution have a long history, but their relation to biology is questioned because of the perceived contingency of evolution. Here we provide an example of a biological process, adaptation, where simulations are argued to approach closer to biology. Adaptation is a common feature of sensory systems, and a plausible component of other biochemical networks because it rescales upstream signals to facilitate downstream processing. We create random gene networks numerically, by linking genes with interactions that model transcription, phosphorylation and protein-protein association. We define a fitness function for adaptation in terms of two functional metrics, and show that any reasonable combination of them will yield the same adaptive networks after repeated rounds of mutation and selection. Convergence to these networks is driven by positive selection and thus fast. There is always a path in parameter space of continuously improving fitness that leads to perfect adaptation, implying that the actual mutation rates we use in the simulation do not bias the results. Our results imply a kinetic view of evolution, i.e., it favors gene networks that can be learned quickly from the random examples supplied by mutation. This formulation allows for deductive predictions of the networks realized in nature.

Biology-Inspired Distributed Consensus in Massively-Deployed Sensor Networks

NASA Technical Reports Server (NTRS)

Jones, Kennie H.; Lodding, Kenneth N.; Olariu, Stephan; Wilson, Larry; Xin, Chunsheng

2005-01-01

Promises of ubiquitous control of the physical environment by large-scale wireless sensor networks open avenues for new applications that are expected to redefine the way we live and work. Most of recent research has concentrated on developing techniques for performing relatively simple tasks in small-scale sensor networks assuming some form of centralized control. The main contribution of this work is to propose a new way of looking at large-scale sensor networks, motivated by lessons learned from the way biological ecosystems are organized. Indeed, we believe that techniques used in small-scale sensor networks are not likely to scale to large networks; that such large-scale networks must be viewed as an ecosystem in which the sensors/effectors are organisms whose autonomous actions, based on local information, combine in a communal way to produce global results. As an example of a useful function, we demonstrate that fully distributed consensus can be attained in a scalable fashion in massively deployed sensor networks where individual motes operate based on local information, making local decisions that are aggregated across the network to achieve globally-meaningful effects.

Origin of the spike-timing-dependent plasticity rule

NASA Astrophysics Data System (ADS)

Cho, Myoung Won; Choi, M. Y.

2016-08-01

A biological synapse changes its efficacy depending on the difference between pre- and post-synaptic spike timings. Formulating spike-timing-dependent interactions in terms of the path integral, we establish a neural-network model, which makes it possible to predict relevant quantities rigorously by means of standard methods in statistical mechanics and field theory. In particular, the biological synaptic plasticity rule is shown to emerge as the optimal form for minimizing the free energy. It is further revealed that maximization of the entropy of neural activities gives rise to the competitive behavior of biological learning. This demonstrates that statistical mechanics helps to understand rigorously key characteristic behaviors of a neural network, thus providing the possibility of physics serving as a useful and relevant framework for probing life.

Real-time cerebellar neuroprosthetic system based on a spiking neural network model of motor learning.

PubMed

Xu, Tao; Xiao, Na; Zhai, Xiaolong; Kwan Chan, Pak; Tin, Chung

2018-02-01

Damage to the brain, as a result of various medical conditions, impacts the everyday life of patients and there is still no complete cure to neurological disorders. Neuroprostheses that can functionally replace the damaged neural circuit have recently emerged as a possible solution to these problems. Here we describe the development of a real-time cerebellar neuroprosthetic system to substitute neural function in cerebellar circuitry for learning delay eyeblink conditioning (DEC). The system was empowered by a biologically realistic spiking neural network (SNN) model of the cerebellar neural circuit, which considers the neuronal population and anatomical connectivity of the network. The model simulated synaptic plasticity critical for learning DEC. This SNN model was carefully implemented on a field programmable gate array (FPGA) platform for real-time simulation. This hardware system was interfaced in in vivo experiments with anesthetized rats and it used neural spikes recorded online from the animal to learn and trigger conditioned eyeblink in the animal during training. This rat-FPGA hybrid system was able to process neuronal spikes in real-time with an embedded cerebellum model of ~10 000 neurons and reproduce learning of DEC with different inter-stimulus intervals. Our results validated that the system performance is physiologically relevant at both the neural (firing pattern) and behavioral (eyeblink pattern) levels. This integrated system provides the sufficient computation power for mimicking the cerebellar circuit in real-time. The system interacts with the biological system naturally at the spike level and can be generalized for including other neural components (neuron types and plasticity) and neural functions for potential neuroprosthetic applications.

Extraction of temporally correlated features from dynamic vision sensors with spike-timing-dependent plasticity.

PubMed

Bichler, Olivier; Querlioz, Damien; Thorpe, Simon J; Bourgoin, Jean-Philippe; Gamrat, Christian

2012-08-01

A biologically inspired approach to learning temporally correlated patterns from a spiking silicon retina is presented. Spikes are generated from the retina in response to relative changes in illumination at the pixel level and transmitted to a feed-forward spiking neural network. Neurons become sensitive to patterns of pixels with correlated activation times, in a fully unsupervised scheme. This is achieved using a special form of Spike-Timing-Dependent Plasticity which depresses synapses that did not recently contribute to the post-synaptic spike activation, regardless of their activation time. Competitive learning is implemented with lateral inhibition. When tested with real-life data, the system is able to extract complex and overlapping temporally correlated features such as car trajectories on a freeway, after only 10 min of traffic learning. Complete trajectories can be learned with a 98% detection rate using a second layer, still with unsupervised learning, and the system may be used as a car counter. The proposed neural network is extremely robust to noise and it can tolerate a high degree of synaptic and neuronal variability with little impact on performance. Such results show that a simple biologically inspired unsupervised learning scheme is capable of generating selectivity to complex meaningful events on the basis of relatively little sensory experience. Copyright © 2012 Elsevier Ltd. All rights reserved.

Persistent homology of time-dependent functional networks constructed from coupled time series

NASA Astrophysics Data System (ADS)

Stolz, Bernadette J.; Harrington, Heather A.; Porter, Mason A.

2017-04-01

We use topological data analysis to study "functional networks" that we construct from time-series data from both experimental and synthetic sources. We use persistent homology with a weight rank clique filtration to gain insights into these functional networks, and we use persistence landscapes to interpret our results. Our first example uses time-series output from networks of coupled Kuramoto oscillators. Our second example consists of biological data in the form of functional magnetic resonance imaging data that were acquired from human subjects during a simple motor-learning task in which subjects were monitored for three days during a five-day period. With these examples, we demonstrate that (1) using persistent homology to study functional networks provides fascinating insights into their properties and (2) the position of the features in a filtration can sometimes play a more vital role than persistence in the interpretation of topological features, even though conventionally the latter is used to distinguish between signal and noise. We find that persistent homology can detect differences in synchronization patterns in our data sets over time, giving insight both on changes in community structure in the networks and on increased synchronization between brain regions that form loops in a functional network during motor learning. For the motor-learning data, persistence landscapes also reveal that on average the majority of changes in the network loops take place on the second of the three days of the learning process.

Synthetic biology routes to bio-artificial intelligence

PubMed Central

Zaikin, Alexey; Saka, Yasushi; Romano, M. Carmen; Giuraniuc, Claudiu V.; Kanakov, Oleg; Laptyeva, Tetyana

2016-01-01

The design of synthetic gene networks (SGNs) has advanced to the extent that novel genetic circuits are now being tested for their ability to recapitulate archetypal learning behaviours first defined in the fields of machine and animal learning. Here, we discuss the biological implementation of a perceptron algorithm for linear classification of input data. An expansion of this biological design that encompasses cellular ‘teachers’ and ‘students’ is also examined. We also discuss implementation of Pavlovian associative learning using SGNs and present an example of such a scheme and in silico simulation of its performance. In addition to designed SGNs, we also consider the option to establish conditions in which a population of SGNs can evolve diversity in order to better contend with complex input data. Finally, we compare recent ethical concerns in the field of artificial intelligence (AI) and the future challenges raised by bio-artificial intelligence (BI). PMID:27903825

Hidden Markov models and other machine learning approaches in computational molecular biology

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

Baldi, P.

1995-12-31

This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. Computational tools are increasingly needed to process the massive amounts of data, to organize and classify sequences, to detect weak similarities, to separate coding from non-coding regions, and reconstruct the underlying evolutionary history. The fundamental problem in machine learning is the same as in scientific reasoning in general, as well as statistical modeling: to come up with a good model for the data. In thismore » tutorial four classes of models are reviewed. They are: Hidden Markov models; artificial Neural Networks; Belief Networks; and Stochastic Grammars. When dealing with DNA and protein primary sequences, Hidden Markov models are one of the most flexible and powerful alignments and data base searches. In this tutorial, attention is focused on the theory of Hidden Markov Models, and how to apply them to problems in molecular biology.« less

From biological neural networks to thinking machines: Transitioning biological organizational principles to computer technology

NASA Technical Reports Server (NTRS)

Ross, Muriel D.

1991-01-01

The three-dimensional organization of the vestibular macula is under study by computer assisted reconstruction and simulation methods as a model for more complex neural systems. One goal of this research is to transition knowledge of biological neural network architecture and functioning to computer technology, to contribute to the development of thinking computers. Maculas are organized as weighted neural networks for parallel distributed processing of information. The network is characterized by non-linearity of its terminal/receptive fields. Wiring appears to develop through constrained randomness. A further property is the presence of two main circuits, highly channeled and distributed modifying, that are connected through feedforward-feedback collaterals and biasing subcircuit. Computer simulations demonstrate that differences in geometry of the feedback (afferent) collaterals affects the timing and the magnitude of voltage changes delivered to the spike initiation zone. Feedforward (efferent) collaterals act as voltage followers and likely inhibit neurons of the distributed modifying circuit. These results illustrate the importance of feedforward-feedback loops, of timing, and of inhibition in refining neural network output. They also suggest that it is the distributed modifying network that is most involved in adaptation, memory, and learning. Tests of macular adaptation, through hyper- and microgravitational studies, support this hypothesis since synapses in the distributed modifying circuit, but not the channeled circuit, are altered. Transitioning knowledge of biological systems to computer technology, however, remains problematical.

Entity recognition in the biomedical domain using a hybrid approach.

PubMed

Basaldella, Marco; Furrer, Lenz; Tasso, Carlo; Rinaldi, Fabio

2017-11-09

This article describes a high-recall, high-precision approach for the extraction of biomedical entities from scientific articles. The approach uses a two-stage pipeline, combining a dictionary-based entity recognizer with a machine-learning classifier. First, the OGER entity recognizer, which has a bias towards high recall, annotates the terms that appear in selected domain ontologies. Subsequently, the Distiller framework uses this information as a feature for a machine learning algorithm to select the relevant entities only. For this step, we compare two different supervised machine-learning algorithms: Conditional Random Fields and Neural Networks. In an in-domain evaluation using the CRAFT corpus, we test the performance of the combined systems when recognizing chemicals, cell types, cellular components, biological processes, molecular functions, organisms, proteins, and biological sequences. Our best system combines dictionary-based candidate generation with Neural-Network-based filtering. It achieves an overall precision of 86% at a recall of 60% on the named entity recognition task, and a precision of 51% at a recall of 49% on the concept recognition task. These results are to our knowledge the best reported so far in this particular task.

Modular neural networks: a survey.

PubMed

Auda, G; Kamel, M

1999-04-01

Modular Neural Networks (MNNs) is a rapidly growing field in artificial Neural Networks (NNs) research. This paper surveys the different motivations for creating MNNs: biological, psychological, hardware, and computational. Then, the general stages of MNN design are outlined and surveyed as well, viz., task decomposition techniques, learning schemes and multi-module decision-making strategies. Advantages and disadvantages of the surveyed methods are pointed out, and an assessment with respect to practical potential is provided. Finally, some general recommendations for future designs are presented.

Prediction of residue-residue contact matrix for protein-protein interaction with Fisher score features and deep learning.

PubMed

Du, Tianchuan; Liao, Li; Wu, Cathy H; Sun, Bilin

2016-11-01

Protein-protein interactions play essential roles in many biological processes. Acquiring knowledge of the residue-residue contact information of two interacting proteins is not only helpful in annotating functions for proteins, but also critical for structure-based drug design. The prediction of the protein residue-residue contact matrix of the interfacial regions is challenging. In this work, we introduced deep learning techniques (specifically, stacked autoencoders) to build deep neural network models to tackled the residue-residue contact prediction problem. In tandem with interaction profile Hidden Markov Models, which was used first to extract Fisher score features from protein sequences, stacked autoencoders were deployed to extract and learn hidden abstract features. The deep learning model showed significant improvement over the traditional machine learning model, Support Vector Machines (SVM), with the overall accuracy increased by 15% from 65.40% to 80.82%. We showed that the stacked autoencoders could extract novel features, which can be utilized by deep neural networks and other classifiers to enhance learning, out of the Fisher score features. It is further shown that deep neural networks have significant advantages over SVM in making use of the newly extracted features. Copyright © 2016. Published by Elsevier Inc.

Neural networks and applications tutorial

NASA Astrophysics Data System (ADS)

Guyon, I.

1991-09-01

The importance of neural networks has grown dramatically during this decade. While only a few years ago they were primarily of academic interest, now dozens of companies and many universities are investigating the potential use of these systems and products are beginning to appear. The idea of building a machine whose architecture is inspired by that of the brain has roots which go far back in history. Nowadays, technological advances of computers and the availability of custom integrated circuits, permit simulations of hundreds or even thousands of neurons. In conjunction, the growing interest in learning machines, non-linear dynamics and parallel computation spurred renewed attention in artificial neural networks. Many tentative applications have been proposed, including decision systems (associative memories, classifiers, data compressors and optimizers), or parametric models for signal processing purposes (system identification, automatic control, noise canceling, etc.). While they do not always outperform standard methods, neural network approaches are already used in some real world applications for pattern recognition and signal processing tasks. The tutorial is divided into six lectures, that where presented at the Third Graduate Summer Course on Computational Physics (September 3-7, 1990) on Parallel Architectures and Applications, organized by the European Physical Society: (1) Introduction: machine learning and biological computation. (2) Adaptive artificial neurons (perceptron, ADALINE, sigmoid units, etc.): learning rules and implementations. (3) Neural network systems: architectures, learning algorithms. (4) Applications: pattern recognition, signal processing, etc. (5) Elements of learning theory: how to build networks which generalize. (6) A case study: a neural network for on-line recognition of handwritten alphanumeric characters.

Functional Interaction Network Construction and Analysis for Disease Discovery.

PubMed

Wu, Guanming; Haw, Robin

2017-01-01

Network-based approaches project seemingly unrelated genes or proteins onto a large-scale network context, therefore providing a holistic visualization and analysis platform for genomic data generated from high-throughput experiments, reducing the dimensionality of data via using network modules and increasing the statistic analysis power. Based on the Reactome database, the most popular and comprehensive open-source biological pathway knowledgebase, we have developed a highly reliable protein functional interaction network covering around 60 % of total human genes and an app called ReactomeFIViz for Cytoscape, the most popular biological network visualization and analysis platform. In this chapter, we describe the detailed procedures on how this functional interaction network is constructed by integrating multiple external data sources, extracting functional interactions from human curated pathway databases, building a machine learning classifier called a Naïve Bayesian Classifier, predicting interactions based on the trained Naïve Bayesian Classifier, and finally constructing the functional interaction database. We also provide an example on how to use ReactomeFIViz for performing network-based data analysis for a list of genes.

Enriching regulatory networks by bootstrap learning using optimised GO-based gene similarity and gene links mined from PubMed abstracts

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

Taylor, Ronald C.; Sanfilippo, Antonio P.; McDermott, Jason E.

2011-02-18

Transcriptional regulatory networks are being determined using “reverse engineering” methods that infer connections based on correlations in gene state. Corroboration of such networks through independent means such as evidence from the biomedical literature is desirable. Here, we explore a novel approach, a bootstrapping version of our previous Cross-Ontological Analytic method (XOA) that can be used for semi-automated annotation and verification of inferred regulatory connections, as well as for discovery of additional functional relationships between the genes. First, we use our annotation and network expansion method on a biological network learned entirely from the literature. We show how new relevant linksmore » between genes can be iteratively derived using a gene similarity measure based on the Gene Ontology that is optimized on the input network at each iteration. Second, we apply our method to annotation, verification, and expansion of a set of regulatory connections found by the Context Likelihood of Relatedness algorithm.« less

Embodied learning of a generative neural model for biological motion perception and inference

PubMed Central

Schrodt, Fabian; Layher, Georg; Neumann, Heiko; Butz, Martin V.

2015-01-01

Although an action observation network and mirror neurons for understanding the actions and intentions of others have been under deep, interdisciplinary consideration over recent years, it remains largely unknown how the brain manages to map visually perceived biological motion of others onto its own motor system. This paper shows how such a mapping may be established, even if the biologically motion is visually perceived from a new vantage point. We introduce a learning artificial neural network model and evaluate it on full body motion tracking recordings. The model implements an embodied, predictive inference approach. It first learns to correlate and segment multimodal sensory streams of own bodily motion. In doing so, it becomes able to anticipate motion progression, to complete missing modal information, and to self-generate learned motion sequences. When biological motion of another person is observed, this self-knowledge is utilized to recognize similar motion patterns and predict their progress. Due to the relative encodings, the model shows strong robustness in recognition despite observing rather large varieties of body morphology and posture dynamics. By additionally equipping the model with the capability to rotate its visual frame of reference, it is able to deduce the visual perspective onto the observed person, establishing full consistency to the embodied self-motion encodings by means of active inference. In further support of its neuro-cognitive plausibility, we also model typical bistable perceptions when crucial depth information is missing. In sum, the introduced neural model proposes a solution to the problem of how the human brain may establish correspondence between observed bodily motion and its own motor system, thus offering a mechanism that supports the development of mirror neurons. PMID:26217215

Embodied learning of a generative neural model for biological motion perception and inference.

PubMed

Schrodt, Fabian; Layher, Georg; Neumann, Heiko; Butz, Martin V

2015-01-01

Although an action observation network and mirror neurons for understanding the actions and intentions of others have been under deep, interdisciplinary consideration over recent years, it remains largely unknown how the brain manages to map visually perceived biological motion of others onto its own motor system. This paper shows how such a mapping may be established, even if the biologically motion is visually perceived from a new vantage point. We introduce a learning artificial neural network model and evaluate it on full body motion tracking recordings. The model implements an embodied, predictive inference approach. It first learns to correlate and segment multimodal sensory streams of own bodily motion. In doing so, it becomes able to anticipate motion progression, to complete missing modal information, and to self-generate learned motion sequences. When biological motion of another person is observed, this self-knowledge is utilized to recognize similar motion patterns and predict their progress. Due to the relative encodings, the model shows strong robustness in recognition despite observing rather large varieties of body morphology and posture dynamics. By additionally equipping the model with the capability to rotate its visual frame of reference, it is able to deduce the visual perspective onto the observed person, establishing full consistency to the embodied self-motion encodings by means of active inference. In further support of its neuro-cognitive plausibility, we also model typical bistable perceptions when crucial depth information is missing. In sum, the introduced neural model proposes a solution to the problem of how the human brain may establish correspondence between observed bodily motion and its own motor system, thus offering a mechanism that supports the development of mirror neurons.

Precise Network Modeling of Systems Genetics Data Using the Bayesian Network Webserver.

PubMed

Ziebarth, Jesse D; Cui, Yan

2017-01-01

The Bayesian Network Webserver (BNW, http://compbio.uthsc.edu/BNW ) is an integrated platform for Bayesian network modeling of biological datasets. It provides a web-based network modeling environment that seamlessly integrates advanced algorithms for probabilistic causal modeling and reasoning with Bayesian networks. BNW is designed for precise modeling of relatively small networks that contain less than 20 nodes. The structure learning algorithms used by BNW guarantee the discovery of the best (most probable) network structure given the data. To facilitate network modeling across multiple biological levels, BNW provides a very flexible interface that allows users to assign network nodes into different tiers and define the relationships between and within the tiers. This function is particularly useful for modeling systems genetics datasets that often consist of multiscalar heterogeneous genotype-to-phenotype data. BNW enables users to, within seconds or minutes, go from having a simply formatted input file containing a dataset to using a network model to make predictions about the interactions between variables and the potential effects of experimental interventions. In this chapter, we will introduce the functions of BNW and show how to model systems genetics datasets with BNW.

Towards the prediction of essential genes by integration of network topology, cellular localization and biological process information

PubMed Central

2009-01-01

Background The identification of essential genes is important for the understanding of the minimal requirements for cellular life and for practical purposes, such as drug design. However, the experimental techniques for essential genes discovery are labor-intensive and time-consuming. Considering these experimental constraints, a computational approach capable of accurately predicting essential genes would be of great value. We therefore present here a machine learning-based computational approach relying on network topological features, cellular localization and biological process information for prediction of essential genes. Results We constructed a decision tree-based meta-classifier and trained it on datasets with individual and grouped attributes-network topological features, cellular compartments and biological processes-to generate various predictors of essential genes. We showed that the predictors with better performances are those generated by datasets with integrated attributes. Using the predictor with all attributes, i.e., network topological features, cellular compartments and biological processes, we obtained the best predictor of essential genes that was then used to classify yeast genes with unknown essentiality status. Finally, we generated decision trees by training the J48 algorithm on datasets with all network topological features, cellular localization and biological process information to discover cellular rules for essentiality. We found that the number of protein physical interactions, the nuclear localization of proteins and the number of regulating transcription factors are the most important factors determining gene essentiality. Conclusion We were able to demonstrate that network topological features, cellular localization and biological process information are reliable predictors of essential genes. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing essentiality. PMID:19758426

Replicating receptive fields of simple and complex cells in primary visual cortex in a neuronal network model with temporal and population sparseness and reliability.

PubMed

Tanaka, Takuma; Aoyagi, Toshio; Kaneko, Takeshi

2012-10-01

We propose a new principle for replicating receptive field properties of neurons in the primary visual cortex. We derive a learning rule for a feedforward network, which maintains a low firing rate for the output neurons (resulting in temporal sparseness) and allows only a small subset of the neurons in the network to fire at any given time (resulting in population sparseness). Our learning rule also sets the firing rates of the output neurons at each time step to near-maximum or near-minimum levels, resulting in neuronal reliability. The learning rule is simple enough to be written in spatially and temporally local forms. After the learning stage is performed using input image patches of natural scenes, output neurons in the model network are found to exhibit simple-cell-like receptive field properties. When the output of these simple-cell-like neurons are input to another model layer using the same learning rule, the second-layer output neurons after learning become less sensitive to the phase of gratings than the simple-cell-like input neurons. In particular, some of the second-layer output neurons become completely phase invariant, owing to the convergence of the connections from first-layer neurons with similar orientation selectivity to second-layer neurons in the model network. We examine the parameter dependencies of the receptive field properties of the model neurons after learning and discuss their biological implications. We also show that the localized learning rule is consistent with experimental results concerning neuronal plasticity and can replicate the receptive fields of simple and complex cells.

Harmonic Training and the Formation of Pitch Representation in a Neural Network Model of the Auditory Brain

PubMed Central

Ahmad, Nasir; Higgins, Irina; Walker, Kerry M. M.; Stringer, Simon M.

2016-01-01

Attempting to explain the perceptual qualities of pitch has proven to be, and remains, a difficult problem. The wide range of sounds which elicit pitch and a lack of agreement across neurophysiological studies on how pitch is encoded by the brain have made this attempt more difficult. In describing the potential neural mechanisms by which pitch may be processed, a number of neural networks have been proposed and implemented. However, no unsupervised neural networks with biologically accurate cochlear inputs have yet been demonstrated. This paper proposes a simple system in which pitch representing neurons are produced in a biologically plausible setting. Purely unsupervised regimes of neural network learning are implemented and these prove to be sufficient in identifying the pitch of sounds with a variety of spectral profiles, including sounds with missing fundamental frequencies and iterated rippled noises. PMID:27047368

Inference of time-delayed gene regulatory networks based on dynamic Bayesian network hybrid learning method

PubMed Central

Yu, Bin; Xu, Jia-Meng; Li, Shan; Chen, Cheng; Chen, Rui-Xin; Wang, Lei; Zhang, Yan; Wang, Ming-Hui

2017-01-01

Gene regulatory networks (GRNs) research reveals complex life phenomena from the perspective of gene interaction, which is an important research field in systems biology. Traditional Bayesian networks have a high computational complexity, and the network structure scoring model has a single feature. Information-based approaches cannot identify the direction of regulation. In order to make up for the shortcomings of the above methods, this paper presents a novel hybrid learning method (DBNCS) based on dynamic Bayesian network (DBN) to construct the multiple time-delayed GRNs for the first time, combining the comprehensive score (CS) with the DBN model. DBNCS algorithm first uses CMI2NI (conditional mutual inclusive information-based network inference) algorithm for network structure profiles learning, namely the construction of search space. Then the redundant regulations are removed by using the recursive optimization algorithm (RO), thereby reduce the false positive rate. Secondly, the network structure profiles are decomposed into a set of cliques without loss, which can significantly reduce the computational complexity. Finally, DBN model is used to identify the direction of gene regulation within the cliques and search for the optimal network structure. The performance of DBNCS algorithm is evaluated by the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in Escherichia coli, and compared with other state-of-the-art methods. The experimental results show the rationality of the algorithm design and the outstanding performance of the GRNs. PMID:29113310

Inference of time-delayed gene regulatory networks based on dynamic Bayesian network hybrid learning method.

PubMed

Yu, Bin; Xu, Jia-Meng; Li, Shan; Chen, Cheng; Chen, Rui-Xin; Wang, Lei; Zhang, Yan; Wang, Ming-Hui

2017-10-06

Gene regulatory networks (GRNs) research reveals complex life phenomena from the perspective of gene interaction, which is an important research field in systems biology. Traditional Bayesian networks have a high computational complexity, and the network structure scoring model has a single feature. Information-based approaches cannot identify the direction of regulation. In order to make up for the shortcomings of the above methods, this paper presents a novel hybrid learning method (DBNCS) based on dynamic Bayesian network (DBN) to construct the multiple time-delayed GRNs for the first time, combining the comprehensive score (CS) with the DBN model. DBNCS algorithm first uses CMI2NI (conditional mutual inclusive information-based network inference) algorithm for network structure profiles learning, namely the construction of search space. Then the redundant regulations are removed by using the recursive optimization algorithm (RO), thereby reduce the false positive rate. Secondly, the network structure profiles are decomposed into a set of cliques without loss, which can significantly reduce the computational complexity. Finally, DBN model is used to identify the direction of gene regulation within the cliques and search for the optimal network structure. The performance of DBNCS algorithm is evaluated by the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in Escherichia coli , and compared with other state-of-the-art methods. The experimental results show the rationality of the algorithm design and the outstanding performance of the GRNs.

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.

Neuro-symbolic representation learning on biological knowledge graphs.

PubMed

Alshahrani, Mona; Khan, Mohammad Asif; Maddouri, Omar; Kinjo, Akira R; Queralt-Rosinach, Núria; Hoehndorf, Robert

2017-09-01

Biological data and knowledge bases increasingly rely on Semantic Web technologies and the use of knowledge graphs for data integration, retrieval and federated queries. In the past years, feature learning methods that are applicable to graph-structured data are becoming available, but have not yet widely been applied and evaluated on structured biological knowledge. Results: We develop a novel method for feature learning on biological knowledge graphs. Our method combines symbolic methods, in particular knowledge representation using symbolic logic and automated reasoning, with neural networks to generate embeddings of nodes that encode for related information within knowledge graphs. Through the use of symbolic logic, these embeddings contain both explicit and implicit information. We apply these embeddings to the prediction of edges in the knowledge graph representing problems of function prediction, finding candidate genes of diseases, protein-protein interactions, or drug target relations, and demonstrate performance that matches and sometimes outperforms traditional approaches based on manually crafted features. Our method can be applied to any biological knowledge graph, and will thereby open up the increasing amount of Semantic Web based knowledge bases in biology to use in machine learning and data analytics. https://github.com/bio-ontology-research-group/walking-rdf-and-owl. robert.hoehndorf@kaust.edu.sa. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

The need to connect: on the cell biology of synapses, behaviors, and networks in science

PubMed Central

Colón-Ramos, Daniel A.

2016-01-01

My laboratory is interested in the cell biology of the synapse. Synapses, which are points of cellular communication between neurons, were first described by Santiago Ramón y Cajal as “protoplasmic kisses that appear to constitute the final ecstasy of an epic love story.” Who would not want to work on that?! My lab examines the biological mechanisms neurons use to find and connect to each other. How are synapses formed during development, maintained during growth, and modified during learning? In this essay, I reflect about my scientific journey to the synapse, the cell biological one, but also a metaphorical synapse—my role as a point of contact between the production of knowledge and its dissemination. In particular, I discuss how the architecture of scientific networks propels knowledge production but can also exclude certain groups in science. PMID:27799494

Efficient reinforcement learning of a reservoir network model of parametric working memory achieved with a cluster population winner-take-all readout mechanism.

PubMed

Cheng, Zhenbo; Deng, Zhidong; Hu, Xiaolin; Zhang, Bo; Yang, Tianming

2015-12-01

The brain often has to make decisions based on information stored in working memory, but the neural circuitry underlying working memory is not fully understood. Many theoretical efforts have been focused on modeling the persistent delay period activity in the prefrontal areas that is believed to represent working memory. Recent experiments reveal that the delay period activity in the prefrontal cortex is neither static nor homogeneous as previously assumed. Models based on reservoir networks have been proposed to model such a dynamical activity pattern. The connections between neurons within a reservoir are random and do not require explicit tuning. Information storage does not depend on the stable states of the network. However, it is not clear how the encoded information can be retrieved for decision making with a biologically realistic algorithm. We therefore built a reservoir-based neural network to model the neuronal responses of the prefrontal cortex in a somatosensory delayed discrimination task. We first illustrate that the neurons in the reservoir exhibit a heterogeneous and dynamical delay period activity observed in previous experiments. Then we show that a cluster population circuit decodes the information from the reservoir with a winner-take-all mechanism and contributes to the decision making. Finally, we show that the model achieves a good performance rapidly by shaping only the readout with reinforcement learning. Our model reproduces important features of previous behavior and neurophysiology data. We illustrate for the first time how task-specific information stored in a reservoir network can be retrieved with a biologically plausible reinforcement learning training scheme. Copyright © 2015 the American Physiological Society.

Synaptic State Matching: A Dynamical Architecture for Predictive Internal Representation and Feature Detection

PubMed Central

Tavazoie, Saeed

2013-01-01

Here we explore the possibility that a core function of sensory cortex is the generation of an internal simulation of sensory environment in real-time. A logical elaboration of this idea leads to a dynamical neural architecture that oscillates between two fundamental network states, one driven by external input, and the other by recurrent synaptic drive in the absence of sensory input. Synaptic strength is modified by a proposed synaptic state matching (SSM) process that ensures equivalence of spike statistics between the two network states. Remarkably, SSM, operating locally at individual synapses, generates accurate and stable network-level predictive internal representations, enabling pattern completion and unsupervised feature detection from noisy sensory input. SSM is a biologically plausible substrate for learning and memory because it brings together sequence learning, feature detection, synaptic homeostasis, and network oscillations under a single unifying computational framework. PMID:23991161

The graph neural network model.

PubMed

Scarselli, Franco; Gori, Marco; Tsoi, Ah Chung; Hagenbuchner, Markus; Monfardini, Gabriele

2009-01-01

Many underlying relationships among data in several areas of science and engineering, e.g., computer vision, molecular chemistry, molecular biology, pattern recognition, and data mining, can be represented in terms of graphs. In this paper, we propose a new neural network model, called graph neural network (GNN) model, that extends existing neural network methods for processing the data represented in graph domains. This GNN model, which can directly process most of the practically useful types of graphs, e.g., acyclic, cyclic, directed, and undirected, implements a function tau(G,n) is an element of IR(m) that maps a graph G and one of its nodes n into an m-dimensional Euclidean space. A supervised learning algorithm is derived to estimate the parameters of the proposed GNN model. The computational cost of the proposed algorithm is also considered. Some experimental results are shown to validate the proposed learning algorithm, and to demonstrate its generalization capabilities.

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

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Opportunities and obstacles for deep learning in biology and medicine.

PubMed

Ching, Travers; Himmelstein, Daniel S; Beaulieu-Jones, Brett K; Kalinin, Alexandr A; Do, Brian T; Way, Gregory P; Ferrero, Enrico; Agapow, Paul-Michael; Zietz, Michael; Hoffman, Michael M; Xie, Wei; Rosen, Gail L; Lengerich, Benjamin J; Israeli, Johnny; Lanchantin, Jack; Woloszynek, Stephen; Carpenter, Anne E; Shrikumar, Avanti; Xu, Jinbo; Cofer, Evan M; Lavender, Christopher A; Turaga, Srinivas C; Alexandari, Amr M; Lu, Zhiyong; Harris, David J; DeCaprio, Dave; Qi, Yanjun; Kundaje, Anshul; Peng, Yifan; Wiley, Laura K; Segler, Marwin H S; Boca, Simina M; Swamidass, S Joshua; Huang, Austin; Gitter, Anthony; Greene, Casey S

2018-04-01

Deep learning describes a class of machine learning algorithms that are capable of combining raw inputs into layers of intermediate features. These algorithms have recently shown impressive results across a variety of domains. Biology and medicine are data-rich disciplines, but the data are complex and often ill-understood. Hence, deep learning techniques may be particularly well suited to solve problems of these fields. We examine applications of deep learning to a variety of biomedical problems-patient classification, fundamental biological processes and treatment of patients-and discuss whether deep learning will be able to transform these tasks or if the biomedical sphere poses unique challenges. Following from an extensive literature review, we find that deep learning has yet to revolutionize biomedicine or definitively resolve any of the most pressing challenges in the field, but promising advances have been made on the prior state of the art. Even though improvements over previous baselines have been modest in general, the recent progress indicates that deep learning methods will provide valuable means for speeding up or aiding human investigation. Though progress has been made linking a specific neural network's prediction to input features, understanding how users should interpret these models to make testable hypotheses about the system under study remains an open challenge. Furthermore, the limited amount of labelled data for training presents problems in some domains, as do legal and privacy constraints on work with sensitive health records. Nonetheless, we foresee deep learning enabling changes at both bench and bedside with the potential to transform several areas of biology and medicine. © 2018 The Authors.

Opportunities and obstacles for deep learning in biology and medicine

PubMed Central

2018-01-01

Deep learning describes a class of machine learning algorithms that are capable of combining raw inputs into layers of intermediate features. These algorithms have recently shown impressive results across a variety of domains. Biology and medicine are data-rich disciplines, but the data are complex and often ill-understood. Hence, deep learning techniques may be particularly well suited to solve problems of these fields. We examine applications of deep learning to a variety of biomedical problems—patient classification, fundamental biological processes and treatment of patients—and discuss whether deep learning will be able to transform these tasks or if the biomedical sphere poses unique challenges. Following from an extensive literature review, we find that deep learning has yet to revolutionize biomedicine or definitively resolve any of the most pressing challenges in the field, but promising advances have been made on the prior state of the art. Even though improvements over previous baselines have been modest in general, the recent progress indicates that deep learning methods will provide valuable means for speeding up or aiding human investigation. Though progress has been made linking a specific neural network's prediction to input features, understanding how users should interpret these models to make testable hypotheses about the system under study remains an open challenge. Furthermore, the limited amount of labelled data for training presents problems in some domains, as do legal and privacy constraints on work with sensitive health records. Nonetheless, we foresee deep learning enabling changes at both bench and bedside with the potential to transform several areas of biology and medicine. PMID:29618526

An Approximation of the Error Backpropagation Algorithm in a Predictive Coding Network with Local Hebbian Synaptic Plasticity

PubMed Central

Whittington, James C. R.; Bogacz, Rafal

2017-01-01

To efficiently learn from feedback, cortical networks need to update synaptic weights on multiple levels of cortical hierarchy. An effective and well-known algorithm for computing such changes in synaptic weights is the error backpropagation algorithm. However, in this algorithm, the change in synaptic weights is a complex function of weights and activities of neurons not directly connected with the synapse being modified, whereas the changes in biological synapses are determined only by the activity of presynaptic and postsynaptic neurons. Several models have been proposed that approximate the backpropagation algorithm with local synaptic plasticity, but these models require complex external control over the network or relatively complex plasticity rules. Here we show that a network developed in the predictive coding framework can efficiently perform supervised learning fully autonomously, employing only simple local Hebbian plasticity. Furthermore, for certain parameters, the weight change in the predictive coding model converges to that of the backpropagation algorithm. This suggests that it is possible for cortical networks with simple Hebbian synaptic plasticity to implement efficient learning algorithms in which synapses in areas on multiple levels of hierarchy are modified to minimize the error on the output. PMID:28333583

An Approximation of the Error Backpropagation Algorithm in a Predictive Coding Network with Local Hebbian Synaptic Plasticity.

PubMed

Whittington, James C R; Bogacz, Rafal

2017-05-01

To efficiently learn from feedback, cortical networks need to update synaptic weights on multiple levels of cortical hierarchy. An effective and well-known algorithm for computing such changes in synaptic weights is the error backpropagation algorithm. However, in this algorithm, the change in synaptic weights is a complex function of weights and activities of neurons not directly connected with the synapse being modified, whereas the changes in biological synapses are determined only by the activity of presynaptic and postsynaptic neurons. Several models have been proposed that approximate the backpropagation algorithm with local synaptic plasticity, but these models require complex external control over the network or relatively complex plasticity rules. Here we show that a network developed in the predictive coding framework can efficiently perform supervised learning fully autonomously, employing only simple local Hebbian plasticity. Furthermore, for certain parameters, the weight change in the predictive coding model converges to that of the backpropagation algorithm. This suggests that it is possible for cortical networks with simple Hebbian synaptic plasticity to implement efficient learning algorithms in which synapses in areas on multiple levels of hierarchy are modified to minimize the error on the output.

Understanding Classrooms through Social Network Analysis: A Primer for Social Network Analysis in Education Research

PubMed Central

Wiggins, Benjamin L.; Goodreau, Steven M.

2014-01-01

Social interactions between students are a major and underexplored part of undergraduate education. Understanding how learning relationships form in undergraduate classrooms, as well as the impacts these relationships have on learning outcomes, can inform educators in unique ways and improve educational reform. Social network analysis (SNA) provides the necessary tool kit for investigating questions involving relational data. We introduce basic concepts in SNA, along with methods for data collection, data processing, and data analysis, using a previously collected example study on an undergraduate biology classroom as a tutorial. We conduct descriptive analyses of the structure of the network of costudying relationships. We explore generative processes that create observed study networks between students and also test for an association between network position and success on exams. We also cover practical issues, such as the unique aspects of human subjects review for network studies. Our aims are to convince readers that using SNA in classroom environments allows rich and informative analyses to take place and to provide some initial tools for doing so, in the process inspiring future educational studies incorporating relational data. PMID:26086650

Real-time cerebellar neuroprosthetic system based on a spiking neural network model of motor learning

NASA Astrophysics Data System (ADS)

Xu, Tao; Xiao, Na; Zhai, Xiaolong; Chan, Pak Kwan; Tin, Chung

2018-02-01

Objective. Damage to the brain, as a result of various medical conditions, impacts the everyday life of patients and there is still no complete cure to neurological disorders. Neuroprostheses that can functionally replace the damaged neural circuit have recently emerged as a possible solution to these problems. Here we describe the development of a real-time cerebellar neuroprosthetic system to substitute neural function in cerebellar circuitry for learning delay eyeblink conditioning (DEC). Approach. The system was empowered by a biologically realistic spiking neural network (SNN) model of the cerebellar neural circuit, which considers the neuronal population and anatomical connectivity of the network. The model simulated synaptic plasticity critical for learning DEC. This SNN model was carefully implemented on a field programmable gate array (FPGA) platform for real-time simulation. This hardware system was interfaced in in vivo experiments with anesthetized rats and it used neural spikes recorded online from the animal to learn and trigger conditioned eyeblink in the animal during training. Main results. This rat-FPGA hybrid system was able to process neuronal spikes in real-time with an embedded cerebellum model of ~10 000 neurons and reproduce learning of DEC with different inter-stimulus intervals. Our results validated that the system performance is physiologically relevant at both the neural (firing pattern) and behavioral (eyeblink pattern) levels. Significance. This integrated system provides the sufficient computation power for mimicking the cerebellar circuit in real-time. The system interacts with the biological system naturally at the spike level and can be generalized for including other neural components (neuron types and plasticity) and neural functions for potential neuroprosthetic applications.

Criticality meets learning: Criticality signatures in a self-organizing recurrent neural network

PubMed Central

Del Papa, Bruno; Priesemann, Viola

2017-01-01

Many experiments have suggested that the brain operates close to a critical state, based on signatures of criticality such as power-law distributed neuronal avalanches. In neural network models, criticality is a dynamical state that maximizes information processing capacities, e.g. sensitivity to input, dynamical range and storage capacity, which makes it a favorable candidate state for brain function. Although models that self-organize towards a critical state have been proposed, the relation between criticality signatures and learning is still unclear. Here, we investigate signatures of criticality in a self-organizing recurrent neural network (SORN). Investigating criticality in the SORN is of particular interest because it has not been developed to show criticality. Instead, the SORN has been shown to exhibit spatio-temporal pattern learning through a combination of neural plasticity mechanisms and it reproduces a number of biological findings on neural variability and the statistics and fluctuations of synaptic efficacies. We show that, after a transient, the SORN spontaneously self-organizes into a dynamical state that shows criticality signatures comparable to those found in experiments. The plasticity mechanisms are necessary to attain that dynamical state, but not to maintain it. Furthermore, onset of external input transiently changes the slope of the avalanche distributions – matching recent experimental findings. Interestingly, the membrane noise level necessary for the occurrence of the criticality signatures reduces the model’s performance in simple learning tasks. Overall, our work shows that the biologically inspired plasticity and homeostasis mechanisms responsible for the SORN’s spatio-temporal learning abilities can give rise to criticality signatures in its activity when driven by random input, but these break down under the structured input of short repeating sequences. PMID:28552964

Sequence-specific bias correction for RNA-seq data using recurrent neural networks.

PubMed

Zhang, Yao-Zhong; Yamaguchi, Rui; Imoto, Seiya; Miyano, Satoru

2017-01-25

The recent success of deep learning techniques in machine learning and artificial intelligence has stimulated a great deal of interest among bioinformaticians, who now wish to bring the power of deep learning to bare on a host of bioinformatical problems. Deep learning is ideally suited for biological problems that require automatic or hierarchical feature representation for biological data when prior knowledge is limited. In this work, we address the sequence-specific bias correction problem for RNA-seq data redusing Recurrent Neural Networks (RNNs) to model nucleotide sequences without pre-determining sequence structures. The sequence-specific bias of a read is then calculated based on the sequence probabilities estimated by RNNs, and used in the estimation of gene abundance. We explore the application of two popular RNN recurrent units for this task and demonstrate that RNN-based approaches provide a flexible way to model nucleotide sequences without knowledge of predetermined sequence structures. Our experiments show that training a RNN-based nucleotide sequence model is efficient and RNN-based bias correction methods compare well with the-state-of-the-art sequence-specific bias correction method on the commonly used MAQC-III data set. RNNs provides an alternative and flexible way to calculate sequence-specific bias without explicitly pre-determining sequence structures.

Path integration of head direction: updating a packet of neural activity at the correct speed using neuronal time constants.

PubMed

Walters, D M; Stringer, S M

2010-07-01

A key question in understanding the neural basis of path integration is how individual, spatially responsive, neurons may self-organize into networks that can, through learning, integrate velocity signals to update a continuous representation of location within an environment. It is of vital importance that this internal representation of position is updated at the correct speed, and in real time, to accurately reflect the motion of the animal. In this article, we present a biologically plausible model of velocity path integration of head direction that can solve this problem using neuronal time constants to effect natural time delays, over which associations can be learned through associative Hebbian learning rules. The model comprises a linked continuous attractor network and competitive network. In simulation, we show that the same model is able to learn two different speeds of rotation when implemented with two different values for the time constant, and without the need to alter any other model parameters. The proposed model could be extended to path integration of place in the environment, and path integration of spatial view.

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

DOE PAGES

Banf, Michael; Rhee, Seung Y.

2017-02-01

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

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

The Brain as an Efficient and Robust Adaptive Learner.

PubMed

Denève, Sophie; Alemi, Alireza; Bourdoukan, Ralph

2017-06-07

Understanding how the brain learns to compute functions reliably, efficiently, and robustly with noisy spiking activity is a fundamental challenge in neuroscience. Most sensory and motor tasks can be described as dynamical systems and could presumably be learned by adjusting connection weights in a recurrent biological neural network. However, this is greatly complicated by the credit assignment problem for learning in recurrent networks, e.g., the contribution of each connection to the global output error cannot be determined based only on locally accessible quantities to the synapse. Combining tools from adaptive control theory and efficient coding theories, we propose that neural circuits can indeed learn complex dynamic tasks with local synaptic plasticity rules as long as they associate two experimentally established neural mechanisms. First, they should receive top-down feedbacks driving both their activity and their synaptic plasticity. Second, inhibitory interneurons should maintain a tight balance between excitation and inhibition in the circuit. The resulting networks could learn arbitrary dynamical systems and produce irregular spike trains as variable as those observed experimentally. Yet, this variability in single neurons may hide an extremely efficient and robust computation at the population level. Copyright © 2017 Elsevier Inc. All rights reserved.

Learning contextual gene set interaction networks of cancer with condition specificity

PubMed Central

2013-01-01

Background Identifying similarities and differences in the molecular constitutions of various types of cancer is one of the key challenges in cancer research. The appearances of a cancer depend on complex molecular interactions, including gene regulatory networks and gene-environment interactions. This complexity makes it challenging to decipher the molecular origin of the cancer. In recent years, many studies reported methods to uncover heterogeneous depictions of complex cancers, which are often categorized into different subtypes. The challenge is to identify diverse molecular contexts within a cancer, to relate them to different subtypes, and to learn underlying molecular interactions specific to molecular contexts so that we can recommend context-specific treatment to patients. Results In this study, we describe a novel method to discern molecular interactions specific to certain molecular contexts. Unlike conventional approaches to build modular networks of individual genes, our focus is to identify cancer-generic and subtype-specific interactions between contextual gene sets, of which each gene set share coherent transcriptional patterns across a subset of samples, termed contextual gene set. We then apply a novel formulation for quantitating the effect of the samples from each subtype on the calculated strength of interactions observed. Two cancer data sets were analyzed to support the validity of condition-specificity of identified interactions. When compared to an existing approach, the proposed method was much more sensitive in identifying condition-specific interactions even in heterogeneous data set. The results also revealed that network components specific to different types of cancer are related to different biological functions than cancer-generic network components. We found not only the results that are consistent with previous studies, but also new hypotheses on the biological mechanisms specific to certain cancer types that warrant further investigations. Conclusions The analysis on the contextual gene sets and characterization of networks of interaction composed of these sets discovered distinct functional differences underlying various types of cancer. The results show that our method successfully reveals many subtype-specific regions in the identified maps of biological contexts, which well represent biological functions that can be connected to specific subtypes. PMID:23418942

Machine learning approaches to the social determinants of health in the health and retirement study.

PubMed

Seligman, Benjamin; Tuljapurkar, Shripad; Rehkopf, David

2018-04-01

Social and economic factors are important predictors of health and of recognized importance for health systems. However, machine learning, used elsewhere in the biomedical literature, has not been extensively applied to study relationships between society and health. We investigate how machine learning may add to our understanding of social determinants of health using data from the Health and Retirement Study. A linear regression of age and gender, and a parsimonious theory-based regression additionally incorporating income, wealth, and education, were used to predict systolic blood pressure, body mass index, waist circumference, and telomere length. Prediction, fit, and interpretability were compared across four machine learning methods: linear regression, penalized regressions, random forests, and neural networks. All models had poor out-of-sample prediction. Most machine learning models performed similarly to the simpler models. However, neural networks greatly outperformed the three other methods. Neural networks also had good fit to the data ( R 2 between 0.4-0.6, versus <0.3 for all others). Across machine learning models, nine variables were frequently selected or highly weighted as predictors: dental visits, current smoking, self-rated health, serial-seven subtractions, probability of receiving an inheritance, probability of leaving an inheritance of at least $10,000, number of children ever born, African-American race, and gender. Some of the machine learning methods do not improve prediction or fit beyond simpler models, however, neural networks performed well. The predictors identified across models suggest underlying social factors that are important predictors of biological indicators of chronic disease, and that the non-linear and interactive relationships between variables fundamental to the neural network approach may be important to consider.

Anticipatory Cognitive Systems: a Theoretical Model

NASA Astrophysics Data System (ADS)

Terenzi, Graziano

This paper deals with the problem of understanding anticipation in biological and cognitive systems. It is argued that a physical theory can be considered as biologically plausible only if it incorporates the ability to describe systems which exhibit anticipatory behaviors. The paper introduces a cognitive level description of anticipation and provides a simple theoretical characterization of anticipatory systems on this level. Specifically, a simple model of a formal anticipatory neuron and a model (i.e. the τ-mirror architecture) of an anticipatory neural network which is based on the former are introduced and discussed. The basic feature of this architecture is that a part of the network learns to represent the behavior of the other part over time, thus constructing an implicit model of its own functioning. As a consequence, the network is capable of self-representation; anticipation, on a oscopic level, is nothing but a consequence of anticipation on a microscopic level. Some learning algorithms are also discussed together with related experimental tasks and possible integrations. The outcome of the paper is a formal characterization of anticipation in cognitive systems which aims at being incorporated in a comprehensive and more general physical theory.

Relation extraction for biological pathway construction using node2vec.

PubMed

Kim, Munui; Baek, Seung Han; Song, Min

2018-06-13

Systems biology is an important field for understanding whole biological mechanisms composed of interactions between biological components. One approach for understanding complex and diverse mechanisms is to analyze biological pathways. However, because these pathways consist of important interactions and information on these interactions is disseminated in a large number of biomedical reports, text-mining techniques are essential for extracting these relationships automatically. In this study, we applied node2vec, an algorithmic framework for feature learning in networks, for relationship extraction. To this end, we extracted genes from paper abstracts using pkde4j, a text-mining tool for detecting entities and relationships. Using the extracted genes, a co-occurrence network was constructed and node2vec was used with the network to generate a latent representation. To demonstrate the efficacy of node2vec in extracting relationships between genes, performance was evaluated for gene-gene interactions involved in a type 2 diabetes pathway. Moreover, we compared the results of node2vec to those of baseline methods such as co-occurrence and DeepWalk. Node2vec outperformed existing methods in detecting relationships in the type 2 diabetes pathway, demonstrating that this method is appropriate for capturing the relatedness between pairs of biological entities involved in biological pathways. The results demonstrated that node2vec is useful for automatic pathway construction.

Collaborative filtering on a family of biological targets.

PubMed

Erhan, Dumitru; L'heureux, Pierre-Jean; Yue, Shi Yi; Bengio, Yoshua

2006-01-01

Building a QSAR model of a new biological target for which few screening data are available is a statistical challenge. However, the new target may be part of a bigger family, for which we have more screening data. Collaborative filtering or, more generally, multi-task learning, is a machine learning approach that improves the generalization performance of an algorithm by using information from related tasks as an inductive bias. We use collaborative filtering techniques for building predictive models that link multiple targets to multiple examples. The more commonalities between the targets, the better the multi-target model that can be built. We show an example of a multi-target neural network that can use family information to produce a predictive model of an undersampled target. We evaluate JRank, a kernel-based method designed for collaborative filtering. We show their performance on compound prioritization for an HTS campaign and the underlying shared representation between targets. JRank outperformed the neural network both in the single- and multi-target models.

Clustering Single-Cell Expression Data Using Random Forest Graphs.

PubMed

Pouyan, Maziyar Baran; Nourani, Mehrdad

2017-07-01

Complex tissues such as brain and bone marrow are made up of multiple cell types. As the study of biological tissue structure progresses, the role of cell-type-specific research becomes increasingly important. Novel sequencing technology such as single-cell cytometry provides researchers access to valuable biological data. Applying machine-learning techniques to these high-throughput datasets provides deep insights into the cellular landscape of the tissue where those cells are a part of. In this paper, we propose the use of random-forest-based single-cell profiling, a new machine-learning-based technique, to profile different cell types of intricate tissues using single-cell cytometry data. Our technique utilizes random forests to capture cell marker dependences and model the cellular populations using the cell network concept. This cellular network helps us discover what cell types are in the tissue. Our experimental results on public-domain datasets indicate promising performance and accuracy of our technique in extracting cell populations of complex tissues.

A reconfigurable on-line learning spiking neuromorphic processor comprising 256 neurons and 128K synapses.

PubMed

Qiao, Ning; Mostafa, Hesham; Corradi, Federico; Osswald, Marc; Stefanini, Fabio; Sumislawska, Dora; Indiveri, Giacomo

2015-01-01

Implementing compact, low-power artificial neural processing systems with real-time on-line learning abilities is still an open challenge. In this paper we present a full-custom mixed-signal VLSI device with neuromorphic learning circuits that emulate the biophysics of real spiking neurons and dynamic synapses for exploring the properties of computational neuroscience models and for building brain-inspired computing systems. The proposed architecture allows the on-chip configuration of a wide range of network connectivities, including recurrent and deep networks, with short-term and long-term plasticity. The device comprises 128 K analog synapse and 256 neuron circuits with biologically plausible dynamics and bi-stable spike-based plasticity mechanisms that endow it with on-line learning abilities. In addition to the analog circuits, the device comprises also asynchronous digital logic circuits for setting different synapse and neuron properties as well as different network configurations. This prototype device, fabricated using a 180 nm 1P6M CMOS process, occupies an area of 51.4 mm(2), and consumes approximately 4 mW for typical experiments, for example involving attractor networks. Here we describe the details of the overall architecture and of the individual circuits and present experimental results that showcase its potential. By supporting a wide range of cortical-like computational modules comprising plasticity mechanisms, this device will enable the realization of intelligent autonomous systems with on-line learning capabilities.

The application of the multi-alternative approach in active neural network models

NASA Astrophysics Data System (ADS)

Podvalny, S.; Vasiljev, E.

2017-02-01

The article refers to the construction of intelligent systems based artificial neuron networks are used. We discuss the basic properties of the non-compliance of artificial neuron networks and their biological prototypes. It is shown here that the main reason for these discrepancies is the structural immutability of the neuron network models in the learning process, that is, their passivity. Based on the modern understanding of the biological nervous system as a structured ensemble of nerve cells, it is proposed to abandon the attempts to simulate its work at the level of the elementary neurons functioning processes and proceed to the reproduction of the information structure of data storage and processing on the basis of the general enough evolutionary principles of multialternativity, i.e. the multi-level structural model, diversity and modularity. The implementation method of these principles is offered, using the faceted memory organization in the neuron network with the rearranging active structure. An example of the implementation of the active facet-type neuron network in the intellectual decision-making system in the conditions of critical events development in the electrical distribution system.

Machine Learning-Assisted Network Inference Approach to Identify a New Class of Genes that Coordinate the Functionality of Cancer Networks.

PubMed

Ghanat Bari, Mehrab; Ung, Choong Yong; Zhang, Cheng; Zhu, Shizhen; Li, Hu

2017-08-01

Emerging evidence indicates the existence of a new class of cancer genes that act as "signal linkers" coordinating oncogenic signals between mutated and differentially expressed genes. While frequently mutated oncogenes and differentially expressed genes, which we term Class I cancer genes, are readily detected by most analytical tools, the new class of cancer-related genes, i.e., Class II, escape detection because they are neither mutated nor differentially expressed. Given this hypothesis, we developed a Machine Learning-Assisted Network Inference (MALANI) algorithm, which assesses all genes regardless of expression or mutational status in the context of cancer etiology. We used 8807 expression arrays, corresponding to 9 cancer types, to build more than 2 × 10 8 Support Vector Machine (SVM) models for reconstructing a cancer network. We found that ~3% of ~19,000 not differentially expressed genes are Class II cancer gene candidates. Some Class II genes that we found, such as SLC19A1 and ATAD3B, have been recently reported to associate with cancer outcomes. To our knowledge, this is the first study that utilizes both machine learning and network biology approaches to uncover Class II cancer genes in coordinating functionality in cancer networks and will illuminate our understanding of how genes are modulated in a tissue-specific network contribute to tumorigenesis and therapy development.

The Role of Multiple Neuromodulators in Reinforcement Learning That Is Based on Competition between Eligibility Traces.

PubMed

Huertas, Marco A; Schwettmann, Sarah E; Shouval, Harel Z

2016-01-01

The ability to maximize reward and avoid punishment is essential for animal survival. Reinforcement learning (RL) refers to the algorithms used by biological or artificial systems to learn how to maximize reward or avoid negative outcomes based on past experiences. While RL is also important in machine learning, the types of mechanistic constraints encountered by biological machinery might be different than those for artificial systems. Two major problems encountered by RL are how to relate a stimulus with a reinforcing signal that is delayed in time (temporal credit assignment), and how to stop learning once the target behaviors are attained (stopping rule). To address the first problem synaptic eligibility traces were introduced, bridging the temporal gap between a stimulus and its reward. Although, these were mere theoretical constructs, recent experiments have provided evidence of their existence. These experiments also reveal that the presence of specific neuromodulators converts the traces into changes in synaptic efficacy. A mechanistic implementation of the stopping rule usually assumes the inhibition of the reward nucleus; however, recent experimental results have shown that learning terminates at the appropriate network state even in setups where the reward nucleus cannot be inhibited. In an effort to describe a learning rule that solves the temporal credit assignment problem and implements a biologically plausible stopping rule, we proposed a model based on two separate synaptic eligibility traces, one for long-term potentiation (LTP) and one for long-term depression (LTD), each obeying different dynamics and having different effective magnitudes. The model has been shown to successfully generate stable learning in recurrent networks. Although, the model assumes the presence of a single neuromodulator, evidence indicates that there are different neuromodulators for expressing the different traces. What could be the role of different neuromodulators for expressing the LTP and LTD traces? Here we expand on our previous model to include several neuromodulators, and illustrate through various examples how different these contribute to learning reward-timing within a wide set of training paradigms and propose further roles that multiple neuromodulators can play in encoding additional information of the rewarding signal.

Exploring information transmission in gene networks using stochastic simulation and machine learning

NASA Astrophysics Data System (ADS)

Park, Kyemyung; Prüstel, Thorsten; Lu, Yong; Narayanan, Manikandan; Martins, Andrew; Tsang, John

How gene regulatory networks operate robustly despite environmental fluctuations and biochemical noise is a fundamental question in biology. Mathematically the stochastic dynamics of a gene regulatory network can be modeled using chemical master equation (CME), but nonlinearity and other challenges render analytical solutions of CMEs difficult to attain. While approaches of approximation and stochastic simulation have been devised for simple models, obtaining a more global picture of a system's behaviors in high-dimensional parameter space without simplifying the system substantially remains a major challenge. Here we present a new framework for understanding and predicting the behaviors of gene regulatory networks in the context of information transmission among genes. Our approach uses stochastic simulation of the network followed by machine learning of the mapping between model parameters and network phenotypes such as information transmission behavior. We also devised ways to visualize high-dimensional phase spaces in intuitive and informative manners. We applied our approach to several gene regulatory circuit motifs, including both feedback and feedforward loops, to reveal underexplored aspects of their operational behaviors. This work is supported by the Intramural Program of NIAID/NIH.

The BEL information extraction workflow (BELIEF): evaluation in the BioCreative V BEL and IAT track

PubMed Central

Madan, Sumit; Hodapp, Sven; Senger, Philipp; Ansari, Sam; Szostak, Justyna; Hoeng, Julia; Peitsch, Manuel; Fluck, Juliane

2016-01-01

Network-based approaches have become extremely important in systems biology to achieve a better understanding of biological mechanisms. For network representation, the Biological Expression Language (BEL) is well designed to collate findings from the scientific literature into biological network models. To facilitate encoding and biocuration of such findings in BEL, a BEL Information Extraction Workflow (BELIEF) was developed. BELIEF provides a web-based curation interface, the BELIEF Dashboard, that incorporates text mining techniques to support the biocurator in the generation of BEL networks. The underlying UIMA-based text mining pipeline (BELIEF Pipeline) uses several named entity recognition processes and relationship extraction methods to detect concepts and BEL relationships in literature. The BELIEF Dashboard allows easy curation of the automatically generated BEL statements and their context annotations. Resulting BEL statements and their context annotations can be syntactically and semantically verified to ensure consistency in the BEL network. In summary, the workflow supports experts in different stages of systems biology network building. Based on the BioCreative V BEL track evaluation, we show that the BELIEF Pipeline automatically extracts relationships with an F-score of 36.4% and fully correct statements can be obtained with an F-score of 30.8%. Participation in the BioCreative V Interactive task (IAT) track with BELIEF revealed a systems usability scale (SUS) of 67. Considering the complexity of the task for new users—learning BEL, working with a completely new interface, and performing complex curation—a score so close to the overall SUS average highlights the usability of BELIEF. Database URL: BELIEF is available at http://www.scaiview.com/belief/ PMID:27694210

The BEL information extraction workflow (BELIEF): evaluation in the BioCreative V BEL and IAT track.

PubMed

Madan, Sumit; Hodapp, Sven; Senger, Philipp; Ansari, Sam; Szostak, Justyna; Hoeng, Julia; Peitsch, Manuel; Fluck, Juliane

2016-01-01

Network-based approaches have become extremely important in systems biology to achieve a better understanding of biological mechanisms. For network representation, the Biological Expression Language (BEL) is well designed to collate findings from the scientific literature into biological network models. To facilitate encoding and biocuration of such findings in BEL, a BEL Information Extraction Workflow (BELIEF) was developed. BELIEF provides a web-based curation interface, the BELIEF Dashboard, that incorporates text mining techniques to support the biocurator in the generation of BEL networks. The underlying UIMA-based text mining pipeline (BELIEF Pipeline) uses several named entity recognition processes and relationship extraction methods to detect concepts and BEL relationships in literature. The BELIEF Dashboard allows easy curation of the automatically generated BEL statements and their context annotations. Resulting BEL statements and their context annotations can be syntactically and semantically verified to ensure consistency in the BEL network. In summary, the workflow supports experts in different stages of systems biology network building. Based on the BioCreative V BEL track evaluation, we show that the BELIEF Pipeline automatically extracts relationships with an F-score of 36.4% and fully correct statements can be obtained with an F-score of 30.8%. Participation in the BioCreative V Interactive task (IAT) track with BELIEF revealed a systems usability scale (SUS) of 67. Considering the complexity of the task for new users-learning BEL, working with a completely new interface, and performing complex curation-a score so close to the overall SUS average highlights the usability of BELIEF.Database URL: BELIEF is available at http://www.scaiview.com/belief/. © The Author(s) 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Building machines that learn and think like people.

PubMed

Lake, Brenden M; Ullman, Tomer D; Tenenbaum, Joshua B; Gershman, Samuel J

2017-01-01

Recent progress in artificial intelligence has renewed interest in building systems that learn and think like people. Many advances have come from using deep neural networks trained end-to-end in tasks such as object recognition, video games, and board games, achieving performance that equals or even beats that of humans in some respects. Despite their biological inspiration and performance achievements, these systems differ from human intelligence in crucial ways. We review progress in cognitive science suggesting that truly human-like learning and thinking machines will have to reach beyond current engineering trends in both what they learn and how they learn it. Specifically, we argue that these machines should (1) build causal models of the world that support explanation and understanding, rather than merely solving pattern recognition problems; (2) ground learning in intuitive theories of physics and psychology to support and enrich the knowledge that is learned; and (3) harness compositionality and learning-to-learn to rapidly acquire and generalize knowledge to new tasks and situations. We suggest concrete challenges and promising routes toward these goals that can combine the strengths of recent neural network advances with more structured cognitive models.

A biological network-based regularized artificial neural network model for robust phenotype prediction from gene expression data.

PubMed

Kang, Tianyu; Ding, Wei; Zhang, Luoyan; Ziemek, Daniel; Zarringhalam, Kourosh

2017-12-19

Stratification of patient subpopulations that respond favorably to treatment or experience and adverse reaction is an essential step toward development of new personalized therapies and diagnostics. It is currently feasible to generate omic-scale biological measurements for all patients in a study, providing an opportunity for machine learning models to identify molecular markers for disease diagnosis and progression. However, the high variability of genetic background in human populations hampers the reproducibility of omic-scale markers. In this paper, we develop a biological network-based regularized artificial neural network model for prediction of phenotype from transcriptomic measurements in clinical trials. To improve model sparsity and the overall reproducibility of the model, we incorporate regularization for simultaneous shrinkage of gene sets based on active upstream regulatory mechanisms into the model. We benchmark our method against various regression, support vector machines and artificial neural network models and demonstrate the ability of our method in predicting the clinical outcomes using clinical trial data on acute rejection in kidney transplantation and response to Infliximab in ulcerative colitis. We show that integration of prior biological knowledge into the classification as developed in this paper, significantly improves the robustness and generalizability of predictions to independent datasets. We provide a Java code of our algorithm along with a parsed version of the STRING DB database. In summary, we present a method for prediction of clinical phenotypes using baseline genome-wide expression data that makes use of prior biological knowledge on gene-regulatory interactions in order to increase robustness and reproducibility of omic-scale markers. The integrated group-wise regularization methods increases the interpretability of biological signatures and gives stable performance estimates across independent test sets.

Neuronal avalanches and learning

NASA Astrophysics Data System (ADS)

de Arcangelis, Lucilla

2011-05-01

Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

A Digital Liquid State Machine With Biologically Inspired Learning and Its Application to Speech Recognition.

PubMed

Zhang, Yong; Li, Peng; Jin, Yingyezhe; Choe, Yoonsuck

2015-11-01

This paper presents a bioinspired digital liquid-state machine (LSM) for low-power very-large-scale-integration (VLSI)-based machine learning applications. To the best of the authors' knowledge, this is the first work that employs a bioinspired spike-based learning algorithm for the LSM. With the proposed online learning, the LSM extracts information from input patterns on the fly without needing intermediate data storage as required in offline learning methods such as ridge regression. The proposed learning rule is local such that each synaptic weight update is based only upon the firing activities of the corresponding presynaptic and postsynaptic neurons without incurring global communications across the neural network. Compared with the backpropagation-based learning, the locality of computation in the proposed approach lends itself to efficient parallel VLSI implementation. We use subsets of the TI46 speech corpus to benchmark the bioinspired digital LSM. To reduce the complexity of the spiking neural network model without performance degradation for speech recognition, we study the impacts of synaptic models on the fading memory of the reservoir and hence the network performance. Moreover, we examine the tradeoffs between synaptic weight resolution, reservoir size, and recognition performance and present techniques to further reduce the overhead of hardware implementation. Our simulation results show that in terms of isolated word recognition evaluated using the TI46 speech corpus, the proposed digital LSM rivals the state-of-the-art hidden Markov-model-based recognizer Sphinx-4 and outperforms all other reported recognizers including the ones that are based upon the LSM or neural networks.

The neural representation of the gender of faces in the primate visual system: A computer modeling study.

PubMed

Minot, Thomas; Dury, Hannah L; Eguchi, Akihiro; Humphreys, Glyn W; Stringer, Simon M

2017-03-01

We use an established neural network model of the primate visual system to show how neurons might learn to encode the gender of faces. The model consists of a hierarchy of 4 competitive neuronal layers with associatively modifiable feedforward synaptic connections between successive layers. During training, the network was presented with many realistic images of male and female faces, during which the synaptic connections are modified using biologically plausible local associative learning rules. After training, we found that different subsets of output neurons have learned to respond exclusively to either male or female faces. With the inclusion of short range excitation within each neuronal layer to implement a self-organizing map architecture, neurons representing either male or female faces were clustered together in the output layer. This learning process is entirely unsupervised, as the gender of the face images is not explicitly labeled and provided to the network as a supervisory training signal. These simulations are extended to training the network on rotating faces. It is found that by using a trace learning rule incorporating a temporal memory trace of recent neuronal activity, neurons responding selectively to either male or female faces were also able to learn to respond invariantly over different views of the faces. This kind of trace learning has been previously shown to operate within the primate visual system by neurophysiological and psychophysical studies. The computer simulations described here predict that similar neurons encoding the gender of faces will be present within the primate visual system. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Convolutional neural network architectures for predicting DNA–protein binding

PubMed Central

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

2016-01-01

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

Professional development strategies for teaching urban biology teachers to use concept maps effectively

NASA Astrophysics Data System (ADS)

McGregor Petgrave, Dahlia M.

Many teachers are not adequately prepared to help urban students who have trouble understanding conceptual ideas in biology because these students have little connection to the natural world. This study explored potential professional development strategies to help urban biology teachers use concept maps effectively with various topics in the biology curriculum. A grounded theory approach was used to develop a substantive professional development model for urban biology teachers. Qualitative data were collected through 16 semi-structured interviews of professional developers experienced in working with concept maps in the urban context. An anonymous online survey was used to collect quantitative data from 56 professional developers and teachers to support the qualitative data. The participants were from New York City, recruited through the NY Biology-Chemistry Professional Development Mentor Network and the NY Biology Teachers' Association. According to the participants, map construction, classroom applications, lesson planning, action research, follow-up workshops, and the creation of learning communities are the most effective professional development strategies. The interviewees also proposed English language learning strategies such as picture maps, native word maps, and content reading materials with underlined words. This study contributes to social change by providing a professional development model to use in planning workshops for urban teachers. Urban teachers improve their own conceptual understanding of biology while learning how to implement concept mapping strategies in the classroom. Students whose teachers are better prepared to teach biology in a conceptual manner have the potential of growing into more scientifically literate citizens.

GeneLab for High Schools: Data Mining for the Next Generation

NASA Technical Reports Server (NTRS)

Blaber, Elizabeth A.; Ly, Diana; Sato, Kevin Y.; Taylor, Elizabeth

2016-01-01

Modern biological sciences have become increasingly based on molecular biology and high-throughput molecular techniques, such as genomics, transcriptomics, and proteomics. NASA Scientists and the NASA Space Biology Program have aimed to examine the fundamental building blocks of life (RNA, DNA and protein) in order to understand the response of living organisms to space and aid in fundamental research discoveries on Earth. In an effort to enable NASA funded science to be available to everyone, NASA has collected the data from omics studies and curated them in a data system called GeneLab. Whilst most college-level interns, academics and other scientists have had some interaction with omics data sets and analysis tools, high school students often have not. Therefore, the Space Biology Program is implementing a new Summer Program for high-school students that aims to inspire the next generation of scientists to learn about and get involved in space research using GeneLabs Data System. The program consists of three main components core learning modules, focused on developing students knowledge on the Space Biology Program and Space Biology research, Genelab and the data system, and previous research conducted on model organisms in space; networking and team work, enabling students to interact with guest lecturers from local universities and their fellow peers, and also enabling them to visit local universities and genomics centers around the Bay area; and finally an independent learning project, whereby students will be required to form small groups, analyze a dataset on the Genelab platform, generate a hypothesis and develop a research plan to test their hypothesis. This program will not only help inspire high-school students to become involved in space-based research but will also help them develop key critical thinking and bioinformatics skills required for most college degrees and furthermore, will enable them to establish networks with their peers and connections with university Professors that may help them achieve their educational goals.

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

PubMed

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

2004-05-01

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

BCDForest: a boosting cascade deep forest model towards the classification of cancer subtypes based on gene expression data.

PubMed

Guo, Yang; Liu, Shuhui; Li, Zhanhuai; Shang, Xuequn

2018-04-11

The classification of cancer subtypes is of great importance to cancer disease diagnosis and therapy. Many supervised learning approaches have been applied to cancer subtype classification in the past few years, especially of deep learning based approaches. Recently, the deep forest model has been proposed as an alternative of deep neural networks to learn hyper-representations by using cascade ensemble decision trees. It has been proved that the deep forest model has competitive or even better performance than deep neural networks in some extent. However, the standard deep forest model may face overfitting and ensemble diversity challenges when dealing with small sample size and high-dimensional biology data. In this paper, we propose a deep learning model, so-called BCDForest, to address cancer subtype classification on small-scale biology datasets, which can be viewed as a modification of the standard deep forest model. The BCDForest distinguishes from the standard deep forest model with the following two main contributions: First, a named multi-class-grained scanning method is proposed to train multiple binary classifiers to encourage diversity of ensemble. Meanwhile, the fitting quality of each classifier is considered in representation learning. Second, we propose a boosting strategy to emphasize more important features in cascade forests, thus to propagate the benefits of discriminative features among cascade layers to improve the classification performance. Systematic comparison experiments on both microarray and RNA-Seq gene expression datasets demonstrate that our method consistently outperforms the state-of-the-art methods in application of cancer subtype classification. The multi-class-grained scanning and boosting strategy in our model provide an effective solution to ease the overfitting challenge and improve the robustness of deep forest model working on small-scale data. Our model provides a useful approach to the classification of cancer subtypes by using deep learning on high-dimensional and small-scale biology data.

Students Mental Representation of Biology Diagrams/Pictures Conventions Based on Formation of Causal Network

NASA Astrophysics Data System (ADS)

Sampurno, A. W.; Rahmat, A.; Diana, S.

2017-09-01

Diagrams/pictures conventions is one form of visual media that often used to assist students in understanding the biological concepts. The effectiveness of use diagrams/pictures in biology learning at school level has also been mostly reported. This study examines the ability of high school students in reading diagrams/pictures biological convention which is described by Mental Representation based on formation of causal networks. The study involved 30 students 11th grade MIA senior high school Banten Indonesia who are studying the excretory system. MR data obtained by Instrument worksheet, developed based on CNET-protocol, in which there are diagrams/drawings of nephron structure and urinary mechanism. Three patterns formed MR, namely Markov chain, feedback control with a single measurement, and repeated feedback control with multiple measurement. The third pattern is the most dominating pattern, differences in the pattern of MR reveal the difference in how and from which point the students begin to uncover important information contained in the diagram to establish a causal networks. Further analysis shows that a difference in the pattern of MR relate to how complex the students process the information contained in the diagrams/pictures.

Undergraduate Students' Development of Social, Cultural, and Human Capital in a Networked Research Experience

ERIC Educational Resources Information Center

Thompson, Jennifer Jo; Conaway, Evan; Dolan, Erin L.

2016-01-01

Recent calls for reform in undergraduate biology education have emphasized integrating research experiences into the learning experiences of all undergraduates. Contemporary science research increasingly demands collaboration across disciplines and institutions to investigate complex research questions, providing new contexts and models for…

Neural coordination can be enhanced by occasional interruption of normal firing patterns: a self-optimizing spiking neural network model.

PubMed

Woodward, Alexander; Froese, Tom; Ikegami, Takashi

2015-02-01

The state space of a conventional Hopfield network typically exhibits many different attractors of which only a small subset satisfies constraints between neurons in a globally optimal fashion. It has recently been demonstrated that combining Hebbian learning with occasional alterations of normal neural states avoids this problem by means of self-organized enlargement of the best basins of attraction. However, so far it is not clear to what extent this process of self-optimization is also operative in real brains. Here we demonstrate that it can be transferred to more biologically plausible neural networks by implementing a self-optimizing spiking neural network model. In addition, by using this spiking neural network to emulate a Hopfield network with Hebbian learning, we attempt to make a connection between rate-based and temporal coding based neural systems. Although further work is required to make this model more realistic, it already suggests that the efficacy of the self-optimizing process is independent from the simplifying assumptions of a conventional Hopfield network. We also discuss natural and cultural processes that could be responsible for occasional alteration of neural firing patterns in actual brains. Copyright © 2014 Elsevier Ltd. All rights reserved.

Imaging learning and memory: classical conditioning.

PubMed

Schreurs, B G; Alkon, D L

2001-12-15

The search for the biological basis of learning and memory has, until recently, been constrained by the limits of technology to classic anatomic and electrophysiologic studies. With the advent of functional imaging, we have begun to delve into what, for many, was a "black box." We review several different types of imaging experiments, including steady state animal experiments that image the functional labeling of fixed tissues, and dynamic human studies based on functional imaging of the intact brain during learning. The data suggest that learning and memory involve a surprising conservation of mechanisms and the integrated networking of a number of structures and processes. Copyright 2001 Wiley-Liss, Inc.

Nonvolatile Memory Materials for Neuromorphic Intelligent Machines.

PubMed

Jeong, Doo Seok; Hwang, Cheol Seong

2018-04-18

Recent progress in deep learning extends the capability of artificial intelligence to various practical tasks, making the deep neural network (DNN) an extremely versatile hypothesis. While such DNN is virtually built on contemporary data centers of the von Neumann architecture, physical (in part) DNN of non-von Neumann architecture, also known as neuromorphic computing, can remarkably improve learning and inference efficiency. Particularly, resistance-based nonvolatile random access memory (NVRAM) highlights its handy and efficient application to the multiply-accumulate (MAC) operation in an analog manner. Here, an overview is given of the available types of resistance-based NVRAMs and their technological maturity from the material- and device-points of view. Examples within the strategy are subsequently addressed in comparison with their benchmarks (virtual DNN in deep learning). A spiking neural network (SNN) is another type of neural network that is more biologically plausible than the DNN. The successful incorporation of resistance-based NVRAM in SNN-based neuromorphic computing offers an efficient solution to the MAC operation and spike timing-based learning in nature. This strategy is exemplified from a material perspective. Intelligent machines are categorized according to their architecture and learning type. Also, the functionality and usefulness of NVRAM-based neuromorphic computing are addressed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neuromodulatory adaptive combination of correlation-based learning in cerebellum and reward-based learning in basal ganglia for goal-directed behavior control

PubMed Central

Dasgupta, Sakyasingha; Wörgötter, Florentin; Manoonpong, Poramate

2014-01-01

Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning) and operant conditioning (reward-based learning). A number of computational and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point toward their complementary role in behavioral learning, and also show the existence of substantial two-way communication between these two brain structures. Based on this notion of co-operative learning, in this paper we hypothesize that the basal ganglia and cerebellar learning systems work in parallel and interact with each other. We envision that such an interaction is influenced by reward modulated heterosynaptic plasticity (RMHP) rule at the thalamus, guiding the overall goal directed behavior. Using a recurrent neural network actor-critic model of the basal ganglia and a feed-forward correlation-based learning model of the cerebellum, we demonstrate that the RMHP rule can effectively balance the outcomes of the two learning systems. This is tested using simulated environments of increasing complexity with a four-wheeled robot in a foraging task in both static and dynamic configurations. Although modeled with a simplified level of biological abstraction, we clearly demonstrate that such a RMHP induced combinatorial learning mechanism, leads to stabler and faster learning of goal-directed behaviors, in comparison to the individual systems. Thus, in this paper we provide a computational model for adaptive combination of the basal ganglia and cerebellum learning systems by way of neuromodulated plasticity for goal-directed decision making in biological and bio-mimetic organisms. PMID:25389391

Neuromodulatory adaptive combination of correlation-based learning in cerebellum and reward-based learning in basal ganglia for goal-directed behavior control.

PubMed

Dasgupta, Sakyasingha; Wörgötter, Florentin; Manoonpong, Poramate

2014-01-01

Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning) and operant conditioning (reward-based learning). A number of computational and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point toward their complementary role in behavioral learning, and also show the existence of substantial two-way communication between these two brain structures. Based on this notion of co-operative learning, in this paper we hypothesize that the basal ganglia and cerebellar learning systems work in parallel and interact with each other. We envision that such an interaction is influenced by reward modulated heterosynaptic plasticity (RMHP) rule at the thalamus, guiding the overall goal directed behavior. Using a recurrent neural network actor-critic model of the basal ganglia and a feed-forward correlation-based learning model of the cerebellum, we demonstrate that the RMHP rule can effectively balance the outcomes of the two learning systems. This is tested using simulated environments of increasing complexity with a four-wheeled robot in a foraging task in both static and dynamic configurations. Although modeled with a simplified level of biological abstraction, we clearly demonstrate that such a RMHP induced combinatorial learning mechanism, leads to stabler and faster learning of goal-directed behaviors, in comparison to the individual systems. Thus, in this paper we provide a computational model for adaptive combination of the basal ganglia and cerebellum learning systems by way of neuromodulated plasticity for goal-directed decision making in biological and bio-mimetic organisms.

Biologically Inspired Model for Visual Cognition Achieving Unsupervised Episodic and Semantic Feature Learning.

PubMed

Qiao, Hong; Li, Yinlin; Li, Fengfu; Xi, Xuanyang; Wu, Wei

2016-10-01

Recently, many biologically inspired visual computational models have been proposed. The design of these models follows the related biological mechanisms and structures, and these models provide new solutions for visual recognition tasks. In this paper, based on the recent biological evidence, we propose a framework to mimic the active and dynamic learning and recognition process of the primate visual cortex. From principle point of view, the main contributions are that the framework can achieve unsupervised learning of episodic features (including key components and their spatial relations) and semantic features (semantic descriptions of the key components), which support higher level cognition of an object. From performance point of view, the advantages of the framework are as follows: 1) learning episodic features without supervision-for a class of objects without a prior knowledge, the key components, their spatial relations and cover regions can be learned automatically through a deep neural network (DNN); 2) learning semantic features based on episodic features-within the cover regions of the key components, the semantic geometrical values of these components can be computed based on contour detection; 3) forming the general knowledge of a class of objects-the general knowledge of a class of objects can be formed, mainly including the key components, their spatial relations and average semantic values, which is a concise description of the class; and 4) achieving higher level cognition and dynamic updating-for a test image, the model can achieve classification and subclass semantic descriptions. And the test samples with high confidence are selected to dynamically update the whole model. Experiments are conducted on face images, and a good performance is achieved in each layer of the DNN and the semantic description learning process. Furthermore, the model can be generalized to recognition tasks of other objects with learning ability.

Lessons learned from the design of chemical space networks and opportunities for new applications.

PubMed

Vogt, Martin; Stumpfe, Dagmar; Maggiora, Gerald M; Bajorath, Jürgen

2016-03-01

The concept of chemical space is of fundamental relevance in chemical informatics and computer-aided drug discovery. In a series of articles published in the Journal of Computer-Aided Molecular Design, principles of chemical space design were evaluated, molecular networks proposed as an alternative to conventional coordinate-based chemical reference spaces, and different types of chemical space networks (CSNs) constructed and analyzed. Central to the generation of CSNs was the way in which molecular similarity relationships were assessed and a primary focal point was the network-based representation of biologically relevant chemical space. The design and comparison of CSNs based upon alternative similarity measures can be viewed as an evolutionary path with interesting lessons learned along the way. CSN design has matured to the point that such chemical space representations can be used in practice. In this contribution, highlights from the sequence of CSN design efforts are discussed in context, providing a perspective for future practical applications.

Lessons learned from the design of chemical space networks and opportunities for new applications

NASA Astrophysics Data System (ADS)

Vogt, Martin; Stumpfe, Dagmar; Maggiora, Gerald M.; Bajorath, Jürgen

2016-03-01

The concept of chemical space is of fundamental relevance in chemical informatics and computer-aided drug discovery. In a series of articles published in the Journal of Computer- Aided Molecular Design, principles of chemical space design were evaluated, molecular networks proposed as an alternative to conventional coordinate-based chemical reference spaces, and different types of chemical space networks (CSNs) constructed and analyzed. Central to the generation of CSNs was the way in which molecular similarity relationships were assessed and a primary focal point was the network-based representation of biologically relevant chemical space. The design and comparison of CSNs based upon alternative similarity measures can be viewed as an evolutionary path with interesting lessons learned along the way. CSN design has matured to the point that such chemical space representations can be used in practice. In this contribution, highlights from the sequence of CSN design efforts are discussed in context, providing a perspective for future practical applications.

Disease gene classification with metagraph representations.

PubMed

Kircali Ata, Sezin; Fang, Yuan; Wu, Min; Li, Xiao-Li; Xiao, Xiaokui

2017-12-01

Protein-protein interaction (PPI) networks play an important role in studying the functional roles of proteins, including their association with diseases. However, protein interaction networks are not sufficient without the support of additional biological knowledge for proteins such as their molecular functions and biological processes. To complement and enrich PPI networks, we propose to exploit biological properties of individual proteins. More specifically, we integrate keywords describing protein properties into the PPI network, and construct a novel PPI-Keywords (PPIK) network consisting of both proteins and keywords as two different types of nodes. As disease proteins tend to have a similar topological characteristics on the PPIK network, we further propose to represent proteins with metagraphs. Different from a traditional network motif or subgraph, a metagraph can capture a particular topological arrangement involving the interactions/associations between both proteins and keywords. Based on the novel metagraph representations for proteins, we further build classifiers for disease protein classification through supervised learning. Our experiments on three different PPI databases demonstrate that the proposed method consistently improves disease protein prediction across various classifiers, by 15.3% in AUC on average. It outperforms the baselines including the diffusion-based methods (e.g., RWR) and the module-based methods by 13.8-32.9% for overall disease protein prediction. For predicting breast cancer genes, it outperforms RWR, PRINCE and the module-based baselines by 6.6-14.2%. Finally, our predictions also turn out to have better correlations with literature findings from PubMed. Copyright © 2017 Elsevier Inc. All rights reserved.

Empirical modeling for intelligent, real-time manufacture control

NASA Technical Reports Server (NTRS)

Xu, Xiaoshu

1994-01-01

Artificial neural systems (ANS), also known as neural networks, are an attempt to develop computer systems that emulate the neural reasoning behavior of biological neural systems (e.g. the human brain). As such, they are loosely based on biological neural networks. The ANS consists of a series of nodes (neurons) and weighted connections (axons) that, when presented with a specific input pattern, can associate specific output patterns. It is essentially a highly complex, nonlinear, mathematical relationship or transform. These constructs have two significant properties that have proven useful to the authors in signal processing and process modeling: noise tolerance and complex pattern recognition. Specifically, the authors have developed a new network learning algorithm that has resulted in the successful application of ANS's to high speed signal processing and to developing models of highly complex processes. Two of the applications, the Weld Bead Geometry Control System and the Welding Penetration Monitoring System, are discussed in the body of this paper.

Structure and inference in annotated networks

PubMed Central

Newman, M. E. J.; Clauset, Aaron

2016-01-01

For many networks of scientific interest we know both the connections of the network and information about the network nodes, such as the age or gender of individuals in a social network. Here we demonstrate how this ‘metadata' can be used to improve our understanding of network structure. We focus in particular on the problem of community detection in networks and develop a mathematically principled approach that combines a network and its metadata to detect communities more accurately than can be done with either alone. Crucially, the method does not assume that the metadata are correlated with the communities we are trying to find. Instead, the method learns whether a correlation exists and correctly uses or ignores the metadata depending on whether they contain useful information. We demonstrate our method on synthetic networks with known structure and on real-world networks, large and small, drawn from social, biological and technological domains. PMID:27306566

Structure and inference in annotated networks

NASA Astrophysics Data System (ADS)

Newman, M. E. J.; Clauset, Aaron

2016-06-01

For many networks of scientific interest we know both the connections of the network and information about the network nodes, such as the age or gender of individuals in a social network. Here we demonstrate how this `metadata' can be used to improve our understanding of network structure. We focus in particular on the problem of community detection in networks and develop a mathematically principled approach that combines a network and its metadata to detect communities more accurately than can be done with either alone. Crucially, the method does not assume that the metadata are correlated with the communities we are trying to find. Instead, the method learns whether a correlation exists and correctly uses or ignores the metadata depending on whether they contain useful information. We demonstrate our method on synthetic networks with known structure and on real-world networks, large and small, drawn from social, biological and technological domains.

A biologically inspired neural network model to transformation invariant object recognition

NASA Astrophysics Data System (ADS)

Iftekharuddin, Khan M.; Li, Yaqin; Siddiqui, Faraz

2007-09-01

Transformation invariant image recognition has been an active research area due to its widespread applications in a variety of fields such as military operations, robotics, medical practices, geographic scene analysis, and many others. The primary goal for this research is detection of objects in the presence of image transformations such as changes in resolution, rotation, translation, scale and occlusion. We investigate a biologically-inspired neural network (NN) model for such transformation-invariant object recognition. In a classical training-testing setup for NN, the performance is largely dependent on the range of transformation or orientation involved in training. However, an even more serious dilemma is that there may not be enough training data available for successful learning or even no training data at all. To alleviate this problem, a biologically inspired reinforcement learning (RL) approach is proposed. In this paper, the RL approach is explored for object recognition with different types of transformations such as changes in scale, size, resolution and rotation. The RL is implemented in an adaptive critic design (ACD) framework, which approximates the neuro-dynamic programming of an action network and a critic network, respectively. Two ACD algorithms such as Heuristic Dynamic Programming (HDP) and Dual Heuristic dynamic Programming (DHP) are investigated to obtain transformation invariant object recognition. The two learning algorithms are evaluated statistically using simulated transformations in images as well as with a large-scale UMIST face database with pose variations. In the face database authentication case, the 90° out-of-plane rotation of faces from 20 different subjects in the UMIST database is used. Our simulations show promising results for both designs for transformation-invariant object recognition and authentication of faces. Comparing the two algorithms, DHP outperforms HDP in learning capability, as DHP takes fewer steps to perform a successful recognition task in general. Further, the residual critic error in DHP is generally smaller than that of HDP, and DHP achieves a 100% success rate more frequently than HDP for individual objects/subjects. On the other hand, HDP is more robust than the DHP as far as success rate across the database is concerned when applied in a stochastic and uncertain environment, and the computational time involved in DHP is more.

Evaluation of machine learning algorithms for classification of primary biological aerosol using a new UV-LIF spectrometer

NASA Astrophysics Data System (ADS)

Ruske, Simon; Topping, David O.; Foot, Virginia E.; Kaye, Paul H.; Stanley, Warren R.; Crawford, Ian; Morse, Andrew P.; Gallagher, Martin W.

2017-03-01

Characterisation of bioaerosols has important implications within environment and public health sectors. Recent developments in ultraviolet light-induced fluorescence (UV-LIF) detectors such as the Wideband Integrated Bioaerosol Spectrometer (WIBS) and the newly introduced Multiparameter Bioaerosol Spectrometer (MBS) have allowed for the real-time collection of fluorescence, size and morphology measurements for the purpose of discriminating between bacteria, fungal spores and pollen.This new generation of instruments has enabled ever larger data sets to be compiled with the aim of studying more complex environments. In real world data sets, particularly those from an urban environment, the population may be dominated by non-biological fluorescent interferents, bringing into question the accuracy of measurements of quantities such as concentrations. It is therefore imperative that we validate the performance of different algorithms which can be used for the task of classification.For unsupervised learning we tested hierarchical agglomerative clustering with various different linkages. For supervised learning, 11 methods were tested, including decision trees, ensemble methods (random forests, gradient boosting and AdaBoost), two implementations for support vector machines (libsvm and liblinear) and Gaussian methods (Gaussian naïve Bayesian, quadratic and linear discriminant analysis, the k-nearest neighbours algorithm and artificial neural networks).The methods were applied to two different data sets produced using the new MBS, which provides multichannel UV-LIF fluorescence signatures for single airborne biological particles. The first data set contained mixed PSLs and the second contained a variety of laboratory-generated aerosol.Clustering in general performs slightly worse than the supervised learning methods, correctly classifying, at best, only 67. 6 and 91. 1 % for the two data sets respectively. For supervised learning the gradient boosting algorithm was found to be the most effective, on average correctly classifying 82. 8 and 98. 27 % of the testing data, respectively, across the two data sets.A possible alternative to gradient boosting is neural networks. We do however note that this method requires much more user input than the other methods, and we suggest that further research should be conducted using this method, especially using parallelised hardware such as the GPU, which would allow for larger networks to be trained, which could possibly yield better results.We also saw that some methods, such as clustering, failed to utilise the additional shape information provided by the instrument, whilst for others, such as the decision trees, ensemble methods and neural networks, improved performance could be attained with the inclusion of such information.

A reconfigurable on-line learning spiking neuromorphic processor comprising 256 neurons and 128K synapses

PubMed Central

Qiao, Ning; Mostafa, Hesham; Corradi, Federico; Osswald, Marc; Stefanini, Fabio; Sumislawska, Dora; Indiveri, Giacomo

2015-01-01

Implementing compact, low-power artificial neural processing systems with real-time on-line learning abilities is still an open challenge. In this paper we present a full-custom mixed-signal VLSI device with neuromorphic learning circuits that emulate the biophysics of real spiking neurons and dynamic synapses for exploring the properties of computational neuroscience models and for building brain-inspired computing systems. The proposed architecture allows the on-chip configuration of a wide range of network connectivities, including recurrent and deep networks, with short-term and long-term plasticity. The device comprises 128 K analog synapse and 256 neuron circuits with biologically plausible dynamics and bi-stable spike-based plasticity mechanisms that endow it with on-line learning abilities. In addition to the analog circuits, the device comprises also asynchronous digital logic circuits for setting different synapse and neuron properties as well as different network configurations. This prototype device, fabricated using a 180 nm 1P6M CMOS process, occupies an area of 51.4 mm2, and consumes approximately 4 mW for typical experiments, for example involving attractor networks. Here we describe the details of the overall architecture and of the individual circuits and present experimental results that showcase its potential. By supporting a wide range of cortical-like computational modules comprising plasticity mechanisms, this device will enable the realization of intelligent autonomous systems with on-line learning capabilities. PMID:25972778

Genetic Insights Into ADHD Biology.

PubMed

Hayman, Victoria; Fernandez, Thomas V

2018-01-01

ADHD is a neurobiological disorder with a large worldwide prevalence causing significant impairment in children, adolescents, and adults. While there is general agreement about genetic contributions toward the disorder, progress in leveraging genetics to learn more about the biology and risk factors for ADHD has been limited. In this perspective, we identified 105 genes from the literature showing at least nominal statistical significance in association with ADHD. We analyzed these genes for enrichment in biological pathways and in known interacting biological networks. We also analyzed the expression patterns of candidate genes across brain regions and across periods of human development. From our analysis, we identify 14 genes that cluster within an interactive gene network, with enrichment in nitric oxide synthase and alpha-1 adrenergic pathways. Furthermore, these genes show enrichment for expression in the cerebellum during childhood through young adulthood, and in the cortex in adolescence and young adulthood. Gene discovery holds great potential for elucidating the unknown biological underpinnings of ADHD. Genome-wide sequencing efforts are underway and are likely to provide important insights that can be leveraged for new treatments and interventions.

WNN 92; Proceedings of the 3rd Workshop on Neural Networks: Academic/Industrial/NASA/Defense, Auburn Univ., AL, Feb. 10-12, 1992 and South Shore Harbour, TX, Nov. 4-6, 1992

NASA Technical Reports Server (NTRS)

Padgett, Mary L. (Editor)

1993-01-01

The present conference discusses such neural networks (NN) related topics as their current development status, NN architectures, NN learning rules, NN optimization methods, NN temporal models, NN control methods, NN pattern recognition systems and applications, biological and biomedical applications of NNs, VLSI design techniques for NNs, NN systems simulation, fuzzy logic, and genetic algorithms. Attention is given to missileborne integrated NNs, adaptive-mixture NNs, implementable learning rules, an NN simulator for travelling salesman problem solutions, similarity-based forecasting, NN control of hypersonic aircraft takeoff, NN control of the Space Shuttle Arm, an adaptive NN robot manipulator controller, a synthetic approach to digital filtering, NNs for speech analysis, adaptive spline networks, an anticipatory fuzzy logic controller, and encoding operations for fuzzy associative memories.

Unsupervised learning of temporal features for word categorization in a spiking neural network model of the auditory brain.

PubMed

Higgins, Irina; Stringer, Simon; Schnupp, Jan

2017-01-01

The nature of the code used in the auditory cortex to represent complex auditory stimuli, such as naturally spoken words, remains a matter of debate. Here we argue that such representations are encoded by stable spatio-temporal patterns of firing within cell assemblies known as polychronous groups, or PGs. We develop a physiologically grounded, unsupervised spiking neural network model of the auditory brain with local, biologically realistic, spike-time dependent plasticity (STDP) learning, and show that the plastic cortical layers of the network develop PGs which convey substantially more information about the speaker independent identity of two naturally spoken word stimuli than does rate encoding that ignores the precise spike timings. We furthermore demonstrate that such informative PGs can only develop if the input spatio-temporal spike patterns to the plastic cortical areas of the model are relatively stable.

Unsupervised learning of temporal features for word categorization in a spiking neural network model of the auditory brain

PubMed Central

Stringer, Simon

2017-01-01

The nature of the code used in the auditory cortex to represent complex auditory stimuli, such as naturally spoken words, remains a matter of debate. Here we argue that such representations are encoded by stable spatio-temporal patterns of firing within cell assemblies known as polychronous groups, or PGs. We develop a physiologically grounded, unsupervised spiking neural network model of the auditory brain with local, biologically realistic, spike-time dependent plasticity (STDP) learning, and show that the plastic cortical layers of the network develop PGs which convey substantially more information about the speaker independent identity of two naturally spoken word stimuli than does rate encoding that ignores the precise spike timings. We furthermore demonstrate that such informative PGs can only develop if the input spatio-temporal spike patterns to the plastic cortical areas of the model are relatively stable. PMID:28797034

A new simple /spl infin/OH neuron model as a biologically plausible principal component analyzer.

PubMed

Jankovic, M V

2003-01-01

A new approach to unsupervised learning in a single-layer neural network is discussed. An algorithm for unsupervised learning based upon the Hebbian learning rule is presented. A simple neuron model is analyzed. A dynamic neural model, which contains both feed-forward and feedback connections between the input and the output, has been adopted. The, proposed learning algorithm could be more correctly named self-supervised rather than unsupervised. The solution proposed here is a modified Hebbian rule, in which the modification of the synaptic strength is proportional not to pre- and postsynaptic activity, but instead to the presynaptic and averaged value of postsynaptic activity. It is shown that the model neuron tends to extract the principal component from a stationary input vector sequence. Usually accepted additional decaying terms for the stabilization of the original Hebbian rule are avoided. Implementation of the basic Hebbian scheme would not lead to unrealistic growth of the synaptic strengths, thanks to the adopted network structure.

Validating module network learning algorithms using simulated data.

PubMed

Michoel, Tom; Maere, Steven; Bonnet, Eric; Joshi, Anagha; Saeys, Yvan; Van den Bulcke, Tim; Van Leemput, Koenraad; van Remortel, Piet; Kuiper, Martin; Marchal, Kathleen; Van de Peer, Yves

2007-05-03

In recent years, several authors have used probabilistic graphical models to learn expression modules and their regulatory programs from gene expression data. Despite the demonstrated success of such algorithms in uncovering biologically relevant regulatory relations, further developments in the area are hampered by a lack of tools to compare the performance of alternative module network learning strategies. Here, we demonstrate the use of the synthetic data generator SynTReN for the purpose of testing and comparing module network learning algorithms. We introduce a software package for learning module networks, called LeMoNe, which incorporates a novel strategy for learning regulatory programs. Novelties include the use of a bottom-up Bayesian hierarchical clustering to construct the regulatory programs, and the use of a conditional entropy measure to assign regulators to the regulation program nodes. Using SynTReN data, we test the performance of LeMoNe in a completely controlled situation and assess the effect of the methodological changes we made with respect to an existing software package, namely Genomica. Additionally, we assess the effect of various parameters, such as the size of the data set and the amount of noise, on the inference performance. Overall, application of Genomica and LeMoNe to simulated data sets gave comparable results. However, LeMoNe offers some advantages, one of them being that the learning process is considerably faster for larger data sets. Additionally, we show that the location of the regulators in the LeMoNe regulation programs and their conditional entropy may be used to prioritize regulators for functional validation, and that the combination of the bottom-up clustering strategy with the conditional entropy-based assignment of regulators improves the handling of missing or hidden regulators. We show that data simulators such as SynTReN are very well suited for the purpose of developing, testing and improving module network algorithms. We used SynTReN data to develop and test an alternative module network learning strategy, which is incorporated in the software package LeMoNe, and we provide evidence that this alternative strategy has several advantages with respect to existing methods.

A new modulated Hebbian learning rule--biologically plausible method for local computation of a principal subspace.

PubMed

Jankovic, Marko; Ogawa, Hidemitsu

2003-08-01

This paper presents one possible implementation of a transformation that performs linear mapping to a lower-dimensional subspace. Principal component subspace will be the one that will be analyzed. Idea implemented in this paper represents generalization of the recently proposed infinity OH neural method for principal component extraction. The calculations in the newly proposed method are performed locally--a feature which is usually considered as desirable from the biological point of view. Comparing to some other wellknown methods, proposed synaptic efficacy learning rule requires less information about the value of the other efficacies to make single efficacy modification. Synaptic efficacies are modified by implementation of Modulated Hebb-type (MH) learning rule. Slightly modified MH algorithm named Modulated Hebb Oja (MHO) algorithm, will be also introduced. Structural similarity of the proposed network with part of the retinal circuit will be presented, too.

Hebbian learning of hand-centred representations in a hierarchical neural network model of the primate visual system.

PubMed

Born, Jannis; Galeazzi, Juan M; Stringer, Simon M

2017-01-01

A subset of neurons in the posterior parietal and premotor areas of the primate brain respond to the locations of visual targets in a hand-centred frame of reference. Such hand-centred visual representations are thought to play an important role in visually-guided reaching to target locations in space. In this paper we show how a biologically plausible, Hebbian learning mechanism may account for the development of localized hand-centred representations in a hierarchical neural network model of the primate visual system, VisNet. The hand-centered neurons developed in the model use an invariance learning mechanism known as continuous transformation (CT) learning. In contrast to previous theoretical proposals for the development of hand-centered visual representations, CT learning does not need a memory trace of recent neuronal activity to be incorporated in the synaptic learning rule. Instead, CT learning relies solely on a Hebbian learning rule, which is able to exploit the spatial overlap that naturally occurs between successive images of a hand-object configuration as it is shifted across different retinal locations due to saccades. Our simulations show how individual neurons in the network model can learn to respond selectively to target objects in particular locations with respect to the hand, irrespective of where the hand-object configuration occurs on the retina. The response properties of these hand-centred neurons further generalise to localised receptive fields in the hand-centred space when tested on novel hand-object configurations that have not been explored during training. Indeed, even when the network is trained with target objects presented across a near continuum of locations around the hand during training, the model continues to develop hand-centred neurons with localised receptive fields in hand-centred space. With the help of principal component analysis, we provide the first theoretical framework that explains the behavior of Hebbian learning in VisNet.

Hebbian learning of hand-centred representations in a hierarchical neural network model of the primate visual system

PubMed Central

Born, Jannis; Stringer, Simon M.

2017-01-01

A subset of neurons in the posterior parietal and premotor areas of the primate brain respond to the locations of visual targets in a hand-centred frame of reference. Such hand-centred visual representations are thought to play an important role in visually-guided reaching to target locations in space. In this paper we show how a biologically plausible, Hebbian learning mechanism may account for the development of localized hand-centred representations in a hierarchical neural network model of the primate visual system, VisNet. The hand-centered neurons developed in the model use an invariance learning mechanism known as continuous transformation (CT) learning. In contrast to previous theoretical proposals for the development of hand-centered visual representations, CT learning does not need a memory trace of recent neuronal activity to be incorporated in the synaptic learning rule. Instead, CT learning relies solely on a Hebbian learning rule, which is able to exploit the spatial overlap that naturally occurs between successive images of a hand-object configuration as it is shifted across different retinal locations due to saccades. Our simulations show how individual neurons in the network model can learn to respond selectively to target objects in particular locations with respect to the hand, irrespective of where the hand-object configuration occurs on the retina. The response properties of these hand-centred neurons further generalise to localised receptive fields in the hand-centred space when tested on novel hand-object configurations that have not been explored during training. Indeed, even when the network is trained with target objects presented across a near continuum of locations around the hand during training, the model continues to develop hand-centred neurons with localised receptive fields in hand-centred space. With the help of principal component analysis, we provide the first theoretical framework that explains the behavior of Hebbian learning in VisNet. PMID:28562618

Resonant spatiotemporal learning in large random recurrent networks.

PubMed

Daucé, Emmanuel; Quoy, Mathias; Doyon, Bernard

2002-09-01

Taking a global analogy with the structure of perceptual biological systems, we present a system composed of two layers of real-valued sigmoidal neurons. The primary layer receives stimulating spatiotemporal signals, and the secondary layer is a fully connected random recurrent network. This secondary layer spontaneously displays complex chaotic dynamics. All connections have a constant time delay. We use for our experiments a Hebbian (covariance) learning rule. This rule slowly modifies the weights under the influence of a periodic stimulus. The effect of learning is twofold: (i) it simplifies the secondary-layer dynamics, which eventually stabilizes to a periodic orbit; and (ii) it connects the secondary layer to the primary layer, and realizes a feedback from the secondary to the primary layer. This feedback signal is added to the incoming signal, and matches it (i.e., the secondary layer performs a one-step prediction of the forthcoming stimulus). After learning, a resonant behavior can be observed: the system resonates with familiar stimuli, which activates a feedback signal. In particular, this resonance allows the recognition and retrieval of partial signals, and dynamic maintenance of the memory of past stimuli. This resonance is highly sensitive to the temporal relationships and to the periodicity of the presented stimuli. When we present stimuli which do not match in time or space, the feedback remains silent. The number of different stimuli for which resonant behavior can be learned is analyzed. As with Hopfield networks, the capacity is proportional to the size of the second, recurrent layer. Moreover, the high capacity displayed allows the implementation of our model on real-time systems interacting with their environment. Such an implementation is reported in the case of a simple behavior-based recognition task on a mobile robot. Finally, we present some functional analogies with biological systems in terms of autonomy and dynamic binding, and present some hypotheses on the computational role of feedback connections.

Bose-Einstein condensates form in heuristics learned by ciliates deciding to signal 'social' commitments.

PubMed

Clark, Kevin B

2010-03-01

Fringe quantum biology theories often adopt the concept of Bose-Einstein condensation when explaining how consciousness, emotion, perception, learning, and reasoning emerge from operations of intact animal nervous systems and other computational media. However, controversial empirical evidence and mathematical formalism concerning decoherence rates of bioprocesses keep these frameworks from satisfactorily accounting for the physical nature of cognitive-like events. This study, inspired by the discovery that preferential attachment rules computed by complex technological networks obey Bose-Einstein statistics, is the first rigorous attempt to examine whether analogues of Bose-Einstein condensation precipitate learned decision making in live biological systems as bioenergetics optimization predicts. By exploiting the ciliate Spirostomum ambiguum's capacity to learn and store behavioral strategies advertising mating availability into heuristics of topologically invariant computational networks, three distinct phases of strategy use were found to map onto statistical distributions described by Bose-Einstein, Fermi-Dirac, and classical Maxwell-Boltzmann behavior. Ciliates that sensitized or habituated signaling patterns to emit brief periods of either deceptive 'harder-to-get' or altruistic 'easier-to-get' serial escape reactions began testing condensed on initially perceived fittest 'courting' solutions. When these ciliates switched from their first strategy choices, Bose-Einstein condensation of strategy use abruptly dissipated into a Maxwell-Boltzmann computational phase no longer dominated by a single fittest strategy. Recursive trial-and-error strategy searches annealed strategy use back into a condensed phase consistent with performance optimization. 'Social' decisions performed by ciliates showing no nonassociative learning were largely governed by Fermi-Dirac statistics, resulting in degenerate distributions of strategy choices. These findings corroborate previous work demonstrating ciliates with improving expertise search grouped 'courting' assurances at quantum efficiencies and verify efficient processing by primitive 'social' intelligences involves network forms of Bose-Einstein condensation coupled to preceding thermodynamic-sensitive computational phases. 2009 Elsevier Ireland Ltd. All rights reserved.

Leadership in a Network of Communities: A Phenomenographic Study

ERIC Educational Resources Information Center

MacGillivray, Alice

2010-01-01

Purpose: Canada's Chemical, Biological, Radiological, and Nuclear Research and Technology Initiative (CRTI) uses an operating model that is unusual in government. It is created to enable cross-boundary capability and capacity building and learning. Some consider it a model for other federal science initiatives. The purpose of this paper is to…

An Initiative to Broaden Diversity in Undergraduate Biomathematics Training

PubMed Central

Chen, Mingxiang; White, Catherine; Clemence, Dominic; Redd, Thomas; Kelkar, Vinaya

2010-01-01

At North Carolina A&T State University (NCATSU), there was a critical need to better coordinate genuine research and classroom experiences for undergraduates early in their academic career. We describe the development and implementation of a faculty alliance across academic departments to increase biomathematics research opportunities for underrepresented minorities. Our faculty alliance is called the Integrative Biomathematical Learning and Empowerment Network for Diversity (iBLEND). The fundamental purpose of the iBLEND alliance was to inspire underrepresented minorities to pursue research careers by increasing the visibility of research conducted at the interface of mathematics and biology at NCATSU. Because of the many positive impacts, iBLEND gained significant buy-in from administration, faculty, and students by 1) working from the ground up with administration to promote campus-wide biomathematics research and training, 2) fostering associations between research and regular undergraduate academic courses, 3) creating and disseminating biomathematics teaching and learning modules, and 4) enhancing learning community support at the interface of mathematics and biology. Currently, iBLEND is viewed as a productive site for graduate schools to recruit underrepresented minority students having specific competencies related to mathematical biology. PMID:20810956

A Retrospective Look at 20 Years of ASM Education Programs (1990-2010) and a Prospective Look at the Next 20 Years (2011-2030).

PubMed

Chang, Amy

2011-01-01

Professional societies provide visibility and legitimacy to the work of their post secondary educator members, advocate best practices in courses and sponsored student research, and establish deep networks and communities that catalyze members to collectively engage in undergraduate teaching and learning scholarship. Within the American Society for Microbiology (ASM), the Education Board, established in the mid-1970s, assumes this role. I have been fortunate enough to watch several pivotal programs support our growth and change the status quo by providing opportunities for biology educators to flourish. In this retrospective review, the background and details I offer about each initiative help explain ASM Education offerings, how our growth has been supported and how the status quo has changed. In this prospective look, I offer my vision of the future in post secondary education where classroom learning is student-centered and focused on global problems affecting our health and environment. For the profession to proliferate, the ASM must provide members as many opportunities in learning biology as they do with advancing biology to new frontiers.

Synthetic biology routes to bio-artificial intelligence.

PubMed

Nesbeth, Darren N; Zaikin, Alexey; Saka, Yasushi; Romano, M Carmen; Giuraniuc, Claudiu V; Kanakov, Oleg; Laptyeva, Tetyana

2016-11-30

The design of synthetic gene networks (SGNs) has advanced to the extent that novel genetic circuits are now being tested for their ability to recapitulate archetypal learning behaviours first defined in the fields of machine and animal learning. Here, we discuss the biological implementation of a perceptron algorithm for linear classification of input data. An expansion of this biological design that encompasses cellular 'teachers' and 'students' is also examined. We also discuss implementation of Pavlovian associative learning using SGNs and present an example of such a scheme and in silico simulation of its performance. In addition to designed SGNs, we also consider the option to establish conditions in which a population of SGNs can evolve diversity in order to better contend with complex input data. Finally, we compare recent ethical concerns in the field of artificial intelligence (AI) and the future challenges raised by bio-artificial intelligence (BI). © 2016 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

Autonomous Optimization of Targeted Stimulation of Neuronal Networks

PubMed Central

Kumar, Sreedhar S.; Wülfing, Jan; Okujeni, Samora; Boedecker, Joschka; Riedmiller, Martin

2016-01-01

Driven by clinical needs and progress in neurotechnology, targeted interaction with neuronal networks is of increasing importance. Yet, the dynamics of interaction between intrinsic ongoing activity in neuronal networks and their response to stimulation is unknown. Nonetheless, electrical stimulation of the brain is increasingly explored as a therapeutic strategy and as a means to artificially inject information into neural circuits. Strategies using regular or event-triggered fixed stimuli discount the influence of ongoing neuronal activity on the stimulation outcome and are therefore not optimal to induce specific responses reliably. Yet, without suitable mechanistic models, it is hardly possible to optimize such interactions, in particular when desired response features are network-dependent and are initially unknown. In this proof-of-principle study, we present an experimental paradigm using reinforcement-learning (RL) to optimize stimulus settings autonomously and evaluate the learned control strategy using phenomenological models. We asked how to (1) capture the interaction of ongoing network activity, electrical stimulation and evoked responses in a quantifiable ‘state’ to formulate a well-posed control problem, (2) find the optimal state for stimulation, and (3) evaluate the quality of the solution found. Electrical stimulation of generic neuronal networks grown from rat cortical tissue in vitro evoked bursts of action potentials (responses). We show that the dynamic interplay of their magnitudes and the probability to be intercepted by spontaneous events defines a trade-off scenario with a network-specific unique optimal latency maximizing stimulus efficacy. An RL controller was set to find this optimum autonomously. Across networks, stimulation efficacy increased in 90% of the sessions after learning and learned latencies strongly agreed with those predicted from open-loop experiments. Our results show that autonomous techniques can exploit quantitative relationships underlying activity-response interaction in biological neuronal networks to choose optimal actions. Simple phenomenological models can be useful to validate the quality of the resulting controllers. PMID:27509295

Autonomous Optimization of Targeted Stimulation of Neuronal Networks.

PubMed

Kumar, Sreedhar S; Wülfing, Jan; Okujeni, Samora; Boedecker, Joschka; Riedmiller, Martin; Egert, Ulrich

2016-08-01

Driven by clinical needs and progress in neurotechnology, targeted interaction with neuronal networks is of increasing importance. Yet, the dynamics of interaction between intrinsic ongoing activity in neuronal networks and their response to stimulation is unknown. Nonetheless, electrical stimulation of the brain is increasingly explored as a therapeutic strategy and as a means to artificially inject information into neural circuits. Strategies using regular or event-triggered fixed stimuli discount the influence of ongoing neuronal activity on the stimulation outcome and are therefore not optimal to induce specific responses reliably. Yet, without suitable mechanistic models, it is hardly possible to optimize such interactions, in particular when desired response features are network-dependent and are initially unknown. In this proof-of-principle study, we present an experimental paradigm using reinforcement-learning (RL) to optimize stimulus settings autonomously and evaluate the learned control strategy using phenomenological models. We asked how to (1) capture the interaction of ongoing network activity, electrical stimulation and evoked responses in a quantifiable 'state' to formulate a well-posed control problem, (2) find the optimal state for stimulation, and (3) evaluate the quality of the solution found. Electrical stimulation of generic neuronal networks grown from rat cortical tissue in vitro evoked bursts of action potentials (responses). We show that the dynamic interplay of their magnitudes and the probability to be intercepted by spontaneous events defines a trade-off scenario with a network-specific unique optimal latency maximizing stimulus efficacy. An RL controller was set to find this optimum autonomously. Across networks, stimulation efficacy increased in 90% of the sessions after learning and learned latencies strongly agreed with those predicted from open-loop experiments. Our results show that autonomous techniques can exploit quantitative relationships underlying activity-response interaction in biological neuronal networks to choose optimal actions. Simple phenomenological models can be useful to validate the quality of the resulting controllers.

Perceptron ensemble of graph-based positive-unlabeled learning for disease gene identification.

PubMed

Jowkar, Gholam-Hossein; Mansoori, Eghbal G

2016-10-01

Identification of disease genes, using computational methods, is an important issue in biomedical and bioinformatics research. According to observations that diseases with the same or similar phenotype have the same biological characteristics, researchers have tried to identify genes by using machine learning tools. In recent attempts, some semi-supervised learning methods, called positive-unlabeled learning, is used for disease gene identification. In this paper, we present a Perceptron ensemble of graph-based positive-unlabeled learning (PEGPUL) on three types of biological attributes: gene ontologies, protein domains and protein-protein interaction networks. In our method, a reliable set of positive and negative genes are extracted using co-training schema. Then, the similarity graph of genes is built using metric learning by concentrating on multi-rank-walk method to perform inference from labeled genes. At last, a Perceptron ensemble is learned from three weighted classifiers: multilevel support vector machine, k-nearest neighbor and decision tree. The main contributions of this paper are: (i) incorporating the statistical properties of gene data through choosing proper metrics, (ii) statistical evaluation of biological features, and (iii) noise robustness characteristic of PEGPUL via using multilevel schema. In order to assess PEGPUL, we have applied it on 12950 disease genes with 949 positive genes from six class of diseases and 12001 unlabeled genes. Compared with some popular disease gene identification methods, the experimental results show that PEGPUL has reasonable performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ion track based tunable device as humidity sensor: a neural network approach

NASA Astrophysics Data System (ADS)

Sharma, Mamta; Sharma, Anuradha; Bhattacherjee, Vandana

2013-01-01

Artificial Neural Network (ANN) has been applied in statistical model development, adaptive control system, pattern recognition in data mining, and decision making under uncertainty. The nonlinear dependence of any sensor output on the input physical variable has been the motivation for many researchers to attempt unconventional modeling techniques such as neural networks and other machine learning approaches. Artificial neural network (ANN) is a computational tool inspired by the network of neurons in biological nervous system. It is a network consisting of arrays of artificial neurons linked together with different weights of connection. The states of the neurons as well as the weights of connections among them evolve according to certain learning rules.. In the present work we focus on the category of sensors which respond to electrical property changes such as impedance or capacitance. Recently, sensor materials have been embedded in etched tracks due to their nanometric dimensions and high aspect ratio which give high surface area available for exposure to sensing material. Various materials can be used for this purpose to probe physical (light intensity, temperature etc.), chemical (humidity, ammonia gas, alcohol etc.) or biological (germs, hormones etc.) parameters. The present work involves the application of TEMPOS structures as humidity sensors. The sample to be studied was prepared using the polymer electrolyte (PEO/NH4ClO4) with CdS nano-particles dispersed in the polymer electrolyte. In the present research we have attempted to correlate the combined effects of voltage and frequency on impedance of humidity sensors using a neural network model and results have indicated that the mean absolute error of the ANN Model for the training data was 3.95% while for the validation data it was 4.65%. The corresponding values for the LR model were 8.28% and 8.35% respectively. It was also demonstrated the percentage improvement of the ANN Model with respect to the linear regression model. This demonstrates the suitability of neural networks to perform such modeling.

A deep learning approach to estimate chemically-treated collagenous tissue nonlinear anisotropic stress-strain responses from microscopy images.

PubMed

Liang, Liang; Liu, Minliang; Sun, Wei

2017-11-01

Biological collagenous tissues comprised of networks of collagen fibers are suitable for a broad spectrum of medical applications owing to their attractive mechanical properties. In this study, we developed a noninvasive approach to estimate collagenous tissue elastic properties directly from microscopy images using Machine Learning (ML) techniques. Glutaraldehyde-treated bovine pericardium (GLBP) tissue, widely used in the fabrication of bioprosthetic heart valves and vascular patches, was chosen to develop a representative application. A Deep Learning model was designed and trained to process second harmonic generation (SHG) images of collagen networks in GLBP tissue samples, and directly predict the tissue elastic mechanical properties. The trained model is capable of identifying the overall tissue stiffness with a classification accuracy of 84%, and predicting the nonlinear anisotropic stress-strain curves with average regression errors of 0.021 and 0.031. Thus, this study demonstrates the feasibility and great potential of using the Deep Learning approach for fast and noninvasive assessment of collagenous tissue elastic properties from microstructural images. In this study, we developed, to our best knowledge, the first Deep Learning-based approach to estimate the elastic properties of collagenous tissues directly from noninvasive second harmonic generation images. The success of this study holds promise for the use of Machine Learning techniques to noninvasively and efficiently estimate the mechanical properties of many structure-based biological materials, and it also enables many potential applications such as serving as a quality control tool to select tissue for the manufacturing of medical devices (e.g. bioprosthetic heart valves). Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The rise of deep learning in drug discovery.

PubMed

Chen, Hongming; Engkvist, Ola; Wang, Yinhai; Olivecrona, Marcus; Blaschke, Thomas

2018-06-01

Over the past decade, deep learning has achieved remarkable success in various artificial intelligence research areas. Evolved from the previous research on artificial neural networks, this technology has shown superior performance to other machine learning algorithms in areas such as image and voice recognition, natural language processing, among others. The first wave of applications of deep learning in pharmaceutical research has emerged in recent years, and its utility has gone beyond bioactivity predictions and has shown promise in addressing diverse problems in drug discovery. Examples will be discussed covering bioactivity prediction, de novo molecular design, synthesis prediction and biological image analysis. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

A gene network simulator to assess reverse engineering algorithms.

PubMed

Di Camillo, Barbara; Toffolo, Gianna; Cobelli, Claudio

2009-03-01

In the context of reverse engineering of biological networks, simulators are helpful to test and compare the accuracy of different reverse-engineering approaches in a variety of experimental conditions. A novel gene-network simulator is presented that resembles some of the main features of transcriptional regulatory networks related to topology, interaction among regulators of transcription, and expression dynamics. The simulator generates network topology according to the current knowledge of biological network organization, including scale-free distribution of the connectivity and clustering coefficient independent of the number of nodes in the network. It uses fuzzy logic to represent interactions among the regulators of each gene, integrated with differential equations to generate continuous data, comparable to real data for variety and dynamic complexity. Finally, the simulator accounts for saturation in the response to regulation and transcription activation thresholds and shows robustness to perturbations. It therefore provides a reliable and versatile test bed for reverse engineering algorithms applied to microarray data. Since the simulator describes regulatory interactions and expression dynamics as two distinct, although interconnected aspects of regulation, it can also be used to test reverse engineering approaches that use both microarray and protein-protein interaction data in the process of learning. A first software release is available at http://www.dei.unipd.it/~dicamill/software/netsim as an R programming language package.

Study on Electro-polymerization Nano-micro Wiring System Imitating Axonal Growth of Artificial Neurons towards Machine Learning

NASA Astrophysics Data System (ADS)

Dang, Nguyen Tuan; Akai-Kasada, Megumi; Asai, Tetsuya; Saito, Akira; Kuwahara, Yuji; Hokkaido University Collaboration

2015-03-01

Machine learning using the artificial neuron network research is supposed to be the best way to understand how the human brain trains itself to process information. In this study, we have successfully developed the programs using supervised machine learning algorithm. However, these supervised learning processes for the neuron network required the very strong computing configuration. Derivation from the necessity of increasing in computing ability and in reduction of power consumption, accelerator circuits become critical. To develop such accelerator circuits using supervised machine learning algorithm, conducting polymer micro/nanowires growing process was realized and applied as a synaptic weigh controller. In this work, high conductivity Polypyrrole (PPy) and Poly (3, 4 - ethylenedioxythiophene) PEDOT wires were potentiostatically grown crosslinking the designated electrodes, which were prefabricated by lithography, when appropriate square wave AC voltage and appropriate frequency were applied. Micro/nanowire growing process emulated the neurotransmitter release process of synapses inside a biological neuron and wire's resistance variation during the growing process was preferred to as the variation of synaptic weigh in machine learning algorithm. In a cooperation with Graduate School of Information Science and Technology, Hokkaido University.

Towards a Rigorous Assessment of Systems Biology Models: The DREAM3 Challenges

PubMed Central

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

Calculation of precise firing statistics in a neural network model

NASA Astrophysics Data System (ADS)

Cho, Myoung Won

2017-08-01

A precise prediction of neural firing dynamics is requisite to understand the function of and the learning process in a biological neural network which works depending on exact spike timings. Basically, the prediction of firing statistics is a delicate manybody problem because the firing probability of a neuron at a time is determined by the summation over all effects from past firing states. A neural network model with the Feynman path integral formulation is recently introduced. In this paper, we present several methods to calculate firing statistics in the model. We apply the methods to some cases and compare the theoretical predictions with simulation results.

Simultaneous learning of instantaneous and time-delayed genetic interactions using novel information theoretic scoring technique

PubMed Central

2012-01-01

Background Understanding gene interactions is a fundamental question in systems biology. Currently, modeling of gene regulations using the Bayesian Network (BN) formalism assumes that genes interact either instantaneously or with a certain amount of time delay. However in reality, biological regulations, both instantaneous and time-delayed, occur simultaneously. A framework that can detect and model both these two types of interactions simultaneously would represent gene regulatory networks more accurately. Results In this paper, we introduce a framework based on the Bayesian Network (BN) formalism that can represent both instantaneous and time-delayed interactions between genes simultaneously. A novel scoring metric having firm mathematical underpinnings is also proposed that, unlike other recent methods, can score both interactions concurrently and takes into account the reality that multiple regulators can regulate a gene jointly, rather than in an isolated pair-wise manner. Further, a gene regulatory network (GRN) inference method employing an evolutionary search that makes use of the framework and the scoring metric is also presented. Conclusion By taking into consideration the biological fact that both instantaneous and time-delayed regulations can occur among genes, our approach models gene interactions with greater accuracy. The proposed framework is efficient and can be used to infer gene networks having multiple orders of instantaneous and time-delayed regulations simultaneously. Experiments are carried out using three different synthetic networks (with three different mechanisms for generating synthetic data) as well as real life networks of Saccharomyces cerevisiae, E. coli and cyanobacteria gene expression data. The results show the effectiveness of our approach. PMID:22691450

Griffin: A Tool for Symbolic Inference of Synchronous Boolean Molecular Networks.

PubMed

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.

A network model of behavioural performance in a rule learning task.

PubMed

Hasselmo, Michael E; Stern, Chantal E

2018-04-19

Humans demonstrate differences in performance on cognitive rule learning tasks which could involve differences in properties of neural circuits. An example model is presented to show how gating of the spread of neural activity could underlie rule learning and the generalization of rules to previously unseen stimuli. This model uses the activity of gating units to regulate the pattern of connectivity between neurons responding to sensory input and subsequent gating units or output units. This model allows analysis of network parameters that could contribute to differences in cognitive rule learning. These network parameters include differences in the parameters of synaptic modification and presynaptic inhibition of synaptic transmission that could be regulated by neuromodulatory influences on neural circuits. Neuromodulatory receptors play an important role in cognitive function, as demonstrated by the fact that drugs that block cholinergic muscarinic receptors can cause cognitive impairments. In discussions of the links between neuromodulatory systems and biologically based traits, the issue of mechanisms through which these linkages are realized is often missing. This model demonstrates potential roles of neural circuit parameters regulated by acetylcholine in learning context-dependent rules, and demonstrates the potential contribution of variation in neural circuit properties and neuromodulatory function to individual differences in cognitive function.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'. © 2018 The Author(s).

A deep learning framework for causal shape transformation.

PubMed

Lore, Kin Gwn; Stoecklein, Daniel; Davies, Michael; Ganapathysubramanian, Baskar; Sarkar, Soumik

2018-02-01

Recurrent neural network (RNN) and Long Short-term Memory (LSTM) networks are the common go-to architecture for exploiting sequential information where the output is dependent on a sequence of inputs. However, in most considered problems, the dependencies typically lie in the latent domain which may not be suitable for applications involving the prediction of a step-wise transformation sequence that is dependent on the previous states only in the visible domain with a known terminal state. We propose a hybrid architecture of convolution neural networks (CNN) and stacked autoencoders (SAE) to learn a sequence of causal actions that nonlinearly transform an input visual pattern or distribution into a target visual pattern or distribution with the same support and demonstrated its practicality in a real-world engineering problem involving the physics of fluids. We solved a high-dimensional one-to-many inverse mapping problem concerning microfluidic flow sculpting, where the use of deep learning methods as an inverse map is very seldom explored. This work serves as a fruitful use-case to applied scientists and engineers in how deep learning can be beneficial as a solution for high-dimensional physical problems, and potentially opening doors to impactful advance in fields such as material sciences and medical biology where multistep topological transformations is a key element. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhancing the Internationalisation of Distance Education in the Biological Sciences: The DUNE Project and Genetic Engineering.

ERIC Educational Resources Information Center

Leach, C. K.; And Others

1997-01-01

Describes the Distance Educational Network of Europe (DUNE) project that aims at enhancing the development of distance education in an international context. Highlights issues relating to the delivery of distance-learning courses in a transnational forum. Describes the genetic engineering course that aims at explaining the core techniques of…

From Innovation to Impact at Scale: Lessons Learned from a Cluster of Research-Community Partnerships

ERIC Educational Resources Information Center

Schindler, Holly S.; Fisher, Philip A.; Shonkoff, Jack P.

2017-01-01

This article presents a description of how an interdisciplinary network of academic researchers, community-based programs, parents, and state agencies have joined together to design, test, and scale a suite of innovative intervention strategies rooted in new knowledge about the biology of adversity. Through a process of cocreation, collective…

Computational methods using genome-wide association studies to predict radiotherapy complications and to identify correlative molecular processes

NASA Astrophysics Data System (ADS)

Oh, Jung Hun; Kerns, Sarah; Ostrer, Harry; Powell, Simon N.; Rosenstein, Barry; Deasy, Joseph O.

2017-02-01

The biological cause of clinically observed variability of normal tissue damage following radiotherapy is poorly understood. We hypothesized that machine/statistical learning methods using single nucleotide polymorphism (SNP)-based genome-wide association studies (GWAS) would identify groups of patients of differing complication risk, and furthermore could be used to identify key biological sources of variability. We developed a novel learning algorithm, called pre-conditioned random forest regression (PRFR), to construct polygenic risk models using hundreds of SNPs, thereby capturing genomic features that confer small differential risk. Predictive models were trained and validated on a cohort of 368 prostate cancer patients for two post-radiotherapy clinical endpoints: late rectal bleeding and erectile dysfunction. The proposed method results in better predictive performance compared with existing computational methods. Gene ontology enrichment analysis and protein-protein interaction network analysis are used to identify key biological processes and proteins that were plausible based on other published studies. In conclusion, we confirm that novel machine learning methods can produce large predictive models (hundreds of SNPs), yielding clinically useful risk stratification models, as well as identifying important underlying biological processes in the radiation damage and tissue repair process. The methods are generally applicable to GWAS data and are not specific to radiotherapy endpoints.

Unified Deep Learning Architecture for Modeling Biology Sequence.

PubMed

Wu, Hongjie; Cao, Chengyuan; Xia, Xiaoyan; Lu, Qiang

2017-10-09

Prediction of the spatial structure or function of biological macromolecules based on their sequence remains an important challenge in bioinformatics. When modeling biological sequences using traditional sequencing models, characteristics, such as long-range interactions between basic units, the complicated and variable output of labeled structures, and the variable length of biological sequences, usually lead to different solutions on a case-by-case basis. This study proposed the use of bidirectional recurrent neural networks based on long short-term memory or a gated recurrent unit to capture long-range interactions by designing the optional reshape operator to adapt to the diversity of the output labels and implementing a training algorithm to support the training of sequence models capable of processing variable-length sequences. Additionally, the merge and pooling operators enhanced the ability to capture short-range interactions between basic units of biological sequences. The proposed deep-learning model and its training algorithm might be capable of solving currently known biological sequence-modeling problems through the use of a unified framework. We validated our model on one of the most difficult biological sequence-modeling problems currently known, with our results indicating the ability of the model to obtain predictions of protein residue interactions that exceeded the accuracy of current popular approaches by 10% based on multiple benchmarks.

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

PubMed Central

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

2013-01-01

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

Quantum neural networks: Current status and prospects for development

NASA Astrophysics Data System (ADS)

Altaisky, M. V.; Kaputkina, N. E.; Krylov, V. A.

2014-11-01

The idea of quantum artificial neural networks, first formulated in [34], unites the artificial neural network concept with the quantum computation paradigm. Quantum artificial neural networks were first systematically considered in the PhD thesis by T. Menneer (1998). Based on the works of Menneer and Narayanan [42, 43], Kouda, Matsui, and Nishimura [35, 36], Altaisky [2, 68], Zhou [67], and others, quantum-inspired learning algorithms for neural networks were developed, and are now used in various training programs and computer games [29, 30]. The first practically realizable scaled hardware-implemented model of the quantum artificial neural network is obtained by D-Wave Systems, Inc. [33]. It is a quantum Hopfield network implemented on the basis of superconducting quantum interference devices (SQUIDs). In this work we analyze possibilities and underlying principles of an alternative way to implement quantum neural networks on the basis of quantum dots. A possibility of using quantum neural network algorithms in automated control systems, associative memory devices, and in modeling biological and social networks is examined.

Efficient Training of Supervised Spiking Neural Network via Accurate Synaptic-Efficiency Adjustment Method.

PubMed

Xie, Xiurui; Qu, Hong; Yi, Zhang; Kurths, Jurgen

2017-06-01

The spiking neural network (SNN) is the third generation of neural networks and performs remarkably well in cognitive tasks, such as pattern recognition. The temporal neural encode mechanism found in biological hippocampus enables SNN to possess more powerful computation capability than networks with other encoding schemes. However, this temporal encoding approach requires neurons to process information serially on time, which reduces learning efficiency significantly. To keep the powerful computation capability of the temporal encoding mechanism and to overcome its low efficiency in the training of SNNs, a new training algorithm, the accurate synaptic-efficiency adjustment method is proposed in this paper. Inspired by the selective attention mechanism of the primate visual system, our algorithm selects only the target spike time as attention areas, and ignores voltage states of the untarget ones, resulting in a significant reduction of training time. Besides, our algorithm employs a cost function based on the voltage difference between the potential of the output neuron and the firing threshold of the SNN, instead of the traditional precise firing time distance. A normalized spike-timing-dependent-plasticity learning window is applied to assigning this error to different synapses for instructing their training. Comprehensive simulations are conducted to investigate the learning properties of our algorithm, with input neurons emitting both single spike and multiple spikes. Simulation results indicate that our algorithm possesses higher learning performance than the existing other methods and achieves the state-of-the-art efficiency in the training of SNN.

Local or distributed activation? The view from biology

NASA Astrophysics Data System (ADS)

Reimers, Mark

2011-06-01

There is considerable disagreement among connectionist modellers over whether to represent distinct properties by distinct nodes of a network or whether properties should be represented by patterns of activity across all nodes. This paper draws on the literature of neuroscience to say that a more subtle way of describing how different brain regions contribute to a behaviour, in terms of individual learning and in terms of degrees of importance, may render the current debate moot: both sides of the 'localist' versus 'distributed' debate emphasise different aspects of biology.

Detection of multiple perturbations in multi-omics biological networks.

PubMed

Griffin, Paula J; Zhang, Yuqing; Johnson, William Evan; Kolaczyk, Eric D

2018-05-17

Cellular mechanism-of-action is of fundamental concern in many biological studies. It is of particular interest for identifying the cause of disease and learning the way in which treatments act against disease. However, pinpointing such mechanisms is difficult, due to the fact that small perturbations to the cell can have wide-ranging downstream effects. Given a snapshot of cellular activity, it can be challenging to tell where a disturbance originated. The presence of an ever-greater variety of high-throughput biological data offers an opportunity to examine cellular behavior from multiple angles, but also presents the statistical challenge of how to effectively analyze data from multiple sources. In this setting, we propose a method for mechanism-of-action inference by extending network filtering to multi-attribute data. We first estimate a joint Gaussian graphical model across multiple data types using penalized regression and filter for network effects. We then apply a set of likelihood ratio tests to identify the most likely site of the original perturbation. In addition, we propose a conditional testing procedure to allow for detection of multiple perturbations. We demonstrate this methodology on paired gene expression and methylation data from The Cancer Genome Atlas (TCGA). © 2018, The International Biometric Society.

Five years of designing wireless sensor networks in the Doñana Biological Reserve (Spain): an applications approach.

PubMed

Larios, Diego F; Barbancho, Julio; Sevillano, José L; Rodríguez, Gustavo; Molina, Francisco J; Gasull, Virginia G; Mora-Merchan, Javier M; León, Carlos

2013-09-10

Wireless Sensor Networks (WSNs) are a technology that is becoming very popular for many applications, and environmental monitoring is one of its most important application areas. This technology solves the lack of flexibility of wired sensor installations and, at the same time, reduces the deployment costs. To demonstrate the advantages of WSN technology, for the last five years we have been deploying some prototypes in the Doñana Biological Reserve, which is an important protected area in Southern Spain. These prototypes not only evaluate the technology, but also solve some of the monitoring problems that have been raised by biologists working in Doñana. This paper presents a review of the work that has been developed during these five years. Here, we demonstrate the enormous potential of using machine learning in wireless sensor networks for environmental and animal monitoring because this approach increases the amount of useful information and reduces the effort that is required by biologists in an environmental monitoring task.

Biological modelling of a computational spiking neural network with neuronal avalanches.

PubMed

Li, Xiumin; Chen, Qing; Xue, Fangzheng

2017-06-28

In recent years, an increasing number of studies have demonstrated that networks in the brain can self-organize into a critical state where dynamics exhibit a mixture of ordered and disordered patterns. This critical branching phenomenon is termed neuronal avalanches. It has been hypothesized that the homeostatic level balanced between stability and plasticity of this critical state may be the optimal state for performing diverse neural computational tasks. However, the critical region for high performance is narrow and sensitive for spiking neural networks (SNNs). In this paper, we investigated the role of the critical state in neural computations based on liquid-state machines, a biologically plausible computational neural network model for real-time computing. The computational performance of an SNN when operating at the critical state and, in particular, with spike-timing-dependent plasticity for updating synaptic weights is investigated. The network is found to show the best computational performance when it is subjected to critical dynamic states. Moreover, the active-neuron-dominant structure refined from synaptic learning can remarkably enhance the robustness of the critical state and further improve computational accuracy. These results may have important implications in the modelling of spiking neural networks with optimal computational performance.This article is part of the themed issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'. © 2017 The Author(s).

Biological modelling of a computational spiking neural network with neuronal avalanches

NASA Astrophysics Data System (ADS)

Li, Xiumin; Chen, Qing; Xue, Fangzheng

2017-05-01

In recent years, an increasing number of studies have demonstrated that networks in the brain can self-organize into a critical state where dynamics exhibit a mixture of ordered and disordered patterns. This critical branching phenomenon is termed neuronal avalanches. It has been hypothesized that the homeostatic level balanced between stability and plasticity of this critical state may be the optimal state for performing diverse neural computational tasks. However, the critical region for high performance is narrow and sensitive for spiking neural networks (SNNs). In this paper, we investigated the role of the critical state in neural computations based on liquid-state machines, a biologically plausible computational neural network model for real-time computing. The computational performance of an SNN when operating at the critical state and, in particular, with spike-timing-dependent plasticity for updating synaptic weights is investigated. The network is found to show the best computational performance when it is subjected to critical dynamic states. Moreover, the active-neuron-dominant structure refined from synaptic learning can remarkably enhance the robustness of the critical state and further improve computational accuracy. These results may have important implications in the modelling of spiking neural networks with optimal computational performance. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

Probing the functions of long non-coding RNAs by exploiting the topology of global association and interaction network.

PubMed

Deng, Lei; Wu, Hongjie; Liu, Chuyao; Zhan, Weihua; Zhang, Jingpu

2018-06-01

Long non-coding RNAs (lncRNAs) are involved in many biological processes, such as immune response, development, differentiation and gene imprinting and are associated with diseases and cancers. But the functions of the vast majority of lncRNAs are still unknown. Predicting the biological functions of lncRNAs is one of the key challenges in the post-genomic era. In our work, We first build a global network including a lncRNA similarity network, a lncRNA-protein association network and a protein-protein interaction network according to the expressions and interactions, then extract the topological feature vectors of the global network. Using these features, we present an SVM-based machine learning approach, PLNRGO, to annotate human lncRNAs. In PLNRGO, we construct a training data set according to the proteins with GO annotations and train a binary classifier for each GO term. We assess the performance of PLNRGO on our manually annotated lncRNA benchmark and a protein-coding gene benchmark with known functional annotations. As a result, the performance of our method is significantly better than that of other state-of-the-art methods in terms of maximum F-measure and coverage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adaptive Neurotechnology for Making Neural Circuits Functional .

NASA Astrophysics Data System (ADS)

Jung, Ranu

2008-03-01

Two of the most important trends in recent technological developments are that technology is increasingly integrated with biological systems and that it is increasingly adaptive in its capabilities. Neuroprosthetic systems that provide lost sensorimotor function after a neural disability offer a platform to investigate this interplay between biological and engineered systems. Adaptive neurotechnology (hardware and software) could be designed to be biomimetic, guided by the physical and programmatic constraints observed in biological systems, and allow for real-time learning, stability, and error correction. An example will present biomimetic neural-network hardware that can be interfaced with the isolated spinal cord of a lower vertebrate to allow phase-locked real-time neural control. Another will present adaptive neural network control algorithms for functional electrical stimulation of the peripheral nervous system to provide desired movements of paralyzed limbs in rodents or people. Ultimately, the frontier lies in being able to utilize the adaptive neurotechnology to promote neuroplasticity in the living system on a long-time scale under co-adaptive conditions.

Reverse engineering of gene regulatory networks.

PubMed

Cho, K H; Choo, S M; Jung, S H; Kim, J R; Choi, H S; Kim, J

2007-05-01

Systems biology is a multi-disciplinary approach to the study of the interactions of various cellular mechanisms and cellular components. Owing to the development of new technologies that simultaneously measure the expression of genetic information, systems biological studies involving gene interactions are increasingly prominent. In this regard, reconstructing gene regulatory networks (GRNs) forms the basis for the dynamical analysis of gene interactions and related effects on cellular control pathways. Various approaches of inferring GRNs from gene expression profiles and biological information, including machine learning approaches, have been reviewed, with a brief introduction of DNA microarray experiments as typical tools for measuring levels of messenger ribonucleic acid (mRNA) expression. In particular, the inference methods are classified according to the required input information, and the main idea of each method is elucidated by comparing its advantages and disadvantages with respect to the other methods. In addition, recent developments in this field are introduced and discussions on the challenges and opportunities for future research are provided.

Review of Statistical Learning Methods in Integrated Omics Studies (An Integrated Information Science).

PubMed

Zeng, Irene Sui Lan; Lumley, Thomas

2018-01-01

Integrated omics is becoming a new channel for investigating the complex molecular system in modern biological science and sets a foundation for systematic learning for precision medicine. The statistical/machine learning methods that have emerged in the past decade for integrated omics are not only innovative but also multidisciplinary with integrated knowledge in biology, medicine, statistics, machine learning, and artificial intelligence. Here, we review the nontrivial classes of learning methods from the statistical aspects and streamline these learning methods within the statistical learning framework. The intriguing findings from the review are that the methods used are generalizable to other disciplines with complex systematic structure, and the integrated omics is part of an integrated information science which has collated and integrated different types of information for inferences and decision making. We review the statistical learning methods of exploratory and supervised learning from 42 publications. We also discuss the strengths and limitations of the extended principal component analysis, cluster analysis, network analysis, and regression methods. Statistical techniques such as penalization for sparsity induction when there are fewer observations than the number of features and using Bayesian approach when there are prior knowledge to be integrated are also included in the commentary. For the completeness of the review, a table of currently available software and packages from 23 publications for omics are summarized in the appendix.

Neural sensitivity to statistical regularities as a fundamental biological process that underlies auditory learning: the role of musical practice.

PubMed

François, Clément; Schön, Daniele

2014-02-01

There is increasing evidence that humans and other nonhuman mammals are sensitive to the statistical structure of auditory input. Indeed, neural sensitivity to statistical regularities seems to be a fundamental biological property underlying auditory learning. In the case of speech, statistical regularities play a crucial role in the acquisition of several linguistic features, from phonotactic to more complex rules such as morphosyntactic rules. Interestingly, a similar sensitivity has been shown with non-speech streams: sequences of sounds changing in frequency or timbre can be segmented on the sole basis of conditional probabilities between adjacent sounds. We recently ran a set of cross-sectional and longitudinal experiments showing that merging music and speech information in song facilitates stream segmentation and, further, that musical practice enhances sensitivity to statistical regularities in speech at both neural and behavioral levels. Based on recent findings showing the involvement of a fronto-temporal network in speech segmentation, we defend the idea that enhanced auditory learning observed in musicians originates via at least three distinct pathways: enhanced low-level auditory processing, enhanced phono-articulatory mapping via the left Inferior Frontal Gyrus and Pre-Motor cortex and increased functional connectivity within the audio-motor network. Finally, we discuss how these data predict a beneficial use of music for optimizing speech acquisition in both normal and impaired populations. Copyright © 2013 Elsevier B.V. All rights reserved.

A Spiking Neural Network System for Robust Sequence Recognition.

PubMed

Yu, Qiang; Yan, Rui; Tang, Huajin; Tan, Kay Chen; Li, Haizhou

2016-03-01

This paper proposes a biologically plausible network architecture with spiking neurons for sequence recognition. This architecture is a unified and consistent system with functional parts of sensory encoding, learning, and decoding. This is the first systematic model attempting to reveal the neural mechanisms considering both the upstream and the downstream neurons together. The whole system is a consistent temporal framework, where the precise timing of spikes is employed for information processing and cognitive computing. Experimental results show that the system is competent to perform the sequence recognition, being robust to noisy sensory inputs and invariant to changes in the intervals between input stimuli within a certain range. The classification ability of the temporal learning rule used in the system is investigated through two benchmark tasks that outperform the other two widely used learning rules for classification. The results also demonstrate the computational power of spiking neurons over perceptrons for processing spatiotemporal patterns. In summary, the system provides a general way with spiking neurons to encode external stimuli into spatiotemporal spikes, to learn the encoded spike patterns with temporal learning rules, and to decode the sequence order with downstream neurons. The system structure would be beneficial for developments in both hardware and software.

Recovering time-varying networks of dependencies in social and biological studies.

PubMed

Ahmed, Amr; Xing, Eric P

2009-07-21

A plausible representation of the relational information among entities in dynamic systems such as a living cell or a social community is a stochastic network that is topologically rewiring and semantically evolving over time. Although there is a rich literature in modeling static or temporally invariant networks, little has been done toward recovering the network structure when the networks are not observable in a dynamic context. In this article, we present a machine learning method called TESLA, which builds on a temporally smoothed l(1)-regularized logistic regression formalism that can be cast as a standard convex-optimization problem and solved efficiently by using generic solvers scalable to large networks. We report promising results on recovering simulated time-varying networks and on reverse engineering the latent sequence of temporally rewiring political and academic social networks from longitudinal data, and the evolving gene networks over >4,000 genes during the life cycle of Drosophila melanogaster from a microarray time course at a resolution limited only by sample frequency.

A computational model of Dopamine and Acetylcholine aberrant learning in Basal Ganglia.

PubMed

Baston, Chiara; Ursino, Mauro

2015-01-01

Basal Ganglia (BG) are implied in many motor and cognitive tasks, such as action selection, and have a central role in many pathologies, primarily Parkinson Disease. In the present work, we use a recently developed biologically inspired BG model to analyze how the dopamine (DA) level can affect the temporal response during action selection, and the capacity to learn new actions following rewards and punishments. The model incorporates the 3 main pathways (direct, indirect and hyperdirect) working in BG functioning. The behavior of 2 alternative networks (the first with normal DA levels, the second with reduced DA) is analyzed both in untrained conditions, and during training performed in different epochs. The results show that reduced DA causes delayed temporal responses in the untrained network, and difficult of learning during training, characterized by the necessity of much more epochs. The results provide interesting hints to understand the behavior of healthy and dopamine depleted subjects, such as parkinsonian patients.

Structure-based control of complex networks with nonlinear dynamics.

PubMed

Zañudo, Jorge Gomez Tejeda; Yang, Gang; Albert, Réka

2017-07-11

What can we learn about controlling a system solely from its underlying network structure? Here we adapt a recently developed framework for control of networks governed by a broad class of nonlinear dynamics that includes the major dynamic models of biological, technological, and social processes. This feedback-based framework provides realizable node overrides that steer a system toward any of its natural long-term dynamic behaviors, regardless of the specific functional forms and system parameters. We use this framework on several real networks, identify the topological characteristics that underlie the predicted node overrides, and compare its predictions to those of structural controllability in control theory. Finally, we demonstrate this framework's applicability in dynamic models of gene regulatory networks and identify nodes whose override is necessary for control in the general case but not in specific model instances.

Unsupervised Learning and Pattern Recognition of Biological Data Structures with Density Functional Theory and Machine Learning.

PubMed

Chen, Chien-Chang; Juan, Hung-Hui; Tsai, Meng-Yuan; Lu, Henry Horng-Shing

2018-01-11

By introducing the methods of machine learning into the density functional theory, we made a detour for the construction of the most probable density function, which can be estimated by learning relevant features from the system of interest. Using the properties of universal functional, the vital core of density functional theory, the most probable cluster numbers and the corresponding cluster boundaries in a studying system can be simultaneously and automatically determined and the plausibility is erected on the Hohenberg-Kohn theorems. For the method validation and pragmatic applications, interdisciplinary problems from physical to biological systems were enumerated. The amalgamation of uncharged atomic clusters validated the unsupervised searching process of the cluster numbers and the corresponding cluster boundaries were exhibited likewise. High accurate clustering results of the Fisher's iris dataset showed the feasibility and the flexibility of the proposed scheme. Brain tumor detections from low-dimensional magnetic resonance imaging datasets and segmentations of high-dimensional neural network imageries in the Brainbow system were also used to inspect the method practicality. The experimental results exhibit the successful connection between the physical theory and the machine learning methods and will benefit the clinical diagnoses.

Inference of genetic network of Xenopus frog egg: improved genetic algorithm.

PubMed

Wu, Shinq-Jen; Chou, Chia-Hsien; Wu, Cheng-Tao; Lee, Tsu-Tian

2006-01-01

An improved genetic algorithm (IGA) is proposed to achieve S-system gene network modeling of Xenopus frog egg. Via the time-courses training datasets from Michaelis-Menten model, the optimal parameters are learned. The S-system can clearly describe activative and inhibitory interaction between genes as generating and consuming process. We concern the mitotic control in cell-cycle of Xenopus frog egg to realize cyclin-Cdc2 and Cdc25 for MPF activity. The proposed IGA can achieve global search with migration and keep the best chromosome with elitism operation. The generated gene regulatory networks can provide biological researchers for further experiments in Xenopus frog egg cell cycle control.

Still searching for the engram.

PubMed

Eichenbaum, Howard

2016-09-01

For nearly a century, neurobiologists have searched for the engram-the neural representation of a memory. Early studies showed that the engram is widely distributed both within and across brain areas and is supported by interactions among large networks of neurons. Subsequent research has identified engrams that support memory within dedicated functional systems for habit learning and emotional memory, but the engram for declarative memories has been elusive. Nevertheless, recent years have brought progress from molecular biological approaches that identify neurons and networks that are necessary and sufficient to support memory, and from recording approaches and population analyses that characterize the information coded by large neural networks. These new directions offer the promise of revealing the engrams for episodic and semantic memories.

From neural-based object recognition toward microelectronic eyes

NASA Technical Reports Server (NTRS)

Sheu, Bing J.; Bang, Sa Hyun

1994-01-01

Engineering neural network systems are best known for their abilities to adapt to the changing characteristics of the surrounding environment by adjusting system parameter values during the learning process. Rapid advances in analog current-mode design techniques have made possible the implementation of major neural network functions in custom VLSI chips. An electrically programmable analog synapse cell with large dynamic range can be realized in a compact silicon area. New designs of the synapse cells, neurons, and analog processor are presented. A synapse cell based on Gilbert multiplier structure can perform the linear multiplication for back-propagation networks. A double differential-pair synapse cell can perform the Gaussian function for radial-basis network. The synapse cells can be biased in the strong inversion region for high-speed operation or biased in the subthreshold region for low-power operation. The voltage gain of the sigmoid-function neurons is externally adjustable which greatly facilitates the search of optimal solutions in certain networks. Various building blocks can be intelligently connected to form useful industrial applications. Efficient data communication is a key system-level design issue for large-scale networks. We also present analog neural processors based on perceptron architecture and Hopfield network for communication applications. Biologically inspired neural networks have played an important role towards the creation of powerful intelligent machines. Accuracy, limitations, and prospects of analog current-mode design of the biologically inspired vision processing chips and cellular neural network chips are key design issues.

Active subnetwork recovery with a mechanism-dependent scoring function; with application to angiogenesis and organogenesis studies

PubMed Central

2013-01-01

Background The learning active subnetworks problem involves finding subnetworks of a bio-molecular network that are active in a particular condition. Many approaches integrate observation data (e.g., gene expression) with the network topology to find candidate subnetworks. Increasingly, pathway databases contain additional annotation information that can be mined to improve prediction accuracy, e.g., interaction mechanism (e.g., transcription, microRNA, cleavage) annotations. We introduce a mechanism-based approach to active subnetwork recovery which exploits such annotations. We suggest that neighboring interactions in a network tend to be co-activated in a way that depends on the “correlation” of their mechanism annotations. e.g., neighboring phosphorylation and de-phosphorylation interactions may be more likely to be co-activated than neighboring phosphorylation and covalent bonding interactions. Results Our method iteratively learns the mechanism correlations and finds the most likely active subnetwork. We use a probabilistic graphical model with a Markov Random Field component which creates dependencies between the states (active or non-active) of neighboring interactions, that incorporates a mechanism-based component to the function. We apply a heuristic-based EM-based algorithm suitable for the problem. We validated our method’s performance using simulated data in networks downloaded from GeneGO against the same approach without the mechanism-based component, and two other existing methods. We validated our methods performance in correctly recovering (1) the true interaction states, and (2) global network properties of the original network against these other methods. We applied our method to networks generated from time-course gene expression studies in angiogenesis and lung organogenesis and validated the findings from a biological perspective against current literature. Conclusions The advantage of our mechanism-based approach is best seen in networks composed of connected regions with a large number of interactions annotated with a subset of mechanisms, e.g., a regulatory region of transcription interactions, or a cleavage cascade region. When applied to real datasets, our method recovered novel and biologically meaningful putative interactions, e.g., interactions from an integrin signaling pathway using the angiogenesis dataset, and a group of regulatory microRNA interactions in an organogenesis network. PMID:23432934

Automatically identifying, counting, and describing wild animals in camera-trap images with deep learning.

PubMed

Norouzzadeh, Mohammad Sadegh; Nguyen, Anh; Kosmala, Margaret; Swanson, Alexandra; Palmer, Meredith S; Packer, Craig; Clune, Jeff

2018-06-19

Having accurate, detailed, and up-to-date information about the location and behavior of animals in the wild would improve our ability to study and conserve ecosystems. We investigate the ability to automatically, accurately, and inexpensively collect such data, which could help catalyze the transformation of many fields of ecology, wildlife biology, zoology, conservation biology, and animal behavior into "big data" sciences. Motion-sensor "camera traps" enable collecting wildlife pictures inexpensively, unobtrusively, and frequently. However, extracting information from these pictures remains an expensive, time-consuming, manual task. We demonstrate that such information can be automatically extracted by deep learning, a cutting-edge type of artificial intelligence. We train deep convolutional neural networks to identify, count, and describe the behaviors of 48 species in the 3.2 million-image Snapshot Serengeti dataset. Our deep neural networks automatically identify animals with >93.8% accuracy, and we expect that number to improve rapidly in years to come. More importantly, if our system classifies only images it is confident about, our system can automate animal identification for 99.3% of the data while still performing at the same 96.6% accuracy as that of crowdsourced teams of human volunteers, saving >8.4 y (i.e., >17,000 h at 40 h/wk) of human labeling effort on this 3.2 million-image dataset. Those efficiency gains highlight the importance of using deep neural networks to automate data extraction from camera-trap images, reducing a roadblock for this widely used technology. Our results suggest that deep learning could enable the inexpensive, unobtrusive, high-volume, and even real-time collection of a wealth of information about vast numbers of animals in the wild. Copyright © 2018 the Author(s). Published by PNAS.

Cooperation of Deterministic Dynamics and Random Noise in Production of Complex Syntactical Avian Song Sequences: A Neural Network Model

PubMed Central

Yamashita, Yuichi; Okumura, Tetsu; Okanoya, Kazuo; Tani, Jun

2011-01-01

How the brain learns and generates temporal sequences is a fundamental issue in neuroscience. The production of birdsongs, a process which involves complex learned sequences, provides researchers with an excellent biological model for this topic. The Bengalese finch in particular learns a highly complex song with syntactical structure. The nucleus HVC (HVC), a premotor nucleus within the avian song system, plays a key role in generating the temporal structures of their songs. From lesion studies, the nucleus interfacialis (NIf) projecting to the HVC is considered one of the essential regions that contribute to the complexity of their songs. However, the types of interaction between the HVC and the NIf that can produce complex syntactical songs remain unclear. In order to investigate the function of interactions between the HVC and NIf, we have proposed a neural network model based on previous biological evidence. The HVC is modeled by a recurrent neural network (RNN) that learns to generate temporal patterns of songs. The NIf is modeled as a mechanism that provides auditory feedback to the HVC and generates random noise that feeds into the HVC. The model showed that complex syntactical songs can be replicated by simple interactions between deterministic dynamics of the RNN and random noise. In the current study, the plausibility of the model is tested by the comparison between the changes in the songs of actual birds induced by pharmacological inhibition of the NIf and the changes in the songs produced by the model resulting from modification of parameters representing NIf functions. The efficacy of the model demonstrates that the changes of songs induced by pharmacological inhibition of the NIf can be interpreted as a trade-off between the effects of noise and the effects of feedback on the dynamics of the RNN of the HVC. These facts suggest that the current model provides a convincing hypothesis for the functional role of NIf–HVC interaction. PMID:21559065

Simulation of a Classically Conditioned Response: Components of the Input Trace and a Cerebellar Neural Network Implementation of the Sutton-Barto-Desmond Model.

DTIC Science & Technology

1987-09-14

set of coordinates that will facilitate discussion. Figure 16 omits some of details included in most textbook renderings of the cerebellum. For...Engineering, BME -24: 449-456 (1977). Hawkins, R.D. and Kandel, E.R. Is there a cell-biological alphabet for simple forms of learning? Psychological Review

Network-based discovery through mechanistic systems biology. Implications for applications--SMEs and drug discovery: where the action is.

PubMed

Benson, Neil

2015-08-01

Phase II attrition remains the most important challenge for drug discovery. Tackling the problem requires improved understanding of the complexity of disease biology. Systems biology approaches to this problem can, in principle, deliver this. This article reviews the reports of the application of mechanistic systems models to drug discovery questions and discusses the added value. Although we are on the journey to the virtual human, the length, path and rate of learning from this remain an open question. Success will be dependent on the will to invest and make the most of the insight generated along the way. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exploring the limits of learning: Segregation of information integration and response selection is required for learning a serial reversal task

PubMed Central

Zanutto, B. Silvano

2017-01-01

Animals are proposed to learn the latent rules governing their environment in order to maximize their chances of survival. However, rules may change without notice, forcing animals to keep a memory of which one is currently at work. Rule switching can lead to situations in which the same stimulus/response pairing is positively and negatively rewarded in the long run, depending on variables that are not accessible to the animal. This fact raises questions on how neural systems are capable of reinforcement learning in environments where the reinforcement is inconsistent. Here we address this issue by asking about which aspects of connectivity, neural excitability and synaptic plasticity are key for a very general, stochastic spiking neural network model to solve a task in which rules change without being cued, taking the serial reversal task (SRT) as paradigm. Contrary to what could be expected, we found strong limitations for biologically plausible networks to solve the SRT. Especially, we proved that no network of neurons can learn a SRT if it is a single neural population that integrates stimuli information and at the same time is responsible of choosing the behavioural response. This limitation is independent of the number of neurons, neuronal dynamics or plasticity rules, and arises from the fact that plasticity is locally computed at each synapse, and that synaptic changes and neuronal activity are mutually dependent processes. We propose and characterize a spiking neural network model that solves the SRT, which relies on separating the functions of stimuli integration and response selection. The model suggests that experimental efforts to understand neural function should focus on the characterization of neural circuits according to their connectivity, neural dynamics, and the degree of modulation of synaptic plasticity with reward. PMID:29077735

Frontal hyperconnectivity related to discounting and reversal learning in cocaine subjects.

PubMed

Camchong, Jazmin; MacDonald, Angus W; Nelson, Brent; Bell, Christopher; Mueller, Bryon A; Specker, Sheila; Lim, Kelvin O

2011-06-01

Functional neuroimaging studies suggest that chronic cocaine use is associated with frontal lobe abnormalities. Functional connectivity (FC) alterations of cocaine-dependent individuals (CD), however, are not yet clear. This is the first study to our knowledge that examines resting FC of anterior cingulate cortex (ACC) in CD. Because ACC is known to integrate inputs from different brain regions to regulate behavior, we hypothesized that CD will have connectivity abnormalities in ACC networks. In addition, we hypothesized that abnormalities would be associated with poor performance in delayed discounting and reversal learning tasks. Resting functional magnetic resonance imaging data were collected to look for FC differences between 27 CD (5 women, age: M = 39.73, SD = 6.14 years) and 24 control subjects (5 women, age: M = 39.76, SD = 7.09 years). Participants were assessed with delayed discounting and reversal learning tasks. With seed-based FC measures, we examined FC in CD and control subjects within five ACC connectivity networks with seeds in subgenual, caudal, dorsal, rostral, and perigenual ACC. The CD showed increased FC within the perigenual ACC network in left middle frontal gyrus, ACC, and middle temporal gyrus when compared with control subjects. The FC abnormalities were significantly positively correlated with task performance in delayed discounting and reversal learning tasks in CD. The present study shows that participants with chronic cocaine-dependency have hyperconnectivity within an ACC network known to be involved in social processing and "mentalizing." In addition, FC abnormalities found in CD were associated with difficulties with delay rewards and slower adaptive learning. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2017-02-01

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

Integrative gene network construction to analyze cancer recurrence using semi-supervised learning.

PubMed

Park, Chihyun; Ahn, Jaegyoon; Kim, Hyunjin; Park, Sanghyun

2014-01-01

The prognosis of cancer recurrence is an important research area in bioinformatics and is challenging due to the small sample sizes compared to the vast number of genes. There have been several attempts to predict cancer recurrence. Most studies employed a supervised approach, which uses only a few labeled samples. Semi-supervised learning can be a great alternative to solve this problem. There have been few attempts based on manifold assumptions to reveal the detailed roles of identified cancer genes in recurrence. In order to predict cancer recurrence, we proposed a novel semi-supervised learning algorithm based on a graph regularization approach. We transformed the gene expression data into a graph structure for semi-supervised learning and integrated protein interaction data with the gene expression data to select functionally-related gene pairs. Then, we predicted the recurrence of cancer by applying a regularization approach to the constructed graph containing both labeled and unlabeled nodes. The average improvement rate of accuracy for three different cancer datasets was 24.9% compared to existing supervised and semi-supervised methods. We performed functional enrichment on the gene networks used for learning. We identified that those gene networks are significantly associated with cancer-recurrence-related biological functions. Our algorithm was developed with standard C++ and is available in Linux and MS Windows formats in the STL library. The executable program is freely available at: http://embio.yonsei.ac.kr/~Park/ssl.php.

Spontaneous scale-free structure in adaptive networks with synchronously dynamical linking

NASA Astrophysics Data System (ADS)

Yuan, Wu-Jie; Zhou, Jian-Fang; Li, Qun; Chen, De-Bao; Wang, Zhen

2013-08-01

Inspired by the anti-Hebbian learning rule in neural systems, we study how the feedback from dynamical synchronization shapes network structure by adding new links. Through extensive numerical simulations, we find that an adaptive network spontaneously forms scale-free structure, as confirmed in many real systems. Moreover, the adaptive process produces two nontrivial power-law behaviors of deviation strength from mean activity of the network and negative degree correlation, which exists widely in technological and biological networks. Importantly, these scalings are robust to variation of the adaptive network parameters, which may have meaningful implications in the scale-free formation and manipulation of dynamical networks. Our study thus suggests an alternative adaptive mechanism for the formation of scale-free structure with negative degree correlation, which means that nodes of high degree tend to connect, on average, with others of low degree and vice versa. The relevance of the results to structure formation and dynamical property in neural networks is briefly discussed as well.

Inference, simulation, modeling, and analysis of complex networks, with special emphasis on complex networks in systems biology

NASA Astrophysics Data System (ADS)

Christensen, Claire Petra

Across diverse fields ranging from physics to biology, sociology, and economics, the technological advances of the past decade have engendered an unprecedented explosion of data on highly complex systems with thousands, if not millions of interacting components. These systems exist at many scales of size and complexity, and it is becoming ever-more apparent that they are, in fact, universal, arising in every field of study. Moreover, they share fundamental properties---chief among these, that the individual interactions of their constituent parts may be well-understood, but the characteristic behaviour produced by the confluence of these interactions---by these complex networks---is unpredictable; in a nutshell, the whole is more than the sum of its parts. There is, perhaps, no better illustration of this concept than the discoveries being made regarding complex networks in the biological sciences. In particular, though the sequencing of the human genome in 2003 was a remarkable feat, scientists understand that the "cellular-level blueprints" for the human being are cellular-level parts lists, but they say nothing (explicitly) about cellular-level processes. The challenge of modern molecular biology is to understand these processes in terms of the networks of parts---in terms of the interactions among proteins, enzymes, genes, and metabolites---as it is these processes that ultimately differentiate animate from inanimate, giving rise to life! It is the goal of systems biology---an umbrella field encapsulating everything from molecular biology to epidemiology in social systems---to understand processes in terms of fundamental networks of core biological parts, be they proteins or people. By virtue of the fact that there are literally countless complex systems, not to mention tools and techniques used to infer, simulate, analyze, and model these systems, it is impossible to give a truly comprehensive account of the history and study of complex systems. The author's own publications have contributed network inference, simulation, modeling, and analysis methods to the much larger body of work in systems biology, and indeed, in network science. The aim of this thesis is therefore twofold: to present this original work in the historical context of network science, but also to provide sufficient review and reference regarding complex systems (with an emphasis on complex networks in systems biology) and tools and techniques for their inference, simulation, analysis, and modeling, such that the reader will be comfortable in seeking out further information on the subject. The review-like Chapters 1, 2, and 4 are intended to convey the co-evolution of network science and the slow but noticeable breakdown of boundaries between disciplines in academia as research and comparison of diverse systems has brought to light the shared properties of these systems. It is the author's hope that theses chapters impart some sense of the remarkable and rapid progress in complex systems research that has led to this unprecedented academic synergy. Chapters 3 and 5 detail the author's original work in the context of complex systems research. Chapter 3 presents the methods and results of a two-stage modeling process that generates candidate gene-regulatory networks of the bacterium B.subtilis from experimentally obtained, yet mathematically underdetermined microchip array data. These networks are then analyzed from a graph theoretical perspective, and their biological viability is critiqued by comparing the networks' graph theoretical properties to those of other biological systems. The results of topological perturbation analyses revealing commonalities in behavior at multiple levels of complexity are also presented, and are shown to be an invaluable means by which to ascertain the level of complexity to which the network inference process is robust to noise. Chapter 5 outlines a learning algorithm for the development of a realistic, evolving social network (a city) into which a disease is introduced. The results of simulations in populations spanning two orders of magnitude are compared to prevaccine era measles data for England and Wales and demonstrate that the simulations are able to capture the quantitative and qualitative features of epidemics in populations as small as 10,000 people. The work presented in Chapter 5 validates the utility of network simulation in concurrently probing contact network dynamics and disease dynamics.

Biological network motif detection and evaluation

PubMed Central

2011-01-01

Background Molecular level of biological data can be constructed into system level of data as biological networks. Network motifs are defined as over-represented small connected subgraphs in networks and they have been used for many biological applications. Since network motif discovery involves computationally challenging processes, previous algorithms have focused on computational efficiency. However, we believe that the biological quality of network motifs is also very important. Results We define biological network motifs as biologically significant subgraphs and traditional network motifs are differentiated as structural network motifs in this paper. We develop five algorithms, namely, EDGEGO-BNM, EDGEBETWEENNESS-BNM, NMF-BNM, NMFGO-BNM and VOLTAGE-BNM, for efficient detection of biological network motifs, and introduce several evaluation measures including motifs included in complex, motifs included in functional module and GO term clustering score in this paper. Experimental results show that EDGEGO-BNM and EDGEBETWEENNESS-BNM perform better than existing algorithms and all of our algorithms are applicable to find structural network motifs as well. Conclusion We provide new approaches to finding network motifs in biological networks. Our algorithms efficiently detect biological network motifs and further improve existing algorithms to find high quality structural network motifs, which would be impossible using existing algorithms. The performances of the algorithms are compared based on our new evaluation measures in biological contexts. We believe that our work gives some guidelines of network motifs research for the biological networks. PMID:22784624

Machine learning and social network analysis applied to Alzheimer's disease biomarkers.

PubMed

Di Deco, Javier; González, Ana M; Díaz, Julia; Mato, Virginia; García-Frank, Daniel; Álvarez-Linera, Juan; Frank, Ana; Hernández-Tamames, Juan A

2013-01-01

Due to the fact that the number of deaths due Alzheimer is increasing, the scientists have a strong interest in early stage diagnostic of this disease. Alzheimer's patients show different kind of brain alterations, such as morphological, biochemical, functional, etc. Currently, using magnetic resonance imaging techniques is possible to obtain a huge amount of biomarkers; being difficult to appraise which of them can explain more properly how the pathology evolves instead of the normal ageing. Machine Learning methods facilitate an efficient analysis of complex data and can be used to discover which biomarkers are more informative. Moreover, automatic models can learn from historical data to suggest the diagnostic of new patients. Social Network Analysis (SNA) views social relationships in terms of network theory consisting of nodes and connections. The resulting graph-based structures are often very complex; there can be many kinds of connections between the nodes. SNA has emerged as a key technique in modern sociology. It has also gained a significant following in medicine, anthropology, biology, information science, etc., and has become a popular topic of speculation and study. This paper presents a review of machine learning and SNA techniques and then, a new approach to analyze the magnetic resonance imaging biomarkers with these techniques, obtaining relevant relationships that can explain the different phenotypes in dementia, in particular, different stages of Alzheimer's disease.

Temporal transcriptional logic of dynamic regulatory networks underlying nitrogen signaling and use in plants.

PubMed

Varala, Kranthi; Marshall-Colón, Amy; Cirrone, Jacopo; Brooks, Matthew D; Pasquino, Angelo V; Léran, Sophie; Mittal, Shipra; Rock, Tara M; Edwards, Molly B; Kim, Grace J; Ruffel, Sandrine; McCombie, W Richard; Shasha, Dennis; Coruzzi, Gloria M

2018-06-19

This study exploits time, the relatively unexplored fourth dimension of gene regulatory networks (GRNs), to learn the temporal transcriptional logic underlying dynamic nitrogen (N) signaling in plants. Our "just-in-time" analysis of time-series transcriptome data uncovered a temporal cascade of cis elements underlying dynamic N signaling. To infer transcription factor (TF)-target edges in a GRN, we applied a time-based machine learning method to 2,174 dynamic N-responsive genes. We experimentally determined a network precision cutoff, using TF-regulated genome-wide targets of three TF hubs (CRF4, SNZ, and CDF1), used to "prune" the network to 155 TFs and 608 targets. This network precision was reconfirmed using genome-wide TF-target regulation data for four additional TFs (TGA1, HHO5/6, and PHL1) not used in network pruning. These higher-confidence edges in the GRN were further filtered by independent TF-target binding data, used to calculate a TF "N-specificity" index. This refined GRN identifies the temporal relationship of known/validated regulators of N signaling (NLP7/8, TGA1/4, NAC4, HRS1, and LBD37/38/39) and 146 additional regulators. Six TFs-CRF4, SNZ, CDF1, HHO5/6, and PHL1-validated herein regulate a significant number of genes in the dynamic N response, targeting 54% of N-uptake/assimilation pathway genes. Phenotypically, inducible overexpression of CRF4 in planta regulates genes resulting in altered biomass, root development, and 15 NO 3 - uptake, specifically under low-N conditions. This dynamic N-signaling GRN now provides the temporal "transcriptional logic" for 155 candidate TFs to improve nitrogen use efficiency with potential agricultural applications. Broadly, these time-based approaches can uncover the temporal transcriptional logic for any biological response system in biology, agriculture, or medicine. Copyright © 2018 the Author(s). Published by PNAS.

Multiagent cooperation and competition with deep reinforcement learning.

PubMed

Tampuu, Ardi; Matiisen, Tambet; Kodelja, Dorian; Kuzovkin, Ilya; Korjus, Kristjan; Aru, Juhan; Aru, Jaan; Vicente, Raul

2017-01-01

Evolution of cooperation and competition can appear when multiple adaptive agents share a biological, social, or technological niche. In the present work we study how cooperation and competition emerge between autonomous agents that learn by reinforcement while using only their raw visual input as the state representation. In particular, we extend the Deep Q-Learning framework to multiagent environments to investigate the interaction between two learning agents in the well-known video game Pong. By manipulating the classical rewarding scheme of Pong we show how competitive and collaborative behaviors emerge. We also describe the progression from competitive to collaborative behavior when the incentive to cooperate is increased. Finally we show how learning by playing against another adaptive agent, instead of against a hard-wired algorithm, results in more robust strategies. The present work shows that Deep Q-Networks can become a useful tool for studying decentralized learning of multiagent systems coping with high-dimensional environments.

Multiagent cooperation and competition with deep reinforcement learning

PubMed Central

Kodelja, Dorian; Kuzovkin, Ilya; Korjus, Kristjan; Aru, Juhan; Aru, Jaan; Vicente, Raul

2017-01-01

Evolution of cooperation and competition can appear when multiple adaptive agents share a biological, social, or technological niche. In the present work we study how cooperation and competition emerge between autonomous agents that learn by reinforcement while using only their raw visual input as the state representation. In particular, we extend the Deep Q-Learning framework to multiagent environments to investigate the interaction between two learning agents in the well-known video game Pong. By manipulating the classical rewarding scheme of Pong we show how competitive and collaborative behaviors emerge. We also describe the progression from competitive to collaborative behavior when the incentive to cooperate is increased. Finally we show how learning by playing against another adaptive agent, instead of against a hard-wired algorithm, results in more robust strategies. The present work shows that Deep Q-Networks can become a useful tool for studying decentralized learning of multiagent systems coping with high-dimensional environments. PMID:28380078

Deep Direct Reinforcement Learning for Financial Signal Representation and Trading.

PubMed

Deng, Yue; Bao, Feng; Kong, Youyong; Ren, Zhiquan; Dai, Qionghai

2017-03-01

Can we train the computer to beat experienced traders for financial assert trading? In this paper, we try to address this challenge by introducing a recurrent deep neural network (NN) for real-time financial signal representation and trading. Our model is inspired by two biological-related learning concepts of deep learning (DL) and reinforcement learning (RL). In the framework, the DL part automatically senses the dynamic market condition for informative feature learning. Then, the RL module interacts with deep representations and makes trading decisions to accumulate the ultimate rewards in an unknown environment. The learning system is implemented in a complex NN that exhibits both the deep and recurrent structures. Hence, we propose a task-aware backpropagation through time method to cope with the gradient vanishing issue in deep training. The robustness of the neural system is verified on both the stock and the commodity future markets under broad testing conditions.

Connectivity Strength-Weighted Sparse Group Representation-Based Brain Network Construction for MCI Classification

PubMed Central

Yu, Renping; Zhang, Han; An, Le; Chen, Xiaobo; Wei, Zhihui; Shen, Dinggang

2017-01-01

Brain functional network analysis has shown great potential in understanding brain functions and also in identifying biomarkers for brain diseases, such as Alzheimer's disease (AD) and its early stage, mild cognitive impairment (MCI). In these applications, accurate construction of biologically meaningful brain network is critical. Sparse learning has been widely used for brain network construction; however, its l1-norm penalty simply penalizes each edge of a brain network equally, without considering the original connectivity strength which is one of the most important inherent linkwise characters. Besides, based on the similarity of the linkwise connectivity, brain network shows prominent group structure (i.e., a set of edges sharing similar attributes). In this article, we propose a novel brain functional network modeling framework with a “connectivity strength-weighted sparse group constraint.” In particular, the network modeling can be optimized by considering both raw connectivity strength and its group structure, without losing the merit of sparsity. Our proposed method is applied to MCI classification, a challenging task for early AD diagnosis. Experimental results based on the resting-state functional MRI, from 50 MCI patients and 49 healthy controls, show that our proposed method is more effective (i.e., achieving a significantly higher classification accuracy, 84.8%) than other competing methods (e.g., sparse representation, accuracy = 65.6%). Post hoc inspection of the informative features further shows more biologically meaningful brain functional connectivities obtained by our proposed method. PMID:28150897

Training Excitatory-Inhibitory Recurrent Neural Networks for Cognitive Tasks: A Simple and Flexible Framework

PubMed Central

Wang, Xiao-Jing

2016-01-01

The ability to simultaneously record from large numbers of neurons in behaving animals has ushered in a new era for the study of the neural circuit mechanisms underlying cognitive functions. One promising approach to uncovering the dynamical and computational principles governing population responses is to analyze model recurrent neural networks (RNNs) that have been optimized to perform the same tasks as behaving animals. Because the optimization of network parameters specifies the desired output but not the manner in which to achieve this output, “trained” networks serve as a source of mechanistic hypotheses and a testing ground for data analyses that link neural computation to behavior. Complete access to the activity and connectivity of the circuit, and the ability to manipulate them arbitrarily, make trained networks a convenient proxy for biological circuits and a valuable platform for theoretical investigation. However, existing RNNs lack basic biological features such as the distinction between excitatory and inhibitory units (Dale’s principle), which are essential if RNNs are to provide insights into the operation of biological circuits. Moreover, trained networks can achieve the same behavioral performance but differ substantially in their structure and dynamics, highlighting the need for a simple and flexible framework for the exploratory training of RNNs. Here, we describe a framework for gradient descent-based training of excitatory-inhibitory RNNs that can incorporate a variety of biological knowledge. We provide an implementation based on the machine learning library Theano, whose automatic differentiation capabilities facilitate modifications and extensions. We validate this framework by applying it to well-known experimental paradigms such as perceptual decision-making, context-dependent integration, multisensory integration, parametric working memory, and motor sequence generation. Our results demonstrate the wide range of neural activity patterns and behavior that can be modeled, and suggest a unified setting in which diverse cognitive computations and mechanisms can be studied. PMID:26928718

Multiple network-constrained regressions expand insights into influenza vaccination responses.

PubMed

Avey, Stefan; Mohanty, Subhasis; Wilson, Jean; Zapata, Heidi; Joshi, Samit R; Siconolfi, Barbara; Tsang, Sui; Shaw, Albert C; Kleinstein, Steven H

2017-07-15

Systems immunology leverages recent technological advancements that enable broad profiling of the immune system to better understand the response to infection and vaccination, as well as the dysregulation that occurs in disease. An increasingly common approach to gain insights from these large-scale profiling experiments involves the application of statistical learning methods to predict disease states or the immune response to perturbations. However, the goal of many systems studies is not to maximize accuracy, but rather to gain biological insights. The predictors identified using current approaches can be biologically uninterpretable or present only one of many equally predictive models, leading to a narrow understanding of the underlying biology. Here we show that incorporating prior biological knowledge within a logistic modeling framework by using network-level constraints on transcriptional profiling data significantly improves interpretability. Moreover, incorporating different types of biological knowledge produces models that highlight distinct aspects of the underlying biology, while maintaining predictive accuracy. We propose a new framework, Logistic Multiple Network-constrained Regression (LogMiNeR), and apply it to understand the mechanisms underlying differential responses to influenza vaccination. Although standard logistic regression approaches were predictive, they were minimally interpretable. Incorporating prior knowledge using LogMiNeR led to models that were equally predictive yet highly interpretable. In this context, B cell-specific genes and mTOR signaling were associated with an effective vaccination response in young adults. Overall, our results demonstrate a new paradigm for analyzing high-dimensional immune profiling data in which multiple networks encoding prior knowledge are incorporated to improve model interpretability. The R source code described in this article is publicly available at https://bitbucket.org/kleinstein/logminer . steven.kleinstein@yale.edu or stefan.avey@yale.edu. 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

Auditory Power-Law Activation Avalanches Exhibit a Fundamental Computational Ground State

NASA Astrophysics Data System (ADS)

Stoop, Ruedi; Gomez, Florian

2016-07-01

The cochlea provides a biological information-processing paradigm that we are only beginning to understand in its full complexity. Our work reveals an interacting network of strongly nonlinear dynamical nodes, on which even a simple sound input triggers subnetworks of activated elements that follow power-law size statistics ("avalanches"). From dynamical systems theory, power-law size distributions relate to a fundamental ground state of biological information processing. Learning destroys these power laws. These results strongly modify the models of mammalian sound processing and provide a novel methodological perspective for understanding how the brain processes information.

MINER: exploratory analysis of gene interaction networks by machine learning from expression data.

PubMed

Kadupitige, Sidath Randeni; Leung, Kin Chun; Sellmeier, Julia; Sivieng, Jane; Catchpoole, Daniel R; Bain, Michael E; Gaëta, Bruno A

2009-12-03

The reconstruction of gene regulatory networks from high-throughput "omics" data has become a major goal in the modelling of living systems. Numerous approaches have been proposed, most of which attempt only "one-shot" reconstruction of the whole network with no intervention from the user, or offer only simple correlation analysis to infer gene dependencies. We have developed MINER (Microarray Interactive Network Exploration and Representation), an application that combines multivariate non-linear tree learning of individual gene regulatory dependencies, visualisation of these dependencies as both trees and networks, and representation of known biological relationships based on common Gene Ontology annotations. MINER allows biologists to explore the dependencies influencing the expression of individual genes in a gene expression data set in the form of decision, model or regression trees, using their domain knowledge to guide the exploration and formulate hypotheses. Multiple trees can then be summarised in the form of a gene network diagram. MINER is being adopted by several of our collaborators and has already led to the discovery of a new significant regulatory relationship with subsequent experimental validation. Unlike most gene regulatory network inference methods, MINER allows the user to start from genes of interest and build the network gene-by-gene, incorporating domain expertise in the process. This approach has been used successfully with RNA microarray data but is applicable to other quantitative data produced by high-throughput technologies such as proteomics and "next generation" DNA sequencing.

Undergraduate students' development of social, cultural, and human capital in a networked research experience

NASA Astrophysics Data System (ADS)

Thompson, Jennifer Jo; Conaway, Evan; Dolan, Erin L.

2016-12-01

Recent calls for reform in undergraduate biology education have emphasized integrating research experiences into the learning experiences of all undergraduates. Contemporary science research increasingly demands collaboration across disciplines and institutions to investigate complex research questions, providing new contexts and models for involving undergraduates in research. In this study, we examined the experiences of undergraduates participating in a multi-institution and interdisciplinary biology research network. Unlike the traditional apprenticeship model of research, in which a student participates in research under the guidance of a single faculty member, students participating in networked research have the opportunity to develop relationships with additional faculty and students working in other areas of the project, at their own and at other institutions. We examined how students in this network develop social ties and to what extent a networked research experience affords opportunities for students to develop social, cultural, and human capital. Most studies of undergraduate involvement in science research have focused on documenting student outcomes rather than elucidating how students gain access to research experiences or how elements of research participation lead to desired student outcomes. By taking a qualitative approach framed by capital theories, we have identified ways that undergraduates utilize and further develop various forms of capital important for success in science research. In our study of the first 16 months of a biology research network, we found that undergraduates drew upon a combination of human, cultural, and social capital to gain access to the network. Within their immediate research groups, students built multidimensional social ties with faculty, peers, and others, yielding social capital that can be drawn upon for information, resources, and support. They reported developing cultural capital in the form of learning to think and work like a scientist—a scientific habitus. They reported developing human capital in the forms of technical, analytical, and communication skills in scientific research. Most of the students had little, direct interaction with network members in other research groups and thus developed little cross-institutional capital. The exception to this trend was at one institution that housed three research groups. Because proximity facilitated shared activities, students across research groups at this institution developed cross-lab ties with faculty and peers through which they developed social, cultural, and human capital. An important long-term concern is whether the capital students have developed will help them access opportunities in science beyond the network. At this point, many undergraduates have had limited opportunities to actually draw on capital beyond the network. Nevertheless, a number of students demonstrated awareness that they had developed resources that they could use in other scientific contexts.

Developmental Self-Construction and -Configuration of Functional Neocortical Neuronal Networks

PubMed Central

Bauer, Roman; Zubler, Frédéric; Pfister, Sabina; Hauri, Andreas; Pfeiffer, Michael; Muir, Dylan R.; Douglas, Rodney J.

2014-01-01

The prenatal development of neural circuits must provide sufficient configuration to support at least a set of core postnatal behaviors. Although knowledge of various genetic and cellular aspects of development is accumulating rapidly, there is less systematic understanding of how these various processes play together in order to construct such functional networks. Here we make some steps toward such understanding by demonstrating through detailed simulations how a competitive co-operative (‘winner-take-all’, WTA) network architecture can arise by development from a single precursor cell. This precursor is granted a simplified gene regulatory network that directs cell mitosis, differentiation, migration, neurite outgrowth and synaptogenesis. Once initial axonal connection patterns are established, their synaptic weights undergo homeostatic unsupervised learning that is shaped by wave-like input patterns. We demonstrate how this autonomous genetically directed developmental sequence can give rise to self-calibrated WTA networks, and compare our simulation results with biological data. PMID:25474693

Distributed multisensory integration in a recurrent network model through supervised learning

NASA Astrophysics Data System (ADS)

Wang, He; Wong, K. Y. Michael

Sensory integration between different modalities has been extensively studied. It is suggested that the brain integrates signals from different modalities in a Bayesian optimal way. However, how the Bayesian rule is implemented in a neural network remains under debate. In this work we propose a biologically plausible recurrent network model, which can perform Bayesian multisensory integration after trained by supervised learning. Our model is composed of two modules, each for one modality. We assume that each module is a recurrent network, whose activity represents the posterior distribution of each stimulus. The feedforward input on each module is the likelihood of each modality. Two modules are integrated through cross-links, which are feedforward connections from the other modality, and reciprocal connections, which are recurrent connections between different modules. By stochastic gradient descent, we successfully trained the feedforward and recurrent coupling matrices simultaneously, both of which resembles the Mexican-hat. We also find that there are more than one set of coupling matrices that can approximate the Bayesian theorem well. Specifically, reciprocal connections and cross-links will compensate each other if one of them is removed. Even though trained with two inputs, the network's performance with only one input is in good accordance with what is predicted by the Bayesian theorem.

Data Mining in Cyber Operations

DTIC Science & Technology

2014-07-01

information processing units intended to mimic the network of neurons in the human brain for performing pattern recognition  Self- organizing maps (SOM...patterns are mined from in order to influence the learning model . An exploratory attack does not alter the training process , but rather uses other...New Jersey: Prentice Hall. 21) Kohonen, T. (1982). Self- organized formation of topologically correct feature maps. Biological Cybernetics , 43, 59–69

New scaling relation for information transfer in biological networks

PubMed Central

Kim, Hyunju; Davies, Paul; Walker, Sara Imari

2015-01-01

We quantify characteristics of the informational architecture of two representative biological networks: the Boolean network model for the cell-cycle regulatory network of the fission yeast Schizosaccharomyces pombe (Davidich et al. 2008 PLoS ONE 3, e1672 (doi:10.1371/journal.pone.0001672)) and that of the budding yeast Saccharomyces cerevisiae (Li et al. 2004 Proc. Natl Acad. Sci. USA 101, 4781–4786 (doi:10.1073/pnas.0305937101)). We compare our results for these biological networks with the same analysis performed on ensembles of two different types of random networks: Erdös–Rényi and scale-free. We show that both biological networks share features in common that are not shared by either random network ensemble. In particular, the biological networks in our study process more information than the random networks on average. Both biological networks also exhibit a scaling relation in information transferred between nodes that distinguishes them from random, where the biological networks stand out as distinct even when compared with random networks that share important topological properties, such as degree distribution, with the biological network. We show that the most biologically distinct regime of this scaling relation is associated with a subset of control nodes that regulate the dynamics and function of each respective biological network. Information processing in biological networks is therefore interpreted as an emergent property of topology (causal structure) and dynamics (function). Our results demonstrate quantitatively how the informational architecture of biologically evolved networks can distinguish them from other classes of network architecture that do not share the same informational properties. PMID:26701883

Network biology: Describing biological systems by complex networks. Comment on "Network science of biological systems at different scales: A review" by M. Gosak et al.

NASA Astrophysics Data System (ADS)

Jalili, Mahdi

2018-03-01

I enjoyed reading Gosak et al. review on analysing biological systems from network science perspective [1]. Network science, first started within Physics community, is now a mature multidisciplinary field of science with many applications ranging from Ecology to biology, medicine, social sciences, engineering and computer science. Gosak et al. discussed how biological systems can be modelled and described by complex network theory which is an important application of network science. Although there has been considerable progress in network biology over the past two decades, this is just the beginning and network science has a great deal to offer to biology and medical sciences.

Study and reflections on the functional and organizational role of neuromessenger nitric oxide in learning: An artificial and biological approach

NASA Astrophysics Data System (ADS)

Suárez Araujo, C. P.

2000-05-01

We present in this work a theoretical and conceptual study and some reflections on a fundamental aspect concerning with the structure and brain function: the Cellular Communication. The main interests of our study are the signal transmission mechanisms and the neuronal mechanisms responsible to learning. We propose the consideration of a new kind of communication mechanisms, different to the synaptic transmission, "Diffusion or Volume Transmission." This new alternative is based on a diffusing messenger as nitric oxide (NO). Our study aims towards the design of a conceptual framework, which covers implications of NO in the artificial neural networks (ANNs), both in neural architecture and learning processing. This conceptual frame might be able to provide possible biological support for many aspects of ANNs and to generate new concepts to improve the structure and operation of them. Some of these new concepts are The Fast Diffusion Neural Propagation (FDNP), the Diffuse Neighborhood (DNB), (1), the Diffusive Hybrid Neuromodulation (DHN), the Virtual Weights. Finally we will propose a new mathematical formulation for the Hebb learning law, taking into account the NO effect. Along the same lines, we will reflect on the possibility of a new formal framework for learning processes in ANNs, which consist of slow and fast learning concerning with co-operation between the classical neurotransmission and FDNP. We will develop this work from a computational neuroscience point of view, proposing a global study framework of diffusion messenger NO (GSFNO), using a hybrid natural/artificial approach. Finally it is important to note that we can consider this paper the first paper of a set of scientific work on nitric oxide (NO) and artificial neural networks (ANNs): NO and ANNs Series. We can say that this paper has a character of search and query on both subjects their implications and co-existence.

Time-ordered product expansions for computational stochastic system biology.

PubMed

Mjolsness, Eric

2013-06-01

The time-ordered product framework of quantum field theory can also be used to understand salient phenomena in stochastic biochemical networks. It is used here to derive Gillespie's stochastic simulation algorithm (SSA) for chemical reaction networks; consequently, the SSA can be interpreted in terms of Feynman diagrams. It is also used here to derive other, more general simulation and parameter-learning algorithms including simulation algorithms for networks of stochastic reaction-like processes operating on parameterized objects, and also hybrid stochastic reaction/differential equation models in which systems of ordinary differential equations evolve the parameters of objects that can also undergo stochastic reactions. Thus, the time-ordered product expansion can be used systematically to derive simulation and parameter-fitting algorithms for stochastic systems.

An artificial bioindicator system for network intrusion detection.

PubMed

Blum, Christian; Lozano, José A; Davidson, Pedro Pinacho

An artificial bioindicator system is developed in order to solve a network intrusion detection problem. The system, inspired by an ecological approach to biological immune systems, evolves a population of agents that learn to survive in their environment. An adaptation process allows the transformation of the agent population into a bioindicator that is capable of reacting to system anomalies. Two characteristics stand out in our proposal. On the one hand, it is able to discover new, previously unseen attacks, and on the other hand, contrary to most of the existing systems for network intrusion detection, it does not need any previous training. We experimentally compare our proposal with three state-of-the-art algorithms and show that it outperforms the competing approaches on widely used benchmark data.

Still searching for the engram

PubMed Central

Eichenbaum, Howard

2016-01-01

For nearly a century neurobiologists have searched for the engram - the neural representation of a memory. Early studies showed that the engram is widely distributed both within and across brain areas and is supported by interactions among large networks of neurons. Subsequent research has identified engrams that support memory within dedicated functional systems for habit learning and emotional memory, but the engram for declarative memories has been elusive. Nevertheless, recent years have brought progress from molecular biological approaches that identify neurons and networks that are necessary and sufficient to support memory, and from recording approaches and population analyses that characterize the information coded by large neural networks. These new directions offer the promise of revealing the engrams for episodic and semantic memories. PMID:26944423

Multilevel functional genomics data integration as a tool for understanding physiology: a network biology perspective.

PubMed

Davidsen, Peter K; Turan, Nil; Egginton, Stuart; Falciani, Francesco

2016-02-01

The overall aim of physiological research is to understand how living systems function in an integrative manner. Consequently, the discipline of physiology has since its infancy attempted to link multiple levels of biological organization. Increasingly this has involved mathematical and computational approaches, typically to model a small number of components spanning several levels of biological organization. With the advent of "omics" technologies, which can characterize the molecular state of a cell or tissue (intended as the level of expression and/or activity of its molecular components), the number of molecular components we can quantify has increased exponentially. Paradoxically, the unprecedented amount of experimental data has made it more difficult to derive conceptual models underlying essential mechanisms regulating mammalian physiology. We present an overview of state-of-the-art methods currently used to identifying biological networks underlying genomewide responses. These are based on a data-driven approach that relies on advanced computational methods designed to "learn" biology from observational data. In this review, we illustrate an application of these computational methodologies using a case study integrating an in vivo model representing the transcriptional state of hypoxic skeletal muscle with a clinical study representing muscle wasting in chronic obstructive pulmonary disease patients. The broader application of these approaches to modeling multiple levels of biological data in the context of modern physiology is discussed. Copyright © 2016 the American Physiological Society.

A Deep Machine Learning Method for Classifying Cyclic Time Series of Biological Signals Using Time-Growing Neural Network.

PubMed

Gharehbaghi, Arash; Linden, Maria

2017-10-12

This paper presents a novel method for learning the cyclic contents of stochastic time series: the deep time-growing neural network (DTGNN). The DTGNN combines supervised and unsupervised methods in different levels of learning for an enhanced performance. It is employed by a multiscale learning structure to classify cyclic time series (CTS), in which the dynamic contents of the time series are preserved in an efficient manner. This paper suggests a systematic procedure for finding the design parameter of the classification method for a one-versus-multiple class application. A novel validation method is also suggested for evaluating the structural risk, both in a quantitative and a qualitative manner. The effect of the DTGNN on the performance of the classifier is statistically validated through the repeated random subsampling using different sets of CTS, from different medical applications. The validation involves four medical databases, comprised of 108 recordings of the electroencephalogram signal, 90 recordings of the electromyogram signal, 130 recordings of the heart sound signal, and 50 recordings of the respiratory sound signal. Results of the statistical validations show that the DTGNN significantly improves the performance of the classification and also exhibits an optimal structural risk.

Objects Classification by Learning-Based Visual Saliency Model and Convolutional Neural Network.

PubMed

Li, Na; Zhao, Xinbo; Yang, Yongjia; Zou, Xiaochun

2016-01-01

Humans can easily classify different kinds of objects whereas it is quite difficult for computers. As a hot and difficult problem, objects classification has been receiving extensive interests with broad prospects. Inspired by neuroscience, deep learning concept is proposed. Convolutional neural network (CNN) as one of the methods of deep learning can be used to solve classification problem. But most of deep learning methods, including CNN, all ignore the human visual information processing mechanism when a person is classifying objects. Therefore, in this paper, inspiring the completed processing that humans classify different kinds of objects, we bring forth a new classification method which combines visual attention model and CNN. Firstly, we use the visual attention model to simulate the processing of human visual selection mechanism. Secondly, we use CNN to simulate the processing of how humans select features and extract the local features of those selected areas. Finally, not only does our classification method depend on those local features, but also it adds the human semantic features to classify objects. Our classification method has apparently advantages in biology. Experimental results demonstrated that our method made the efficiency of classification improve significantly.

Neural networks and the experience and cultivation of mind.

PubMed

Werbos, Paul J

2012-08-01

Hard core neural network research includes development of mathematical models of cognitive prediction and optimization aimed at dual use, both as models of what we see in brain circuits and behavior, and as useful general-purpose engineering technology. The pathway and principles now exist to let us someday replicate learning abilities as elevated as what we see in the brain of the mouse-but how can this help us today in understanding and maximizing the much greater potential of the human mind, as addressed by many schools of thought all over the world for centuries? This paper discusses how we might use what we have learned at a lower level to better illuminate key phenomena in first person and clinical human experience such as Freud's "psychic energy", the role of traumatic experience, the interpretation of dreams, creativity, the cultivation of sanity and sensitivity, and the biological foundations of language. Published by Elsevier Ltd.

Evolving neural networks through augmenting topologies.

PubMed

Stanley, Kenneth O; Miikkulainen, Risto

2002-01-01

An important question in neuroevolution is how to gain an advantage from evolving neural network topologies along with weights. We present a method, NeuroEvolution of Augmenting Topologies (NEAT), which outperforms the best fixed-topology method on a challenging benchmark reinforcement learning task. We claim that the increased efficiency is due to (1) employing a principled method of crossover of different topologies, (2) protecting structural innovation using speciation, and (3) incrementally growing from minimal structure. We test this claim through a series of ablation studies that demonstrate that each component is necessary to the system as a whole and to each other. What results is significantly faster learning. NEAT is also an important contribution to GAs because it shows how it is possible for evolution to both optimize and complexify solutions simultaneously, offering the possibility of evolving increasingly complex solutions over generations, and strengthening the analogy with biological evolution.

On the biological plausibility of grandmother cells: implications for neural network theories in psychology and neuroscience.

PubMed

Bowers, Jeffrey S

2009-01-01

A fundamental claim associated with parallel distributed processing (PDP) theories of cognition is that knowledge is coded in a distributed manner in mind and brain. This approach rejects the claim that knowledge is coded in a localist fashion, with words, objects, and simple concepts (e.g. "dog"), that is, coded with their own dedicated representations. One of the putative advantages of this approach is that the theories are biologically plausible. Indeed, advocates of the PDP approach often highlight the close parallels between distributed representations learned in connectionist models and neural coding in brain and often dismiss localist (grandmother cell) theories as biologically implausible. The author reviews a range a data that strongly challenge this claim and shows that localist models provide a better account of single-cell recording studies. The author also contrast local and alternative distributed coding schemes (sparse and coarse coding) and argues that common rejection of grandmother cell theories in neuroscience is due to a misunderstanding about how localist models behave. The author concludes that the localist representations embedded in theories of perception and cognition are consistent with neuroscience; biology only calls into question the distributed representations often learned in PDP models.

Revealing biological information using data structuring and automated learning.

PubMed

Mohorianu, Irina; Moulton, Vincent

2010-11-01

The intermediary steps between a biological hypothesis, concretized in the input data, and meaningful results, validated using biological experiments, commonly employ bioinformatics tools. Starting with storage of the data and ending with a statistical analysis of the significance of the results, every step in a bioinformatics analysis has been intensively studied and the resulting methods and models patented. This review summarizes the bioinformatics patents that have been developed mainly for the study of genes, and points out the universal applicability of bioinformatics methods to other related studies such as RNA interference. More specifically, we overview the steps undertaken in the majority of bioinformatics analyses, highlighting, for each, various approaches that have been developed to reveal details from different perspectives. First we consider data warehousing, the first task that has to be performed efficiently, optimizing the structure of the database, in order to facilitate both the subsequent steps and the retrieval of information. Next, we review data mining, which occupies the central part of most bioinformatics analyses, presenting patents concerning differential expression, unsupervised and supervised learning. Last, we discuss how networks of interactions of genes or other players in the cell may be created, which help draw biological conclusions and have been described in several patents.

Statistics and dynamics of attractor networks with inter-correlated patterns

NASA Astrophysics Data System (ADS)

Kropff, E.

2007-02-01

In an embodied feature representation view, the semantic memory represents concepts in the brain by the associated activation of the features that describe it, each one of them processed in a differentiated region of the cortex. This system has been modeled with a Potts attractor network. Several studies of feature representation show that the correlation between patterns plays a crucial role in semantic memory. The present work focuses on two aspects of the effect of correlations in attractor networks. In first place, it assesses how a Potts network can store a set of patterns with non-trivial correlations between them. This is done through a simple and biologically plausible modification to the classical learning rule. In second place, it studies the complexity of latching transitions between attractor states, and how this complexity can be controlled.

Plastic Synaptic Networks of the Amygdala for the Acquisition, Expression, and Extinction of Conditioned Fear

PubMed Central

Pape, Hans-Christian; Pare, Denis

2009-01-01

The last ten years have witnessed a surge of interest for the mechanisms underlying the acquisition and extinction of classically conditioned fear responses. In part, this results from the realization that abnormalities in fear learning mechanisms likely participate to the development and/or maintenance of human anxiety disorders. The simplicity and robustness of this learning paradigm, coupled to the fact that the underlying circuitry is evolutionarily well conserved makes it an ideal model to study the basic biology of memory and identify genetic factors and neuronal systems that regulate the normal and pathological expressions of learned fear. Critical advances have been made in determining how modified neuronal functions upon fear acquisition become stabilized during fear memory consolidation and how these processes are controlled in the course of fear memory extinction. With these advances, came the realization that activity in remote neuronal networks must be coordinated for these events to take place. In this paper, we review these mechanisms of coordinated network activity and the molecular cascades leading to enduring fear memory, and allowing for their extinction. We will focus on Pavlovian fear conditioning as a model and the amygdala as a key component for the acquisition and extinction of fear responses. PMID:20393190

Learning in networks: individual teacher learning versus organizational learning in a regional health-promoting schools network.

PubMed

Flaschberger, Edith; Gugglberger, Lisa; Dietscher, Christina

2013-12-01

To change a school into a health-promoting organization, organizational learning is required. The evaluation of an Austrian regional health-promoting schools network provides qualitative data on the views of the different stakeholders on learning in this network (steering group, network coordinator and representatives of the network schools; n = 26). Through thematic analysis and deep-structure analyses, the following three forms of learning in the network were identified: (A) individual learning through input offered by the network coordination, (B) individual learning between the network schools, i.e. through exchange between the representatives of different schools and (C) learning within the participating schools, i.e. organizational learning. Learning between (B) or within the participating schools (C) seems to be rare in the network; concepts of individual teacher learning are prevalent. Difficulties detected relating to the transfer of information from the network to the member schools included barriers to organizational learning such as the lack of collaboration, coordination and communication in the network schools, which might be effects of the school system in which the observed network is located. To ensure connectivity of the information offered by the network, more emphasis should be put on linking health promotion to school development and the core processes of schools.

Five Years of Designing Wireless Sensor Networks in the Doñana Biological Reserve (Spain): An Applications Approach

PubMed Central

Larios, Diego F.; Barbancho, Julio; Sevillano, José L.; Rodríguez, Gustavo; Molina, Francisco J.; Gasull, Virginia G.; Mora-Merchan, Javier M.; León, Carlos

2013-01-01

Wireless Sensor Networks (WSNs) are a technology that is becoming very popular for many applications, and environmental monitoring is one of its most important application areas. This technology solves the lack of flexibility of wired sensor installations and, at the same time, reduces the deployment costs. To demonstrate the advantages of WSN technology, for the last five years we have been deploying some prototypes in the Doñana Biological Reserve, which is an important protected area in Southern Spain. These prototypes not only evaluate the technology, but also solve some of the monitoring problems that have been raised by biologists working in Doñana. This paper presents a review of the work that has been developed during these five years. Here, we demonstrate the enormous potential of using machine learning in wireless sensor networks for environmental and animal monitoring because this approach increases the amount of useful information and reduces the effort that is required by biologists in an environmental monitoring task. PMID:24025554

Using High Performance Computing to Examine the Processes of Neurogenesis Underlying Pattern Separation and Completion of Episodic Information.

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

Aimone, James Bradley; Bernard, Michael Lewis; Vineyard, Craig Michael

2014-10-01

Adult neurogenesis in the hippocampus region of the brain is a neurobiological process that is believed to contribute to the brain's advanced abilities in complex pattern recognition and cognition. Here, we describe how realistic scale simulations of the neurogenesis process can offer both a unique perspective on the biological relevance of this process and confer computational insights that are suggestive of novel machine learning techniques. First, supercomputer based scaling studies of the neurogenesis process demonstrate how a small fraction of adult-born neurons have a uniquely larger impact in biologically realistic scaled networks. Second, we describe a novel technical approach bymore » which the information content of ensembles of neurons can be estimated. Finally, we illustrate several examples of broader algorithmic impact of neurogenesis, including both extending existing machine learning approaches and novel approaches for intelligent sensing.« less

An immune-inspired semi-supervised algorithm for breast cancer diagnosis.

PubMed

Peng, Lingxi; Chen, Wenbin; Zhou, Wubai; Li, Fufang; Yang, Jin; Zhang, Jiandong

2016-10-01

Breast cancer is the most frequently and world widely diagnosed life-threatening cancer, which is the leading cause of cancer death among women. Early accurate diagnosis can be a big plus in treating breast cancer. Researchers have approached this problem using various data mining and machine learning techniques such as support vector machine, artificial neural network, etc. The computer immunology is also an intelligent method inspired by biological immune system, which has been successfully applied in pattern recognition, combination optimization, machine learning, etc. However, most of these diagnosis methods belong to a supervised diagnosis method. It is very expensive to obtain labeled data in biology and medicine. In this paper, we seamlessly integrate the state-of-the-art research on life science with artificial intelligence, and propose a semi-supervised learning algorithm to reduce the need for labeled data. We use two well-known benchmark breast cancer datasets in our study, which are acquired from the UCI machine learning repository. Extensive experiments are conducted and evaluated on those two datasets. Our experimental results demonstrate the effectiveness and efficiency of our proposed algorithm, which proves that our algorithm is a promising automatic diagnosis method for breast cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.

PubMed

Hu, Pingzhao; Janga, Sarath Chandra; Babu, Mohan; Díaz-Mejía, J Javier; Butland, Gareth; Yang, Wenhong; Pogoutse, Oxana; Guo, Xinghua; Phanse, Sadhna; Wong, Peter; Chandran, Shamanta; Christopoulos, Constantine; Nazarians-Armavil, Anaies; Nasseri, Negin Karimi; Musso, Gabriel; Ali, Mehrab; Nazemof, Nazila; Eroukova, Veronika; Golshani, Ashkan; Paccanaro, Alberto; Greenblatt, Jack F; Moreno-Hagelsieb, Gabriel; Emili, Andrew

2009-04-28

One-third of the 4,225 protein-coding genes of Escherichia coli K-12 remain functionally unannotated (orphans). Many map to distant clades such as Archaea, suggesting involvement in basic prokaryotic traits, whereas others appear restricted to E. coli, including pathogenic strains. To elucidate the orphans' biological roles, we performed an extensive proteomic survey using affinity-tagged E. coli strains and generated comprehensive genomic context inferences to derive a high-confidence compendium for virtually the entire proteome consisting of 5,993 putative physical interactions and 74,776 putative functional associations, most of which are novel. Clustering of the respective probabilistic networks revealed putative orphan membership in discrete multiprotein complexes and functional modules together with annotated gene products, whereas a machine-learning strategy based on network integration implicated the orphans in specific biological processes. We provide additional experimental evidence supporting orphan participation in protein synthesis, amino acid metabolism, biofilm formation, motility, and assembly of the bacterial cell envelope. This resource provides a "systems-wide" functional blueprint of a model microbe, with insights into the biological and evolutionary significance of previously uncharacterized proteins.

Applications of artificial neural networks in medical science.

PubMed

Patel, Jigneshkumar L; Goyal, Ramesh K

2007-09-01

Computer technology has been advanced tremendously and the interest has been increased for the potential use of 'Artificial Intelligence (AI)' in medicine and biological research. One of the most interesting and extensively studied branches of AI is the 'Artificial Neural Networks (ANNs)'. Basically, ANNs are the mathematical algorithms, generated by computers. ANNs learn from standard data and capture the knowledge contained in the data. Trained ANNs approach the functionality of small biological neural cluster in a very fundamental manner. They are the digitized model of biological brain and can detect complex nonlinear relationships between dependent as well as independent variables in a data where human brain may fail to detect. Nowadays, ANNs are widely used for medical applications in various disciplines of medicine especially in cardiology. ANNs have been extensively applied in diagnosis, electronic signal analysis, medical image analysis and radiology. ANNs have been used by many authors for modeling in medicine and clinical research. Applications of ANNs are increasing in pharmacoepidemiology and medical data mining. In this paper, authors have summarized various applications of ANNs in medical science.

View-tolerant face recognition and Hebbian learning imply mirror-symmetric neural tuning to head orientation

PubMed Central

Leibo, Joel Z.; Liao, Qianli; Freiwald, Winrich A.; Anselmi, Fabio; Poggio, Tomaso

2017-01-01

SUMMARY The primate brain contains a hierarchy of visual areas, dubbed the ventral stream, which rapidly computes object representations that are both specific for object identity and robust against identity-preserving transformations like depth-rotations [1, 2]. Current computational models of object recognition, including recent deep learning networks, generate these properties through a hierarchy of alternating selectivity-increasing filtering and tolerance-increasing pooling operations, similar to simple-complex cells operations [3, 4, 5, 6]. Here we prove that a class of hierarchical architectures and a broad set of biologically plausible learning rules generate approximate invariance to identity-preserving transformations at the top level of the processing hierarchy. However, all past models tested failed to reproduce the most salient property of an intermediate representation of a three-level face-processing hierarchy in the brain: mirror-symmetric tuning to head orientation [7]. Here we demonstrate that one specific biologically-plausible Hebb-type learning rule generates mirror-symmetric tuning to bilaterally symmetric stimuli like faces at intermediate levels of the architecture and show why it does so. Thus the tuning properties of individual cells inside the visual stream appear to result from group properties of the stimuli they encode and to reflect the learning rules that sculpted the information-processing system within which they reside. PMID:27916522

Elastic network model of learned maintained contacts to predict protein motion

PubMed Central

Putz, Ines

2017-01-01

We present a novel elastic network model, lmcENM, to determine protein motion even for localized functional motions that involve substantial changes in the protein’s contact topology. Existing elastic network models assume that the contact topology remains unchanged throughout the motion and are thus most appropriate to simulate highly collective function-related movements. lmcENM uses machine learning to differentiate breaking from maintained contacts. We show that lmcENM accurately captures functional transitions unexplained by the classical ENM and three reference ENM variants, while preserving the simplicity of classical ENM. We demonstrate the effectiveness of our approach on a large set of proteins covering different motion types. Our results suggest that accurately predicting a “deformation-invariant” contact topology offers a promising route to increase the general applicability of ENMs. We also find that to correctly predict this contact topology a combination of several features seems to be relevant which may vary slightly depending on the protein. Additionally, we present case studies of two biologically interesting systems, Ferric Citrate membrane transporter FecA and Arachidonate 15-Lipoxygenase. PMID:28854238

The visual development of hand-centered receptive fields in a neural network model of the primate visual system trained with experimentally recorded human gaze changes

PubMed Central

Galeazzi, Juan M.; Navajas, Joaquín; Mender, Bedeho M. W.; Quian Quiroga, Rodrigo; Minini, Loredana; Stringer, Simon M.

2016-01-01

ABSTRACT Neurons have been found in the primate brain that respond to objects in specific locations in hand-centered coordinates. A key theoretical challenge is to explain how such hand-centered neuronal responses may develop through visual experience. In this paper we show how hand-centered visual receptive fields can develop using an artificial neural network model, VisNet, of the primate visual system when driven by gaze changes recorded from human test subjects as they completed a jigsaw. A camera mounted on the head captured images of the hand and jigsaw, while eye movements were recorded using an eye-tracking device. This combination of data allowed us to reconstruct the retinal images seen as humans undertook the jigsaw task. These retinal images were then fed into the neural network model during self-organization of its synaptic connectivity using a biologically plausible trace learning rule. A trace learning mechanism encourages neurons in the model to learn to respond to input images that tend to occur in close temporal proximity. In the data recorded from human subjects, we found that the participant’s gaze often shifted through a sequence of locations around a fixed spatial configuration of the hand and one of the jigsaw pieces. In this case, trace learning should bind these retinal images together onto the same subset of output neurons. The simulation results consequently confirmed that some cells learned to respond selectively to the hand and a jigsaw piece in a fixed spatial configuration across different retinal views. PMID:27253452

The visual development of hand-centered receptive fields in a neural network model of the primate visual system trained with experimentally recorded human gaze changes.

PubMed

Galeazzi, Juan M; Navajas, Joaquín; Mender, Bedeho M W; Quian Quiroga, Rodrigo; Minini, Loredana; Stringer, Simon M

2016-01-01

Neurons have been found in the primate brain that respond to objects in specific locations in hand-centered coordinates. A key theoretical challenge is to explain how such hand-centered neuronal responses may develop through visual experience. In this paper we show how hand-centered visual receptive fields can develop using an artificial neural network model, VisNet, of the primate visual system when driven by gaze changes recorded from human test subjects as they completed a jigsaw. A camera mounted on the head captured images of the hand and jigsaw, while eye movements were recorded using an eye-tracking device. This combination of data allowed us to reconstruct the retinal images seen as humans undertook the jigsaw task. These retinal images were then fed into the neural network model during self-organization of its synaptic connectivity using a biologically plausible trace learning rule. A trace learning mechanism encourages neurons in the model to learn to respond to input images that tend to occur in close temporal proximity. In the data recorded from human subjects, we found that the participant's gaze often shifted through a sequence of locations around a fixed spatial configuration of the hand and one of the jigsaw pieces. In this case, trace learning should bind these retinal images together onto the same subset of output neurons. The simulation results consequently confirmed that some cells learned to respond selectively to the hand and a jigsaw piece in a fixed spatial configuration across different retinal views.

Learning through ferroelectric domain dynamics in solid-state synapses

NASA Astrophysics Data System (ADS)

Boyn, Sören; Grollier, Julie; Lecerf, Gwendal; Xu, Bin; Locatelli, Nicolas; Fusil, Stéphane; Girod, Stéphanie; Carrétéro, Cécile; Garcia, Karin; Xavier, Stéphane; Tomas, Jean; Bellaiche, Laurent; Bibes, Manuel; Barthélémy, Agnès; Saïghi, Sylvain; Garcia, Vincent

2017-04-01

In the brain, learning is achieved through the ability of synapses to reconfigure the strength by which they connect neurons (synaptic plasticity). In promising solid-state synapses called memristors, conductance can be finely tuned by voltage pulses and set to evolve according to a biological learning rule called spike-timing-dependent plasticity (STDP). Future neuromorphic architectures will comprise billions of such nanosynapses, which require a clear understanding of the physical mechanisms responsible for plasticity. Here we report on synapses based on ferroelectric tunnel junctions and show that STDP can be harnessed from inhomogeneous polarization switching. Through combined scanning probe imaging, electrical transport and atomic-scale molecular dynamics, we demonstrate that conductance variations can be modelled by the nucleation-dominated reversal of domains. Based on this physical model, our simulations show that arrays of ferroelectric nanosynapses can autonomously learn to recognize patterns in a predictable way, opening the path towards unsupervised learning in spiking neural networks.

Visual recognition and inference using dynamic overcomplete sparse learning.

PubMed

Murray, Joseph F; Kreutz-Delgado, Kenneth

2007-09-01

We present a hierarchical architecture and learning algorithm for visual recognition and other visual inference tasks such as imagination, reconstruction of occluded images, and expectation-driven segmentation. Using properties of biological vision for guidance, we posit a stochastic generative world model and from it develop a simplified world model (SWM) based on a tractable variational approximation that is designed to enforce sparse coding. Recent developments in computational methods for learning overcomplete representations (Lewicki & Sejnowski, 2000; Teh, Welling, Osindero, & Hinton, 2003) suggest that overcompleteness can be useful for visual tasks, and we use an overcomplete dictionary learning algorithm (Kreutz-Delgado, et al., 2003) as a preprocessing stage to produce accurate, sparse codings of images. Inference is performed by constructing a dynamic multilayer network with feedforward, feedback, and lateral connections, which is trained to approximate the SWM. Learning is done with a variant of the back-propagation-through-time algorithm, which encourages convergence to desired states within a fixed number of iterations. Vision tasks require large networks, and to make learning efficient, we take advantage of the sparsity of each layer to update only a small subset of elements in a large weight matrix at each iteration. Experiments on a set of rotated objects demonstrate various types of visual inference and show that increasing the degree of overcompleteness improves recognition performance in difficult scenes with occluded objects in clutter.

Neural learning circuits utilizing nano-crystalline silicon transistors and memristors.

PubMed

Cantley, Kurtis D; Subramaniam, Anand; Stiegler, Harvey J; Chapman, Richard A; Vogel, Eric M

2012-04-01

Properties of neural circuits are demonstrated via SPICE simulations and their applications are discussed. The neuron and synapse subcircuits include ambipolar nano-crystalline silicon transistor and memristor device models based on measured data. Neuron circuit characteristics and the Hebbian synaptic learning rule are shown to be similar to biology. Changes in the average firing rate learning rule depending on various circuit parameters are also presented. The subcircuits are then connected into larger neural networks that demonstrate fundamental properties including associative learning and pulse coincidence detection. Learned extraction of a fundamental frequency component from noisy inputs is demonstrated. It is then shown that if the fundamental sinusoid of one neuron input is out of phase with the rest, its synaptic connection changes differently than the others. Such behavior indicates that the system can learn to detect which signals are important in the general population, and that there is a spike-timing-dependent component of the learning mechanism. Finally, future circuit design and considerations are discussed, including requirements for the memristive device.

Parenclitic Network Analysis of Methylation Data for Cancer Identification

PubMed Central

Karsakov, Alexander; Bartlett, Thomas; Ryblov, Artem; Meyerov, Iosif; Ivanchenko, Mikhail; Zaikin, Alexey

2017-01-01

We make use of ideas from the theory of complex networks to implement a machine learning classification of human DNA methylation data, that carry signatures of cancer development. The data were obtained from patients with various kinds of cancers and represented as parenclictic networks, wherein nodes correspond to genes, and edges are weighted according to pairwise variation from control group subjects. We demonstrate that for the 10 types of cancer under study, it is possible to obtain a high performance of binary classification between cancer-positive and negative samples based on network measures. Remarkably, an accuracy as high as 93−99% is achieved with only 12 network topology indices, in a dramatic reduction of complexity from the original 15295 gene methylation levels. Moreover, it was found that the parenclictic networks are scale-free in cancer-negative subjects, and deviate from the power-law node degree distribution in cancer. The node centrality ranking and arising modular structure could provide insights into the systems biology of cancer. PMID:28107365

MIIC online: a web server to reconstruct causal or non-causal networks from non-perturbative data.

PubMed

Sella, Nadir; Verny, Louis; Uguzzoni, Guido; Affeldt, Séverine; Isambert, Hervé

2018-07-01

We present a web server running the MIIC algorithm, a network learning method combining constraint-based and information-theoretic frameworks to reconstruct causal, non-causal or mixed networks from non-perturbative data, without the need for an a priori choice on the class of reconstructed network. Starting from a fully connected network, the algorithm first removes dispensable edges by iteratively subtracting the most significant information contributions from indirect paths between each pair of variables. The remaining edges are then filtered based on their confidence assessment or oriented based on the signature of causality in observational data. MIIC online server can be used for a broad range of biological data, including possible unobserved (latent) variables, from single-cell gene expression data to protein sequence evolution and outperforms or matches state-of-the-art methods for either causal or non-causal network reconstruction. MIIC online can be freely accessed at https://miic.curie.fr. Supplementary data are available at Bioinformatics online.

Network embedding-based representation learning for single cell RNA-seq data.

PubMed

Li, Xiangyu; Chen, Weizheng; Chen, Yang; Zhang, Xuegong; Gu, Jin; Zhang, Michael Q

2017-11-02

Single cell RNA-seq (scRNA-seq) techniques can reveal valuable insights of cell-to-cell heterogeneities. Projection of high-dimensional data into a low-dimensional subspace is a powerful strategy in general for mining such big data. However, scRNA-seq suffers from higher noise and lower coverage than traditional bulk RNA-seq, hence bringing in new computational difficulties. One major challenge is how to deal with the frequent drop-out events. The events, usually caused by the stochastic burst effect in gene transcription and the technical failure of RNA transcript capture, often render traditional dimension reduction methods work inefficiently. To overcome this problem, we have developed a novel Single Cell Representation Learning (SCRL) method based on network embedding. This method can efficiently implement data-driven non-linear projection and incorporate prior biological knowledge (such as pathway information) to learn more meaningful low-dimensional representations for both cells and genes. Benchmark results show that SCRL outperforms other dimensional reduction methods on several recent scRNA-seq datasets. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Connectivity strength-weighted sparse group representation-based brain network construction for MCI classification.

PubMed

Yu, Renping; Zhang, Han; An, Le; Chen, Xiaobo; Wei, Zhihui; Shen, Dinggang

2017-05-01

Brain functional network analysis has shown great potential in understanding brain functions and also in identifying biomarkers for brain diseases, such as Alzheimer's disease (AD) and its early stage, mild cognitive impairment (MCI). In these applications, accurate construction of biologically meaningful brain network is critical. Sparse learning has been widely used for brain network construction; however, its l 1 -norm penalty simply penalizes each edge of a brain network equally, without considering the original connectivity strength which is one of the most important inherent linkwise characters. Besides, based on the similarity of the linkwise connectivity, brain network shows prominent group structure (i.e., a set of edges sharing similar attributes). In this article, we propose a novel brain functional network modeling framework with a "connectivity strength-weighted sparse group constraint." In particular, the network modeling can be optimized by considering both raw connectivity strength and its group structure, without losing the merit of sparsity. Our proposed method is applied to MCI classification, a challenging task for early AD diagnosis. Experimental results based on the resting-state functional MRI, from 50 MCI patients and 49 healthy controls, show that our proposed method is more effective (i.e., achieving a significantly higher classification accuracy, 84.8%) than other competing methods (e.g., sparse representation, accuracy = 65.6%). Post hoc inspection of the informative features further shows more biologically meaningful brain functional connectivities obtained by our proposed method. Hum Brain Mapp 38:2370-2383, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Neuromimetic Circuits with Synaptic Devices Based on Strongly Correlated Electron Systems

NASA Astrophysics Data System (ADS)

Ha, Sieu D.; Shi, Jian; Meroz, Yasmine; Mahadevan, L.; Ramanathan, Shriram

2014-12-01

Strongly correlated electron systems such as the rare-earth nickelates (R NiO3 , R denotes a rare-earth element) can exhibit synapselike continuous long-term potentiation and depression when gated with ionic liquids; exploiting the extreme sensitivity of coupled charge, spin, orbital, and lattice degrees of freedom to stoichiometry. We present experimental real-time, device-level classical conditioning and unlearning using nickelate-based synaptic devices in an electronic circuit compatible with both excitatory and inhibitory neurons. We establish a physical model for the device behavior based on electric-field-driven coupled ionic-electronic diffusion that can be utilized for design of more complex systems. We use the model to simulate a variety of associate and nonassociative learning mechanisms, as well as a feedforward recurrent network for storing memory. Our circuit intuitively parallels biological neural architectures, and it can be readily generalized to other forms of cellular learning and extinction. The simulation of neural function with electronic device analogs may provide insight into biological processes such as decision making, learning, and adaptation, while facilitating advanced parallel information processing in hardware.

A computational model of the development of separate representations of facial identity and expression in the primate visual system.

PubMed

Tromans, James Matthew; Harris, Mitchell; Stringer, Simon Maitland

2011-01-01

Experimental studies have provided evidence that the visual processing areas of the primate brain represent facial identity and facial expression within different subpopulations of neurons. For example, in non-human primates there is evidence that cells within the inferior temporal gyrus (TE) respond primarily to facial identity, while cells within the superior temporal sulcus (STS) respond to facial expression. More recently, it has been found that the orbitofrontal cortex (OFC) of non-human primates contains some cells that respond exclusively to changes in facial identity, while other cells respond exclusively to facial expression. How might the primate visual system develop physically separate representations of facial identity and expression given that the visual system is always exposed to simultaneous combinations of facial identity and expression during learning? In this paper, a biologically plausible neural network model, VisNet, of the ventral visual pathway is trained on a set of carefully-designed cartoon faces with different identities and expressions. The VisNet model architecture is composed of a hierarchical series of four Self-Organising Maps (SOMs), with associative learning in the feedforward synaptic connections between successive layers. During learning, the network develops separate clusters of cells that respond exclusively to either facial identity or facial expression. We interpret the performance of the network in terms of the learning properties of SOMs, which are able to exploit the statistical indendependence between facial identity and expression.

Object recognition with hierarchical discriminant saliency networks.

PubMed

Han, Sunhyoung; Vasconcelos, Nuno

2014-01-01

The benefits of integrating attention and object recognition are investigated. While attention is frequently modeled as a pre-processor for recognition, we investigate the hypothesis that attention is an intrinsic component of recognition and vice-versa. This hypothesis is tested with a recognition model, the hierarchical discriminant saliency network (HDSN), whose layers are top-down saliency detectors, tuned for a visual class according to the principles of discriminant saliency. As a model of neural computation, the HDSN has two possible implementations. In a biologically plausible implementation, all layers comply with the standard neurophysiological model of visual cortex, with sub-layers of simple and complex units that implement a combination of filtering, divisive normalization, pooling, and non-linearities. In a convolutional neural network implementation, all layers are convolutional and implement a combination of filtering, rectification, and pooling. The rectification is performed with a parametric extension of the now popular rectified linear units (ReLUs), whose parameters can be tuned for the detection of target object classes. This enables a number of functional enhancements over neural network models that lack a connection to saliency, including optimal feature denoising mechanisms for recognition, modulation of saliency responses by the discriminant power of the underlying features, and the ability to detect both feature presence and absence. In either implementation, each layer has a precise statistical interpretation, and all parameters are tuned by statistical learning. Each saliency detection layer learns more discriminant saliency templates than its predecessors and higher layers have larger pooling fields. This enables the HDSN to simultaneously achieve high selectivity to target object classes and invariance. The performance of the network in saliency and object recognition tasks is compared to those of models from the biological and computer vision literatures. This demonstrates benefits for all the functional enhancements of the HDSN, the class tuning inherent to discriminant saliency, and saliency layers based on templates of increasing target selectivity and invariance. Altogether, these experiments suggest that there are non-trivial benefits in integrating attention and recognition.

Design Automation in Synthetic Biology.

PubMed

Appleton, Evan; Madsen, Curtis; Roehner, Nicholas; Densmore, Douglas

2017-04-03

Design automation refers to a category of software tools for designing systems that work together in a workflow for designing, building, testing, and analyzing systems with a target behavior. In synthetic biology, these tools are called bio-design automation (BDA) tools. In this review, we discuss the BDA tools areas-specify, design, build, test, and learn-and introduce the existing software tools designed to solve problems in these areas. We then detail the functionality of some of these tools and show how they can be used together to create the desired behavior of two types of modern synthetic genetic regulatory networks. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

A Deep Learning Framework for Robust and Accurate Prediction of ncRNA-Protein Interactions Using Evolutionary Information.

PubMed

Yi, Hai-Cheng; You, Zhu-Hong; Huang, De-Shuang; Li, Xiao; Jiang, Tong-Hai; Li, Li-Ping

2018-06-01

The interactions between non-coding RNAs (ncRNAs) and proteins play an important role in many biological processes, and their biological functions are primarily achieved by binding with a variety of proteins. High-throughput biological techniques are used to identify protein molecules bound with specific ncRNA, but they are usually expensive and time consuming. Deep learning provides a powerful solution to computationally predict RNA-protein interactions. In this work, we propose the RPI-SAN model by using the deep-learning stacked auto-encoder network to mine the hidden high-level features from RNA and protein sequences and feed them into a random forest (RF) model to predict ncRNA binding proteins. Stacked assembling is further used to improve the accuracy of the proposed method. Four benchmark datasets, including RPI2241, RPI488, RPI1807, and NPInter v2.0, were employed for the unbiased evaluation of five established prediction tools: RPI-Pred, IPMiner, RPISeq-RF, lncPro, and RPI-SAN. The experimental results show that our RPI-SAN model achieves much better performance than other methods, with accuracies of 90.77%, 89.7%, 96.1%, and 99.33%, respectively. It is anticipated that RPI-SAN can be used as an effective computational tool for future biomedical researches and can accurately predict the potential ncRNA-protein interacted pairs, which provides reliable guidance for biological research. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Neural Networks

NASA Astrophysics Data System (ADS)

Schwindling, Jerome

2010-04-01

This course presents an overview of the concepts of the neural networks and their aplication in the framework of High energy physics analyses. After a brief introduction on the concept of neural networks, the concept is explained in the frame of neuro-biology, introducing the concept of multi-layer perceptron, learning and their use as data classifer. The concept is then presented in a second part using in more details the mathematical approach focussing on typical use cases faced in particle physics. Finally, the last part presents the best way to use such statistical tools in view of event classifers, putting the emphasis on the setup of the multi-layer perceptron. The full article (15 p.) corresponding to this lecture is written in french and is provided in the proceedings of the book SOS 2008.

A Collaborative Learning Network Approach to Improvement: The CUSP Learning Network.

PubMed

Weaver, Sallie J; Lofthus, Jennifer; Sawyer, Melinda; Greer, Lee; Opett, Kristin; Reynolds, Catherine; Wyskiel, Rhonda; Peditto, Stephanie; Pronovost, Peter J

2015-04-01

Collaborative improvement networks draw on the science of collaborative organizational learning and communities of practice to facilitate peer-to-peer learning, coaching, and local adaption. Although significant improvements in patient safety and quality have been achieved through collaborative methods, insight regarding how collaborative networks are used by members is needed. Improvement Strategy: The Comprehensive Unit-based Safety Program (CUSP) Learning Network is a multi-institutional collaborative network that is designed to facilitate peer-to-peer learning and coaching specifically related to CUSP. Member organizations implement all or part of the CUSP methodology to improve organizational safety culture, patient safety, and care quality. Qualitative case studies developed by participating members examine the impact of network participation across three levels of analysis (unit, hospital, health system). In addition, results of a satisfaction survey designed to evaluate member experiences were collected to inform network development. Common themes across case studies suggest that members found value in collaborative learning and sharing strategies across organizational boundaries related to a specific improvement strategy. The CUSP Learning Network is an example of network-based collaborative learning in action. Although this learning network focuses on a particular improvement methodology-CUSP-there is clear potential for member-driven learning networks to grow around other methods or topic areas. Such collaborative learning networks may offer a way to develop an infrastructure for longer-term support of improvement efforts and to more quickly diffuse creative sustainment strategies.

Resolution enhancement of wide-field interferometric microscopy by coupled deep autoencoders.

PubMed

Işil, Çağatay; Yorulmaz, Mustafa; Solmaz, Berkan; Turhan, Adil Burak; Yurdakul, Celalettin; Ünlü, Selim; Ozbay, Ekmel; Koç, Aykut

2018-04-01

Wide-field interferometric microscopy is a highly sensitive, label-free, and low-cost biosensing imaging technique capable of visualizing individual biological nanoparticles such as viral pathogens and exosomes. However, further resolution enhancement is necessary to increase detection and classification accuracy of subdiffraction-limited nanoparticles. In this study, we propose a deep-learning approach, based on coupled deep autoencoders, to improve resolution of images of L-shaped nanostructures. During training, our method utilizes microscope image patches and their corresponding manual truth image patches in order to learn the transformation between them. Following training, the designed network reconstructs denoised and resolution-enhanced image patches for unseen input.

Communal Cooperation in Sensor Networks for Situation Management

NASA Technical Reports Server (NTRS)

Jones, Kennie H.; Lodding, Kenneth N.; Olariu, Stephan; Wilson, Larry; Xin,Chunsheng

2006-01-01

Situation management is a rapidly evolving science where managed sources are processed as realtime streams of events and fused in a way that maximizes comprehension, thus enabling better decisions for action. Sensor networks provide a new technology that promises ubiquitous input and action throughout an environment, which can substantially improve information available to the process. Here we describe a NASA program that requires improvements in sensor networks and situation management. We present an approach for massively deployed sensor networks that does not rely on centralized control but is founded in lessons learned from the way biological ecosystems are organized. In this approach, fully distributed data aggregation and integration can be performed in a scalable fashion where individual motes operate based on local information, making local decisions that achieve globally-meaningful results. This exemplifies the robust, fault-tolerant infrastructure required for successful situation management systems.

Hidden Markov induced Dynamic Bayesian Network for recovering time evolving gene regulatory networks

NASA Astrophysics Data System (ADS)

Zhu, Shijia; Wang, Yadong

2015-12-01

Dynamic Bayesian Networks (DBN) have been widely used to recover gene regulatory relationships from time-series data in computational systems biology. Its standard assumption is ‘stationarity’, and therefore, several research efforts have been recently proposed to relax this restriction. However, those methods suffer from three challenges: long running time, low accuracy and reliance on parameter settings. To address these problems, we propose a novel non-stationary DBN model by extending each hidden node of Hidden Markov Model into a DBN (called HMDBN), which properly handles the underlying time-evolving networks. Correspondingly, an improved structural EM algorithm is proposed to learn the HMDBN. It dramatically reduces searching space, thereby substantially improving computational efficiency. Additionally, we derived a novel generalized Bayesian Information Criterion under the non-stationary assumption (called BWBIC), which can help significantly improve the reconstruction accuracy and largely reduce over-fitting. Moreover, the re-estimation formulas for all parameters of our model are derived, enabling us to avoid reliance on parameter settings. Compared to the state-of-the-art methods, the experimental evaluation of our proposed method on both synthetic and real biological data demonstrates more stably high prediction accuracy and significantly improved computation efficiency, even with no prior knowledge and parameter settings.

Decoding the encoding of functional brain networks: An fMRI classification comparison of non-negative matrix factorization (NMF), independent component analysis (ICA), and sparse coding algorithms.

PubMed

Xie, Jianwen; Douglas, Pamela K; Wu, Ying Nian; Brody, Arthur L; Anderson, Ariana E

2017-04-15

Brain networks in fMRI are typically identified using spatial independent component analysis (ICA), yet other mathematical constraints provide alternate biologically-plausible frameworks for generating brain networks. Non-negative matrix factorization (NMF) would suppress negative BOLD signal by enforcing positivity. Spatial sparse coding algorithms (L1 Regularized Learning and K-SVD) would impose local specialization and a discouragement of multitasking, where the total observed activity in a single voxel originates from a restricted number of possible brain networks. The assumptions of independence, positivity, and sparsity to encode task-related brain networks are compared; the resulting brain networks within scan for different constraints are used as basis functions to encode observed functional activity. These encodings are then decoded using machine learning, by using the time series weights to predict within scan whether a subject is viewing a video, listening to an audio cue, or at rest, in 304 fMRI scans from 51 subjects. The sparse coding algorithm of L1 Regularized Learning outperformed 4 variations of ICA (p<0.001) for predicting the task being performed within each scan using artifact-cleaned components. The NMF algorithms, which suppressed negative BOLD signal, had the poorest accuracy compared to the ICA and sparse coding algorithms. Holding constant the effect of the extraction algorithm, encodings using sparser spatial networks (containing more zero-valued voxels) had higher classification accuracy (p<0.001). Lower classification accuracy occurred when the extracted spatial maps contained more CSF regions (p<0.001). The success of sparse coding algorithms suggests that algorithms which enforce sparsity, discourage multitasking, and promote local specialization may capture better the underlying source processes than those which allow inexhaustible local processes such as ICA. Negative BOLD signal may capture task-related activations. Copyright © 2017 Elsevier B.V. All rights reserved.

Managing biological networks by using text mining and computer-aided curation

NASA Astrophysics Data System (ADS)

Yu, Seok Jong; Cho, Yongseong; Lee, Min-Ho; Lim, Jongtae; Yoo, Jaesoo

2015-11-01

In order to understand a biological mechanism in a cell, a researcher should collect a huge number of protein interactions with experimental data from experiments and the literature. Text mining systems that extract biological interactions from papers have been used to construct biological networks for a few decades. Even though the text mining of literature is necessary to construct a biological network, few systems with a text mining tool are available for biologists who want to construct their own biological networks. We have developed a biological network construction system called BioKnowledge Viewer that can generate a biological interaction network by using a text mining tool and biological taggers. It also Boolean simulation software to provide a biological modeling system to simulate the model that is made with the text mining tool. A user can download PubMed articles and construct a biological network by using the Multi-level Knowledge Emergence Model (KMEM), MetaMap, and A Biomedical Named Entity Recognizer (ABNER) as a text mining tool. To evaluate the system, we constructed an aging-related biological network that consist 9,415 nodes (genes) by using manual curation. With network analysis, we found that several genes, including JNK, AP-1, and BCL-2, were highly related in aging biological network. We provide a semi-automatic curation environment so that users can obtain a graph database for managing text mining results that are generated in the server system and can navigate the network with BioKnowledge Viewer, which is freely available at http://bioknowledgeviewer.kisti.re.kr.

Comparative Study on Interaction of Form and Motion Processing Streams by Applying Two Different Classifiers in Mechanism for Recognition of Biological Movement

PubMed Central

2014-01-01

Research on psychophysics, neurophysiology, and functional imaging shows particular representation of biological movements which contains two pathways. The visual perception of biological movements formed through the visual system called dorsal and ventral processing streams. Ventral processing stream is associated with the form information extraction; on the other hand, dorsal processing stream provides motion information. Active basic model (ABM) as hierarchical representation of the human object had revealed novelty in form pathway due to applying Gabor based supervised object recognition method. It creates more biological plausibility along with similarity with original model. Fuzzy inference system is used for motion pattern information in motion pathway creating more robustness in recognition process. Besides, interaction of these paths is intriguing and many studies in various fields considered it. Here, the interaction of the pathways to get more appropriated results has been investigated. Extreme learning machine (ELM) has been implied for classification unit of this model, due to having the main properties of artificial neural networks, but crosses from the difficulty of training time substantially diminished in it. Here, there will be a comparison between two different configurations, interactions using synergetic neural network and ELM, in terms of accuracy and compatibility. PMID:25276860

SCENERY: a web application for (causal) network reconstruction from cytometry data

PubMed Central

Papoutsoglou, Georgios; Athineou, Giorgos; Lagani, Vincenzo; Xanthopoulos, Iordanis; Schmidt, Angelika; Éliás, Szabolcs; Tegnér, Jesper

2017-01-01

Abstract Flow and mass cytometry technologies can probe proteins as biological markers in thousands of individual cells simultaneously, providing unprecedented opportunities for reconstructing networks of protein interactions through machine learning algorithms. The network reconstruction (NR) problem has been well-studied by the machine learning community. However, the potentials of available methods remain largely unknown to the cytometry community, mainly due to their intrinsic complexity and the lack of comprehensive, powerful and easy-to-use NR software implementations specific for cytometry data. To bridge this gap, we present Single CEll NEtwork Reconstruction sYstem (SCENERY), a web server featuring several standard and advanced cytometry data analysis methods coupled with NR algorithms in a user-friendly, on-line environment. In SCENERY, users may upload their data and set their own study design. The server offers several data analysis options categorized into three classes of methods: data (pre)processing, statistical analysis and NR. The server also provides interactive visualization and download of results as ready-to-publish images or multimedia reports. Its core is modular and based on the widely-used and robust R platform allowing power users to extend its functionalities by submitting their own NR methods. SCENERY is available at scenery.csd.uoc.gr or http://mensxmachina.org/en/software/. PMID:28525568

Gene networks associated with conditional fear in mice identified using a systems genetics approach

PubMed Central

2011-01-01

Background Our understanding of the genetic basis of learning and memory remains shrouded in mystery. To explore the genetic networks governing the biology of conditional fear, we used a systems genetics approach to analyze a hybrid mouse diversity panel (HMDP) with high mapping resolution. Results A total of 27 behavioral quantitative trait loci were mapped with a false discovery rate of 5%. By integrating fear phenotypes, transcript profiling data from hippocampus and striatum and also genotype information, two gene co-expression networks correlated with context-dependent immobility were identified. We prioritized the key markers and genes in these pathways using intramodular connectivity measures and structural equation modeling. Highly connected genes in the context fear modules included Psmd6, Ube2a and Usp33, suggesting an important role for ubiquitination in learning and memory. In addition, we surveyed the architecture of brain transcript regulation and demonstrated preservation of gene co-expression modules in hippocampus and striatum, while also highlighting important differences. Rps15a, Kif3a, Stard7, 6330503K22RIK, and Plvap were among the individual genes whose transcript abundance were strongly associated with fear phenotypes. Conclusion Application of our multi-faceted mapping strategy permits an increasingly detailed characterization of the genetic networks underlying behavior. PMID:21410935

The Knowledge-Integrated Network Biomarkers Discovery for Major Adverse Cardiac Events

PubMed Central

Jin, Guangxu; Zhou, Xiaobo; Wang, Honghui; Zhao, Hong; Cui, Kemi; Zhang, Xiang-Sun; Chen, Luonan; Hazen, Stanley L.; Li, King; Wong, Stephen T. C.

2010-01-01

The mass spectrometry (MS) technology in clinical proteomics is very promising for discovery of new biomarkers for diseases management. To overcome the obstacles of data noises in MS analysis, we proposed a new approach of knowledge-integrated biomarker discovery using data from Major Adverse Cardiac Events (MACE) patients. We first built up a cardiovascular-related network based on protein information coming from protein annotations in Uniprot, protein–protein interaction (PPI), and signal transduction database. Distinct from the previous machine learning methods in MS data processing, we then used statistical methods to discover biomarkers in cardiovascular-related network. Through the tradeoff between known protein information and data noises in mass spectrometry data, we finally could firmly identify those high-confident biomarkers. Most importantly, aided by protein–protein interaction network, that is, cardiovascular-related network, we proposed a new type of biomarkers, that is, network biomarkers, composed of a set of proteins and the interactions among them. The candidate network biomarkers can classify the two groups of patients more accurately than current single ones without consideration of biological molecular interaction. PMID:18665624

A compound memristive synapse model for statistical learning through STDP in spiking neural networks

PubMed Central

Bill, Johannes; Legenstein, Robert

2014-01-01

Memristors have recently emerged as promising circuit elements to mimic the function of biological synapses in neuromorphic computing. The fabrication of reliable nanoscale memristive synapses, that feature continuous conductance changes based on the timing of pre- and postsynaptic spikes, has however turned out to be challenging. In this article, we propose an alternative approach, the compound memristive synapse, that circumvents this problem by the use of memristors with binary memristive states. A compound memristive synapse employs multiple bistable memristors in parallel to jointly form one synapse, thereby providing a spectrum of synaptic efficacies. We investigate the computational implications of synaptic plasticity in the compound synapse by integrating the recently observed phenomenon of stochastic filament formation into an abstract model of stochastic switching. Using this abstract model, we first show how standard pulsing schemes give rise to spike-timing dependent plasticity (STDP) with a stabilizing weight dependence in compound synapses. In a next step, we study unsupervised learning with compound synapses in networks of spiking neurons organized in a winner-take-all architecture. Our theoretical analysis reveals that compound-synapse STDP implements generalized Expectation-Maximization in the spiking network. Specifically, the emergent synapse configuration represents the most salient features of the input distribution in a Mixture-of-Gaussians generative model. Furthermore, the network's spike response to spiking input streams approximates a well-defined Bayesian posterior distribution. We show in computer simulations how such networks learn to represent high-dimensional distributions over images of handwritten digits with high fidelity even in presence of substantial device variations and under severe noise conditions. Therefore, the compound memristive synapse may provide a synaptic design principle for future neuromorphic architectures. PMID:25565943

Leveraging multiple gene networks to prioritize GWAS candidate genes via network representation learning.

PubMed

Wu, Mengmeng; Zeng, Wanwen; Liu, Wenqiang; Lv, Hairong; Chen, Ting; Jiang, Rui

2018-06-03

Genome-wide association studies (GWAS) have successfully discovered a number of disease-associated genetic variants in the past decade, providing an unprecedented opportunity for deciphering genetic basis of human inherited diseases. However, it is still a challenging task to extract biological knowledge from the GWAS data, due to such issues as missing heritability and weak interpretability. Indeed, the fact that the majority of discovered loci fall into noncoding regions without clear links to genes has been preventing the characterization of their functions and appealing for a sophisticated approach to bridge genetic and genomic studies. Towards this problem, network-based prioritization of candidate genes, which performs integrated analysis of gene networks with GWAS data, has emerged as a promising direction and attracted much attention. However, most existing methods overlook the sparse and noisy properties of gene networks and thus may lead to suboptimal performance. Motivated by this understanding, we proposed a novel method called REGENT for integrating multiple gene networks with GWAS data to prioritize candidate genes for complex diseases. We leveraged a technique called the network representation learning to embed a gene network into a compact and robust feature space, and then designed a hierarchical statistical model to integrate features of multiple gene networks with GWAS data for the effective inference of genes associated with a disease of interest. We applied our method to six complex diseases and demonstrated the superior performance of REGENT over existing approaches in recovering known disease-associated genes. We further conducted a pathway analysis and showed that the ability of REGENT to discover disease-associated pathways. We expect to see applications of our method to a broad spectrum of diseases for post-GWAS analysis. REGENT is freely available at https://github.com/wmmthu/REGENT. Copyright © 2018 Elsevier Inc. All rights reserved.

Networks’ Characteristics Matter for Systems Biology

PubMed Central

Rider, Andrew K.; Milenković, Tijana; Siwo, Geoffrey H.; Pinapati, Richard S.; Emrich, Scott J.; Ferdig, Michael T.; Chawla, Nitesh V.

2015-01-01

A fundamental goal of systems biology is to create models that describe relationships between biological components. Networks are an increasingly popular approach to this problem. However, a scientist interested in modeling biological (e.g., gene expression) data as a network is quickly confounded by the fundamental problem: how to construct the network? It is fairly easy to construct a network, but is it the network for the problem being considered? This is an important problem with three fundamental issues: How to weight edges in the network in order to capture actual biological interactions? What is the effect of the type of biological experiment used to collect the data from which the network is constructed? How to prune the weighted edges (or what cut-off to apply)? Differences in the construction of networks could lead to different biological interpretations. Indeed, we find that there are statistically significant dissimilarities in the functional content and topology between gene co-expression networks constructed using different edge weighting methods, data types, and edge cut-offs. We show that different types of known interactions, such as those found through Affinity Capture-Luminescence or Synthetic Lethality experiments, appear in significantly varying amounts in networks constructed in different ways. Hence, we demonstrate that different biological questions may be answered by the different networks. Consequently, we posit that the approach taken to build a network can be matched to biological questions to get targeted answers. More study is required to understand the implications of different network inference approaches and to draw reliable conclusions from networks used in the field of systems biology. PMID:26500772

Identification of Cell Cycle-Regulated Genes by Convolutional Neural Network.

PubMed

Liu, Chenglin; Cui, Peng; Huang, Tao

2017-01-01

The cell cycle-regulated genes express periodically with the cell cycle stages, and the identification and study of these genes can provide a deep understanding of the cell cycle process. Large false positives and low overlaps are big problems in cell cycle-regulated gene detection. Here, a computational framework called DLGene was proposed for cell cycle-regulated gene detection. It is based on the convolutional neural network, a deep learning algorithm representing raw form of data pattern without assumption of their distribution. First, the expression data was transformed to categorical state data to denote the changing state of gene expression, and four different expression patterns were revealed for the reported cell cycle-regulated genes. Then, DLGene was applied to discriminate the non-cell cycle gene and the four subtypes of cell cycle genes. Its performances were compared with six traditional machine learning methods. At last, the biological functions of representative cell cycle genes for each subtype are analyzed. Our method showed better and more balanced performance of sensitivity and specificity comparing to other machine learning algorithms. The cell cycle genes had very different expression pattern with non-cell cycle genes and among the cell-cycle genes, there were four subtypes. Our method not only detects the cell cycle genes, but also describes its expression pattern, such as when its highest expression level is reached and how it changes with time. For each type, we analyzed the biological functions of the representative genes and such results provided novel insight to the cell cycle mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Causal biological network database: a comprehensive platform of causal biological network models focused on the pulmonary and vascular systems

PubMed Central

Boué, Stéphanie; Talikka, Marja; Westra, Jurjen Willem; Hayes, William; Di Fabio, Anselmo; Park, Jennifer; Schlage, Walter K.; Sewer, Alain; Fields, Brett; Ansari, Sam; Martin, Florian; Veljkovic, Emilija; Kenney, Renee; Peitsch, Manuel C.; Hoeng, Julia

2015-01-01

With the wealth of publications and data available, powerful and transparent computational approaches are required to represent measured data and scientific knowledge in a computable and searchable format. We developed a set of biological network models, scripted in the Biological Expression Language, that reflect causal signaling pathways across a wide range of biological processes, including cell fate, cell stress, cell proliferation, inflammation, tissue repair and angiogenesis in the pulmonary and cardiovascular context. This comprehensive collection of networks is now freely available to the scientific community in a centralized web-based repository, the Causal Biological Network database, which is composed of over 120 manually curated and well annotated biological network models and can be accessed at http://causalbionet.com. The website accesses a MongoDB, which stores all versions of the networks as JSON objects and allows users to search for genes, proteins, biological processes, small molecules and keywords in the network descriptions to retrieve biological networks of interest. The content of the networks can be visualized and browsed. Nodes and edges can be filtered and all supporting evidence for the edges can be browsed and is linked to the original articles in PubMed. Moreover, networks may be downloaded for further visualization and evaluation. Database URL: http://causalbionet.com PMID:25887162

Realization of synaptic learning and memory functions in Y2O3 based memristive device fabricated by dual ion beam sputtering

NASA Astrophysics Data System (ADS)

Das, Mangal; Kumar, Amitesh; Singh, Rohit; Than Htay, Myo; Mukherjee, Shaibal

2018-02-01

Single synaptic device with inherent learning and memory functions is demonstrated based on a forming-free amorphous Y2O3 (yttria) memristor fabricated by dual ion beam sputtering system. Synaptic functions such as nonlinear transmission characteristics, long-term plasticity, short-term plasticity and ‘learning behavior (LB)’ are achieved using a single synaptic device based on cost-effective metal-insulator-semiconductor (MIS) structure. An ‘LB’ function is demonstrated, for the first time in the literature, for a yttria based memristor, which bears a resemblance to certain memory functions of biological systems. The realization of key synaptic functions in a cost-effective MIS structure would promote much cheaper synapse for artificial neural network.

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

PubMed

Wang, Xiaosheng; Gotoh, Osamu

2010-03-24

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

Experimental resource pulses influence social-network dynamics and the potential for information flow in tool-using crows

PubMed Central

St Clair, James J. H.; Burns, Zackory T.; Bettaney, Elaine M.; Morrissey, Michael B.; Otis, Brian; Ryder, Thomas B.; Fleischer, Robert C.; James, Richard; Rutz, Christian

2015-01-01

Social-network dynamics have profound consequences for biological processes such as information flow, but are notoriously difficult to measure in the wild. We used novel transceiver technology to chart association patterns across 19 days in a wild population of the New Caledonian crow—a tool-using species that may socially learn, and culturally accumulate, tool-related information. To examine the causes and consequences of changing network topology, we manipulated the environmental availability of the crows' preferred tool-extracted prey, and simulated, in silico, the diffusion of information across field-recorded time-ordered networks. Here we show that network structure responds quickly to environmental change and that novel information can potentially spread rapidly within multi-family communities, especially when tool-use opportunities are plentiful. At the same time, we report surprisingly limited social contact between neighbouring crow communities. Such scale dependence in information-flow dynamics is likely to influence the evolution and maintenance of material cultures. PMID:26529116

Structure-based control of complex networks with nonlinear dynamics

NASA Astrophysics Data System (ADS)

Zanudo, Jorge G. T.; Yang, Gang; Albert, Reka

What can we learn about controlling a system solely from its underlying network structure? Here we use a framework for control of networks governed by a broad class of nonlinear dynamics that includes the major dynamic models of biological, technological, and social processes. This feedback-based framework provides realizable node overrides that steer a system towards any of its natural long term dynamic behaviors, regardless of the dynamic details and system parameters. We use this framework on several real networks, identify the topological characteristics that underlie the predicted node overrides, and compare its predictions to those of classical structural control theory. Finally, we demonstrate this framework's applicability in dynamic models of gene regulatory networks and identify nodes whose override is necessary for control in the general case, but not in specific model instances. This work was supported by NSF Grants PHY 1205840 and IIS 1160995. JGTZ is a recipient of a Stand Up To Cancer - The V Foundation Convergence Scholar Award.

Approximate, computationally efficient online learning in Bayesian spiking neurons.

PubMed

Kuhlmann, Levin; Hauser-Raspe, Michael; Manton, Jonathan H; Grayden, David B; Tapson, Jonathan; van Schaik, André

2014-03-01

Bayesian spiking neurons (BSNs) provide a probabilistic interpretation of how neurons perform inference and learning. Online learning in BSNs typically involves parameter estimation based on maximum-likelihood expectation-maximization (ML-EM) which is computationally slow and limits the potential of studying networks of BSNs. An online learning algorithm, fast learning (FL), is presented that is more computationally efficient than the benchmark ML-EM for a fixed number of time steps as the number of inputs to a BSN increases (e.g., 16.5 times faster run times for 20 inputs). Although ML-EM appears to converge 2.0 to 3.6 times faster than FL, the computational cost of ML-EM means that ML-EM takes longer to simulate to convergence than FL. FL also provides reasonable convergence performance that is robust to initialization of parameter estimates that are far from the true parameter values. However, parameter estimation depends on the range of true parameter values. Nevertheless, for a physiologically meaningful range of parameter values, FL gives very good average estimation accuracy, despite its approximate nature. The FL algorithm therefore provides an efficient tool, complementary to ML-EM, for exploring BSN networks in more detail in order to better understand their biological relevance. Moreover, the simplicity of the FL algorithm means it can be easily implemented in neuromorphic VLSI such that one can take advantage of the energy-efficient spike coding of BSNs.

Global adaptation in networks of selfish components: emergent associative memory at the system scale.

PubMed

Watson, Richard A; Mills, Rob; Buckley, C L

2011-01-01

In some circumstances complex adaptive systems composed of numerous self-interested agents can self-organize into structures that enhance global adaptation, efficiency, or function. However, the general conditions for such an outcome are poorly understood and present a fundamental open question for domains as varied as ecology, sociology, economics, organismic biology, and technological infrastructure design. In contrast, sufficient conditions for artificial neural networks to form structures that perform collective computational processes such as associative memory/recall, classification, generalization, and optimization are well understood. Such global functions within a single agent or organism are not wholly surprising, since the mechanisms (e.g., Hebbian learning) that create these neural organizations may be selected for this purpose; but agents in a multi-agent system have no obvious reason to adhere to such a structuring protocol or produce such global behaviors when acting from individual self-interest. However, Hebbian learning is actually a very simple and fully distributed habituation or positive feedback principle. Here we show that when self-interested agents can modify how they are affected by other agents (e.g., when they can influence which other agents they interact with), then, in adapting these inter-agent relationships to maximize their own utility, they will necessarily alter them in a manner homologous with Hebbian learning. Multi-agent systems with adaptable relationships will thereby exhibit the same system-level behaviors as neural networks under Hebbian learning. For example, improved global efficiency in multi-agent systems can be explained by the inherent ability of associative memory to generalize by idealizing stored patterns and/or creating new combinations of subpatterns. Thus distributed multi-agent systems can spontaneously exhibit adaptive global behaviors in the same sense, and by the same mechanism, as with the organizational principles familiar in connectionist models of organismic learning.

Use of a virtual human performance laboratory to improve integration of mathematics and biology in sports science curricula in Sweden and the United States.

PubMed

Garza, D; Besier, T; Johnston, T; Rolston, B; Schorsch, A; Matheson, G; Annerstedt, C; Lindh, J; Rydmark, M

2007-01-01

New fields such as bioengineering are exploring the role of the physical sciences in traditional biological approaches to problems, with exciting results in device innovation, medicine, and research biology. The integration of mathematics, biomechanics, and material sciences into the undergraduate biology curriculum will better prepare students for these opportunities and enhance cooperation among faculty and students at the university level. We propose the study of sports science as the basis for introduction of this interdisciplinary program. This novel integrated approach will require a virtual human performance laboratory dual-hosted in Sweden and the United States. We have designed a course model that involves cooperative learning between students at Göteborg University and Stanford University, utilizes new technologies, encourages development of original research and will rely on frequent self-assessment and reflective learning. We will compare outcomes between this course and a more traditional didactic format as well as assess the effectiveness of multiple web-hosted virtual environments. We anticipate the grant will result in a network of original faculty and student research in exercise science and pedagogy as well as provide the opportunity for implementation of the model in more advance training levels and K-12 programs.

Deep learning in mammography and breast histology, an overview and future trends.

PubMed

Hamidinekoo, Azam; Denton, Erika; Rampun, Andrik; Honnor, Kate; Zwiggelaar, Reyer

2018-07-01

Recent improvements in biomedical image analysis using deep learning based neural networks could be exploited to enhance the performance of Computer Aided Diagnosis (CAD) systems. Considering the importance of breast cancer worldwide and the promising results reported by deep learning based methods in breast imaging, an overview of the recent state-of-the-art deep learning based CAD systems developed for mammography and breast histopathology images is presented. In this study, the relationship between mammography and histopathology phenotypes is described, which takes biological aspects into account. We propose a computer based breast cancer modelling approach: the Mammography-Histology-Phenotype-Linking-Model, which develops a mapping of features/phenotypes between mammographic abnormalities and their histopathological representation. Challenges are discussed along with the potential contribution of such a system to clinical decision making and treatment management. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Building adaptive connectionist-based controllers: review of experiments in human-robot interaction, collective robotics, and computational neuroscience

NASA Astrophysics Data System (ADS)

Billard, Aude

2000-10-01

This paper summarizes a number of experiments in biologically inspired robotics. The common feature to all experiments is the use of artificial neural networks as the building blocks for the controllers. The experiments speak in favor of using a connectionist approach for designing adaptive and flexible robot controllers, and for modeling neurological processes. I present 1) DRAMA, a novel connectionist architecture, which has general property for learning time series and extracting spatio-temporal regularities in multi-modal and highly noisy data; 2) Robota, a doll-shaped robot, which imitates and learns a proto-language; 3) an experiment in collective robotics, where a group of 4 to 15 Khepera robots learn dynamically the topography of an environment whose features change frequently; 4) an abstract, computational model of primate ability to learn by imitation; 5) a model for the control of locomotor gaits in a quadruped legged robot.

A neural network approach for image reconstruction in electron magnetic resonance tomography.

PubMed

Durairaj, D Christopher; Krishna, Murali C; Murugesan, Ramachandran

2007-10-01

An object-oriented, artificial neural network (ANN) based, application system for reconstruction of two-dimensional spatial images in electron magnetic resonance (EMR) tomography is presented. The standard back propagation algorithm is utilized to train a three-layer sigmoidal feed-forward, supervised, ANN to perform the image reconstruction. The network learns the relationship between the 'ideal' images that are reconstructed using filtered back projection (FBP) technique and the corresponding projection data (sinograms). The input layer of the network is provided with a training set that contains projection data from various phantoms as well as in vivo objects, acquired from an EMR imager. Twenty five different network configurations are investigated to test the ability of the generalization of the network. The trained ANN then reconstructs two-dimensional temporal spatial images that present the distribution of free radicals in biological systems. Image reconstruction by the trained neural network shows better time complexity than the conventional iterative reconstruction algorithms such as multiplicative algebraic reconstruction technique (MART). The network is further explored for image reconstruction from 'noisy' EMR data and the results show better performance than the FBP method. The network is also tested for its ability to reconstruct from limited-angle EMR data set.

View-Tolerant Face Recognition and Hebbian Learning Imply Mirror-Symmetric Neural Tuning to Head Orientation.

PubMed

Leibo, Joel Z; Liao, Qianli; Anselmi, Fabio; Freiwald, Winrich A; Poggio, Tomaso

2017-01-09

The primate brain contains a hierarchy of visual areas, dubbed the ventral stream, which rapidly computes object representations that are both specific for object identity and robust against identity-preserving transformations, like depth rotations [1, 2]. Current computational models of object recognition, including recent deep-learning networks, generate these properties through a hierarchy of alternating selectivity-increasing filtering and tolerance-increasing pooling operations, similar to simple-complex cells operations [3-6]. Here, we prove that a class of hierarchical architectures and a broad set of biologically plausible learning rules generate approximate invariance to identity-preserving transformations at the top level of the processing hierarchy. However, all past models tested failed to reproduce the most salient property of an intermediate representation of a three-level face-processing hierarchy in the brain: mirror-symmetric tuning to head orientation [7]. Here, we demonstrate that one specific biologically plausible Hebb-type learning rule generates mirror-symmetric tuning to bilaterally symmetric stimuli, like faces, at intermediate levels of the architecture and show why it does so. Thus, the tuning properties of individual cells inside the visual stream appear to result from group properties of the stimuli they encode and to reflect the learning rules that sculpted the information-processing system within which they reside. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pattern Storage, Bifurcations, and Groupwise Correlation Structure of an Exactly Solvable Asymmetric Neural Network Model.

PubMed

Fasoli, Diego; Cattani, Anna; Panzeri, Stefano

2018-05-01

Despite their biological plausibility, neural network models with asymmetric weights are rarely solved analytically, and closed-form solutions are available only in some limiting cases or in some mean-field approximations. We found exact analytical solutions of an asymmetric spin model of neural networks with arbitrary size without resorting to any approximation, and we comprehensively studied its dynamical and statistical properties. The network had discrete time evolution equations and binary firing rates, and it could be driven by noise with any distribution. We found analytical expressions of the conditional and stationary joint probability distributions of the membrane potentials and the firing rates. By manipulating the conditional probability distribution of the firing rates, we extend to stochastic networks the associating learning rule previously introduced by Personnaz and coworkers. The new learning rule allowed the safe storage, under the presence of noise, of point and cyclic attractors, with useful implications for content-addressable memories. Furthermore, we studied the bifurcation structure of the network dynamics in the zero-noise limit. We analytically derived examples of the codimension 1 and codimension 2 bifurcation diagrams of the network, which describe how the neuronal dynamics changes with the external stimuli. This showed that the network may undergo transitions among multistable regimes, oscillatory behavior elicited by asymmetric synaptic connections, and various forms of spontaneous symmetry breaking. We also calculated analytically groupwise correlations of neural activity in the network in the stationary regime. This revealed neuronal regimes where, statistically, the membrane potentials and the firing rates are either synchronous or asynchronous. Our results are valid for networks with any number of neurons, although our equations can be realistically solved only for small networks. For completeness, we also derived the network equations in the thermodynamic limit of infinite network size and we analytically studied their local bifurcations. All the analytical results were extensively validated by numerical simulations.

Learning Analytics for Networked Learning Models

ERIC Educational Resources Information Center

Joksimovic, Srecko; Hatala, Marek; Gaševic, Dragan

2014-01-01

Teaching and learning in networked settings has attracted significant attention recently. The central topic of networked learning research is human-human and human-information interactions occurring within a networked learning environment. The nature of these interactions is highly complex and usually requires a multi-dimensional approach to…

The discovery of structural form

PubMed Central

Kemp, Charles; Tenenbaum, Joshua B.

2008-01-01

Algorithms for finding structure in data have become increasingly important both as tools for scientific data analysis and as models of human learning, yet they suffer from a critical limitation. Scientists discover qualitatively new forms of structure in observed data: For instance, Linnaeus recognized the hierarchical organization of biological species, and Mendeleev recognized the periodic structure of the chemical elements. Analogous insights play a pivotal role in cognitive development: Children discover that object category labels can be organized into hierarchies, friendship networks are organized into cliques, and comparative relations (e.g., “bigger than” or “better than”) respect a transitive order. Standard algorithms, however, can only learn structures of a single form that must be specified in advance: For instance, algorithms for hierarchical clustering create tree structures, whereas algorithms for dimensionality-reduction create low-dimensional spaces. Here, we present a computational model that learns structures of many different forms and that discovers which form is best for a given dataset. The model makes probabilistic inferences over a space of graph grammars representing trees, linear orders, multidimensional spaces, rings, dominance hierarchies, cliques, and other forms and successfully discovers the underlying structure of a variety of physical, biological, and social domains. Our approach brings structure learning methods closer to human abilities and may lead to a deeper computational understanding of cognitive development. PMID:18669663

Multiple brain networks underpinning word learning from fluent speech revealed by independent component analysis.

PubMed

López-Barroso, Diana; Ripollés, Pablo; Marco-Pallarés, Josep; Mohammadi, Bahram; Münte, Thomas F; Bachoud-Lévi, Anne-Catherine; Rodriguez-Fornells, Antoni; de Diego-Balaguer, Ruth

2015-04-15

Although neuroimaging studies using standard subtraction-based analysis from functional magnetic resonance imaging (fMRI) have suggested that frontal and temporal regions are involved in word learning from fluent speech, the possible contribution of different brain networks during this type of learning is still largely unknown. Indeed, univariate fMRI analyses cannot identify the full extent of distributed networks that are engaged by a complex task such as word learning. Here we used Independent Component Analysis (ICA) to characterize the different brain networks subserving word learning from an artificial language speech stream. Results were replicated in a second cohort of participants with a different linguistic background. Four spatially independent networks were associated with the task in both cohorts: (i) a dorsal Auditory-Premotor network; (ii) a dorsal Sensory-Motor network; (iii) a dorsal Fronto-Parietal network; and (iv) a ventral Fronto-Temporal network. The level of engagement of these networks varied through the learning period with only the dorsal Auditory-Premotor network being engaged across all blocks. In addition, the connectivity strength of this network in the second block of the learning phase correlated with the individual variability in word learning performance. These findings suggest that: (i) word learning relies on segregated connectivity patterns involving dorsal and ventral networks; and (ii) specifically, the dorsal auditory-premotor network connectivity strength is directly correlated with word learning performance. Copyright © 2015 Elsevier Inc. All rights reserved.

Causal biological network database: a comprehensive platform of causal biological network models focused on the pulmonary and vascular systems.

PubMed

Boué, Stéphanie; Talikka, Marja; Westra, Jurjen Willem; Hayes, William; Di Fabio, Anselmo; Park, Jennifer; Schlage, Walter K; Sewer, Alain; Fields, Brett; Ansari, Sam; Martin, Florian; Veljkovic, Emilija; Kenney, Renee; Peitsch, Manuel C; Hoeng, Julia

2015-01-01

With the wealth of publications and data available, powerful and transparent computational approaches are required to represent measured data and scientific knowledge in a computable and searchable format. We developed a set of biological network models, scripted in the Biological Expression Language, that reflect causal signaling pathways across a wide range of biological processes, including cell fate, cell stress, cell proliferation, inflammation, tissue repair and angiogenesis in the pulmonary and cardiovascular context. This comprehensive collection of networks is now freely available to the scientific community in a centralized web-based repository, the Causal Biological Network database, which is composed of over 120 manually curated and well annotated biological network models and can be accessed at http://causalbionet.com. The website accesses a MongoDB, which stores all versions of the networks as JSON objects and allows users to search for genes, proteins, biological processes, small molecules and keywords in the network descriptions to retrieve biological networks of interest. The content of the networks can be visualized and browsed. Nodes and edges can be filtered and all supporting evidence for the edges can be browsed and is linked to the original articles in PubMed. Moreover, networks may be downloaded for further visualization and evaluation. Database URL: http://causalbionet.com © The Author(s) 2015. Published by Oxford University Press.

International institute for collaborative cell biology and biochemistry--history and memoirs from an international network for biological sciences.

PubMed

Cameron, L C

2013-01-01

I was invited to write this essay on the occasion of my selection as the recipient of the 2012 Bruce Alberts Award for Excellence in Science Education from the American Society for Cell Biology (ASCB). Receiving this award is an enormous honor. When I read the email announcement for the first time, it was more than a surprise to me, it was unbelievable. I joined ASCB in 1996, when I presented a poster and received a travel award. Since then, I have attended almost every ASCB meeting. I will try to use this essay to share with readers one of the best experiences in my life. Because this is an essay, I take the liberty of mixing some of my thoughts with data in a way that it not usual in scientific writing. I hope that this sacrifice of the format will achieve the goal of conveying what I have learned over the past 20 yr, during which time a group of colleagues and friends created a nexus of knowledge and wisdom. We have worked together to build a network capable of sharing and inspiring science all over the world.

An Imperfect Dopaminergic Error Signal Can Drive Temporal-Difference Learning

PubMed Central

Potjans, Wiebke; Diesmann, Markus; Morrison, Abigail

2011-01-01

An open problem in the field of computational neuroscience is how to link synaptic plasticity to system-level learning. A promising framework in this context is temporal-difference (TD) learning. Experimental evidence that supports the hypothesis that the mammalian brain performs temporal-difference learning includes the resemblance of the phasic activity of the midbrain dopaminergic neurons to the TD error and the discovery that cortico-striatal synaptic plasticity is modulated by dopamine. However, as the phasic dopaminergic signal does not reproduce all the properties of the theoretical TD error, it is unclear whether it is capable of driving behavior adaptation in complex tasks. Here, we present a spiking temporal-difference learning model based on the actor-critic architecture. The model dynamically generates a dopaminergic signal with realistic firing rates and exploits this signal to modulate the plasticity of synapses as a third factor. The predictions of our proposed plasticity dynamics are in good agreement with experimental results with respect to dopamine, pre- and post-synaptic activity. An analytical mapping from the parameters of our proposed plasticity dynamics to those of the classical discrete-time TD algorithm reveals that the biological constraints of the dopaminergic signal entail a modified TD algorithm with self-adapting learning parameters and an adapting offset. We show that the neuronal network is able to learn a task with sparse positive rewards as fast as the corresponding classical discrete-time TD algorithm. However, the performance of the neuronal network is impaired with respect to the traditional algorithm on a task with both positive and negative rewards and breaks down entirely on a task with purely negative rewards. Our model demonstrates that the asymmetry of a realistic dopaminergic signal enables TD learning when learning is driven by positive rewards but not when driven by negative rewards. PMID:21589888

Node fingerprinting: an efficient heuristic for aligning biological networks.

PubMed

Radu, Alex; Charleston, Michael

2014-10-01

With the continuing increase in availability of biological data and improvements to biological models, biological network analysis has become a promising area of research. An emerging technique for the analysis of biological networks is through network alignment. Network alignment has been used to calculate genetic distance, similarities between regulatory structures, and the effect of external forces on gene expression, and to depict conditional activity of expression modules in cancer. Network alignment is algorithmically complex, and therefore we must rely on heuristics, ideally as efficient and accurate as possible. The majority of current techniques for network alignment rely on precomputed information, such as with protein sequence alignment, or on tunable network alignment parameters, which may introduce an increased computational overhead. Our presented algorithm, which we call Node Fingerprinting (NF), is appropriate for performing global pairwise network alignment without precomputation or tuning, can be fully parallelized, and is able to quickly compute an accurate alignment between two biological networks. It has performed as well as or better than existing algorithms on biological and simulated data, and with fewer computational resources. The algorithmic validation performed demonstrates the low computational resource requirements of NF.

A multilevel layout algorithm for visualizing physical and genetic interaction networks, with emphasis on their modular organization.

PubMed

Tuikkala, Johannes; Vähämaa, Heidi; Salmela, Pekka; Nevalainen, Olli S; Aittokallio, Tero

2012-03-26

Graph drawing is an integral part of many systems biology studies, enabling visual exploration and mining of large-scale biological networks. While a number of layout algorithms are available in popular network analysis platforms, such as Cytoscape, it remains poorly understood how well their solutions reflect the underlying biological processes that give rise to the network connectivity structure. Moreover, visualizations obtained using conventional layout algorithms, such as those based on the force-directed drawing approach, may become uninformative when applied to larger networks with dense or clustered connectivity structure. We implemented a modified layout plug-in, named Multilevel Layout, which applies the conventional layout algorithms within a multilevel optimization framework to better capture the hierarchical modularity of many biological networks. Using a wide variety of real life biological networks, we carried out a systematic evaluation of the method in comparison with other layout algorithms in Cytoscape. The multilevel approach provided both biologically relevant and visually pleasant layout solutions in most network types, hence complementing the layout options available in Cytoscape. In particular, it could improve drawing of large-scale networks of yeast genetic interactions and human physical interactions. In more general terms, the biological evaluation framework developed here enables one to assess the layout solutions from any existing or future graph drawing algorithm as well as to optimize their performance for a given network type or structure. By making use of the multilevel modular organization when visualizing biological networks, together with the biological evaluation of the layout solutions, one can generate convenient visualizations for many network biology applications.

Multichannel Convolutional Neural Network for Biological Relation Extraction.

PubMed

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.

Critical neural networks with short- and long-term plasticity.

PubMed

Michiels van Kessenich, L; Luković, M; de Arcangelis, L; Herrmann, H J

2018-03-01

In recent years self organized critical neuronal models have provided insights regarding the origin of the experimentally observed avalanching behavior of neuronal systems. It has been shown that dynamical synapses, as a form of short-term plasticity, can cause critical neuronal dynamics. Whereas long-term plasticity, such as Hebbian or activity dependent plasticity, have a crucial role in shaping the network structure and endowing neural systems with learning abilities. In this work we provide a model which combines both plasticity mechanisms, acting on two different time scales. The measured avalanche statistics are compatible with experimental results for both the avalanche size and duration distribution with biologically observed percentages of inhibitory neurons. The time series of neuronal activity exhibits temporal bursts leading to 1/f decay in the power spectrum. The presence of long-term plasticity gives the system the ability to learn binary rules such as xor, providing the foundation of future research on more complicated tasks such as pattern recognition.

Critical neural networks with short- and long-term plasticity

NASA Astrophysics Data System (ADS)

Michiels van Kessenich, L.; Luković, M.; de Arcangelis, L.; Herrmann, H. J.

2018-03-01

In recent years self organized critical neuronal models have provided insights regarding the origin of the experimentally observed avalanching behavior of neuronal systems. It has been shown that dynamical synapses, as a form of short-term plasticity, can cause critical neuronal dynamics. Whereas long-term plasticity, such as Hebbian or activity dependent plasticity, have a crucial role in shaping the network structure and endowing neural systems with learning abilities. In this work we provide a model which combines both plasticity mechanisms, acting on two different time scales. The measured avalanche statistics are compatible with experimental results for both the avalanche size and duration distribution with biologically observed percentages of inhibitory neurons. The time series of neuronal activity exhibits temporal bursts leading to 1 /f decay in the power spectrum. The presence of long-term plasticity gives the system the ability to learn binary rules such as xor, providing the foundation of future research on more complicated tasks such as pattern recognition.

Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits.

PubMed

Kohara, Keigo; Pignatelli, Michele; Rivest, Alexander J; Jung, Hae-Yoon; Kitamura, Takashi; Suh, Junghyup; Frank, Dominic; Kajikawa, Koichiro; Mise, Nathan; Obata, Yuichi; Wickersham, Ian R; Tonegawa, Susumu

2014-02-01

The formation and recall of episodic memory requires precise information processing by the entorhinal-hippocampal network. For several decades, the trisynaptic circuit entorhinal cortex layer II (ECII)→dentate gyrus→CA3→CA1 and the monosynaptic circuit ECIII→CA1 have been considered the primary substrates of the network responsible for learning and memory. Circuits linked to another hippocampal region, CA2, have only recently come to light. Using highly cell type-specific transgenic mouse lines, optogenetics and patch-clamp recordings, we found that dentate gyrus cells, long believed to not project to CA2, send functional monosynaptic inputs to CA2 pyramidal cells through abundant longitudinal projections. CA2 innervated CA1 to complete an alternate trisynaptic circuit, but, unlike CA3, projected preferentially to the deep, rather than to the superficial, sublayer of CA1. Furthermore, contrary to existing knowledge, ECIII did not project to CA2. Our results allow a deeper understanding of the biology of learning and memory.

Robust short-term memory without synaptic learning.

PubMed

Johnson, Samuel; Marro, J; Torres, Joaquín J

2013-01-01

Short-term memory in the brain cannot in general be explained the way long-term memory can--as a gradual modification of synaptic weights--since it takes place too quickly. Theories based on some form of cellular bistability, however, do not seem able to account for the fact that noisy neurons can collectively store information in a robust manner. We show how a sufficiently clustered network of simple model neurons can be instantly induced into metastable states capable of retaining information for a short time (a few seconds). The mechanism is robust to different network topologies and kinds of neural model. This could constitute a viable means available to the brain for sensory and/or short-term memory with no need of synaptic learning. Relevant phenomena described by neurobiology and psychology, such as local synchronization of synaptic inputs and power-law statistics of forgetting avalanches, emerge naturally from this mechanism, and we suggest possible experiments to test its viability in more biological settings.

Relational Analysis of High School Students' Cognitive Self-Regulated Learning Strategies and Conceptions of Learning Biology

ERIC Educational Resources Information Center

Sadi, Özlem

2017-01-01

The purpose of this study was to analyze the relation between students' cognitive learning strategies and conceptions of learning biology. The two scales, "Cognitive Learning Strategies" and "Conceptions of Learning Biology", were revised and adapted to biology in order to measure the students' learning strategies and…

Inner and Outer Recursive Neural Networks for Chemoinformatics Applications.

PubMed

Urban, Gregor; Subrahmanya, Niranjan; Baldi, Pierre

2018-02-26

Deep learning methods applied to problems in chemoinformatics often require the use of recursive neural networks to handle data with graphical structure and variable size. We present a useful classification of recursive neural network approaches into two classes, the inner and outer approach. The inner approach uses recursion inside the underlying graph, to essentially "crawl" the edges of the graph, while the outer approach uses recursion outside the underlying graph, to aggregate information over progressively longer distances in an orthogonal direction. We illustrate the inner and outer approaches on several examples. More importantly, we provide open-source implementations [available at www.github.com/Chemoinformatics/InnerOuterRNN and cdb.ics.uci.edu ] for both approaches in Tensorflow which can be used in combination with training data to produce efficient models for predicting the physical, chemical, and biological properties of small molecules.

ISMB 2016 offers outstanding science, networking, and celebration

PubMed Central

Fogg, Christiana

2016-01-01

The annual international conference on Intelligent Systems for Molecular Biology (ISMB) is the major meeting of the International Society for Computational Biology (ISCB). Over the past 23 years the ISMB conference has grown to become the world's largest bioinformatics/computational biology conference. ISMB 2016 will be the year's most important computational biology event globally. The conferences provide a multidisciplinary forum for disseminating the latest developments in bioinformatics/computational biology. ISMB brings together scientists from computer science, molecular biology, mathematics, statistics and related fields. Its principal focus is on the development and application of advanced computational methods for biological problems. ISMB 2016 offers the strongest scientific program and the broadest scope of any international bioinformatics/computational biology conference. Building on past successes, the conference is designed to cater to variety of disciplines within the bioinformatics/computational biology community.  ISMB 2016 takes place July 8 - 12 at the Swan and Dolphin Hotel in Orlando, Florida, United States. For two days preceding the conference, additional opportunities including Satellite Meetings, Student Council Symposium, and a selection of Special Interest Group Meetings and Applied Knowledge Exchange Sessions (AKES) are all offered to enable registered participants to learn more on the latest methods and tools within specialty research areas. PMID:27347392

ISMB 2016 offers outstanding science, networking, and celebration.

PubMed

Fogg, Christiana

2016-01-01

The annual international conference on Intelligent Systems for Molecular Biology (ISMB) is the major meeting of the International Society for Computational Biology (ISCB). Over the past 23 years the ISMB conference has grown to become the world's largest bioinformatics/computational biology conference. ISMB 2016 will be the year's most important computational biology event globally. The conferences provide a multidisciplinary forum for disseminating the latest developments in bioinformatics/computational biology. ISMB brings together scientists from computer science, molecular biology, mathematics, statistics and related fields. Its principal focus is on the development and application of advanced computational methods for biological problems. ISMB 2016 offers the strongest scientific program and the broadest scope of any international bioinformatics/computational biology conference. Building on past successes, the conference is designed to cater to variety of disciplines within the bioinformatics/computational biology community.  ISMB 2016 takes place July 8 - 12 at the Swan and Dolphin Hotel in Orlando, Florida, United States. For two days preceding the conference, additional opportunities including Satellite Meetings, Student Council Symposium, and a selection of Special Interest Group Meetings and Applied Knowledge Exchange Sessions (AKES) are all offered to enable registered participants to learn more on the latest methods and tools within specialty research areas.

Toward synthesizing executable models in biology.

PubMed

Fisher, Jasmin; Piterman, Nir; Bodik, Rastislav

2014-01-01

Over the last decade, executable models of biological behaviors have repeatedly provided new scientific discoveries, uncovered novel insights, and directed new experimental avenues. These models are computer programs whose execution mechanistically simulates aspects of the cell's behaviors. If the observed behavior of the program agrees with the observed biological behavior, then the program explains the phenomena. This approach has proven beneficial for gaining new biological insights and directing new experimental avenues. One advantage of this approach is that techniques for analysis of computer programs can be applied to the analysis of executable models. For example, one can confirm that a model agrees with experiments for all possible executions of the model (corresponding to all environmental conditions), even if there are a huge number of executions. Various formal methods have been adapted for this context, for example, model checking or symbolic analysis of state spaces. To avoid manual construction of executable models, one can apply synthesis, a method to produce programs automatically from high-level specifications. In the context of biological modeling, synthesis would correspond to extracting executable models from experimental data. We survey recent results about the usage of the techniques underlying synthesis of computer programs for the inference of biological models from experimental data. We describe synthesis of biological models from curated mutation experiment data, inferring network connectivity models from phosphoproteomic data, and synthesis of Boolean networks from gene expression data. While much work has been done on automated analysis of similar datasets using machine learning and artificial intelligence, using synthesis techniques provides new opportunities such as efficient computation of disambiguating experiments, as well as the ability to produce different kinds of models automatically from biological data.

Unsupervised Feature Learning With Winner-Takes-All Based STDP

PubMed Central

Ferré, Paul; Mamalet, Franck; Thorpe, Simon J.

2018-01-01

We present a novel strategy for unsupervised feature learning in image applications inspired by the Spike-Timing-Dependent-Plasticity (STDP) biological learning rule. We show equivalence between rank order coding Leaky-Integrate-and-Fire neurons and ReLU artificial neurons when applied to non-temporal data. We apply this to images using rank-order coding, which allows us to perform a full network simulation with a single feed-forward pass using GPU hardware. Next we introduce a binary STDP learning rule compatible with training on batches of images. Two mechanisms to stabilize the training are also presented : a Winner-Takes-All (WTA) framework which selects the most relevant patches to learn from along the spatial dimensions, and a simple feature-wise normalization as homeostatic process. This learning process allows us to train multi-layer architectures of convolutional sparse features. We apply our method to extract features from the MNIST, ETH80, CIFAR-10, and STL-10 datasets and show that these features are relevant for classification. We finally compare these results with several other state of the art unsupervised learning methods. PMID:29674961

A neural network model of memory and higher cognitive functions.

PubMed

Vogel, David D

2005-01-01

I first describe a neural network model of associative memory in a small region of the brain. The model depends, unconventionally, on disinhibition of inhibitory links between excitatory neurons rather than long-term potentiation (LTP) of excitatory projections. The model may be shown to have advantages over traditional neural network models both in terms of information storage capacity and biological plausibility. The learning and recall algorithms are independent of network architecture, and require no thresholds or finely graded synaptic strengths. Several copies of this local network are then connected by means of many, weak, reciprocal, excitatory projections that allow one region to control the recall of information in another to produce behaviors analogous to serial memory, classical and operant conditioning, secondary reinforcement, refabrication of memory, and fabrication of possible future events. The network distinguishes between perceived and recalled events, and can predicate its response on the absence as well as the presence of particular stimuli. Some of these behaviors are achieved in ways that seem to provide instances of self-awareness and imagination, suggesting that consciousness may emerge as an epiphenomenon in simple brains.

The Impacts of Network Centrality and Self-Regulation on an E-Learning Environment with the Support of Social Network Awareness

ERIC Educational Resources Information Center

Lin, Jian-Wei; Huang, Hsieh-Hong; Chuang, Yuh-Shy

2015-01-01

An e-learning environment that supports social network awareness (SNA) is a highly effective means of increasing peer interaction and assisting student learning by raising awareness of social and learning contexts of peers. Network centrality profoundly impacts student learning in an SNA-related e-learning environment. Additionally,…

The Dichotomy in Degree Correlation of Biological Networks

PubMed Central

Hao, Dapeng; Li, Chuanxing

2011-01-01

Most complex networks from different areas such as biology, sociology or technology, show a correlation on node degree where the possibility of a link between two nodes depends on their connectivity. It is widely believed that complex networks are either disassortative (links between hubs are systematically suppressed) or assortative (links between hubs are enhanced). In this paper, we analyze a variety of biological networks and find that they generally show a dichotomous degree correlation. We find that many properties of biological networks can be explained by this dichotomy in degree correlation, including the neighborhood connectivity, the sickle-shaped clustering coefficient distribution and the modularity structure. This dichotomy distinguishes biological networks from real disassortative networks or assortative networks such as the Internet and social networks. We suggest that the modular structure of networks accounts for the dichotomy in degree correlation and vice versa, shedding light on the source of modularity in biological networks. We further show that a robust and well connected network necessitates the dichotomy of degree correlation, suggestive of an evolutionary motivation for its existence. Finally, we suggest that a dichotomous degree correlation favors a centrally connected modular network, by which the integrity of network and specificity of modules might be reconciled. PMID:22164269

The Relationships Between Epistemic Beliefs in Biology and Approaches to Learning Biology Among Biology-Major University Students in Taiwan

NASA Astrophysics Data System (ADS)

Lin, Yi-Chun; Liang, Jyh-Chong; Tsai, Chin-Chung

2012-12-01

The aim of this study was to investigate the relationships between students' epistemic beliefs in biology and their approaches to learning biology. To this end, two instruments, the epistemic beliefs in biology and the approaches to learning biology surveys, were developed and administered to 520 university biology students, respectively. By and large, it was found that the students reflected "mixed" motives in biology learning, while those who had more sophisticated epistemic beliefs tended to employ deep strategies. In addition, the results of paired t tests revealed that the female students were more likely to possess beliefs about biological knowledge residing in external authorities, to believe in a right answer, and to utilize rote learning as a learning strategy. Moreover, compared to juniors and seniors, freshmen and sophomores tended to hold less mature views on all factors of epistemic beliefs regarding biology. Another comparison indicated that theoretical biology students (e.g. students majoring in the Department of Biology) tended to have more mature beliefs in learning biology and more advanced strategies for biology learning than those students studying applied biology (e.g. in the Department of Biotechnology). Stepwise regression analysis, in general, indicated that students who valued the role of experiments and justify epistemic assumptions and knowledge claims based on evidence were more oriented towards having mixed motives and utilizing deep strategies to learn biology. In contrast, students who believed in the certainty of biological knowledge were more likely to adopt rote learning strategies and to aim to qualify in biology.

Automated analysis of high-content microscopy data with deep learning.

PubMed

Kraus, Oren Z; Grys, Ben T; Ba, Jimmy; Chong, Yolanda; Frey, Brendan J; Boone, Charles; Andrews, Brenda J

2017-04-18

Existing computational pipelines for quantitative analysis of high-content microscopy data rely on traditional machine learning approaches that fail to accurately classify more than a single dataset without substantial tuning and training, requiring extensive analysis. Here, we demonstrate that the application of deep learning to biological image data can overcome the pitfalls associated with conventional machine learning classifiers. Using a deep convolutional neural network (DeepLoc) to analyze yeast cell images, we show improved performance over traditional approaches in the automated classification of protein subcellular localization. We also demonstrate the ability of DeepLoc to classify highly divergent image sets, including images of pheromone-arrested cells with abnormal cellular morphology, as well as images generated in different genetic backgrounds and in different laboratories. We offer an open-source implementation that enables updating DeepLoc on new microscopy datasets. This study highlights deep learning as an important tool for the expedited analysis of high-content microscopy data. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Learning through ferroelectric domain dynamics in solid-state synapses

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

Boyn, Soren; Grollier, Julie; Lecerf, Gwendal

In the brain, learning is achieved through the ability of synapses to reconfigure the strength by which they connect neurons (synaptic plasticity). In promising solid-state synapses called memristors, conductance can be finely tuned by voltage pulses and set to evolve according to a biological learning rule called spike-timing-dependent plasticity (STDP). Future neuromorphic architectures will comprise billions of such nanosynapses, which require a clear understanding of the physical mechanisms responsible for plasticity. Here we report on synapses based on ferroelectric tunnel junctions and show that STDP can be harnessed from inhomogeneous polarization switching. Through combined scanning probe imaging, electrical transport andmore » atomic-scale molecular dynamics, we demonstrate that conductance variations can be modelled by the nucleation-dominated reversal of domains. Finally, based on this physical model, our simulations show that arrays of ferroelectric nanosynapses can autonomously learn to recognize patterns in a predictable way, opening the path towards unsupervised learning in spiking neural networks.« less

Designing Anticancer Peptides by Constructive Machine Learning.

PubMed

Grisoni, Francesca; Neuhaus, Claudia S; Gabernet, Gisela; Müller, Alex T; Hiss, Jan A; Schneider, Gisbert

2018-04-21

Constructive (generative) machine learning enables the automated generation of novel chemical structures without the need for explicit molecular design rules. This study presents the experimental application of such a deep machine learning model to design membranolytic anticancer peptides (ACPs) de novo. A recurrent neural network with long short-term memory cells was trained on α-helical cationic amphipathic peptide sequences and then fine-tuned with 26 known ACPs by transfer learning. This optimized model was used to generate unique and novel amino acid sequences. Twelve of the peptides were synthesized and tested for their activity on MCF7 human breast adenocarcinoma cells and selectivity against human erythrocytes. Ten of these peptides were active against cancer cells. Six of the active peptides killed MCF7 cancer cells without affecting human erythrocytes with at least threefold selectivity. These results advocate constructive machine learning for the automated design of peptides with desired biological activities. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Learning through ferroelectric domain dynamics in solid-state synapses

DOE PAGES

Boyn, Soren; Grollier, Julie; Lecerf, Gwendal; ...

2017-04-03

In the brain, learning is achieved through the ability of synapses to reconfigure the strength by which they connect neurons (synaptic plasticity). In promising solid-state synapses called memristors, conductance can be finely tuned by voltage pulses and set to evolve according to a biological learning rule called spike-timing-dependent plasticity (STDP). Future neuromorphic architectures will comprise billions of such nanosynapses, which require a clear understanding of the physical mechanisms responsible for plasticity. Here we report on synapses based on ferroelectric tunnel junctions and show that STDP can be harnessed from inhomogeneous polarization switching. Through combined scanning probe imaging, electrical transport andmore » atomic-scale molecular dynamics, we demonstrate that conductance variations can be modelled by the nucleation-dominated reversal of domains. Finally, based on this physical model, our simulations show that arrays of ferroelectric nanosynapses can autonomously learn to recognize patterns in a predictable way, opening the path towards unsupervised learning in spiking neural networks.« less

Biomimetic Models for An Ecological Approach to Massively-Deployed Sensor Networks

NASA Technical Reports Server (NTRS)

Jones, Kennie H.; Lodding, Kenneth N.; Olariu, Stephan; Wilson, Larry; Xin, Chunsheng

2005-01-01

Promises of ubiquitous control of the physical environment by massively-deployed wireless sensor networks open avenues for new applications that will redefine the way we live and work. Due to small size and low cost of sensor devices, visionaries promise systems enabled by deployment of massive numbers of sensors ubiquitous throughout our environment working in concert. Recent research has concentrated on developing techniques for performing relatively simple tasks with minimal energy expense, assuming some form of centralized control. Unfortunately, centralized control is not conducive to parallel activities and does not scale to massive size networks. Execution of simple tasks in sparse networks will not lead to the sophisticated applications predicted. We propose a new way of looking at massively-deployed sensor networks, motivated by lessons learned from the way biological ecosystems are organized. We demonstrate that in such a model, fully distributed data aggregation can be performed in a scalable fashion in massively deployed sensor networks, where motes operate on local information, making local decisions that are aggregated across the network to achieve globally-meaningful effects. We show that such architectures may be used to facilitate communication and synchronization in a fault-tolerant manner, while balancing workload and required energy expenditure throughout the network.

Learning multivariate distributions by competitive assembly of marginals.

PubMed

Sánchez-Vega, Francisco; Younes, Laurent; Geman, Donald

2013-02-01

We present a new framework for learning high-dimensional multivariate probability distributions from estimated marginals. The approach is motivated by compositional models and Bayesian networks, and designed to adapt to small sample sizes. We start with a large, overlapping set of elementary statistical building blocks, or "primitives," which are low-dimensional marginal distributions learned from data. Each variable may appear in many primitives. Subsets of primitives are combined in a Lego-like fashion to construct a probabilistic graphical model; only a small fraction of the primitives will participate in any valid construction. Since primitives can be precomputed, parameter estimation and structure search are separated. Model complexity is controlled by strong biases; we adapt the primitives to the amount of training data and impose rules which restrict the merging of them into allowable compositions. The likelihood of the data decomposes into a sum of local gains, one for each primitive in the final structure. We focus on a specific subclass of networks which are binary forests. Structure optimization corresponds to an integer linear program and the maximizing composition can be computed for reasonably large numbers of variables. Performance is evaluated using both synthetic data and real datasets from natural language processing and computational biology.

Teachers' Motives for Learning in Networks: Costs, Rewards and Community Interest

ERIC Educational Resources Information Center

van den Beemt, Antoine; Ketelaar, Evelien; Diepstraten, Isabelle; de Laat, Maarten

2018-01-01

Background: This paper discusses teachers' perspectives on learning networks and their motives for participating in these networks. Although it is widely held that teachers' learning may be developed through learning networks, not all teachers participate in such networks. Purpose: The theme of reciprocity, central to studies in the area of…

Up the ANTe: Understanding Entrepreneurial Leadership Learning through Actor-Network Theory

ERIC Educational Resources Information Center

Smith, Sue; Kempster, Steve; Barnes, Stewart

2017-01-01

This article explores the role of educators in supporting the development of entrepreneurial leadership learning by creating peer learning networks of owner-managers of small businesses. Using actor-network theory, the authors think through the process of constructing and maintaining a peer learning network (conceived of as an actor-network) and…

Controllability and observability of Boolean networks arising from biology

NASA Astrophysics Data System (ADS)

Li, Rui; Yang, Meng; Chu, Tianguang

2015-02-01

Boolean networks are currently receiving considerable attention as a computational scheme for system level analysis and modeling of biological systems. Studying control-related problems in Boolean networks may reveal new insights into the intrinsic control in complex biological systems and enable us to develop strategies for manipulating biological systems using exogenous inputs. This paper considers controllability and observability of Boolean biological networks. We propose a new approach, which draws from the rich theory of symbolic computation, to solve the problems. Consequently, simple necessary and sufficient conditions for reachability, controllability, and observability are obtained, and algorithmic tests for controllability and observability which are based on the Gröbner basis method are presented. As practical applications, we apply the proposed approach to several different biological systems, namely, the mammalian cell-cycle network, the T-cell activation network, the large granular lymphocyte survival signaling network, and the Drosophila segment polarity network, gaining novel insights into the control and/or monitoring of the specific biological systems.

Features of Knowledge Building in Biology: Understanding Undergraduate Students’ Ideas about Molecular Mechanisms

PubMed Central

Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S.

2016-01-01

Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. PMID:26931398

Optimal network alignment with graphlet degree vectors.

PubMed

Milenković, Tijana; Ng, Weng Leong; Hayes, Wayne; Przulj, Natasa

2010-06-30

Important biological information is encoded in the topology of biological networks. Comparative analyses of biological networks are proving to be valuable, as they can lead to transfer of knowledge between species and give deeper insights into biological function, disease, and evolution. We introduce a new method that uses the Hungarian algorithm to produce optimal global alignment between two networks using any cost function. We design a cost function based solely on network topology and use it in our network alignment. Our method can be applied to any two networks, not just biological ones, since it is based only on network topology. We use our new method to align protein-protein interaction networks of two eukaryotic species and demonstrate that our alignment exposes large and topologically complex regions of network similarity. At the same time, our alignment is biologically valid, since many of the aligned protein pairs perform the same biological function. From the alignment, we predict function of yet unannotated proteins, many of which we validate in the literature. Also, we apply our method to find topological similarities between metabolic networks of different species and build phylogenetic trees based on our network alignment score. The phylogenetic trees obtained in this way bear a striking resemblance to the ones obtained by sequence alignments. Our method detects topologically similar regions in large networks that are statistically significant. It does this independent of protein sequence or any other information external to network topology.

Expansion of the Gene Ontology knowledgebase and resources

PubMed Central

2017-01-01

The Gene Ontology (GO) is a comprehensive resource of computable knowledge regarding the functions of genes and gene products. As such, it is extensively used by the biomedical research community for the analysis of -omics and related data. Our continued focus is on improving the quality and utility of the GO resources, and we welcome and encourage input from researchers in all areas of biology. In this update, we summarize the current contents of the GO knowledgebase, and present several new features and improvements that have been made to the ontology, the annotations and the tools. Among the highlights are 1) developments that facilitate access to, and application of, the GO knowledgebase, and 2) extensions to the resource as well as increasing support for descriptions of causal models of biological systems and network biology. To learn more, visit http://geneontology.org/. PMID:27899567

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology

PubMed Central

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view. PMID:23515240

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology.

PubMed

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view.

BioNSi: A Discrete Biological Network Simulator Tool.

PubMed

Rubinstein, Amir; Bracha, Noga; Rudner, Liat; Zucker, Noga; Sloin, Hadas E; Chor, Benny

2016-08-05

Modeling and simulation of biological networks is an effective and widely used research methodology. The Biological Network Simulator (BioNSi) is a tool for modeling biological networks and simulating their discrete-time dynamics, implemented as a Cytoscape App. BioNSi includes a visual representation of the network that enables researchers to construct, set the parameters, and observe network behavior under various conditions. To construct a network instance in BioNSi, only partial, qualitative biological data suffices. The tool is aimed for use by experimental biologists and requires no prior computational or mathematical expertise. BioNSi is freely available at http://bionsi.wix.com/bionsi , where a complete user guide and a step-by-step manual can also be found.

A multilevel layout algorithm for visualizing physical and genetic interaction networks, with emphasis on their modular organization

PubMed Central

2012-01-01

Background Graph drawing is an integral part of many systems biology studies, enabling visual exploration and mining of large-scale biological networks. While a number of layout algorithms are available in popular network analysis platforms, such as Cytoscape, it remains poorly understood how well their solutions reflect the underlying biological processes that give rise to the network connectivity structure. Moreover, visualizations obtained using conventional layout algorithms, such as those based on the force-directed drawing approach, may become uninformative when applied to larger networks with dense or clustered connectivity structure. Methods We implemented a modified layout plug-in, named Multilevel Layout, which applies the conventional layout algorithms within a multilevel optimization framework to better capture the hierarchical modularity of many biological networks. Using a wide variety of real life biological networks, we carried out a systematic evaluation of the method in comparison with other layout algorithms in Cytoscape. Results The multilevel approach provided both biologically relevant and visually pleasant layout solutions in most network types, hence complementing the layout options available in Cytoscape. In particular, it could improve drawing of large-scale networks of yeast genetic interactions and human physical interactions. In more general terms, the biological evaluation framework developed here enables one to assess the layout solutions from any existing or future graph drawing algorithm as well as to optimize their performance for a given network type or structure. Conclusions By making use of the multilevel modular organization when visualizing biological networks, together with the biological evaluation of the layout solutions, one can generate convenient visualizations for many network biology applications. PMID:22448851

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology

PubMed Central

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental disturbances, is also proposed, together with a simulation example. PMID:23515190

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology.

PubMed

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental disturbances, is also proposed, together with a simulation example.

OWL reasoning framework over big biological knowledge network.

PubMed

Chen, Huajun; Chen, Xi; Gu, Peiqin; Wu, Zhaohui; Yu, Tong

2014-01-01

Recently, huge amounts of data are generated in the domain of biology. Embedded with domain knowledge from different disciplines, the isolated biological resources are implicitly connected. Thus it has shaped a big network of versatile biological knowledge. Faced with such massive, disparate, and interlinked biological data, providing an efficient way to model, integrate, and analyze the big biological network becomes a challenge. In this paper, we present a general OWL (web ontology language) reasoning framework to study the implicit relationships among biological entities. A comprehensive biological ontology across traditional Chinese medicine (TCM) and western medicine (WM) is used to create a conceptual model for the biological network. Then corresponding biological data is integrated into a biological knowledge network as the data model. Based on the conceptual model and data model, a scalable OWL reasoning method is utilized to infer the potential associations between biological entities from the biological network. In our experiment, we focus on the association discovery between TCM and WM. The derived associations are quite useful for biologists to promote the development of novel drugs and TCM modernization. The experimental results show that the system achieves high efficiency, accuracy, scalability, and effectivity.

OWL Reasoning Framework over Big Biological Knowledge Network

PubMed Central

Chen, Huajun; Chen, Xi; Gu, Peiqin; Wu, Zhaohui; Yu, Tong

2014-01-01

Recently, huge amounts of data are generated in the domain of biology. Embedded with domain knowledge from different disciplines, the isolated biological resources are implicitly connected. Thus it has shaped a big network of versatile biological knowledge. Faced with such massive, disparate, and interlinked biological data, providing an efficient way to model, integrate, and analyze the big biological network becomes a challenge. In this paper, we present a general OWL (web ontology language) reasoning framework to study the implicit relationships among biological entities. A comprehensive biological ontology across traditional Chinese medicine (TCM) and western medicine (WM) is used to create a conceptual model for the biological network. Then corresponding biological data is integrated into a biological knowledge network as the data model. Based on the conceptual model and data model, a scalable OWL reasoning method is utilized to infer the potential associations between biological entities from the biological network. In our experiment, we focus on the association discovery between TCM and WM. The derived associations are quite useful for biologists to promote the development of novel drugs and TCM modernization. The experimental results show that the system achieves high efficiency, accuracy, scalability, and effectivity. PMID:24877076

How Attention Can Create Synaptic Tags for the Learning of Working Memories in Sequential Tasks

PubMed Central

Rombouts, Jaldert O.; Bohte, Sander M.; Roelfsema, Pieter R.

2015-01-01

Intelligence is our ability to learn appropriate responses to new stimuli and situations. Neurons in association cortex are thought to be essential for this ability. During learning these neurons become tuned to relevant features and start to represent them with persistent activity during memory delays. This learning process is not well understood. Here we develop a biologically plausible learning scheme that explains how trial-and-error learning induces neuronal selectivity and working memory representations for task-relevant information. We propose that the response selection stage sends attentional feedback signals to earlier processing levels, forming synaptic tags at those connections responsible for the stimulus-response mapping. Globally released neuromodulators then interact with tagged synapses to determine their plasticity. The resulting learning rule endows neural networks with the capacity to create new working memory representations of task relevant information as persistent activity. It is remarkably generic: it explains how association neurons learn to store task-relevant information for linear as well as non-linear stimulus-response mappings, how they become tuned to category boundaries or analog variables, depending on the task demands, and how they learn to integrate probabilistic evidence for perceptual decisions. PMID:25742003

Synergistic target combination prediction from curated signaling networks: Machine learning meets systems biology and pharmacology.

PubMed

Chua, Huey Eng; Bhowmick, Sourav S; Tucker-Kellogg, Lisa

2017-10-01

Given a signaling network, the target combination prediction problem aims to predict efficacious and safe target combinations for combination therapy. State-of-the-art in silico methods use Monte Carlo simulated annealing (mcsa) to modify a candidate solution stochastically, and use the Metropolis criterion to accept or reject the proposed modifications. However, such stochastic modifications ignore the impact of the choice of targets and their activities on the combination's therapeutic effect and off-target effects, which directly affect the solution quality. In this paper, we present mascot, a method that addresses this limitation by leveraging two additional heuristic criteria to minimize off-target effects and achieve synergy for candidate modification. Specifically, off-target effects measure the unintended response of a signaling network to the target combination and is often associated with toxicity. Synergy occurs when a pair of targets exerts effects that are greater than the sum of their individual effects, and is generally a beneficial strategy for maximizing effect while minimizing toxicity. mascot leverages on a machine learning-based target prioritization method which prioritizes potential targets in a given disease-associated network to select more effective targets (better therapeutic effect and/or lower off-target effects); and on Loewe additivity theory from pharmacology which assesses the non-additive effects in a combination drug treatment to select synergistic target activities. Our experimental study on two disease-related signaling networks demonstrates the superiority of mascot in comparison to existing approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

Survey of local and global biological network alignment: the need to reconcile the two sides of the same coin.

PubMed

Guzzi, Pietro Hiram; Milenkovic, Tijana

2018-05-01

Analogous to genomic sequence alignment that allows for across-species transfer of biological knowledge between conserved sequence regions, biological network alignment can be used to guide the knowledge transfer between conserved regions of molecular networks of different species. Hence, biological network alignment can be used to redefine the traditional notion of a sequence-based homology to a new notion of network-based homology. Analogous to genomic sequence alignment, there exist local and global biological network alignments. Here, we survey prominent and recent computational approaches of each network alignment type and discuss their (dis)advantages. Then, as it was recently shown that the two approach types are complementary, in the sense that they capture different slices of cellular functioning, we discuss the need to reconcile the two network alignment types and present a recent first step in this direction. We conclude with some open research problems on this topic and comment on the usefulness of network alignment in other domains besides computational biology.

Applying dynamic Bayesian networks to perturbed gene expression data.

PubMed

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.

Multilayer network modeling of integrated biological systems. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

NASA Astrophysics Data System (ADS)

De Domenico, Manlio

2018-03-01

Biological systems, from a cell to the human brain, are inherently complex. A powerful representation of such systems, described by an intricate web of relationships across multiple scales, is provided by complex networks. Recently, several studies are highlighting how simple networks - obtained by aggregating or neglecting temporal or categorical description of biological data - are not able to account for the richness of information characterizing biological systems. More complex models, namely multilayer networks, are needed to account for interdependencies, often varying across time, of biological interacting units within a cell, a tissue or parts of an organism.

Deconstructing Memory in Drosophila

PubMed Central

Margulies, Carla; Tully, Tim; Dubnau, Josh

2011-01-01

Unlike most organ systems, which have evolved to maintain homeostasis, the brain has been selected to sense and adapt to environmental stimuli by constantly altering interactions in a gene network that functions within a larger neural network. This unique feature of the central nervous system provides a remarkable plasticity of behavior, but also makes experimental investigations challenging. Each experimental intervention ramifies through both gene and neural networks, resulting in unpredicted and sometimes confusing phenotypic adaptations. Experimental dissection of mechanisms underlying behavioral plasticity ultimately must accomplish an integration across many levels of biological organization, including genetic pathways acting within individual neurons, neural network interactions which feed back to gene function, and phenotypic observations at the behavioral level. This dissection will be more easily accomplished for model systems such as Drosophila, which, compared with mammals, have relatively simple and manipulable nervous systems and genomes. The evolutionary conservation of behavioral phenotype and the underlying gene function ensures that much of what we learn in such model systems will be relevant to human cognition. In this essay, we have not attempted to review the entire Drosophila memory field. Instead, we have tried to discuss particular findings that provide some level of intellectual synthesis across three levels of biological organization: behavior, neural circuitry and biochemical pathways. We have attempted to use this integrative approach to evaluate distinct mechanistic hypotheses, and to propose critical experiments that will advance this field. PMID:16139203

MitProNet: A Knowledgebase and Analysis Platform of Proteome, Interactome and Diseases for Mammalian Mitochondria

PubMed Central

Mao, Song; Chai, Xiaoqiang; Hu, Yuling; Hou, Xugang; Tang, Yiheng; Bi, Cheng; Li, Xiao

2014-01-01

Mitochondrion plays a central role in diverse biological processes in most eukaryotes, and its dysfunctions are critically involved in a large number of diseases and the aging process. A systematic identification of mitochondrial proteomes and characterization of functional linkages among mitochondrial proteins are fundamental in understanding the mechanisms underlying biological functions and human diseases associated with mitochondria. Here we present a database MitProNet which provides a comprehensive knowledgebase for mitochondrial proteome, interactome and human diseases. First an inventory of mammalian mitochondrial proteins was compiled by widely collecting proteomic datasets, and the proteins were classified by machine learning to achieve a high-confidence list of mitochondrial proteins. The current version of MitProNet covers 1124 high-confidence proteins, and the remainders were further classified as middle- or low-confidence. An organelle-specific network of functional linkages among mitochondrial proteins was then generated by integrating genomic features encoded by a wide range of datasets including genomic context, gene expression profiles, protein-protein interactions, functional similarity and metabolic pathways. The functional-linkage network should be a valuable resource for the study of biological functions of mitochondrial proteins and human mitochondrial diseases. Furthermore, we utilized the network to predict candidate genes for mitochondrial diseases using prioritization algorithms. All proteins, functional linkages and disease candidate genes in MitProNet were annotated according to the information collected from their original sources including GO, GEO, OMIM, KEGG, MIPS, HPRD and so on. MitProNet features a user-friendly graphic visualization interface to present functional analysis of linkage networks. As an up-to-date database and analysis platform, MitProNet should be particularly helpful in comprehensive studies of complicated biological mechanisms underlying mitochondrial functions and human mitochondrial diseases. MitProNet is freely accessible at http://bio.scu.edu.cn:8085/MitProNet. PMID:25347823

Blending Formal and Informal Learning Networks for Online Learning

ERIC Educational Resources Information Center

Czerkawski, Betül C.

2016-01-01

With the emergence of social software and the advance of web-based technologies, online learning networks provide invaluable opportunities for learning, whether formal or informal. Unlike top-down, instructor-centered, and carefully planned formal learning settings, informal learning networks offer more bottom-up, student-centered participatory…

Biology Question Generation from a Semantic Network

NASA Astrophysics Data System (ADS)

Zhang, Lishan

Science instructors need questions for use in exams, homework assignments, class discussions, reviews, and other instructional activities. Textbooks never have enough questions, so instructors must find them from other sources or generate their own questions. In order to supply instructors with biology questions, a semantic network approach was developed for generating open response biology questions. The generated questions were compared to professional authorized questions. To boost students' learning experience, adaptive selection was built on the generated questions. Bayesian Knowledge Tracing was used as embedded assessment of the student's current competence so that a suitable question could be selected based on the student's previous performance. A between-subjects experiment with 42 participants was performed, where half of the participants studied with adaptive selected questions and the rest studied with mal-adaptive order of questions. Both groups significantly improved their test scores, and the participants in adaptive group registered larger learning gains than participants in the control group. To explore the possibility of generating rich instructional feedback for machine-generated questions, a question-paragraph mapping task was identified. Given a set of questions and a list of paragraphs for a textbook, the goal of the task was to map the related paragraphs to each question. An algorithm was developed whose performance was comparable to human annotators. A multiple-choice question with high quality distractors (incorrect answers) can be pedagogically valuable as well as being much easier to grade than open-response questions. Thus, an algorithm was developed to generate good distractors for multiple-choice questions. The machine-generated multiple-choice questions were compared to human-generated questions in terms of three measures: question difficulty, question discrimination and distractor usefulness. By recruiting 200 participants from Amazon Mechanical Turk, it turned out that the two types of questions performed very closely on all the three measures.

Enhancement of COPD biological networks using a web-based collaboration interface

PubMed Central

Boue, Stephanie; Fields, Brett; Hoeng, Julia; Park, Jennifer; Peitsch, Manuel C.; Schlage, Walter K.; Talikka, Marja; Binenbaum, Ilona; Bondarenko, Vladimir; Bulgakov, Oleg V.; Cherkasova, Vera; Diaz-Diaz, Norberto; Fedorova, Larisa; Guryanova, Svetlana; Guzova, Julia; Igorevna Koroleva, Galina; Kozhemyakina, Elena; Kumar, Rahul; Lavid, Noa; Lu, Qingxian; Menon, Swapna; Ouliel, Yael; Peterson, Samantha C.; Prokhorov, Alexander; Sanders, Edward; Schrier, Sarah; Schwaitzer Neta, Golan; Shvydchenko, Irina; Tallam, Aravind; Villa-Fombuena, Gema; Wu, John; Yudkevich, Ilya; Zelikman, Mariya

2015-01-01

The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks. We report the construction of 50 biological network models relevant to lung biology and early COPD using an integrative systems biology and collaborative crowd-verification approach. By combining traditional literature curation with a data-driven approach that predicts molecular activities from transcriptomics data, we constructed an initial COPD network model set based on a previously published non-diseased lung-relevant model set. The crowd was given the opportunity to enhance and refine the networks on a website ( https://bionet.sbvimprover.com/) and to add mechanistic detail, as well as critically review existing evidence and evidence added by other users, so as to enhance the accuracy of the biological representation of the processes captured in the networks. Finally, scientists and experts in the field discussed and refined the networks during an in-person jamboree meeting. Here, we describe examples of the changes made to three of these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2 Signaling. We describe an innovative approach to biological network construction that combines literature and data mining and a crowdsourcing approach to generate a comprehensive set of COPD-relevant models that can be used to help understand the mechanisms related to lung pathobiology. Registered users of the website can freely browse and download the networks. PMID:25767696

Enhancement of COPD biological networks using a web-based collaboration interface.

PubMed

Boue, Stephanie; Fields, Brett; Hoeng, Julia; Park, Jennifer; Peitsch, Manuel C; Schlage, Walter K; Talikka, Marja; Binenbaum, Ilona; Bondarenko, Vladimir; Bulgakov, Oleg V; Cherkasova, Vera; Diaz-Diaz, Norberto; Fedorova, Larisa; Guryanova, Svetlana; Guzova, Julia; Igorevna Koroleva, Galina; Kozhemyakina, Elena; Kumar, Rahul; Lavid, Noa; Lu, Qingxian; Menon, Swapna; Ouliel, Yael; Peterson, Samantha C; Prokhorov, Alexander; Sanders, Edward; Schrier, Sarah; Schwaitzer Neta, Golan; Shvydchenko, Irina; Tallam, Aravind; Villa-Fombuena, Gema; Wu, John; Yudkevich, Ilya; Zelikman, Mariya

2015-01-01

The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks. We report the construction of 50 biological network models relevant to lung biology and early COPD using an integrative systems biology and collaborative crowd-verification approach. By combining traditional literature curation with a data-driven approach that predicts molecular activities from transcriptomics data, we constructed an initial COPD network model set based on a previously published non-diseased lung-relevant model set. The crowd was given the opportunity to enhance and refine the networks on a website ( https://bionet.sbvimprover.com/) and to add mechanistic detail, as well as critically review existing evidence and evidence added by other users, so as to enhance the accuracy of the biological representation of the processes captured in the networks. Finally, scientists and experts in the field discussed and refined the networks during an in-person jamboree meeting. Here, we describe examples of the changes made to three of these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2 Signaling. We describe an innovative approach to biological network construction that combines literature and data mining and a crowdsourcing approach to generate a comprehensive set of COPD-relevant models that can be used to help understand the mechanisms related to lung pathobiology. Registered users of the website can freely browse and download the networks.

A deep learning method for lincRNA detection using auto-encoder algorithm.

PubMed

Yu, Ning; Yu, Zeng; Pan, Yi

2017-12-06

RNA sequencing technique (RNA-seq) enables scientists to develop novel data-driven methods for discovering more unidentified lincRNAs. Meantime, knowledge-based technologies are experiencing a potential revolution ignited by the new deep learning methods. By scanning the newly found data set from RNA-seq, scientists have found that: (1) the expression of lincRNAs appears to be regulated, that is, the relevance exists along the DNA sequences; (2) lincRNAs contain some conversed patterns/motifs tethered together by non-conserved regions. The two evidences give the reasoning for adopting knowledge-based deep learning methods in lincRNA detection. Similar to coding region transcription, non-coding regions are split at transcriptional sites. However, regulatory RNAs rather than message RNAs are generated. That is, the transcribed RNAs participate the biological process as regulatory units instead of generating proteins. Identifying these transcriptional regions from non-coding regions is the first step towards lincRNA recognition. The auto-encoder method achieves 100% and 92.4% prediction accuracy on transcription sites over the putative data sets. The experimental results also show the excellent performance of predictive deep neural network on the lincRNA data sets compared with support vector machine and traditional neural network. In addition, it is validated through the newly discovered lincRNA data set and one unreported transcription site is found by feeding the whole annotated sequences through the deep learning machine, which indicates that deep learning method has the extensive ability for lincRNA prediction. The transcriptional sequences of lincRNAs are collected from the annotated human DNA genome data. Subsequently, a two-layer deep neural network is developed for the lincRNA detection, which adopts the auto-encoder algorithm and utilizes different encoding schemes to obtain the best performance over intergenic DNA sequence data. Driven by those newly annotated lincRNA data, deep learning methods based on auto-encoder algorithm can exert their capability in knowledge learning in order to capture the useful features and the information correlation along DNA genome sequences for lincRNA detection. As our knowledge, this is the first application to adopt the deep learning techniques for identifying lincRNA transcription sequences.

SCENERY: a web application for (causal) network reconstruction from cytometry data.

PubMed

Papoutsoglou, Georgios; Athineou, Giorgos; Lagani, Vincenzo; Xanthopoulos, Iordanis; Schmidt, Angelika; Éliás, Szabolcs; Tegnér, Jesper; Tsamardinos, Ioannis

2017-07-03

Flow and mass cytometry technologies can probe proteins as biological markers in thousands of individual cells simultaneously, providing unprecedented opportunities for reconstructing networks of protein interactions through machine learning algorithms. The network reconstruction (NR) problem has been well-studied by the machine learning community. However, the potentials of available methods remain largely unknown to the cytometry community, mainly due to their intrinsic complexity and the lack of comprehensive, powerful and easy-to-use NR software implementations specific for cytometry data. To bridge this gap, we present Single CEll NEtwork Reconstruction sYstem (SCENERY), a web server featuring several standard and advanced cytometry data analysis methods coupled with NR algorithms in a user-friendly, on-line environment. In SCENERY, users may upload their data and set their own study design. The server offers several data analysis options categorized into three classes of methods: data (pre)processing, statistical analysis and NR. The server also provides interactive visualization and download of results as ready-to-publish images or multimedia reports. Its core is modular and based on the widely-used and robust R platform allowing power users to extend its functionalities by submitting their own NR methods. SCENERY is available at scenery.csd.uoc.gr or http://mensxmachina.org/en/software/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

A framework for plasticity implementation on the SpiNNaker neural architecture.

PubMed

Galluppi, Francesco; Lagorce, Xavier; Stromatias, Evangelos; Pfeiffer, Michael; Plana, Luis A; Furber, Steve B; Benosman, Ryad B

2014-01-01

Many of the precise biological mechanisms of synaptic plasticity remain elusive, but simulations of neural networks have greatly enhanced our understanding of how specific global functions arise from the massively parallel computation of neurons and local Hebbian or spike-timing dependent plasticity rules. For simulating large portions of neural tissue, this has created an increasingly strong need for large scale simulations of plastic neural networks on special purpose hardware platforms, because synaptic transmissions and updates are badly matched to computing style supported by current architectures. Because of the great diversity of biological plasticity phenomena and the corresponding diversity of models, there is a great need for testing various hypotheses about plasticity before committing to one hardware implementation. Here we present a novel framework for investigating different plasticity approaches on the SpiNNaker distributed digital neural simulation platform. The key innovation of the proposed architecture is to exploit the reconfigurability of the ARM processors inside SpiNNaker, dedicating a subset of them exclusively to process synaptic plasticity updates, while the rest perform the usual neural and synaptic simulations. We demonstrate the flexibility of the proposed approach by showing the implementation of a variety of spike- and rate-based learning rules, including standard Spike-Timing dependent plasticity (STDP), voltage-dependent STDP, and the rate-based BCM rule. We analyze their performance and validate them by running classical learning experiments in real time on a 4-chip SpiNNaker board. The result is an efficient, modular, flexible and scalable framework, which provides a valuable tool for the fast and easy exploration of learning models of very different kinds on the parallel and reconfigurable SpiNNaker system.

Predicting RNA-protein binding sites and motifs through combining local and global deep convolutional neural networks.

PubMed

Pan, Xiaoyong; Shen, Hong-Bin

2018-05-02

RNA-binding proteins (RBPs) take over 5∼10% of the eukaryotic proteome and play key roles in many biological processes, e.g. gene regulation. Experimental detection of RBP binding sites is still time-intensive and high-costly. Instead, computational prediction of the RBP binding sites using pattern learned from existing annotation knowledge is a fast approach. From the biological point of view, the local structure context derived from local sequences will be recognized by specific RBPs. However, in computational modeling using deep learning, to our best knowledge, only global representations of entire RNA sequences are employed. So far, the local sequence information is ignored in the deep model construction process. In this study, we present a computational method iDeepE to predict RNA-protein binding sites from RNA sequences by combining global and local convolutional neural networks (CNNs). For the global CNN, we pad the RNA sequences into the same length. For the local CNN, we split a RNA sequence into multiple overlapping fixed-length subsequences, where each subsequence is a signal channel of the whole sequence. Next, we train deep CNNs for multiple subsequences and the padded sequences to learn high-level features, respectively. Finally, the outputs from local and global CNNs are combined to improve the prediction. iDeepE demonstrates a better performance over state-of-the-art methods on two large-scale datasets derived from CLIP-seq. We also find that the local CNN run 1.8 times faster than the global CNN with comparable performance when using GPUs. Our results show that iDeepE has captured experimentally verified binding motifs. https://github.com/xypan1232/iDeepE. xypan172436@gmail.com or hbshen@sjtu.edu.cn. Supplementary data are available at Bioinformatics online.

A framework for plasticity implementation on the SpiNNaker neural architecture

PubMed Central

Galluppi, Francesco; Lagorce, Xavier; Stromatias, Evangelos; Pfeiffer, Michael; Plana, Luis A.; Furber, Steve B.; Benosman, Ryad B.

2015-01-01

Many of the precise biological mechanisms of synaptic plasticity remain elusive, but simulations of neural networks have greatly enhanced our understanding of how specific global functions arise from the massively parallel computation of neurons and local Hebbian or spike-timing dependent plasticity rules. For simulating large portions of neural tissue, this has created an increasingly strong need for large scale simulations of plastic neural networks on special purpose hardware platforms, because synaptic transmissions and updates are badly matched to computing style supported by current architectures. Because of the great diversity of biological plasticity phenomena and the corresponding diversity of models, there is a great need for testing various hypotheses about plasticity before committing to one hardware implementation. Here we present a novel framework for investigating different plasticity approaches on the SpiNNaker distributed digital neural simulation platform. The key innovation of the proposed architecture is to exploit the reconfigurability of the ARM processors inside SpiNNaker, dedicating a subset of them exclusively to process synaptic plasticity updates, while the rest perform the usual neural and synaptic simulations. We demonstrate the flexibility of the proposed approach by showing the implementation of a variety of spike- and rate-based learning rules, including standard Spike-Timing dependent plasticity (STDP), voltage-dependent STDP, and the rate-based BCM rule. We analyze their performance and validate them by running classical learning experiments in real time on a 4-chip SpiNNaker board. The result is an efficient, modular, flexible and scalable framework, which provides a valuable tool for the fast and easy exploration of learning models of very different kinds on the parallel and reconfigurable SpiNNaker system. PMID:25653580

A Conceptual Framework for Organizing Active Learning Experiences in Biology Instruction

ERIC Educational Resources Information Center

Gardner, Joel; Belland, Brian R.

2012-01-01

Introductory biology courses form a cornerstone of undergraduate instruction. However, the predominantly used lecture approach fails to produce higher-order biology learning. Research shows that active learning strategies can increase student learning, yet few biology instructors use all identified active learning strategies. In this paper, we…

Learning a Markov Logic network for supervised gene regulatory network inference

PubMed Central

2013-01-01

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

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

PubMed

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

2013-09-12

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

Constructing of Research-Oriented Learning Mode Based on Network Environment

ERIC Educational Resources Information Center

Wang, Ying; Li, Bing; Xie, Bai-zhi

2007-01-01

Research-oriented learning mode that based on network is significant to cultivate comprehensive-developing innovative person with network teaching in education for all-around development. This paper establishes a research-oriented learning mode by aiming at the problems existing in research-oriented learning based on network environment, and…

Features of Knowledge Building in Biology: Understanding Undergraduate Students' Ideas about Molecular Mechanisms.

PubMed

Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S

2016-01-01

Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. © 2016 K. Southard et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

System level mechanisms of adaptation, learning, memory formation and evolvability: the role of chaperone and other networks.

PubMed

Gyurko, David M; Soti, Csaba; Stetak, Attila; Csermely, Peter

2014-05-01

During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here, we describe first the protein structure networks of molecular chaperones, then characterize chaperone containing sub-networks of interactomes called as chaperone-networks or chaperomes. We review the role of molecular chaperones in short-term adaptation of cellular networks in response to stress, and in long-term adaptation discussing their putative functions in the regulation of evolvability. We provide a general overview of possible network mechanisms of adaptation, learning and memory formation. We propose that changes of network rigidity play a key role in learning and memory formation processes. Flexible network topology provides ' learning-competent' state. Here, networks may have much less modular boundaries than locally rigid, highly modular networks, where the learnt information has already been consolidated in a memory formation process. Since modular boundaries are efficient filters of information, in the 'learning-competent' state information filtering may be much smaller, than after memory formation. This mechanism restricts high information transfer to the 'learning competent' state. After memory formation, modular boundary-induced segregation and information filtering protect the stored information. The flexible networks of young organisms are generally in a 'learning competent' state. On the contrary, locally rigid networks of old organisms have lost their 'learning competent' state, but store and protect their learnt information efficiently. We anticipate that the above mechanism may operate at the level of both protein-protein interaction and neuronal networks.

Role of the cerebellum in reaching movements in humans. II. A neural model of the intermediate cerebellum.

PubMed

Schweighofer, N; Spoelstra, J; Arbib, M A; Kawato, M

1998-01-01

The cerebellum is essential for the control of multijoint movements; when the cerebellum is lesioned, the performance error is more than the summed errors produced by single joints. In the companion paper (Schweighofer et al., 1998), a functional anatomical model for visually guided arm movement was proposed. The model comprised a basic feedforward/feedback controller with realistic transmission delays and was connected to a two-link, six-muscle, planar arm. In the present study, we examined the role of the cerebellum in reaching movements by embedding a novel, detailed cerebellar neural network in this functional control model. We could derive realistic cerebellar inputs and the role of the cerebellum in learning to control the arm was assessed. This cerebellar network learned the part of the inverse dynamics of the arm not provided by the basic feedforward/feedback controller. Despite realistically low inferior olive firing rates and noisy mossy fibre inputs, the model could reduce the error between intended and planned movements. The responses of the different cell groups were comparable to those of biological cell groups. In particular, the modelled Purkinje cells exhibited directional tuning after learning and the parallel fibres, due to their length, provide Purkinje cells with the input required for this coordination task. The inferior olive responses contained two different components; the earlier response, locked to movement onset, was always present and the later response disappeared after learning. These results support the theory that the cerebellum is involved in motor learning.

Optical selectionist approach to optical connectionist systems

NASA Astrophysics Data System (ADS)

Caulfield, H. John

1994-03-01

Two broad approaches to computing are known - connectionist (which includes Turing Machines but is demonstrably more powerful) and selectionist. Human computer engineers tend to prefer the connectionist approach which includes neural networks. Nature uses both but may show an overall preference for selectionism. "Looking back into the history of biology, it appears that whenever a phenomenon resembles learning, an instructive theory was first proposed to account for the underlying mechanisms. In every case, this was later replaced by a selective theory." - N. K. Jeme, Nobelist in Immunology.

A systematic approach to infer biological relevance and biases of gene network structures.

PubMed

Antonov, Alexey V; Tetko, Igor V; Mewes, Hans W

2006-01-10

The development of high-throughput technologies has generated the need for bioinformatics approaches to assess the biological relevance of gene networks. Although several tools have been proposed for analysing the enrichment of functional categories in a set of genes, none of them is suitable for evaluating the biological relevance of the gene network. We propose a procedure and develop a web-based resource (BIOREL) to estimate the functional bias (biological relevance) of any given genetic network by integrating different sources of biological information. The weights of the edges in the network may be either binary or continuous. These essential features make our web tool unique among many similar services. BIOREL provides standardized estimations of the network biases extracted from independent data. By the analyses of real data we demonstrate that the potential application of BIOREL ranges from various benchmarking purposes to systematic analysis of the network biology.

On the Interplay between the Evolvability and Network Robustness in an Evolutionary Biological Network: A Systems Biology Approach

PubMed Central

Chen, Bor-Sen; Lin, Ying-Po

2011-01-01

In the evolutionary process, the random transmission and mutation of genes provide biological diversities for natural selection. In order to preserve functional phenotypes between generations, gene networks need to evolve robustly under the influence of random perturbations. Therefore, the robustness of the phenotype, in the evolutionary process, exerts a selection force on gene networks to keep network functions. However, gene networks need to adjust, by variations in genetic content, to generate phenotypes for new challenges in the network’s evolution, ie, the evolvability. Hence, there should be some interplay between the evolvability and network robustness in evolutionary gene networks. In this study, the interplay between the evolvability and network robustness of a gene network and a biochemical network is discussed from a nonlinear stochastic system point of view. It was found that if the genetic robustness plus environmental robustness is less than the network robustness, the phenotype of the biological network is robust in evolution. The tradeoff between the genetic robustness and environmental robustness in evolution is discussed from the stochastic stability robustness and sensitivity of the nonlinear stochastic biological network, which may be relevant to the statistical tradeoff between bias and variance, the so-called bias/variance dilemma. Further, the tradeoff could be considered as an antagonistic pleiotropic action of a gene network and discussed from the systems biology perspective. PMID:22084563

Accelerating Learning By Neural Networks

NASA Technical Reports Server (NTRS)

Toomarian, Nikzad; Barhen, Jacob

1992-01-01

Electronic neural networks made to learn faster by use of terminal teacher forcing. Method of supervised learning involves addition of teacher forcing functions to excitations fed as inputs to output neurons. Initially, teacher forcing functions are strong enough to force outputs to desired values; subsequently, these functions decay with time. When learning successfully completed, terminal teacher forcing vanishes, and dynamics or neural network become equivalent to those of conventional neural network. Simulated neural network with terminal teacher forcing learned to produce close approximation of circular trajectory in 400 iterations.

Reconstruction of the experimentally supported human protein interactome: what can we learn?

PubMed

Klapa, Maria I; Tsafou, Kalliopi; Theodoridis, Evangelos; Tsakalidis, Athanasios; Moschonas, Nicholas K

2013-10-02

Understanding the topology and dynamics of the human protein-protein interaction (PPI) network will significantly contribute to biomedical research, therefore its systematic reconstruction is required. Several meta-databases integrate source PPI datasets, but the protein node sets of their networks vary depending on the PPI data combined. Due to this inherent heterogeneity, the way in which the human PPI network expands via multiple dataset integration has not been comprehensively analyzed. We aim at assembling the human interactome in a global structured way and exploring it to gain insights of biological relevance. First, we defined the UniProtKB manually reviewed human "complete" proteome as the reference protein-node set and then we mined five major source PPI datasets for direct PPIs exclusively between the reference proteins. We updated the protein and publication identifiers and normalized all PPIs to the UniProt identifier level. The reconstructed interactome covers approximately 60% of the human proteome and has a scale-free structure. No apparent differentiating gene functional classification characteristics were identified for the unrepresented proteins. The source dataset integration augments the network mainly in PPIs. Polyubiquitin emerged as the highest-degree node, but the inclusion of most of its identified PPIs may be reconsidered. The high number (>300) of connections of the subsequent fifteen proteins correlates well with their essential biological role. According to the power-law network structure, the unrepresented proteins should mainly have up to four connections with equally poorly-connected interactors. Reconstructing the human interactome based on the a priori definition of the protein nodes enabled us to identify the currently included part of the human "complete" proteome, and discuss the role of the proteins within the network topology with respect to their function. As the network expansion has to comply with the scale-free theory, we suggest that the core of the human interactome has essentially emerged. Thus, it could be employed in systems biology and biomedical research, despite the considerable number of currently unrepresented proteins. The latter are probably involved in specialized physiological conditions, justifying the scarcity of related PPI information, and their identification can assist in designing relevant functional experiments and targeted text mining algorithms.

Hierarchical thinking in network biology: the unbiased modularization of biochemical networks.

PubMed

Papin, Jason A; Reed, Jennifer L; Palsson, Bernhard O

2004-12-01

As reconstructed biochemical reaction networks continue to grow in size and scope, there is a growing need to describe the functional modules within them. Such modules facilitate the study of biological processes by deconstructing complex biological networks into conceptually simple entities. The definition of network modules is often based on intuitive reasoning. As an alternative, methods are being developed for defining biochemical network modules in an unbiased fashion. These unbiased network modules are mathematically derived from the structure of the whole network under consideration.

Network congestion control algorithm based on Actor-Critic reinforcement learning model

NASA Astrophysics Data System (ADS)

Xu, Tao; Gong, Lina; Zhang, Wei; Li, Xuhong; Wang, Xia; Pan, Wenwen

2018-04-01

Aiming at the network congestion control problem, a congestion control algorithm based on Actor-Critic reinforcement learning model is designed. Through the genetic algorithm in the congestion control strategy, the network congestion problems can be better found and prevented. According to Actor-Critic reinforcement learning, the simulation experiment of network congestion control algorithm is designed. The simulation experiments verify that the AQM controller can predict the dynamic characteristics of the network system. Moreover, the learning strategy is adopted to optimize the network performance, and the dropping probability of packets is adaptively adjusted so as to improve the network performance and avoid congestion. Based on the above finding, it is concluded that the network congestion control algorithm based on Actor-Critic reinforcement learning model can effectively avoid the occurrence of TCP network congestion.

Deep machine learning provides state-of-the-art performance in image-based plant phenotyping.

PubMed

Pound, Michael P; Atkinson, Jonathan A; Townsend, Alexandra J; Wilson, Michael H; Griffiths, Marcus; Jackson, Aaron S; Bulat, Adrian; Tzimiropoulos, Georgios; Wells, Darren M; Murchie, Erik H; Pridmore, Tony P; French, Andrew P

2017-10-01

In plant phenotyping, it has become important to be able to measure many features on large image sets in order to aid genetic discovery. The size of the datasets, now often captured robotically, often precludes manual inspection, hence the motivation for finding a fully automated approach. Deep learning is an emerging field that promises unparalleled results on many data analysis problems. Building on artificial neural networks, deep approaches have many more hidden layers in the network, and hence have greater discriminative and predictive power. We demonstrate the use of such approaches as part of a plant phenotyping pipeline. We show the success offered by such techniques when applied to the challenging problem of image-based plant phenotyping and demonstrate state-of-the-art results (>97% accuracy) for root and shoot feature identification and localization. We use fully automated trait identification using deep learning to identify quantitative trait loci in root architecture datasets. The majority (12 out of 14) of manually identified quantitative trait loci were also discovered using our automated approach based on deep learning detection to locate plant features. We have shown deep learning-based phenotyping to have very good detection and localization accuracy in validation and testing image sets. We have shown that such features can be used to derive meaningful biological traits, which in turn can be used in quantitative trait loci discovery pipelines. This process can be completely automated. We predict a paradigm shift in image-based phenotyping bought about by such deep learning approaches, given sufficient training sets. © The Authors 2017. Published by Oxford University Press.

Models of vocal learning in the songbird: Historical frameworks and the stabilizing critic.

PubMed

Nick, Teresa A

2015-10-01

Birdsong is a form of sensorimotor learning that involves a mirror-like system that activates with both song hearing and production. Early models of song learning, based on behavioral measures, identified key features of vocal plasticity, such as the requirements for memorization of a tutor song and auditory feedback during song practice. The concept of a comparator, which compares the memory of the tutor song to auditory feedback, featured prominently. Later models focused on linking anatomically-defined neural modules to behavioral concepts, such as the comparator. Exploiting the anatomical modularity of the songbird brain, localized lesions illuminated mechanisms of the neural song system. More recent models have integrated neuronal mechanisms identified in other systems with observations in songbirds. While these models explain multiple aspects of song learning, they must incorporate computational elements based on unknown biological mechanisms to bridge the motor-to-sensory delay and/or transform motor signals into the sensory domain. Here, I introduce the stabilizing critic hypothesis, which enables sensorimotor learning by (1) placing a purely sensory comparator afferent of the song system and (2) endowing song system disinhibitory interneuron networks with the capacity both to bridge the motor-sensory delay through prolonged bursting and to stabilize song segments selectively based on the comparator signal. These proposed networks stabilize an otherwise variable signal generated by both putative mirror neurons and a cortical-basal ganglia-thalamic loop. This stabilized signal then temporally converges with a matched premotor signal in the efferent song motor cortex, promoting spike-timing-dependent plasticity in the premotor circuitry and behavioral song learning. © 2014 Wiley Periodicals, Inc.

Addressing Health Literacy Challenges With a Cutting-Edge Infectious Disease Curriculum for the High School Biology Classroom.

PubMed

Jacque, Berri; Koch-Weser, Susan; Faux, Russell; Meiri, Karina

2016-02-01

This study reports the secondary analysis of evaluation data from an innovative high school biology curriculum focused on infectious disease (ID) to examine the health literacy implications of teaching claims evaluation, data interpretation, and risk assessment skills in the context of 21st-Century health science. The curriculum was implemented between 2010 and 2013 in Biology II classes held in four public high schools (three in Massachusetts and one in Ohio), plus a private school in Virginia. A quasi-experimental design was used in which student participants (n = 273) were compared to an age-matched, nonparticipant, peer group (N = 125). Participants in each school setting demonstrated increases in conceptual content knowledge (Cohen's d > 1.89) as well as in understanding how to apply scientific principles to health claims evaluation and risk assessment (Cohen's d > 1.76) and in self-efficacy toward learning about ID (Cohen's d > 2.27). Participants also displayed enhanced communication about ID within their social networks relative to the comparison group (p < .05). The data show that integrating the claims evaluation, data interpretation, and risk assessment skills critical for 21st-century health literacy health into high school biology classrooms is effective at fostering both the skills and self-efficacy pertinent to health literacy learning in diverse populations. © 2015 Society for Public Health Education.

Cooperative Learning for Distributed In-Network Traffic Classification

NASA Astrophysics Data System (ADS)

Joseph, S. B.; Loo, H. R.; Ismail, I.; Andromeda, T.; Marsono, M. N.

2017-04-01

Inspired by the concept of autonomic distributed/decentralized network management schemes, we consider the issue of information exchange among distributed network nodes to network performance and promote scalability for in-network monitoring. In this paper, we propose a cooperative learning algorithm for propagation and synchronization of network information among autonomic distributed network nodes for online traffic classification. The results show that network nodes with sharing capability perform better with a higher average accuracy of 89.21% (sharing data) and 88.37% (sharing clusters) compared to 88.06% for nodes without cooperative learning capability. The overall performance indicates that cooperative learning is promising for distributed in-network traffic classification.

Community-Reviewed Biological Network Models for Toxicology and Drug Discovery Applications

PubMed Central

Namasivayam, Aishwarya Alex; Morales, Alejandro Ferreiro; Lacave, Ángela María Fajardo; Tallam, Aravind; Simovic, Borislav; Alfaro, David Garrido; Bobbili, Dheeraj Reddy; Martin, Florian; Androsova, Ganna; Shvydchenko, Irina; Park, Jennifer; Calvo, Jorge Val; Hoeng, Julia; Peitsch, Manuel C.; Racero, Manuel González Vélez; Biryukov, Maria; Talikka, Marja; Pérez, Modesto Berraquero; Rohatgi, Neha; Díaz-Díaz, Noberto; Mandarapu, Rajesh; Ruiz, Rubén Amián; Davidyan, Sergey; Narayanasamy, Shaman; Boué, Stéphanie; Guryanova, Svetlana; Arbas, Susana Martínez; Menon, Swapna; Xiang, Yang

2016-01-01

Biological network models offer a framework for understanding disease by describing the relationships between the mechanisms involved in the regulation of biological processes. Crowdsourcing can efficiently gather feedback from a wide audience with varying expertise. In the Network Verification Challenge, scientists verified and enhanced a set of 46 biological networks relevant to lung and chronic obstructive pulmonary disease. The networks were built using Biological Expression Language and contain detailed information for each node and edge, including supporting evidence from the literature. Network scoring of public transcriptomics data inferred perturbation of a subset of mechanisms and networks that matched the measured outcomes. These results, based on a computable network approach, can be used to identify novel mechanisms activated in disease, quantitatively compare different treatments and time points, and allow for assessment of data with low signal. These networks are periodically verified by the crowd to maintain an up-to-date suite of networks for toxicology and drug discovery applications. PMID:27429547

node2vec: Scalable Feature Learning for Networks

PubMed Central

Grover, Aditya; Leskovec, Jure

2016-01-01

Prediction tasks over nodes and edges in networks require careful effort in engineering features used by learning algorithms. Recent research in the broader field of representation learning has led to significant progress in automating prediction by learning the features themselves. However, present feature learning approaches are not expressive enough to capture the diversity of connectivity patterns observed in networks. Here we propose node2vec, an algorithmic framework for learning continuous feature representations for nodes in networks. In node2vec, we learn a mapping of nodes to a low-dimensional space of features that maximizes the likelihood of preserving network neighborhoods of nodes. We define a flexible notion of a node’s network neighborhood and design a biased random walk procedure, which efficiently explores diverse neighborhoods. Our algorithm generalizes prior work which is based on rigid notions of network neighborhoods, and we argue that the added flexibility in exploring neighborhoods is the key to learning richer representations. We demonstrate the efficacy of node2vec over existing state-of-the-art techniques on multi-label classification and link prediction in several real-world networks from diverse domains. Taken together, our work represents a new way for efficiently learning state-of-the-art task-independent representations in complex networks. PMID:27853626

An Overview of data science uses in bioimage informatics.

PubMed

Chessel, Anatole

2017-02-15

This review aims at providing a practical overview of the use of statistical features and associated data science methods in bioimage informatics. To achieve a quantitative link between images and biological concepts, one typically replaces an object coming from an image (a segmented cell or intracellular object, a pattern of expression or localisation, even a whole image) by a vector of numbers. They range from carefully crafted biologically relevant measurements to features learnt through deep neural networks. This replacement allows for the use of practical algorithms for visualisation, comparison and inference, such as the ones from machine learning or multivariate statistics. While originating mainly, for biology, in high content screening, those methods are integral to the use of data science for the quantitative analysis of microscopy images to gain biological insight, and they are sure to gather more interest as the need to make sense of the increasing amount of acquired imaging data grows more pressing. Copyright © 2017 Elsevier Inc. All rights reserved.

Thinking on building the network cardiovasology of Chinese medicine.

PubMed

Yu, Gui; Wang, Jie

2012-11-01

With advances in complex network theory, the thinking and methods regarding complex systems have changed revolutionarily. Network biology and network pharmacology were built by applying network-based approaches in biomedical research. The cardiovascular system may be regarded as a complex network, and cardiovascular diseases may be taken as the damage of structure and function of the cardiovascular network. Although Chinese medicine (CM) is effective in treating cardiovascular diseases, its mechanisms are still unclear. With the guidance of complex network theory, network biology and network pharmacology, network-based approaches could be used in the study of CM in preventing and treating cardiovascular diseases. A new discipline-network cardiovasology of CM was, therefore, developed. In this paper, complex network theory, network biology and network pharmacology were introduced and the connotation of "disease-syndrome-formula-herb" was illustrated from the network angle. Network biology could be used to analyze cardiovascular diseases and syndromes and network pharmacology could be used to analyze CM formulas and herbs. The "network-network"-based approaches could provide a new view for elucidating the mechanisms of CM treatment.

Predicting human protein function with multi-task deep neural networks.

PubMed

Fa, Rui; Cozzetto, Domenico; Wan, Cen; Jones, David T

2018-01-01

Machine learning methods for protein function prediction are urgently needed, especially now that a substantial fraction of known sequences remains unannotated despite the extensive use of functional assignments based on sequence similarity. One major bottleneck supervised learning faces in protein function prediction is the structured, multi-label nature of the problem, because biological roles are represented by lists of terms from hierarchically organised controlled vocabularies such as the Gene Ontology. In this work, we build on recent developments in the area of deep learning and investigate the usefulness of multi-task deep neural networks (MTDNN), which consist of upstream shared layers upon which are stacked in parallel as many independent modules (additional hidden layers with their own output units) as the number of output GO terms (the tasks). MTDNN learns individual tasks partially using shared representations and partially from task-specific characteristics. When no close homologues with experimentally validated functions can be identified, MTDNN gives more accurate predictions than baseline methods based on annotation frequencies in public databases or homology transfers. More importantly, the results show that MTDNN binary classification accuracy is higher than alternative machine learning-based methods that do not exploit commonalities and differences among prediction tasks. Interestingly, compared with a single-task predictor, the performance improvement is not linearly correlated with the number of tasks in MTDNN, but medium size models provide more improvement in our case. One of advantages of MTDNN is that given a set of features, there is no requirement for MTDNN to have a bootstrap feature selection procedure as what traditional machine learning algorithms do. Overall, the results indicate that the proposed MTDNN algorithm improves the performance of protein function prediction. On the other hand, there is still large room for deep learning techniques to further enhance prediction ability.

[The discussion of the infiltrative model of mathematical knowledge to genetics teaching].

PubMed

Liu, Jun; Luo, Pei-Gao

2011-11-01

Genetics, the core course of biological field, is an importance major-basic course in curriculum of many majors related with biology. Due to strong theoretical and practical as well as abstract of genetics, it is too difficult to study on genetics for many students. At the same time, mathematics is one of the basic courses in curriculum of the major related natural science, which has close relationship with the establishment, development and modification of genetics. In this paper, to establish the intrinsic logistic relationship and construct the integral knowledge network and to help students improving the analytic, comprehensive and logistic abilities, we applied some mathematical infiltrative model genetic knowledge in genetics teaching, which could help students more deeply learn and understand genetic knowledge.

Impact of environmental inputs on reverse-engineering approach to network structures.

PubMed

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.

Novel insights into embryonic stem cell self-renewal revealed through comparative human and mouse systems biology networks.

PubMed

Dowell, Karen G; Simons, Allen K; Bai, Hao; Kell, Braden; Wang, Zack Z; Yun, Kyuson; Hibbs, Matthew A

2014-05-01

Embryonic stem cells (ESCs), characterized by their ability to both self-renew and differentiate into multiple cell lineages, are a powerful model for biomedical research and developmental biology. Human and mouse ESCs share many features, yet have distinctive aspects, including fundamental differences in the signaling pathways and cell cycle controls that support self-renewal. Here, we explore the molecular basis of human ESC self-renewal using Bayesian network machine learning to integrate cell-type-specific, high-throughput data for gene function discovery. We integrated high-throughput ESC data from 83 human studies (~1.8 million data points collected under 1,100 conditions) and 62 mouse studies (~2.4 million data points collected under 1,085 conditions) into separate human and mouse predictive networks focused on ESC self-renewal to analyze shared and distinct functional relationships among protein-coding gene orthologs. Computational evaluations show that these networks are highly accurate, literature validation confirms their biological relevance, and reverse transcriptase polymerase chain reaction (RT-PCR) validation supports our predictions. Our results reflect the importance of key regulatory genes known to be strongly associated with self-renewal and pluripotency in both species (e.g., POU5F1, SOX2, and NANOG), identify metabolic differences between species (e.g., threonine metabolism), clarify differences between human and mouse ESC developmental signaling pathways (e.g., leukemia inhibitory factor (LIF)-activated JAK/STAT in mouse; NODAL/ACTIVIN-A-activated fibroblast growth factor in human), and reveal many novel genes and pathways predicted to be functionally associated with self-renewal in each species. These interactive networks are available online at www.StemSight.org for stem cell researchers to develop new hypotheses, discover potential mechanisms involving sparsely annotated genes, and prioritize genes of interest for experimental validation. © 2013 AlphaMed Press.

Exploring Neural Network Models with Hierarchical Memories and Their Use in Modeling Biological Systems

NASA Astrophysics Data System (ADS)

Pusuluri, Sai Teja

Energy landscapes are often used as metaphors for phenomena in biology, social sciences and finance. Different methods have been implemented in the past for the construction of energy landscapes. Neural network models based on spin glass physics provide an excellent mathematical framework for the construction of energy landscapes. This framework uses a minimal number of parameters and constructs the landscape using data from the actual phenomena. In the past neural network models were used to mimic the storage and retrieval process of memories (patterns) in the brain. With advances in the field now, these models are being used in machine learning, deep learning and modeling of complex phenomena. Most of the past literature focuses on increasing the storage capacity and stability of stored patterns in the network but does not study these models from a modeling perspective or an energy landscape perspective. This dissertation focuses on neural network models both from a modeling perspective and from an energy landscape perspective. I firstly show how the cellular interconversion phenomenon can be modeled as a transition between attractor states on an epigenetic landscape constructed using neural network models. The model allows the identification of a reaction coordinate of cellular interconversion by analyzing experimental and simulation time course data. Monte Carlo simulations of the model show that the initial phase of cellular interconversion is a Poisson process and the later phase of cellular interconversion is a deterministic process. Secondly, I explore the static features of landscapes generated using neural network models, such as sizes of basins of attraction and densities of metastable states. The simulation results show that the static landscape features are strongly dependent on the correlation strength and correlation structure between patterns. Using different hierarchical structures of the correlation between patterns affects the landscape features. These results show how the static landscape features can be controlled by adjusting the correlations between patterns. Finally, I explore the dynamical features of landscapes generated using neural network models such as the stability of minima and the transition rates between minima. The results from this project show that the stability depends on the correlations between patterns. It is also found that the transition rates between minima strongly depend on the type of bias applied and the correlation between patterns. The results from this part of the dissertation can be useful in engineering an energy landscape without even having the complete information about the associated minima of the landscape.

Molecular communication and networking: opportunities and challenges.

PubMed

Nakano, Tadashi; Moore, Michael J; Wei, Fang; Vasilakos, Athanasios V; Shuai, Jianwei

2012-06-01

The ability of engineered biological nanomachines to communicate with biological systems at the molecular level is anticipated to enable future applications such as monitoring the condition of a human body, regenerating biological tissues and organs, and interfacing artificial devices with neural systems. From the viewpoint of communication theory and engineering, molecular communication is proposed as a new paradigm for engineered biological nanomachines to communicate with the natural biological nanomachines which form a biological system. Distinct from the current telecommunication paradigm, molecular communication uses molecules as the carriers of information; sender biological nanomachines encode information on molecules and release the molecules in the environment, the molecules then propagate in the environment to receiver biological nanomachines, and the receiver biological nanomachines biochemically react with the molecules to decode information. Current molecular communication research is limited to small-scale networks of several biological nanomachines. Key challenges to bridge the gap between current research and practical applications include developing robust and scalable techniques to create a functional network from a large number of biological nanomachines. Developing networking mechanisms and communication protocols is anticipated to introduce new avenues into integrating engineered and natural biological nanomachines into a single networked system. In this paper, we present the state-of-the-art in the area of molecular communication by discussing its architecture, features, applications, design, engineering, and physical modeling. We then discuss challenges and opportunities in developing networking mechanisms and communication protocols to create a network from a large number of bio-nanomachines for future applications.

Peer Learning Network: Implementing and Sustaining Cooperative Learning by Teacher Collaboration

ERIC Educational Resources Information Center

Miquel, Ester; Duran, David

2017-01-01

This article describes an in-service teachers', staff-development model "Peer Learning Network" and presents results about its efficiency. "Peer Learning Network" promotes three levels of peer learning simultaneously (among pupils, teachers, and schools). It supports pairs of teachers from several schools, who are linked…

The Integration of Personal Learning Environments & Open Network Learning Environments

ERIC Educational Resources Information Center

Tu, Chih-Hsiung; Sujo-Montes, Laura; Yen, Cherng-Jyh; Chan, Junn-Yih; Blocher, Michael

2012-01-01

Learning management systems traditionally provide structures to guide online learners to achieve their learning goals. Web 2.0 technology empowers learners to create, share, and organize their personal learning environments in open network environments; and allows learners to engage in social networking and collaborating activities. Advanced…

The World as Functional Learning Environment: An Intercultural Learning Network. Interactive Technology Laboratory Report #7.

ERIC Educational Resources Information Center

Cohen, Moshe; And Others

Electronic networks provide new opportunities to create functional learning environments which allow students in many different locations to carry out joint educational activities. A set of participant observation studies was conducted in the context of a cross-cultural, cross-language network called the Intercultural Learning Network in order to…

VANLO - Interactive visual exploration of aligned biological networks

PubMed Central

Brasch, Steffen; Linsen, Lars; Fuellen, Georg

2009-01-01

Background Protein-protein interaction (PPI) is fundamental to many biological processes. In the course of evolution, biological networks such as protein-protein interaction networks have developed. Biological networks of different species can be aligned by finding instances (e.g. proteins) with the same common ancestor in the evolutionary process, so-called orthologs. For a better understanding of the evolution of biological networks, such aligned networks have to be explored. Visualization can play a key role in making the various relationships transparent. Results We present a novel visualization system for aligned biological networks in 3D space that naturally embeds existing 2D layouts. In addition to displaying the intra-network connectivities, we also provide insight into how the individual networks relate to each other by placing aligned entities on top of each other in separate layers. We optimize the layout of the entire alignment graph in a global fashion that takes into account inter- as well as intra-network relationships. The layout algorithm includes a step of merging aligned networks into one graph, laying out the graph with respect to application-specific requirements, splitting the merged graph again into individual networks, and displaying the network alignment in layers. In addition to representing the data in a static way, we also provide different interaction techniques to explore the data with respect to application-specific tasks. Conclusion Our system provides an intuitive global understanding of aligned PPI networks and it allows the investigation of key biological questions. We evaluate our system by applying it to real-world examples documenting how our system can be used to investigate the data with respect to these key questions. Our tool VANLO (Visualization of Aligned Networks with Layout Optimization) can be accessed at . PMID:19821976

Revisiting the variation of clustering coefficient of biological networks suggests new modular structure.

PubMed

Hao, Dapeng; Ren, Cong; Li, Chuanxing

2012-05-01

A central idea in biology is the hierarchical organization of cellular processes. A commonly used method to identify the hierarchical modular organization of network relies on detecting a global signature known as variation of clustering coefficient (so-called modularity scaling). Although several studies have suggested other possible origins of this signature, it is still widely used nowadays to identify hierarchical modularity, especially in the analysis of biological networks. Therefore, a further and systematical investigation of this signature for different types of biological networks is necessary. We analyzed a variety of biological networks and found that the commonly used signature of hierarchical modularity is actually the reflection of spoke-like topology, suggesting a different view of network architecture. We proved that the existence of super-hubs is the origin that the clustering coefficient of a node follows a particular scaling law with degree k in metabolic networks. To study the modularity of biological networks, we systematically investigated the relationship between repulsion of hubs and variation of clustering coefficient. We provided direct evidences for repulsion between hubs being the underlying origin of the variation of clustering coefficient, and found that for biological networks having no anti-correlation between hubs, such as gene co-expression network, the clustering coefficient doesn't show dependence of degree. Here we have shown that the variation of clustering coefficient is neither sufficient nor exclusive for a network to be hierarchical. Our results suggest the existence of spoke-like modules as opposed to "deterministic model" of hierarchical modularity, and suggest the need to reconsider the organizational principle of biological hierarchy.

The post-genomic era of biological network alignment.

PubMed

Faisal, Fazle E; Meng, Lei; Crawford, Joseph; Milenković, Tijana

2015-12-01

Biological network alignment aims to find regions of topological and functional (dis)similarities between molecular networks of different species. Then, network alignment can guide the transfer of biological knowledge from well-studied model species to less well-studied species between conserved (aligned) network regions, thus complementing valuable insights that have already been provided by genomic sequence alignment. Here, we review computational challenges behind the network alignment problem, existing approaches for solving the problem, ways of evaluating their alignment quality, and the approaches' biomedical applications. We discuss recent innovative efforts of improving the existing view of network alignment. We conclude with open research questions in comparative biological network research that could further our understanding of principles of life, evolution, disease, and therapeutics.

Multi-agent-based bio-network for systems biology: protein-protein interaction network as an example.

PubMed

Ren, Li-Hong; Ding, Yong-Sheng; Shen, Yi-Zhen; Zhang, Xiang-Feng

2008-10-01

Recently, a collective effort from multiple research areas has been made to understand biological systems at the system level. This research requires the ability to simulate particular biological systems as cells, organs, organisms, and communities. In this paper, a novel bio-network simulation platform is proposed for system biology studies by combining agent approaches. We consider a biological system as a set of active computational components interacting with each other and with an external environment. Then, we propose a bio-network platform for simulating the behaviors of biological systems and modelling them in terms of bio-entities and society-entities. As a demonstration, we discuss how a protein-protein interaction (PPI) network can be seen as a society of autonomous interactive components. From interactions among small PPI networks, a large PPI network can emerge that has a remarkable ability to accomplish a complex function or task. We also simulate the evolution of the PPI networks by using the bio-operators of the bio-entities. Based on the proposed approach, various simulators with different functions can be embedded in the simulation platform, and further research can be done from design to development, including complexity validation of the biological system.

The Relationships between Epistemic Beliefs in Biology and Approaches to Learning Biology among Biology-Major University Students in Taiwan

ERIC Educational Resources Information Center

Lin, Yi-Chun; Liang, Jyh-Chong; Tsai, Chin-Chung

2012-01-01

The aim of this study was to investigate the relationships between students' epistemic beliefs in biology and their approaches to learning biology. To this end, two instruments, the epistemic beliefs in biology and the approaches to learning biology surveys, were developed and administered to 520 university biology students, respectively. By and…

PROPER: global protein interaction network alignment through percolation matching.

PubMed

Kazemi, Ehsan; Hassani, Hamed; Grossglauser, Matthias; Pezeshgi Modarres, Hassan

2016-12-12

The alignment of protein-protein interaction (PPI) networks enables us to uncover the relationships between different species, which leads to a deeper understanding of biological systems. Network alignment can be used to transfer biological knowledge between species. Although different PPI-network alignment algorithms were introduced during the last decade, developing an accurate and scalable algorithm that can find alignments with high biological and structural similarities among PPI networks is still challenging. In this paper, we introduce a new global network alignment algorithm for PPI networks called PROPER. Compared to other global network alignment methods, our algorithm shows higher accuracy and speed over real PPI datasets and synthetic networks. We show that the PROPER algorithm can detect large portions of conserved biological pathways between species. Also, using a simple parsimonious evolutionary model, we explain why PROPER performs well based on several different comparison criteria. We highlight that PROPER has high potential in further applications such as detecting biological pathways, finding protein complexes and PPI prediction. The PROPER algorithm is available at http://proper.epfl.ch .

Learning complex temporal patterns with resource-dependent spike timing-dependent plasticity.

PubMed

Hunzinger, Jason F; Chan, Victor H; Froemke, Robert C

2012-07-01

Studies of spike timing-dependent plasticity (STDP) have revealed that long-term changes in the strength of a synapse may be modulated substantially by temporal relationships between multiple presynaptic and postsynaptic spikes. Whereas long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength have been modeled as distinct or separate functional mechanisms, here, we propose a new shared resource model. A functional consequence of our model is fast, stable, and diverse unsupervised learning of temporal multispike patterns with a biologically consistent spiking neural network. Due to interdependencies between LTP and LTD, dendritic delays, and proactive homeostatic aspects of the model, neurons are equipped to learn to decode temporally coded information within spike bursts. Moreover, neurons learn spike timing with few exposures in substantial noise and jitter. Surprisingly, despite having only one parameter, the model also accurately predicts in vitro observations of STDP in more complex multispike trains, as well as rate-dependent effects. We discuss candidate commonalities in natural long-term plasticity mechanisms.

Autonomous learning in gesture recognition by using lobe component analysis

NASA Astrophysics Data System (ADS)

Lu, Jian; Weng, Juyang

2007-02-01

Gesture recognition is a new human-machine interface method implemented by pattern recognition(PR).In order to assure robot safety when gesture is used in robot control, it is required to implement the interface reliably and accurately. Similar with other PR applications, 1) feature selection (or model establishment) and 2) training from samples, affect the performance of gesture recognition largely. For 1), a simple model with 6 feature points at shoulders, elbows, and hands, is established. The gestures to be recognized are restricted to still arm gestures, and the movement of arms is not considered. These restrictions are to reduce the misrecognition, but are not so unreasonable. For 2), a new biological network method, called lobe component analysis(LCA), is used in unsupervised learning. Lobe components, corresponding to high-concentrations in probability of the neuronal input, are orientation selective cells follow Hebbian rule and lateral inhibition. Due to the advantage of LCA method for balanced learning between global and local features, large amount of samples can be used in learning efficiently.

Somato-dendritic Synaptic Plasticity and Error-backpropagation in Active Dendrites

PubMed Central

Schiess, Mathieu; Urbanczik, Robert; Senn, Walter

2016-01-01

In the last decade dendrites of cortical neurons have been shown to nonlinearly combine synaptic inputs by evoking local dendritic spikes. It has been suggested that these nonlinearities raise the computational power of a single neuron, making it comparable to a 2-layer network of point neurons. But how these nonlinearities can be incorporated into the synaptic plasticity to optimally support learning remains unclear. We present a theoretically derived synaptic plasticity rule for supervised and reinforcement learning that depends on the timing of the presynaptic, the dendritic and the postsynaptic spikes. For supervised learning, the rule can be seen as a biological version of the classical error-backpropagation algorithm applied to the dendritic case. When modulated by a delayed reward signal, the same plasticity is shown to maximize the expected reward in reinforcement learning for various coding scenarios. Our framework makes specific experimental predictions and highlights the unique advantage of active dendrites for implementing powerful synaptic plasticity rules that have access to downstream information via backpropagation of action potentials. PMID:26841235

Do Sophisticated Epistemic Beliefs Predict Meaningful Learning? Findings from a Structural Equation Model of Undergraduate Biology Learning

ERIC Educational Resources Information Center

Lee, Silvia Wen-Yu; Liang, Jyh-Chong; Tsai, Chin-Chung

2016-01-01

This study investigated the relationships among college students' epistemic beliefs in biology (EBB), conceptions of learning biology (COLB), and strategies of learning biology (SLB). EBB includes four dimensions, namely "multiple-source," "uncertainty," "development," and "justification." COLB is further…

Counting motifs in dynamic networks.

PubMed

Mukherjee, Kingshuk; Hasan, Md Mahmudul; Boucher, Christina; Kahveci, Tamer

2018-04-11

A network motif is a sub-network that occurs frequently in a given network. Detection of such motifs is important since they uncover functions and local properties of the given biological network. Finding motifs is however a computationally challenging task as it requires solving the costly subgraph isomorphism problem. Moreover, the topology of biological networks change over time. These changing networks are called dynamic biological networks. As the network evolves, frequency of each motif in the network also changes. Computing the frequency of a given motif from scratch in a dynamic network as the network topology evolves is infeasible, particularly for large and fast evolving networks. In this article, we design and develop a scalable method for counting the number of motifs in a dynamic biological network. Our method incrementally updates the frequency of each motif as the underlying network's topology evolves. Our experiments demonstrate that our method can update the frequency of each motif in orders of magnitude faster than counting the motif embeddings every time the network changes. If the network evolves more frequently, the margin with which our method outperforms the existing static methods, increases. We evaluated our method extensively using synthetic and real datasets, and show that our method is highly accurate(≥ 96%) and that it can be scaled to large dense networks. The results on real data demonstrate the utility of our method in revealing interesting insights on the evolution of biological processes.

Spatiotemporal Computations of an Excitable and Plastic Brain: Neuronal Plasticity Leads to Noise-Robust and Noise-Constructive Computations

PubMed Central

Toutounji, Hazem; Pipa, Gordon

2014-01-01

It is a long-established fact that neuronal plasticity occupies the central role in generating neural function and computation. Nevertheless, no unifying account exists of how neurons in a recurrent cortical network learn to compute on temporally and spatially extended stimuli. However, these stimuli constitute the norm, rather than the exception, of the brain's input. Here, we introduce a geometric theory of learning spatiotemporal computations through neuronal plasticity. To that end, we rigorously formulate the problem of neural representations as a relation in space between stimulus-induced neural activity and the asymptotic dynamics of excitable cortical networks. Backed up by computer simulations and numerical analysis, we show that two canonical and widely spread forms of neuronal plasticity, that is, spike-timing-dependent synaptic plasticity and intrinsic plasticity, are both necessary for creating neural representations, such that these computations become realizable. Interestingly, the effects of these forms of plasticity on the emerging neural code relate to properties necessary for both combating and utilizing noise. The neural dynamics also exhibits features of the most likely stimulus in the network's spontaneous activity. These properties of the spatiotemporal neural code resulting from plasticity, having their grounding in nature, further consolidate the biological relevance of our findings. PMID:24651447

Nationwide network of total solar eclipse high altitude balloon flights

NASA Astrophysics Data System (ADS)

Des Jardins, A. C.

2017-12-01

Three years ago we envisioned tapping into the strength of the National Space Grant Program to make the most of a rare astronomical event to engage the general public through education and to create meaningful long-lasting partnerships with other private and public entities. We believe strongly in giving student participants career-making opportunities through the use of the most cutting edge tools, resources, and communication. The NASA Space Grant network was in a unique position to engage the public in the eclipse in an awe-inspiring and educational way at a surprisingly small cost. In addition to public engagement, the multidisciplinary project presented an in-depth hands-on learning opportunity for the thousands of student participants. The project used a network of high altitude ballooning teams positioned along the path of totality from Oregon to South Carolina to conduct coordinated collaborative activities during the eclipse. These activities included 1) capturing and streaming live video of the eclipse from near space, 2) partnering with NASA Ames on a space biology experiment, and 3) conducting high-resolution atmospheric radiosonde measurements. This presentation will summarize the challenges, results, lessons learned, and professional evaluation from developing, training, and coordinating the collaboration. Details of the live streaming HD video and radiosonde activities are described in separate submissions to this session.

Spiking Neural Networks Based on OxRAM Synapses for Real-Time Unsupervised Spike Sorting.

PubMed

Werner, Thilo; Vianello, Elisa; Bichler, Olivier; Garbin, Daniele; Cattaert, Daniel; Yvert, Blaise; De Salvo, Barbara; Perniola, Luca

2016-01-01

In this paper, we present an alternative approach to perform spike sorting of complex brain signals based on spiking neural networks (SNN). The proposed architecture is suitable for hardware implementation by using resistive random access memory (RRAM) technology for the implementation of synapses whose low latency (<1μs) enables real-time spike sorting. This offers promising advantages to conventional spike sorting techniques for brain-computer interfaces (BCI) and neural prosthesis applications. Moreover, the ultra-low power consumption of the RRAM synapses of the spiking neural network (nW range) may enable the design of autonomous implantable devices for rehabilitation purposes. We demonstrate an original methodology to use Oxide based RRAM (OxRAM) as easy to program and low energy (<75 pJ) synapses. Synaptic weights are modulated through the application of an online learning strategy inspired by biological Spike Timing Dependent Plasticity. Real spiking data have been recorded both intra- and extracellularly from an in-vitro preparation of the Crayfish sensory-motor system and used for validation of the proposed OxRAM based SNN. This artificial SNN is able to identify, learn, recognize and distinguish between different spike shapes in the input signal with a recognition rate about 90% without any supervision.

Social Learning Network Analysis Model to Identify Learning Patterns Using Ontology Clustering Techniques and Meaningful Learning

ERIC Educational Resources Information Center

Firdausiah Mansur, Andi Besse; Yusof, Norazah

2013-01-01

Clustering on Social Learning Network still not explored widely, especially when the network focuses on e-learning system. Any conventional methods are not really suitable for the e-learning data. SNA requires content analysis, which involves human intervention and need to be carried out manually. Some of the previous clustering techniques need…

GA-based fuzzy reinforcement learning for control of a magnetic bearing system.

PubMed

Lin, C T; Jou, C P

2000-01-01

This paper proposes a TD (temporal difference) and GA (genetic algorithm)-based reinforcement (TDGAR) learning method and applies it to the control of a real magnetic bearing system. The TDGAR learning scheme is a new hybrid GA, which integrates the TD prediction method and the GA to perform the reinforcement learning task. The TDGAR learning system is composed of two integrated feedforward networks. One neural network acts as a critic network to guide the learning of the other network (the action network) which determines the outputs (actions) of the TDGAR learning system. The action network can be a normal neural network or a neural fuzzy network. Using the TD prediction method, the critic network can predict the external reinforcement signal and provide a more informative internal reinforcement signal to the action network. The action network uses the GA to adapt itself according to the internal reinforcement signal. The key concept of the TDGAR learning scheme is to formulate the internal reinforcement signal as the fitness function for the GA such that the GA can evaluate the candidate solutions (chromosomes) regularly, even during periods without external feedback from the environment. This enables the GA to proceed to new generations regularly without waiting for the arrival of the external reinforcement signal. This can usually accelerate the GA learning since a reinforcement signal may only be available at a time long after a sequence of actions has occurred in the reinforcement learning problem. The proposed TDGAR learning system has been used to control an active magnetic bearing (AMB) system in practice. A systematic design procedure is developed to achieve successful integration of all the subsystems including magnetic suspension, mechanical structure, and controller training. The results show that the TDGAR learning scheme can successfully find a neural controller or a neural fuzzy controller for a self-designed magnetic bearing system.

Modular analysis of biological networks.

PubMed

Kaltenbach, Hans-Michael; Stelling, Jörg

2012-01-01

The analysis of complex biological networks has traditionally relied on decomposition into smaller, semi-autonomous units such as individual signaling pathways. With the increased scope of systems biology (models), rational approaches to modularization have become an important topic. With increasing acceptance of de facto modularity in biology, widely different definitions of what constitutes a module have sparked controversies. Here, we therefore review prominent classes of modular approaches based on formal network representations. Despite some promising research directions, several important theoretical challenges remain open on the way to formal, function-centered modular decompositions for dynamic biological networks.

Measuring the Evolutionary Rewiring of Biological Networks

PubMed Central

Shou, Chong; Bhardwaj, Nitin; Lam, Hugo Y. K.; Yan, Koon-Kiu; Kim, Philip M.; Snyder, Michael; Gerstein, Mark B.

2011-01-01

We have accumulated a large amount of biological network data and expect even more to come. Soon, we anticipate being able to compare many different biological networks as we commonly do for molecular sequences. It has long been believed that many of these networks change, or “rewire”, at different rates. It is therefore important to develop a framework to quantify the differences between networks in a unified fashion. We developed such a formalism based on analogy to simple models of sequence evolution, and used it to conduct a systematic study of network rewiring on all the currently available biological networks. We found that, similar to sequences, biological networks show a decreased rate of change at large time divergences, because of saturation in potential substitutions. However, different types of biological networks consistently rewire at different rates. Using comparative genomics and proteomics data, we found a consistent ordering of the rewiring rates: transcription regulatory, phosphorylation regulatory, genetic interaction, miRNA regulatory, protein interaction, and metabolic pathway network, from fast to slow. This ordering was found in all comparisons we did of matched networks between organisms. To gain further intuition on network rewiring, we compared our observed rewirings with those obtained from simulation. We also investigated how readily our formalism could be mapped to other network contexts; in particular, we showed how it could be applied to analyze changes in a range of “commonplace” networks such as family trees, co-authorships and linux-kernel function dependencies. PMID:21253555

What Makes Biology Learning Difficult and Effective: Students' Views

ERIC Educational Resources Information Center

Cimer, Atilla

2012-01-01

The present study aims to determine the biological topics that students have difficulties learning, the reasons why secondary school students have difficulties in learning biology, and ways to improve the effectiveness of students' biology learning. For these purposes, a self-administered questionnaire including three open-ended questions was…

Learning in a Network: A "Third Way" between School Learning and Workplace Learning?

ERIC Educational Resources Information Center

Bottrup, Pernille

2005-01-01

Purpose--The aim of this article is to examine network-based learning and discuss how participation in network can enhance organisational learning. Design/methodology/approach--In recent years, companies have increased their collaboration with other organisations, suppliers, customers, etc., in order to meet challenges from a globalised market.…

Phase transitions in semisupervised clustering of sparse networks

NASA Astrophysics Data System (ADS)

Zhang, Pan; Moore, Cristopher; Zdeborová, Lenka

2014-11-01

Predicting labels of nodes in a network, such as community memberships or demographic variables, is an important problem with applications in social and biological networks. A recently discovered phase transition puts fundamental limits on the accuracy of these predictions if we have access only to the network topology. However, if we know the correct labels of some fraction α of the nodes, we can do better. We study the phase diagram of this semisupervised learning problem for networks generated by the stochastic block model. We use the cavity method and the associated belief propagation algorithm to study what accuracy can be achieved as a function of α . For k =2 groups, we find that the detectability transition disappears for any α >0 , in agreement with previous work. For larger k where a hard but detectable regime exists, we find that the easy/hard transition (the point at which efficient algorithms can do better than chance) becomes a line of transitions where the accuracy jumps discontinuously at a critical value of α . This line ends in a critical point with a second-order transition, beyond which the accuracy is a continuous function of α . We demonstrate qualitatively similar transitions in two real-world networks.

How Neural Networks Learn from Experience.

ERIC Educational Resources Information Center

Hinton, Geoffrey E.

1992-01-01

Discusses computational studies of learning in artificial neural networks and findings that may provide insights into the learning abilities of the human brain. Describes efforts to test theories about brain information processing, using artificial neural networks. Vignettes include information concerning how a neural network represents…

Interactome Networks and Human Disease

PubMed Central

Vidal, Marc; Cusick, Michael E.; Barabási, Albert-László

2011-01-01

Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease. PMID:21414488

Deep Learning Neural Networks and Bayesian Neural Networks in Data Analysis

NASA Astrophysics Data System (ADS)

Chernoded, Andrey; Dudko, Lev; Myagkov, Igor; Volkov, Petr

2017-10-01

Most of the modern analyses in high energy physics use signal-versus-background classification techniques of machine learning methods and neural networks in particular. Deep learning neural network is the most promising modern technique to separate signal and background and now days can be widely and successfully implemented as a part of physical analysis. In this article we compare Deep learning and Bayesian neural networks application as a classifiers in an instance of top quark analysis.

Quantitative learning strategies based on word networks

NASA Astrophysics Data System (ADS)

Zhao, Yue-Tian-Yi; Jia, Zi-Yang; Tang, Yong; Xiong, Jason Jie; Zhang, Yi-Cheng

2018-02-01

Learning English requires a considerable effort, but the way that vocabulary is introduced in textbooks is not optimized for learning efficiency. With the increasing population of English learners, learning process optimization will have significant impact and improvement towards English learning and teaching. The recent developments of big data analysis and complex network science provide additional opportunities to design and further investigate the strategies in English learning. In this paper, quantitative English learning strategies based on word network and word usage information are proposed. The strategies integrate the words frequency with topological structural information. By analyzing the influence of connected learned words, the learning weights for the unlearned words and dynamically updating of the network are studied and analyzed. The results suggest that quantitative strategies significantly improve learning efficiency while maintaining effectiveness. Especially, the optimized-weight-first strategy and segmented strategies outperform other strategies. The results provide opportunities for researchers and practitioners to reconsider the way of English teaching and designing vocabularies quantitatively by balancing the efficiency and learning costs based on the word network.

A high-capacity model for one shot association learning in the brain

PubMed Central

Einarsson, Hafsteinn; Lengler, Johannes; Steger, Angelika

2014-01-01

We present a high-capacity model for one-shot association learning (hetero-associative memory) in sparse networks. We assume that basic patterns are pre-learned in networks and associations between two patterns are presented only once and have to be learned immediately. The model is a combination of an Amit-Fusi like network sparsely connected to a Willshaw type network. The learning procedure is palimpsest and comes from earlier work on one-shot pattern learning. However, in our setup we can enhance the capacity of the network by iterative retrieval. This yields a model for sparse brain-like networks in which populations of a few thousand neurons are capable of learning hundreds of associations even if they are presented only once. The analysis of the model is based on a novel result by Janson et al. on bootstrap percolation in random graphs. PMID:25426060

Adaptive categorization of ART networks in robot behavior learning using game-theoretic formulation.

PubMed

Fung, Wai-keung; Liu, Yun-hui

2003-12-01

Adaptive Resonance Theory (ART) networks are employed in robot behavior learning. Two of the difficulties in online robot behavior learning, namely, (1) exponential memory increases with time, (2) difficulty for operators to specify learning tasks accuracy and control learning attention before learning. In order to remedy the aforementioned difficulties, an adaptive categorization mechanism is introduced in ART networks for perceptual and action patterns categorization in this paper. A game-theoretic formulation of adaptive categorization for ART networks is proposed for vigilance parameter adaptation for category size control on the categories formed. The proposed vigilance parameter update rule can help improving categorization performance in the aspect of category number stability and solve the problem of selecting initial vigilance parameter prior to pattern categorization in traditional ART networks. Behavior learning using physical robot is conducted to demonstrate the effectiveness of the proposed adaptive categorization mechanism in ART networks.

A high-capacity model for one shot association learning in the brain.

PubMed

Einarsson, Hafsteinn; Lengler, Johannes; Steger, Angelika

2014-01-01

We present a high-capacity model for one-shot association learning (hetero-associative memory) in sparse networks. We assume that basic patterns are pre-learned in networks and associations between two patterns are presented only once and have to be learned immediately. The model is a combination of an Amit-Fusi like network sparsely connected to a Willshaw type network. The learning procedure is palimpsest and comes from earlier work on one-shot pattern learning. However, in our setup we can enhance the capacity of the network by iterative retrieval. This yields a model for sparse brain-like networks in which populations of a few thousand neurons are capable of learning hundreds of associations even if they are presented only once. The analysis of the model is based on a novel result by Janson et al. on bootstrap percolation in random graphs.

The Structural Underpinnings of Policy Learning: A Classroom Policy Simulation

NASA Astrophysics Data System (ADS)

Bird, Stephen

This paper investigates the relationship between the centrality of individual actors in a social network structure and their policy learning performance. In a dynamic comparable to real-world policy networks, results from a classroom simulation demonstrate a strong relationship between centrality in social learning networks and grade performance. Previous research indicates that social network centrality should have a positive effect on learning in other contexts and this link is tested in a policy learning context. Second, the distinction between collaborative learning versus information diffusion processes in policy learning is examined. Third, frequency of interaction is analyzed to determine whether consistent, frequent tics have a greater impact on the learning process. Finally, the data arc analyzed to determine if the benefits of centrality have limitations or thresholds when benefits no longer accrue. These results demonstrate the importance of network structure, and support a collaborative conceptualization of the policy learning process.

A Spiking Neurocomputational Model of High-Frequency Oscillatory Brain Responses to Words and Pseudowords

PubMed Central

Garagnani, Max; Lucchese, Guglielmo; Tomasello, Rosario; Wennekers, Thomas; Pulvermüller, Friedemann

2017-01-01

Experimental evidence indicates that neurophysiological responses to well-known meaningful sensory items and symbols (such as familiar objects, faces, or words) differ from those to matched but novel and senseless materials (unknown objects, scrambled faces, and pseudowords). Spectral responses in the high beta- and gamma-band have been observed to be generally stronger to familiar stimuli than to unfamiliar ones. These differences have been hypothesized to be caused by the activation of distributed neuronal circuits or cell assemblies, which act as long-term memory traces for learned familiar items only. Here, we simulated word learning using a biologically constrained neurocomputational model of the left-hemispheric cortical areas known to be relevant for language and conceptual processing. The 12-area spiking neural-network architecture implemented replicates physiological and connectivity features of primary, secondary, and higher-association cortices in the frontal, temporal, and occipital lobes of the human brain. We simulated elementary aspects of word learning in it, focussing specifically on semantic grounding in action and perception. As a result of spike-driven Hebbian synaptic plasticity mechanisms, distributed, stimulus-specific cell-assembly (CA) circuits spontaneously emerged in the network. After training, presentation of one of the learned “word” forms to the model correlate of primary auditory cortex induced periodic bursts of activity within the corresponding CA, leading to oscillatory phenomena in the entire network and spontaneous across-area neural synchronization. Crucially, Morlet wavelet analysis of the network's responses recorded during presentation of learned meaningful “word” and novel, senseless “pseudoword” patterns revealed stronger induced spectral power in the gamma-band for the former than the latter, closely mirroring differences found in neurophysiological data. Furthermore, coherence analysis of the simulated responses uncovered dissociated category specific patterns of synchronous oscillations in distant cortical areas, including indirectly connected primary sensorimotor areas. Bridging the gap between cellular-level mechanisms, neuronal-population behavior, and cognitive function, the present model constitutes the first spiking, neurobiologically, and anatomically realistic model able to explain high-frequency oscillatory phenomena indexing language processing on the basis of dynamics and competitive interactions of distributed cell-assembly circuits which emerge in the brain as a result of Hebbian learning and sensorimotor experience. PMID:28149276

How Are Television Networks Involved in Distance Learning?

ERIC Educational Resources Information Center

Bucher, Katherine

1996-01-01

Reviews the involvement of various television networks in distance learning, including public broadcasting stations, Cable in the Classroom, Arts and Entertainment Network, Black Entertainment Television, C-SPAN, CNN (Cable News Network), The Discovery Channel, The Learning Channel, Mind Extension University, The Weather Channel, National Teacher…

Rethinking the learning of belief network probabilities

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

Musick, R.

Belief networks are a powerful tool for knowledge discovery that provide concise, understandable probabilistic models of data. There are methods grounded in probability theory to incrementally update the relationships described by the belief network when new information is seen, to perform complex inferences over any set of variables in the data, to incorporate domain expertise and prior knowledge into the model, and to automatically learn the model from data. This paper concentrates on part of the belief network induction problem, that of learning the quantitative structure (the conditional probabilities), given the qualitative structure. In particular, the current practice of rotemore » learning the probabilities in belief networks can be significantly improved upon. We advance the idea of applying any learning algorithm to the task of conditional probability learning in belief networks, discuss potential benefits, and show results of applying neutral networks and other algorithms to a medium sized car insurance belief network. The results demonstrate from 10 to 100% improvements in model error rates over the current approaches.« less

Multichannel microformulators for massively parallel machine learning and automated design of biological experiments

NASA Astrophysics Data System (ADS)

Wikswo, John; Kolli, Aditya; Shankaran, Harish; Wagoner, Matthew; Mettetal, Jerome; Reiserer, Ronald; Gerken, Gregory; Britt, Clayton; Schaffer, David

Genetic, proteomic, and metabolic networks describing biological signaling can have 102 to 103 nodes. Transcriptomics and mass spectrometry can quantify 104 different dynamical experimental variables recorded from in vitro experiments with a time resolution approaching 1 s. It is difficult to infer metabolic and signaling models from such massive data sets, and it is unlikely that causality can be determined simply from observed temporal correlations. There is a need to design and apply specific system perturbations, which will be difficult to perform manually with 10 to 102 externally controlled variables. Machine learning and optimal experimental design can select an experiment that best discriminates between multiple conflicting models, but a remaining problem is to control in real time multiple variables in the form of concentrations of growth factors, toxins, nutrients and other signaling molecules. With time-division multiplexing, a microfluidic MicroFormulator (μF) can create in real time complex mixtures of reagents in volumes suitable for biological experiments. Initial 96-channel μF implementations control the exposure profile of cells in a 96-well plate to different temporal profiles of drugs; future experiments will include challenge compounds. Funded in part by AstraZeneca, NIH/NCATS HHSN271201600009C and UH3TR000491, and VIIBRE.

Homeostatic plasticity for single node delay-coupled reservoir computing.

PubMed

Toutounji, Hazem; Schumacher, Johannes; Pipa, Gordon

2015-06-01

Supplementing a differential equation with delays results in an infinite-dimensional dynamical system. This property provides the basis for a reservoir computing architecture, where the recurrent neural network is replaced by a single nonlinear node, delay-coupled to itself. Instead of the spatial topology of a network, subunits in the delay-coupled reservoir are multiplexed in time along one delay span of the system. The computational power of the reservoir is contingent on this temporal multiplexing. Here, we learn optimal temporal multiplexing by means of a biologically inspired homeostatic plasticity mechanism. Plasticity acts locally and changes the distances between the subunits along the delay, depending on how responsive these subunits are to the input. After analytically deriving the learning mechanism, we illustrate its role in improving the reservoir's computational power. To this end, we investigate, first, the increase of the reservoir's memory capacity. Second, we predict a NARMA-10 time series, showing that plasticity reduces the normalized root-mean-square error by more than 20%. Third, we discuss plasticity's influence on the reservoir's input-information capacity, the coupling strength between subunits, and the distribution of the readout coefficients.

Exploring biological interaction networks with tailored weighted quasi-bicliques

PubMed Central

2012-01-01

Background Biological networks provide fundamental insights into the functional characterization of genes and their products, the characterization of DNA-protein interactions, the identification of regulatory mechanisms, and other biological tasks. Due to the experimental and biological complexity, their computational exploitation faces many algorithmic challenges. Results We introduce novel weighted quasi-biclique problems to identify functional modules in biological networks when represented by bipartite graphs. In difference to previous quasi-biclique problems, we include biological interaction levels by using edge-weighted quasi-bicliques. While we prove that our problems are NP-hard, we also describe IP formulations to compute exact solutions for moderately sized networks. Conclusions We verify the effectiveness of our IP solutions using both simulation and empirical data. The simulation shows high quasi-biclique recall rates, and the empirical data corroborate the abilities of our weighted quasi-bicliques in extracting features and recovering missing interactions from biological networks. PMID:22759421

sbv IMPROVER: Modern Approach to Systems Biology.

PubMed

Guryanova, Svetlana; Guryanova, Anna

2017-01-01

The increasing amount and variety of data in biosciences call for innovative methods of visualization, scientific verification, and pathway analysis. Novel approaches to biological networks and research quality control are important because of their role in development of new products, improvement, and acceleration of existing health policies and research for novel ways of solving scientific challenges. One such approach is sbv IMPROVER. It is a platform that uses crowdsourcing and verification to create biological networks with easy public access. It contains 120 networks built in Biological Expression Language (BEL) to interpret data from PubMed articles with high-quality verification available for free on the CBN database. Computable, human-readable biological networks with a structured syntax are a powerful way of representing biological information generated from high-density data. This article presents sbv IMPROVER, a crowd-verification approach for the visualization and expansion of biological networks.

The Latin American Biological Dosimetry Network (LBDNet).

PubMed

García, O; Di Giorgio, M; Radl, A; Taja, M R; Sapienza, C E; Deminge, M M; Fernández Rearte, J; Stuck Oliveira, M; Valdivia, P; Lamadrid, A I; González, J E; Romero, I; Mandina, T; Guerrero-Carbajal, C; ArceoMaldonado, C; Cortina Ramírez, G E; Espinoza, M; Martínez-López, W; Di Tomasso, M

2016-09-01

Biological Dosimetry is a necessary support for national radiation protection programmes and emergency response schemes. The Latin American Biological Dosimetry Network (LBDNet) was formally founded in 2007 to provide early biological dosimetry assistance in case of radiation emergencies in the Latin American Region. Here are presented the main topics considered in the foundational document of the network, which comprise: mission, partners, concept of operation, including the mechanism to request support for biological dosimetry assistance in the region, and the network capabilities. The process for network activation and the role of the coordinating laboratory during biological dosimetry emergency response is also presented. This information is preceded by historical remarks on biological dosimetry cooperation in Latin America. A summary of the main experimental and practical results already obtained by the LBDNet is also included. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cascade Back-Propagation Learning in Neural Networks

NASA Technical Reports Server (NTRS)

Duong, Tuan A.

2003-01-01

The cascade back-propagation (CBP) algorithm is the basis of a conceptual design for accelerating learning in artificial neural networks. The neural networks would be implemented as analog very-large-scale integrated (VLSI) circuits, and circuits to implement the CBP algorithm would be fabricated on the same VLSI circuit chips with the neural networks. Heretofore, artificial neural networks have learned slowly because it has been necessary to train them via software, for lack of a good on-chip learning technique. The CBP algorithm is an on-chip technique that provides for continuous learning in real time. Artificial neural networks are trained by example: A network is presented with training inputs for which the correct outputs are known, and the algorithm strives to adjust the weights of synaptic connections in the network to make the actual outputs approach the correct outputs. The input data are generally divided into three parts. Two of the parts, called the "training" and "cross-validation" sets, respectively, must be such that the corresponding input/output pairs are known. During training, the cross-validation set enables verification of the status of the input-to-output transformation learned by the network to avoid over-learning. The third part of the data, termed the "test" set, consists of the inputs that are required to be transformed into outputs; this set may or may not include the training set and/or the cross-validation set. Proposed neural-network circuitry for on-chip learning would be divided into two distinct networks; one for training and one for validation. Both networks would share the same synaptic weights.

Learning in Artificial Neural Systems

NASA Technical Reports Server (NTRS)

Matheus, Christopher J.; Hohensee, William E.

1987-01-01

This paper presents an overview and analysis of learning in Artificial Neural Systems (ANS's). It begins with a general introduction to neural networks and connectionist approaches to information processing. The basis for learning in ANS's is then described, and compared with classical Machine learning. While similar in some ways, ANS learning deviates from tradition in its dependence on the modification of individual weights to bring about changes in a knowledge representation distributed across connections in a network. This unique form of learning is analyzed from two aspects: the selection of an appropriate network architecture for representing the problem, and the choice of a suitable learning rule capable of reproducing the desired function within the given network. The various network architectures are classified, and then identified with explicit restrictions on the types of functions they are capable of representing. The learning rules, i.e., algorithms that specify how the network weights are modified, are similarly taxonomized, and where possible, the limitations inherent to specific classes of rules are outlined.

Turkish High School Student's Perceptions of Learning Environment in Biology Classrooms and Their Attitudes toward Biology.

ERIC Educational Resources Information Center

Cakiroglu, Jale; Telli, Sibel; Cakiroglu, Erdinc

The purpose of this study was to examine Turkish high school students' perceptions of learning environment in biology classrooms and to investigate relationships between learning environment and students' attitudes toward biology. Secondly, the study aimed to investigate the differences in students' perceptions of learning environments in biology…