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      Topological Cluster Analysis Reveals the Systemic Organization of the Caenorhabditis elegans Connectome

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The modular organization of networks of individual neurons interwoven through synapses has not been fully explored due to the incredible complexity of the connectivity architecture. Here we use the modularity-based community detection method for directed, weighted networks to examine hierarchically organized modules in the complete wiring diagram (connectome) of Caenorhabditis elegans ( C. elegans) and to investigate their topological properties. Incorporating bilateral symmetry of the network as an important cue for proper cluster assignment, we identified anatomical clusters in the C. elegans connectome, including a body-spanning cluster, which correspond to experimentally identified functional circuits. Moreover, the hierarchical organization of the five clusters explains the systemic cooperation (e.g., mechanosensation, chemosensation, and navigation) that occurs among the structurally segregated biological circuits to produce higher-order complex behaviors.

          Author Summary

          Caenorhabditis elegans ( C. elegans) is a tiny worm whose neuronal network is fully revealed. Since the modular organization in a network of individual neurons interwoven through synapses is not yet fully explored owing to incredibly complex connectivity architecture, this study is designed to investigate hierarchically organized modules in this complete wiring diagram (connectome) of this worm. We used the modularity-based community detection algorithm and found that C. elegans had 5 anatomical clusters in the C. elegans connectome, which corresponded to experimentally-identified functional circuits. We found that the hierarchical organization of the 5 clusters explains the systemic cooperation including mechanosensation, chemosensation, and navigation that occurs among the structurally-segregated biological circuits to produce higher-order complex behaviors.

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          Most cited references29

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          Disrupted small-world networks in schizophrenia.

          The human brain has been described as a large, sparse, complex network characterized by efficient small-world properties, which assure that the brain generates and integrates information with high efficiency. Many previous neuroimaging studies have provided consistent evidence of 'dysfunctional connectivity' among the brain regions in schizophrenia; however, little is known about whether or not this dysfunctional connectivity causes disruption of the topological properties of brain functional networks. To this end, we investigated the topological properties of human brain functional networks derived from resting-state functional magnetic resonance imaging (fMRI). Data was obtained from 31 schizophrenia patients and 31 healthy subjects; then functional connectivity between 90 cortical and sub-cortical regions was estimated by partial correlation analysis and thresholded to construct a set of undirected graphs. Our findings demonstrated that the brain functional networks had efficient small-world properties in the healthy subjects; whereas these properties were disrupted in the patients with schizophrenia. Brain functional networks have efficient small-world properties which support efficient parallel information transfer at a relatively low cost. More importantly, in patients with schizophrenia the small-world topological properties are significantly altered in many brain regions in the prefrontal, parietal and temporal lobes. These findings are consistent with a hypothesis of dysfunctional integration of the brain in this illness. Specifically, we found that these altered topological measurements correlate with illness duration in schizophrenia. Detection and estimation of these alterations could prove helpful for understanding the pathophysiological mechanism as well as for evaluation of the severity of schizophrenia.
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            Communication in neuronal networks.

            Brains perform with remarkable efficiency, are capable of prodigious computation, and are marvels of communication. We are beginning to understand some of the geometric, biophysical, and energy constraints that have governed the evolution of cortical networks. To operate efficiently within these constraints, nature has optimized the structure and function of cortical networks with design principles similar to those used in electronic networks. The brain also exploits the adaptability of biological systems to reconfigure in response to changing needs.
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              Finding community structure in networks using the eigenvectors of matrices.

              We consider the problem of detecting communities or modules in networks, groups of vertices with a higher-than-average density of edges connecting them. Previous work indicates that a robust approach to this problem is the maximization of the benefit function known as "modularity" over possible divisions of a network. Here we show that this maximization process can be written in terms of the eigenspectrum of a matrix we call the modularity matrix, which plays a role in community detection similar to that played by the graph Laplacian in graph partitioning calculations. This result leads us to a number of possible algorithms for detecting community structure, as well as several other results, including a spectral measure of bipartite structure in networks and a centrality measure that identifies vertices that occupy central positions within the communities to which they belong. The algorithms and measures proposed are illustrated with applications to a variety of real-world complex networks.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Comput Biol
                plos
                ploscomp
                PLoS Computational Biology
                Public Library of Science (San Francisco, USA )
                1553-734X
                1553-7358
                May 2011
                May 2011
                19 May 2011
                : 7
                : 5
                : e1001139
                Affiliations
                [1 ]Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
                [2 ]Department of Political Science, University of California, San Diego, California, United States of America
                [3 ]Research Center for Cellulomics, Institute of Molecular Biology and Genetics School of Biological Sciences, Department of Biophysics and Chemical Biology, Seoul National University, Seoul, Republic of Korea
                [4 ]Center for Complex Network Research, Department of Physics, Northeastern University, Boston, Massachusetts, United States of America
                [5 ]Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Harvard University, Boston, Massachusetts, United States of America
                University College London, United Kingdom
                Author notes

                Conceived and designed the experiments: YS JL JJ. Performed the experiments: YS. Analyzed the data: YS MKC JL JJ. Contributed reagents/materials/analysis tools: YS. Wrote the paper: YS MKC YYA JL JJ.

                Article
                09-PLCB-RA-1182R3
                10.1371/journal.pcbi.1001139
                3098222
                21625578
                17a64893-af6b-40f7-b5f2-481fd1ea83bf
                Sohn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 20 October 2009
                : 20 April 2011
                Page count
                Pages: 10
                Categories
                Research Article
                Neuroscience/Behavioral Neuroscience

                Quantitative & Systems biology
                Quantitative & Systems biology

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