Colored Motifs Reveal Computational Building Blocks in the C. elegans Brain

BACKGROUND Complex networks can often be decomposed into less complex sub-networks whose structures can give hints about the functional organization of the network as a whole. However, these structural motifs can only tell one part of the functional story because in this analysis each node and edge is treated on an equal footing. In real networks, two motifs that are topologically identical but whose nodes perform very different functions will play very different roles in the network. METHODOLOGY/PRINCIPAL FINDINGS Here, we combine structural information derived from the topology of the neuronal network of the nematode C. elegans with information about the biological function of these nodes, thus coloring nodes by function. We discover that particular colorations of motifs are significantly more abundant in the worm brain than expected by chance, and have particular computational functions that emphasize the feed-forward structure of information processing in the network, while evading feedback loops. Interneurons are strongly over-represented among the common motifs, supporting the notion that these motifs process and transduce the information from the sensor neurons towards the muscles. Some of the most common motifs identified in the search for significant colored motifs play a crucial role in the system of neurons controlling the worm's locomotion. CONCLUSIONS/SIGNIFICANCE The analysis of complex networks in terms of colored motifs combines two independent data sets to generate insight about these networks that cannot be obtained with either data set alone. The method is general and should allow a decomposition of any complex networks into its functional (rather than topological) motifs as long as both wiring and functional information is available.

[1]  Lav R. Varshney,et al.  Structural Properties of the Caenorhabditis elegans Neuronal Network , 2009, PLoS Comput. Biol..

[2]  Mark E. J. Newman,et al.  Structure and Dynamics of Networks , 2009 .

[3]  J. Livet,et al.  A technicolour approach to the connectome , 2008, Nature Reviews Neuroscience.

[4]  Paul W. Sternberg,et al.  Systems level circuit model of C. elegans undulatory locomotion: mathematical modeling and molecular genetics , 2007, Journal of Computational Neuroscience.

[5]  M. Koelle,et al.  Biogenic amine neurotransmitters in C. elegans. , 2007, WormBook : the online review of C. elegans biology.

[6]  Sebastian Wernicke,et al.  Efficient Detection of Network Motifs , 2006, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[7]  J. Stark,et al.  Network motifs: structure does not determine function , 2006, BMC Genomics.

[8]  Sebastian Wernicke,et al.  FANMOD: a tool for fast network motif detection , 2006, Bioinform..

[9]  Wei-Po Lee,et al.  Differential evolutionary conservation of motif modes in the yeast protein interaction network , 2006, BMC Genomics.

[10]  Robb Mackay Linked: How Everything is Connected to Everything Else and What It Means for Business, Science and Everyday Life , 2005 .

[11]  E. Callaway,et al.  Fine-scale specificity of cortical networks depends on inhibitory cell type and connectivity , 2005, Nature Neuroscience.

[12]  Andre Levchenko,et al.  Dynamic Properties of Network Motifs Contribute to Biological Network Organization , 2005, PLoS biology.

[13]  P. J. Sjöström,et al.  Highly Nonrandom Features of Synaptic Connectivity in Local Cortical Circuits , 2005, PLoS biology.

[14]  Aaron Kershenbaum,et al.  Lasting impressions: motifs in protein-protein maps may provide footprints of evolutionary events. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[15]  U. Alon,et al.  Search for computational modules in the C. elegans brain , 2004, BMC Biology.

[16]  O. Sporns,et al.  Motifs in Brain Networks , 2004, PLoS biology.

[17]  S. Shen-Orr,et al.  Superfamilies of Evolved and Designed Networks , 2004, Science.

[18]  Z. Oltvai,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[19]  Z N Oltvai,et al.  Evolutionary conservation of motif constituents in the yeast protein interaction network , 2003, Nature Genetics.

[20]  Katherine C. Chen,et al.  Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. , 2003, Current opinion in cell biology.

[21]  Mark E. J. Newman,et al.  The Structure and Function of Complex Networks , 2003, SIAM Rev..

[22]  S. Dudoit,et al.  Multiple Hypothesis Testing in Microarray Experiments , 2003 .

[23]  S. Shen-Orr,et al.  Network motifs: simple building blocks of complex networks. , 2002, Science.

[24]  S. Shen-Orr,et al.  Network motifs in the transcriptional regulation network of Escherichia coli , 2002, Nature Genetics.

[25]  Edward L White,et al.  Specificity of cortical synaptic connectivity: Emphasis on perspectives gained from quantitative electron microscopy , 2002, Journal of neurocytology.

[26]  J. Hopfield,et al.  From molecular to modular cell biology , 1999, Nature.

[27]  G. E. Thomas Resampling‐Based Multiple Testing: Examples and Methods for p‐Value Adjustment , 1994 .

[28]  P. Erdös,et al.  Theory of the locomotion of nematodes: control of the somatic motor neurons by interneurons. , 1993, Mathematical biosciences.

[29]  S. S. Young,et al.  Resampling-Based Multiple Testing: Examples and Methods for p-Value Adjustment , 1993 .

[30]  W. Yamamoto,et al.  AY's Neuroanatomy of C. elegans for Computation , 1992 .

[31]  DH Hall,et al.  The posterior nervous system of the nematode Caenorhabditis elegans: serial reconstruction of identified neurons and complete pattern of synaptic interactions , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  S. Brenner,et al.  The structure of the nervous system of the nematode Caenorhabditis elegans. , 1986, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[33]  J. White,et al.  Neuronal connectivity in Caenorhabditis elegans , 1985, Trends in Neurosciences.

[34]  M. Koelle,et al.  Biogenic amine neurotransmitters in C. , 2007 .

[35]  J. Richmond Synaptic function. , 2005, WormBook : the online review of C. elegans biology.

[36]  Diego Rasskin-Gutman,et al.  Modularity. Understanding the Development and Evolution of Natural Complex Systems , 2005 .

[37]  S. Shen-Orr,et al.  Networks Network Motifs : Simple Building Blocks of Complex , 2002 .