Computational inference of the molecular logic for synaptic connectivity in C. elegans.
BACKGROUND
The nematode C. elegans is an ideal model organism in which to investigate the biomolecular mechanisms underlying the connectivity of neurons, because synaptic connections are described in a comprehensive wiring diagram and methods for defining gene expression profiles of individual neurons are now available.


RESULTS
Here we present computational techniques linking these two types of information. A systems-based approach (EMBP: Entropy Minimization and Boolean Parsimony) identifies sets of synergistically interacting genes whose joint expression predicts neural connectivity. We introduce an information theoretic measure of the multivariate synergy, a fundamental concept in systems biology, connecting the members of these gene sets. We present and validate our preliminary results based on publicly available information, and demonstrate that their synergy is exceptionally high indicating joint involvement in pathways. Our strategy provides a robust methodology that will yield increasingly more accurate results as more neuron-specific gene expression data emerge. Ultimately, we expect our approach to provide important clues for universal mechanisms of neural interconnectivity.
Varadan
Vinay
V
Center for Computational Biology and Bioinformatics (C2B2), and Department of Electrical Engineering, Columbia University, New York, NY 10027, USA.
Miller
David M
DM
Anastassiou
Dimitris
D
D000818:Animals; D001921:Brain / Q000502:physiology; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods; D016015:Logistic Models; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009434:Neural Pathways / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins