Guan Lab

Department of Computational Medicine & Bioinformatics
Wed, 11/06/2013 - 10:22 -- gl_admin
TitleA genomewide functional network for the laboratory mouse.
Publication TypeJournal Article
Year of Publication2008
AuthorsGuan Y, Myers CL, Lu R, Lemischka IR, Bult CJ, Troyanskaya OG
JournalPLoS Comput Biol
Volume4
Issue9
Paginatione1000165
Date Published2008
ISSN1553-7358
KeywordsAnimals, Bayes Theorem, Cell Differentiation, Cluster Analysis, Computational Biology, Database Management Systems, Databases, Genetic, Down-Regulation, Gene Regulatory Networks, Genomics, Homeodomain Proteins, Internet, MAP Kinase Signaling System, Mice, Mice, Knockout, Models, Statistical, Phenotype, Proteomics, Saccharomyces cerevisiae, Species Specificity, User-Computer Interface
Abstract

Establishing a functional network is invaluable to our understanding of gene function, pathways, and systems-level properties of an organism and can be a powerful resource in directing targeted experiments. In this study, we present a functional network for the laboratory mouse based on a Bayesian integration of diverse genetic and functional genomic data. The resulting network includes probabilistic functional linkages among 20,581 protein-coding genes. We show that this network can accurately predict novel functional assignments and network components and present experimental evidence for predictions related to Nanog homeobox (Nanog), a critical gene in mouse embryonic stem cell pluripotency. An analysis of the global topology of the mouse functional network reveals multiple biologically relevant systems-level features of the mouse proteome. Specifically, we identify the clustering coefficient as a critical characteristic of central modulators that affect diverse pathways as well as genes associated with different phenotype traits and diseases. In addition, a cross-species comparison of functional interactomes on a genomic scale revealed distinct functional characteristics of conserved neighborhoods as compared to subnetworks specific to higher organisms. Thus, our global functional network for the laboratory mouse provides the community with a key resource for discovering protein functions and novel pathway components as well as a tool for exploring systems-level topological and evolutionary features of cellular interactomes. To facilitate exploration of this network by the biomedical research community, we illustrate its application in function and disease gene discovery through an interactive, Web-based, publicly available interface at http://mouseNET.princeton.edu.

DOI10.1371/journal.pcbi.1000165
Alternate JournalPLoS Comput. Biol.
PubMed ID18818725
PubMed Central IDPMC2527685
Grant ListP50 GM071508 / GM / NIGMS NIH HHS / United States
R01 GM071966 / GM / NIGMS NIH HHS / United States