An Improved, Bias-Reduced Probabilistic Functional Gene Network of Baker's Yeast, Saccharomyces cerevisiae

dc.creatorLee, Insuken
dc.creatorLi, Zhihuaen
dc.creatorMarcotte, Edward M.en
dc.description.abstractBackground: Probabilistic functional gene networks are powerful theoretical frameworks for integrating heterogeneous functional genomics and proteomics data into objective models of cellular systems. Such networks provide syntheses of millions of discrete experimental observations, spanning DNA microarray experiments, physical protein interactions, genetic interactions, and comparative genomics; the resulting networks can then be easily applied to generate testable hypotheses regarding specific gene functions and associations. Methodology/Principal Findings: We report a significantly improved version (v. 2) of a probabilistic functional gene network [1] of the baker's yeast, Saccharomyces cerevisiae. We describe our optimization methods and illustrate their effects in three major areas: the reduction of functional bias in network training reference sets, the application of a probabilistic model for calculating confidences in pair-wise protein physical or genetic interactions, and the introduction of simple thresholds that eliminate many false positive mRNA co-expression relationships. Using the network, we predict and experimentally verify the function of the yeast RNA binding protein Puf6 in 60S ribosomal subunit biogenesis. Conclusions/Significance: YeastNet v. 2, constructed using these optimizations together with additional data, shows significant reduction in bias and improvements in precision and recall, in total covering 102,803 linkages among 5,483 yeast proteins (95% of the validated proteome). YeastNet is available from
dc.description.departmentCellular and Molecular Biologyen
dc.description.sponsorshipThis work was supported by grants from the N.S.F. (IIS-0325116, EIA-0219061), N.I.H. (GM06779-01,GM076536-01), Welch (F-1515), and a Packard Fellowship (EMM). These agencies were not involved in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.en
dc.identifier.citationLee I, Li Z, Marcotte EM (2007) An Improved, Bias-Reduced Probabilistic Functional Gene Network of Baker's Yeast, Saccharomyces cerevisiae. PLoS ONE 2(10): e988. doi:10.1371/journal.pone.0000988en
dc.publisherPublic Library of Scienceen
dc.rightsAttribution 3.0 United Statesen
dc.subjectGene expressionen
dc.subjectGenetic networksen
dc.subjectGenomic databasesen
dc.subjectProtein interaction networksen
dc.subjectProtein interactionsen
dc.subjectProtein-protein interactionsen
dc.titleAn Improved, Bias-Reduced Probabilistic Functional Gene Network of Baker's Yeast, Saccharomyces cerevisiaeen

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