Refining regulatory interaction data in yeast using GEMINI.

Abstract

<p><b>A.</b> GEMINI was evaluated for its ability to preferentially retain the gold-standard interactions (blue edges) and the indirect interactions (green edges). The hyper-geometric p-values for enrichment with various data sets are shown. <b>B.</b> Running GEMINI on the network derived using Yeastract resulted in the elimination of āˆ¼9,000 phenotype-inconsistent interactions and produced a refined integrated network model that was more highly enriched for known interactions than the original network (p-value<10<sup>āˆ’172</sup>, hyper-geometric test). Most of the interactions eliminated by GEMINI were found to have little supporting experimental evidence (interactions that did have strong supporting evidence were preferentially retained). <b>C.</b> The number of true interactions (direct and indirect) recalled was significantly higher than could be recalled using mutual information (MI) or correlation (Corr)-based approaches, which rely on gene expression alone (estimated from the same gene expression dataset and for networks of the same size). We also measured the best prediction obtained by MI and correlation over all possible cut offs and this was still significantly lower than the enrichment obtained by GEMINI. The supplementary <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003370#pcbi.1003370.s001" target="_blank">figures S1</a> and <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003370#pcbi.1003370.s002" target="_blank">S2</a> show the enrichment for direct interactions over the entire range of thresholds for both MI and correlation. The number of interactions recalled by random sampling from the Yeastract database (DB) is also shown, as a reference.</p

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