RT Journal Article
SR Electronic
T1 Predictability of Genetic Interactions from Functional Gene Modules
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 049627
DO 10.1101/049627
A1 Jonathan H. Young
A1 Edward M. Marcotte
YR 2016
UL http://biorxiv.org/content/early/2016/04/25/049627.abstract
AB Characterizing genetic interactions is crucial to understanding cellular and organismal response to gene-level perturbations. Such knowledge can inform the selection of candidate disease therapy targets. Yet experimentally determining whether genes interact is technically non-trivial and time-consuming. High-fidelity prediction of different classes of genetic interactions in multiple organisms would substantially alleviate this experimental burden. Under the hypothesis that functionally-related genes tend to share common genetic interaction partners, we evaluate a computational approach to predict genetic interactions in Homo sapiens, Drosophila melanogaster, and Saccharomyces cerevisiae. By leveraging knowledge of functional relationships between genes, we cross-validate predictions on known genetic interactions and observe high-predictive power of multiple classes of genetic interactions in all three organisms. Additionally, our method suggests high-confidence candidate interaction pairs that can be directly experimentally tested. A web application is provided for users to query genes for predicted novel genetic interaction partners. Finally, by subsampling the known yeast genetic interaction network, we found that novel genetic interactions are predictable even when knowledge of currently known interactions is minimal.