Modularity and directionality in genetic interaction maps

Ariel Jaimovich, Ruty Rinott, Maya Schuldiner*, Hanah Margalit, Nir Friedman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Motivation: Genetic interactions between genes reflect functional relationships caused by a wide range of molecular mechanisms. Large-scale genetic interaction assays lead to a wealth of information about the functional relations between genes. However, the vast number of observed interactions, along with experimental noise, makes the interpretation of such assays a major challenge. Results: Here, we introduce a computational approach to organize genetic interactions and show that the bulk of observed interactions can be organized in a hierarchy of modules. Revealing this organization enables insights into the function of cellular machineries and highlights global properties of interaction maps. To gain further insight into the nature of these interactions, we integrated data from genetic screens under a wide range of conditions to reveal that more than a third of observed aggravating (i.e. synthetic sick/lethal) interactions are unidirectional, where one gene can buffer the effects of perturbing another gene but not vice versa. Furthermore, most modules of genes that have multiple aggravating interactions were found to be involved in such unidirectional interactions. We demonstrate that the identification of external stimuli that mimic the effect of specific gene knockouts provides insights into the role of individual modules in maintaining cellular integrity. Availability: We designed a freely accessible web tool that includes all our findings, and is specifically intended to allow effective browsing of our results (http://compbio.cs.huji.ac.il/GIAnalysis). Contact: maya.schuldiner@weizmann.ac.il; hanahm@ekmd.huji.ac.il; nir@cs.huji.ac.il. Supplementary information: Supplementary data are available at Bioinformatics online.

Original languageAmerican English
Article numberbtq197
Pages (from-to)i228-i236
JournalBioinformatics
Volume26
Issue number12
DOIs
StatePublished - 1 Jun 2010

Bibliographical note

Funding Information:
Funding: Eshkol fellowship from the Israeli Ministry of Science (to A.J.); Rudin Foundation (to R.R.); Human Frontiers Science Program Career Development Award (to M.S.); European Union grant 3D-Repertoire, contract number LSHG-CT-2005-512028 (to H.M.); National Institutes of Health grant 1R01CA119176-01 (to N.F.).

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