Modularity and directionality in genetic interaction maps.
BACKGROUND
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.


BACKGROUND
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).


BACKGROUND
Supplementary data are available at Bioinformatics online.
School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Ariel
A
Jaimovich
Ruty
R
Rinott
Maya
M
Schuldiner
Hanah
H
Margalit
Nir
N
Friedman
D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D053263:Gene Regulatory Networks; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
D029701:Saccharomyces cerevisiae Proteins