Abstract
If perturbing two genes together has a stronger or weaker effect than expected, they are said to genetically interact. Genetic interactions are important because they help map gene function, and functionally related genes have similar genetic interaction patterns. Mapping quantitative (positive and negative) genetic interactions on a global scale has recently become possible. This data clearly shows groups of genes connected by predominantly positive or negative interactions, termed monochromatic groups. These groups often correspond to functional modules, like biological processes or complexes, or connections between modules. However it is not yet known how these patterns globally relate to known functional modules. Here we systematically study the monochromatic nature of known biological processes using the largest quantitative genetic interaction data set available, which includes fitness measurements for ∼5.4 million gene pairs in the yeast Saccharomyces cerevisiae. We find that only 10% of biological processes, as defined by Gene Ontology annotations, and less than 1% of inter-process connections are monochromatic. Further, we show that protein complexes are responsible for a surprisingly large fraction of these patterns. This suggests that complexes play a central role in shaping the monochromatic landscape of biological processes. Altogether this work shows that both positive and negative monochromatic patterns are found in known biological processes and in their connections and that protein complexes play an important role in these patterns. The monochromatic processes, complexes and connections we find chart a hierarchical and modular map of sensitive and redundant biological systems in the yeast cell that will be useful for gene function prediction and comparison across phenotypes and organisms. Furthermore the analysis methods we develop are applicable to other species for which genetic interactions will progressively become more available.
Highlights
One of the major goals in biology is to understand how molecules are organized within the cell, how they interact to mediate biological processes and how process failure leads to disease
Global scale mapping of quantitative genetic interactions has been performed. This data clearly shows groups of genes connected by predominantly positive or negative interactions, termed monochromatic groups. These groups often correspond to functional modules, such as biological processes or protein complexes, or connections between modules, but it is not yet known how these patterns globally relate to known functional modules
We systematically evaluate the monochromatic nature of known biological processes and their connections in the yeast Saccharomyces cerevisiae
Summary
One of the major goals in biology is to understand how molecules are organized within the cell, how they interact to mediate biological processes and how process failure leads to disease. Genetic perturbations, such as gene mutations, are often used to better understand the function of a gene and to study the relationship between genotype and phenotype [1]. Genetic interactions have proven useful to predict gene function [6] and organize biological processes [7,8,9] and are complementary to other functional interaction data such as protein-protein interactions [10]. We systematically evaluate how genetic interaction data relates to known biological processes. We review previous work in this area to place our work into context
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