title: Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways.
abstract: A genetic interaction (GI) is defined when the mutation of one gene modifies the phenotypic expression associated with the mutation of a second gene. Genome-wide efforts to map GIs in yeast revealed structural and functional properties of a GI network. This provided insights into the mechanisms underlying the robustness of yeast to genetic and environmental insults, and also into the link existing between genotype and phenotype. While a significant conservation of GIs and GI network structure has been reported between distant yeast species, such a conservation is not clear between unicellular and multicellular organisms. Structural and functional characterization of a GI network in these latter organisms is consequently of high interest. In this study, we present an in-depth characterization of ~1.5K GIs in the nematode Caenorhabditis elegans. We identify and characterize six distinct classes of GIs by examining a wide-range of structural and functional properties of genes and network, including co-expression, phenotypical manifestations, relationship with protein-protein interaction dense subnetworks (PDS) and pathways, molecular and biological functions, gene essentiality and pleiotropy. Our study shows that GI classes link genes within pathways and display distinctive properties, specifically towards PDS. It suggests a model in which pathways are composed of PDS-centric and PDS-independent GIs coordinating molecular machines through two specific classes of GIs involving pleiotropic and non-pleiotropic connectors. Our study provides the first in-depth characterization of a GI network within pathways of a multicellular organism. It also suggests a model to understand better how GIs control system robustness and evolution.
authors.affiliation: Department of Chemistry, Université du Québec à Montréal, Montréal, Québec, Canada.|Pharmaqam, Université du Québec à Montréal, Montréal, Québec, Canada.|Biomed, Université du Québec à Montréal, Montréal, Québec, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Boucher
authors.affiliation: McGill Centre for Bioinformatics, McGill University, Montréal, Québec, Canada.|School of Computer Science, McGill University, Montréal, Québec, Canada.
authors.forename: Anna Y
authors.initials: AY
authors.lastname: Lee
authors.affiliation: McGill Centre for Bioinformatics, McGill University, Montréal, Québec, Canada.|School of Computer Science, McGill University, Montréal, Québec, Canada.|Rosalind and Morris Goodman Cancer Centre, McGill University, Montréal, Québec, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallett
authors.affiliation: Department of Chemistry, Université du Québec à Montréal, Montréal, Québec, Canada.|Pharmaqam, Université du Québec à Montréal, Montréal, Québec, Canada.|Biomed, Université du Québec à Montréal, Montréal, Québec, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jenna
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D053263:Gene Regulatory Networks / Q000235:genetics*; D008954:Models, Biological; D060066:Protein Interaction Maps / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins