ArticleJournal of biology2007
A global analysis of genetic interactions in Caenorhabditis elegans.
Article in Journal of biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed.
- Coincident evolution and functional adaptation of the taxonomically restricted genes ivph-3 and gon-14 in Caenorhabditis nematodes.Biology open · 2025Article
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- A mathematical framework for the quantitative analysis of genetic buffering.PLoS genetics · 2025Article
- Pleiotropy, epistasis and the genetic architecture of quantitative traits.Nature reviews. Genetics · 2024Review
- Reconstruction of gene regulatory networks for Caenorhabditis elegans using tree-shaped gene expression data.Briefings in bioinformatics · 2024Article
- Review
- SLOAD: a comprehensive database of cancer-specific synthetic lethal interactions for precision cancer therapy via multi-omics analysis.Database : the journal of biological databases and curation · 2022Article
- SIN-3 functions through multi-protein interaction to regulate apoptosis, autophagy, and longevity in Caenorhabditis elegans.Scientific reports · 2022Article
- The FGFR4 Homolog KIN-9 Regulates Lifespan and Stress Responses inFrontiers in aging · 2022Article
- Mapping the multiscale structure of biological systems.Cell systems · 2021Review
- The conserved transmembrane protein TMEM-39 coordinates with COPII to promote collagen secretion and regulate ER stress response.PLoS genetics · 2021Article
- The AncestralG3 (Bethesda, Md.) · 2020Article
- Genetic Modifiers and Rare Mendelian Disease.Genes · 2020Review
- Genome-wide synthetic lethal CRISPR screen identifies FIS1 as a genetic interactor of ALS-linked C9ORF72.Brain research · 2020Article
- Broadly conserved roles of TMEM131 family proteins in intracellular collagen assembly and secretory cargo trafficking.Science advances · 2020Article
- Review
- Birth and death of Mx genes and the presence/absence of genes regulating Mx transcription are correlated with the diversity of anti-pathogenicity in vertebrate species.Molecular genetics and genomics : MGG · 2019Article
- Modular epistasis and the compensatory evolution of gene deletion mutants.PLoS genetics · 2019Article
- Synthetic lethal interaction between oxidative stress response and DNA damage repair in the budding yeast and its application to targeted anticancer therapy.Journal of microbiology (Seoul, Korea) · 2019Review
- Ancient Function of Teneurins in Tissue Organization and Neuronal Guidance in the NematodeFrontiers in neuroscience · 2019Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
backgroundUnderstanding gene function and genetic relationships is fundamental to our efforts to better understand biological systems. Previous studies systematically describing genetic interactions on a global scale have either focused on core biological processes in protozoans or surveyed catastrophic interactions in metazoans. Here, we describe a reliable high-throughput approach capable of revealing both weak and strong genetic interactions in the nematode Caenorhabditis elegans.
resultsWe investigated interactions between 11 'query' mutants in conserved signal transduction pathways and hundreds of 'target' genes compromised by RNA interference (RNAi). Mutant-RNAi combinations that grew more slowly than controls were identified, and genetic interactions inferred through an unbiased global analysis of the interaction matrix. A network of 1,246 interactions was uncovered, establishing the largest metazoan genetic-interaction network to date. We refer to this approach as systematic genetic interaction analysis (SGI). To investigate how genetic interactions connect genes on a global scale, we superimposed the SGI network on existing networks of physical, genetic, phenotypic and coexpression interactions. We identified 56 putative functional modules within the superimposed network, one of which regulates fat accumulation and is coordinated by interactions with bar-1(ga80), which encodes a homolog of beta-catenin. We also discovered that SGI interactions link distinct subnetworks on a global scale. Finally, we showed that the properties of genetic networks are conserved between C. elegans and Saccharomyces cerevisiae, but that the connectivity of interactions within the current networks is not.
conclusionsSynthetic genetic interactions may reveal redundancy among functional modules on a global scale, which is a previously unappreciated level of organization within metazoan systems. Although the buffering between functional modules may differ between species, studying these differences may provide insight into the evolution of divergent form and function.
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