Systematic interpretation of genetic interactions using protein networks
Open accessAbstract
Genetic interaction analysis,in which two mutations have a combined effect not exhibited by either mutation alone, is a powerful and widespread tool for establishing functional linkages between genes. In the yeast Saccharomyces cerevisiae, ongoing screens have generated >4,800 such genetic interaction data. We demonstrate that by combining these data with information on protein-protein, prote in-DNA or metabolic networks, it is possible to uncover physical mechanisms behind many of the observed genetic effects. Using a probabilistic model, we found that 1,922 genetic interactions are significantly associated with either between- or within-pathway explanations encoded in the physical networks, covering approximately 40% of known genetic interactions. These models predict new functions for 343 proteins and suggest that between-pathway explanations are better than within-pathway explanations at interpreting genetic interactions identified in systematic screens. This study provides a road map for how genetic and physical interactions can be integrated to reveal pathway organization and function.
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Literature broadly has reported common co-regulation of genes in protein complexes at both transcription and translational levels.
“This is a unique finding since literature broadly has reported common co-regulation of genes in protein complexes at both transcription and translational levels96–102.”
From EXOSC3 G191 Variants Trigger System-Wide Recalibration of RNA Processing Machinery (2026) · cites this paper as [98]
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- Authors
- Kelley, R., & Ideker, T.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Ideker, Trey
- ORCID
- Ideker, Trey
- Venue
- Nature Biotechnology
- Published
- 2005-05
- Volume
- 23
- Issue
- 5
- Pages
- 561-566
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC2814446
- OpenAlex
- W2013520054
- Cited by
- 437
- References
- 3
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 9 · 2020: 12 · 2019: 13 · 2018: 12 · 2017: 28 · 2016: 11 · 2015: 22 · 2014: 18 · 2013: 34 · 2012: 30
- FWCI
- 12.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- National Institute of General Medical Sciences (R01GM070743, GM070743-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- genetic interactions, protein-protein interaction network, metabolic networks, protein-DNA interactions, gene function prediction, probabilistic models, Saccharomyces cerevisiae, functional genomics
- MeSH terms
- Algorithms, Computer Simulation, Gene Expression Regulation, Models, Genetic, Saccharomyces cerevisiae, Signal Transduction, Protein Interaction Mapping, Saccharomyces cerevisiae Proteins
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