Comprehensive curation and analysis of global interaction networks in Saccharomyces cerevisiae
Open accessAbstract
Background: The study of complex biological networks and prediction of gene function has been enabled by high-throughput (HTP) methods for detection of genetic and protein interactions. Sparse coverage in HTP datasets may, however, distort network properties and confound predictions. Although a vast number of well substantiated interactions are recorded in the scientific literature, these data have not yet been distilled into networks that enable system-level inference. Results: We describe here a comprehensive database of genetic and protein interactions, and associated experimental evidence, for the budding yeast Saccharomyces cerevisiae , as manually curated from over 31,793 abstracts and online publications. This literature-curated (LC) dataset contains 33,311 interactions, on the order of all extant HTP datasets combined. Surprisingly, HTP protein-interaction datasets currently achieve only around 14% coverage of the interactions in the literature. The LC network nevertheless shares attributes with HTP networks, including scale-free connectivity and correlations between interactions, abundance, localization, and expression. We find that essential genes or proteins are enriched for interactions with other essential genes or proteins, suggesting that the global network may be functionally unified. This interconnectivity is supported by a substantial overlap of protein and genetic interactions in the LC dataset. We show that the LC dataset considerably improves the predictive power of network-analysis approaches. The full LC dataset is available at the BioGRID ( http://www.thebiogrid.org ) and SGD ( http://www.yeastgenome.org/ ) databases. Conclusion: Comprehensive datasets of biological interactions derived from the primary literature provide critical benchmarks for HTP methods, augment functional prediction, and reveal system-level attributes of biological networks.
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Y2H, APMS, and other high-throughput experimental approaches have identified many pairs of interacting proteins in yeast and other organisms, but there are discrepancies between sets generated using different methods and considerable false positive and false negative rates.
“Yeast two hybrid (Y2H), affinity-purification mass spectrometry (APMS), and other high-throughput experimental approaches have identified many pairs of interacting proteins in yeast and other organisms (1–5), but there are discrepancies between sets generated using the different methods and considerable false positive and false negative rates (6–8).”
From Computed structures of core eukaryotic protein complexes (2021) · cites this paper as [3]
47% of the gold standard PPIs were confidently predicted (AF contact probability > 0.67), with lower ratios (31% and 24%) for candidate PPIs from the literature or supported by low-throughput experiments according to BIOGRID.
“We found that 47% of the gold standard PPIs were confidently predicted, with lower ratios (31% and 24%) for candidate PPIs from the literature (http://interactome.dfci.harvard.edu/S_cerevisiae/download/LC_multiple.txt) (3) or supported by low-throughput experiments according to BIOGRID (21) (Fig. 1D).”
From Computed structures of core eukaryotic protein complexes (2021) · cites this paper as [3]
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- Authors
- Reguly, T., Breitkreutz, A., Boucher, L., Breitkreutz, B.-J., Hon, G. C., Myers, C. L., Parsons, A., Friesen, H., Oughtred, R., Tong, A., Stark, C., Ho, Y., Botstein, D., Andrews, B., Boone, C., Troyanskya, O. G., Ideker, T., Dolinski, K., Batada, N. N., & Tyers, M.
- Affiliations
- Mount Sinai Hospital (CA)
- University of California San Diego (US)
- Princeton University (US)
- University of Toronto (CA)
- Corresponding author
- Tyers, Mike
- ORCID
- Venue
- Journal of Biology
- Published
- 2006-06-08
- Volume
- 5
- Issue
- 4
- Pages
- 11-11
- ISSN
- 1475-4924 (ISSN-L)
- OpenAlex
- W2152336513
- Cited by
- 326
- References
- 115
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2022: 5 · 2021: 3 · 2020: 9 · 2019: 7 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 14 · 2014: 10 · 2013: 18 · 2012: 30
- FWCI
- 20.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Biology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- TSpace (University of Toronto) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Canada Research Chairs
- Terry Fox Foundation
- National Institutes of Health
- Canadian Institutes of Health Research
- National Cancer Institute
- 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
- Saccharomyces cerevisiae, genetic interactions, protein-protein interaction, interaction networks, literature curation, BioGRID, SGD, scale-free networks, essential genes, gene function prediction
- MeSH terms
- Saccharomyces cerevisiae, Computational Biology, Protein Interaction Mapping, Saccharomyces cerevisiae Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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