Protein interactions: is seeing believing?
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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 [8]
The ratio of confidently predicted PPIs is even lower for protein pairs identified by Y2H (18%) or APMS (14%) screens, consistent with the known larger fraction of false positives in large-scale experimental screens.
“The ratio of confidently predicted PPIs is even lower for protein pairs identified by Y2H (18%) or APMS (14%) screens (table S1), consistent with the known larger fraction of false positives in large-scale experimental screens (8,22).”
From Computed structures of core eukaryotic protein complexes (2021) · cites this paper as [8]
Cites
Lai, J. S., & Herr, W. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.15.6958 · Cited by 451 · see citing works
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Nyborg, J. K., & Peersen, O. B. (2004) · Biochemical Journal · doi:10.1042/bj20041096 · Cited by 99 · see citing works
The CBP/p300 TAZ1 domain in its native state is not a binding partner of MDM2
Dunzendorfer-Matt, T., Martinez‐Yamout, M. A., Dyson, H. J., & Wright, P. E. (2004) · Biochemical Journal · doi:10.1042/bj20040564 · Cited by 42 · see citing works
Riley, L. G., Ralston, G. B., & Weiss, A. S. (1996) · Protein Engineering Design and Selection · doi:10.1093/protein/9.2.223 · Cited by 29 · see citing works
Fletcher, S., Bowden, S. E. H., & Marrion, N. V. (2003) · Neuropharmacology · doi:10.1016/s0028-3908(03)00049-2 · Cited by 25 · see citing works
Lee, B. M., Buck‐Koehntop, B. A., Martinez‐Yamout, M. A., Dyson, H. J., & Wright, P. E. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.06.021 · Cited by 24 · see citing works
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Computed structures of core eukaryotic protein complexes
Humphreys, I. R., Pei, J., Baek, M., Krishnakumar, A., Anishchenko, I., Ovchinnikov, S., Zhang, J., Ness, T. J., Banjade, S., Bagde, S. R., et al. (2021) · Science · doi:10.1126/science.abm4805 · Cited by 542 · see citing works
Computed cancer interactome explains the effects of somatic mutations in cancers
Zhang, J., Pei, J., Durham, J., Bos, T., & Cong, Q. (2022) · Protein Science · doi:10.1002/pro.4479 · Cited by 31 · see citing works
Structural assembly of the bacterial essential interactome
Gómez Borrego, J., & Torrent Burgas, M. (2024) · eLife · doi:10.7554/elife.94919 · Cited by 16 · see citing works
Milestone Review: Unlocking the Proteomics of Glycine Receptor Complexes
Fraser, S. D., Klaassen, R. V., Villmann, C., Smit, A. B., & Harvey, R. J. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70061 · Cited by 10 · see citing works
“Additionally, true direct interactors can fail to be affinity purified due to factors such as improper folding or lack of post-translational modification of bait proteins (Mackay et al. 2007).”
- Authors
- MACKAY, J., SUNDE, M., LOWRY, J., CROSSLEY, M., & MATTHEWS, J.
- Affiliations
- The University of Sydney (AU)
- Corresponding author
- MACKAY, J
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 32
- Issue
- 12
- Pages
- 530-531
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W2021799858
- Cited by
- 100
- References
- 7
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 17 · 2016: 4 · 2015: 6 · 2014: 7 · 2013: 7 · 2012: 4
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biomedical Text Mining and Ontologies
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- protein-protein interaction, protein interaction maps, bioinformatics
- MeSH terms
- Calorimetry, Protein Binding, Proteins, Nuclear Magnetic Resonance, Biomolecular
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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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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