State of the interactomes: an evaluation of molecular networks for generating biological insights
Open accessPublished version of a preprint
Abstract
Advancements in genomic and proteomic technologies have powered the creation of large gene and protein networks (“interactomes”) for understanding biological systems. However, the proliferation of interactomes complicates the selection of networks for specific applications. Here, we present a comprehensive evaluation of 45 current human interactomes, encompassing protein-protein interactions as well as gene regulatory, signaling, colocalization, and genetic interaction networks. Our analysis shows that large composite networks such as HumanNet, STRING, and FunCoup are most effective for identifying disease genes, while smaller networks such as DIP, Reactome, and SIGNOR demonstrate stronger performance in interaction prediction. Our study provides a benchmark for interactomes across diverse biological applications and clarifies factors that influence network performance. Furthermore, our evaluation pipeline paves the way for continued assessment of emerging and updated interaction networks in the future.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
ColabFold - Making protein folding accessible to all
Mirdita, M., Schütze, K., Moriwaki, Y., Heo, L., Ovchinnikov, S., & Steinegger, M. (2021) · doi:10.1101/2021.08.15.456425 · Cited by 9,391 · see citing works
UniProt: the Universal Protein Knowledgebase in 2023
The UniProt Consortium, Bateman, A., Martin, M.-J., Orchard, S., Magrane, M., Ahmad, S., Alpi, E., Bowler-Barnett, E. H., Britto, R., Bye-A-Jee, H., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkac1052 · Cited by 7,210 · see citing works
Protein complex prediction with AlphaFold-Multimer
Evans, R., O’Neill, M., Pritzel, A., Antropova, N., Senior, A., Green, T., Žídek, A., Bates, R., Blackwell, S., Yim, J., et al. (2021) · doi:10.1101/2021.10.04.463034 · Cited by 3,808 · see citing works
ConsensusPathDB--a database for integrating human functional interaction networks
Kamburov, A., Wierling, C., Lehrach, H., & Herwig, R. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn698 · Cited by 565 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Analysis of intracellular and intercellular crosstalk from omics data
Chiodi, A., Pelucchi, P., & Mosca, E. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.10.552776
- Authors
- Wright, S. N., Colton, S., Schaffer, L. V., Pillich, R. T., Churas, C., Pratt, D., & Ideker, T.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Ideker, Trey
- ORCID
- Venue
- Molecular Systems Biology
- Published
- 2024-12-09
- Volume
- 21
- Issue
- 1
- Pages
- 1-29
- ISSN
- 1744-4292 (ISSN-L)
- PMC
- PMC11697402
- OpenAlex
- W4405173687
- Cited by
- 32
- References
- 5
- Citations by year
- 2026: 16 · 2025: 11 · 2024: 5
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Molecular Systems Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- PubMed Central (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- HHS | NIH | National Human Genome Research Institute (U24 HG012107)
- HHS | NIH | National Cancer Institute (U24 CA269436)
- HHS | NIH | National Institute of General Medical Sciences (P41 GM103504)
- HHS | NIH | National Institute on Drug Abuse (P50 DA037844)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- protein-protein interaction network, gene regulatory networks, signaling networks, genetic interaction networks, interaction prediction, disease gene identification, network benchmarking, strings, Reactome, DIP
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
