A structure-informed atlas of human-virus interactions
Open accessAbstract
While knowledge of protein-protein interactions (PPIs) is critical for understanding virus-host relationships, limitations on the scalability of high-throughput methods have hampered their identification beyond a number of well-studied viruses. Here, we implement an in silico computational framework (pathogen host interactome prediction using structure similarity [P-HIPSTer]) that employs structural information to predict ∼282,000 pan viral-human PPIs with an experimental validation rate of ∼76%. In addition to rediscovering known biology, P-HIPSTer has yielded a series of new findings: the discovery of shared and unique machinery employed across human-infecting viruses, a likely role for ZIKV-ESR1 interactions in modulating viral replication, the identification of PPIs that discriminate between human papilloma viruses (HPVs) with high and low oncogenic potential, and a structure-enabled history of evolutionary selective pressure imposed on the human proteome. Further, P-HIPSTer enables discovery of previously unappreciated cellular circuits that act on human-infecting viruses and provides insight into experimentally intractable viruses.
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Viral-human PPI data were added from P-HIPSTer to help explore PPIs between viral pathogens and human proteins.
“Given the COVID-19 pandemic, viral-human PPI data were added from P-HIPSTer (20) to help explore PPIs between viral pathogens and human proteins.”
From TCRD and pharos 2021: mining the human proteome for disease biology (2021) · cites this paper as [20]
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CRISPR/Cas9 Screens Reveal Epstein-Barr Virus-Transformed B Cell Host Dependency Factors
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Molecular Signature of HPV-Induced Carcinogenesis: pRb, p53 and Gene Expression Profiling
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Cellular factors required for papillomavirus DNA replication
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Self-citationRho GTPases Modulate Entry of Ebola Virus and Vesicular Stomatitis Virus Pseudotyped Vectors
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Nucleolin as Activator of Human Papillomavirus Type 18 Oncogene Transcription in Cervical Cancer
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Incidence of Zika Virus Disease by Age and Sex — Puerto Rico, November 1, 2015–October 20, 2016
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A computational interactome and functional annotation for the human proteome
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Molecular principles of human virus protein–protein interactions
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T Cell Immunity and Zika Virus Vaccine Development
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Flagged first, then by citations
Research works printed but not linked: 1
- Frank E, Hall MA, and Witten IH (2016). The WEKA Workbench Online Appendix for “Data Mining: Practical Machine Learning Tools and Techniques”, Fourth edn (Morgan Kaufmann).
Cited by
Sorted by citations
A critical overview of computational approaches employed for COVID-19 drug discovery
Muratov, E. N., Amaro, R., Andrade, C. H., Brown, N., Ekins, S., Fourches, D., Isayev, O., Kozakov, D., Medina-Franco, J. L., Merz, K. M., et al. (2021) · Chemical Society Reviews · doi:10.1039/d0cs01065k · Cited by 206 · see citing works
Viral Infections, the Microbiome, and Probiotics
Harper, A., Vijayakumar, V., Ouwehand, A. C., ter Haar, J., Obis, D., Espadaler, J., Binda, S., Desiraju, S., & Day, R. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.596166 · Cited by 177 · see citing works
TCRD and pharos 2021: mining the human proteome for disease biology
Sheils, T. K., Mathias, S. L., Kelleher, K. J., Siramshetty, V. B., Nguyen, D.-T., Bologa, C. G., Jensen, L. J., Vidović, D., Koleti, A., Schürer, S. C., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa993 · Cited by 160 · see citing works
LAB-Bench: Measuring Capabilities of Language Models for Biology Research
Laurent, J. M., Janizek, J. D., Ruzo, M., Hinks, M. M., Hammerling, M. J., Narayanan, S., Ponnapati, M., White, A. D., & Rodriques, S. G. (2024) · arXiv · doi:10.48550/arxiv.2407.10362 · Cited by 21 · see citing works
“Each question in this task (viral_ppi_task.json) is automatically generated using data from the P-HIPSter database [27], which is accessible as either a standalone webserver, and also has annotations collected into Enrichr gene sets [24].”
Method
- Authors
- Lasso, G., Mayer, S. V., Winkelmann, E. R., Chu, T., Elliot, O., Patino-Galindo, J. A., Park, K., Rabadan, R., Honig, B., & Shapira, S. D.
- Affiliations
- Columbia University Irving Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Honig, Barry
- Shapira, Sagi D.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 178
- Issue
- 6
- Pages
- 1526-1541.e16
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6736651
- OpenAlex
- W2970491619
- Cited by
- 133
- References
- 151
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 12 · 2023: 15 · 2022: 16 · 2021: 40 · 2020: 27 · 2019: 2
- FWCI
- 7.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- host-virus interaction, protein-protein interaction, structural similarity, interactome prediction, Zika virus, ESR1, human papillomavirus, oncogenicity, human proteome
- MeSH terms
- Zika Virus, Animals, Atlases as Topic, Chlorocebus aethiops, Computer Simulation, Humans, Vero Cells, Viral Proteins, Proteome, Protein Interaction Mapping, Host-Pathogen Interactions, HEK293 Cells, MCF-7 Cells, Datasets as Topic
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 ›
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