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A Structure Informed Atlas of Pan-Viral Interactions Reveals Features of Human Infection

37 Pages Posted: 5 Mar 2019 Sneak Peek Status: Published

See all articles by Gorka Lasso

Gorka Lasso

Columbia University - Department of Systems Biology; Columbia University - Department of Microbiology and Immunology

Sandra V. Mayer

Columbia University - Department of Systems Biology; Columbia University - Department of Microbiology and Immunology

Evandro R. Winkelmann

Columbia University - Department of Systems Biology; Columbia University - Department of Microbiology and Immunology

Tim Chu

Columbia University - Department of Systems Biology

Oliver Elliot

Columbia University - Department of Systems Biology

Juan Angel Patino-Galindo

Columbia University - Department of Systems Biology

Kernyu Park

Columbia University - Department of Biomedical Informatics

Raul Rabadan

Columbia University - Department of Systems Biology; Columbia University - Department of Biomedical Informatics

Barry Honig

Columbia University - Department of Systems Biology

Sagi Shapira

Columbia University - Department of Systems Biology; Columbia University - Department of Microbiology and Immunology

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Abstract

While knowledge of protein-protein interactions 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 (termed P-HIPSTer; (Pathogen Host Interactome Prediction using STructurE similaRity) that employs structural information to predict pan viral-human protein-protein interactions. We generate ~280,000 high confidence predictions with an experimental validation rate of ~76%. The resulting inventory identifies specific interactions that play a role in ZIKV and HPV infection and generates novel hypotheses that were functionally interrogated. We demonstrate that P-HIPSTer rediscovers known biology, identifies key regulatory networks mediating virus-human dynamics and reveals novel insights into shared and unique machinery employed across the human virome. Finally, P-HIPSTer reveals a history of evolutionary selective pressure imposed on the human proteome, recapitulating what is known while providing unique insights made possible by the large-scale structure-based P-HIPSTer database

Suggested Citation

Lasso, Gorka and Mayer, Sandra V. and Winkelmann, Evandro R. and Chu, Tim and Elliot, Oliver and Patino-Galindo, Juan Angel and Park, Kernyu and Rabadan, Raul and Honig, Barry and Shapira, Sagi, A Structure Informed Atlas of Pan-Viral Interactions Reveals Features of Human Infection (March 5, 2019). Available at SSRN: https://ssrn.com/abstract=3346979 or http://dx.doi.org/10.2139/ssrn.3346979
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Gorka Lasso

Columbia University - Department of Systems Biology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Columbia University - Department of Microbiology and Immunology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Sandra V. Mayer

Columbia University - Department of Systems Biology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Columbia University - Department of Microbiology and Immunology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Evandro R. Winkelmann

Columbia University - Department of Systems Biology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Columbia University - Department of Microbiology and Immunology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Tim Chu

Columbia University - Department of Systems Biology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Oliver Elliot

Columbia University - Department of Systems Biology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Juan Angel Patino-Galindo

Columbia University - Department of Systems Biology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Kernyu Park

Columbia University - Department of Biomedical Informatics

3022 Broadway
New York, NY 10027
United States

Raul Rabadan

Columbia University - Department of Systems Biology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Columbia University - Department of Biomedical Informatics

3022 Broadway
New York, NY 10027
United States

Barry Honig

Columbia University - Department of Systems Biology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Sagi Shapira (Contact Author)

Columbia University - Department of Systems Biology ( email )

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Columbia University - Department of Microbiology and Immunology ( email )

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

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