Learning from prepandemic data to forecast viral escape

Nicole N. Thadani, Sarah Gurev, Pascal Notin, Noor Youssef, Nathan J. Rollins, Daniel Ritter, Chris Sander, Yarin Gal and Debora S. Marks ()
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Nicole N. Thadani: Harvard Medical School
Sarah Gurev: Harvard Medical School
Pascal Notin: University of Oxford
Noor Youssef: Harvard Medical School
Nathan J. Rollins: Harvard Medical School
Daniel Ritter: Harvard Medical School
Chris Sander: Harvard Medical School
Yarin Gal: University of Oxford
Debora S. Marks: Harvard Medical School

Nature, 2023, vol. 622, issue 7984, 818-825

Abstract: Abstract Effective pandemic preparedness relies on anticipating viral mutations that are able to evade host immune responses to facilitate vaccine and therapeutic design. However, current strategies for viral evolution prediction are not available early in a pandemic—experimental approaches require host polyclonal antibodies to test against1–16, and existing computational methods draw heavily from current strain prevalence to make reliable predictions of variants of concern17–19. To address this, we developed EVEscape, a generalizable modular framework that combines fitness predictions from a deep learning model of historical sequences with biophysical and structural information. EVEscape quantifies the viral escape potential of mutations at scale and has the advantage of being applicable before surveillance sequencing, experimental scans or three-dimensional structures of antibody complexes are available. We demonstrate that EVEscape, trained on sequences available before 2020, is as accurate as high-throughput experimental scans at anticipating pandemic variation for SARS-CoV-2 and is generalizable to other viruses including influenza, HIV and understudied viruses with pandemic potential such as Lassa and Nipah. We provide continually revised escape scores for all current strains of SARS-CoV-2 and predict probable further mutations to forecast emerging strains as a tool for continuing vaccine development ( evescape.org ).

Date: 2023
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DOI: 10.1038/s41586-023-06617-0

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