Spin models inferred from patient-derived viral sequence data faithfully describe HIV fitness landscapes
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Shekhar-2013-Spin models inferred.pdf
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Author(s)
Shekhar, Karthik
Ruberman, Claire
Ferguson, Andrew L.
Kardar, Mehran
Barton, John P.
Chakraborty, Arup K
Date Issued
December 2013
Journal
Physical Review E
Publisher
American Physical Society
Citation
Shekhar, Karthik, Claire Ruberman, Andrew Ferguson, John Barton, Mehran Kardar, and Arup Chakraborty. “Spin Models Inferred from Patient-Derived Viral Sequence Data Faithfully Describe HIV Fitness Landscapes.” Phys. Rev. E 88, no. 6 (December 2013). © 2013 American Physical Society
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Final published version
Abstract
Mutational escape from vaccine-induced immune responses has thwarted the development of a successful vaccine against AIDS, whose causative agent is HIV, a highly mutable virus. Knowing the virus' fitness as a function of its proteomic sequence can enable rational design of potent vaccines, as this information can focus vaccine-induced immune responses to target mutational vulnerabilities of the virus. Spin models have been proposed as a means to infer intrinsic fitness landscapes of HIV proteins from patient-derived viral protein sequences. These sequences are the product of nonequilibrium viral evolution driven by patient-specific immune responses and are subject to phylogenetic constraints. How can such sequence data allow inference of intrinsic fitness landscapes? We combined computer simulations and variational theory á la Feynman to show that, in most circumstances, spin models inferred from patient-derived viral sequences reflect the correct rank order of the fitness of mutant viral strains. Our findings are relevant for diverse viruses.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Physics
Ragon Institute of MGH, MIT and Harvard
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1103/PhysRevE.88.062705
