Identification of drug resistance mutations in HIV from constraints on natural evolution

• Main Authors: Barton, John P. (Contributor), Kardar, Mehran (Contributor), Butler, Thomas Charles (Author), Chakraborty, Arup K (Author)
• Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science (Contributor), Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor), Massachusetts Institute of Technology. Department of Chemistry (Contributor), Massachusetts Institute of Technology. Department of Physics (Contributor), Ragon Institute of MGH, MIT and Harvard (Contributor), Butler, Thomas C. (Contributor), Chakraborty, Arup K. (Contributor)
• Format: Article
• Language: English
• Published: American Physical Society, 2016-02-22T16:14:26Z.
• Subjects: Article
• Online Access: Get fulltext

Human immunodeficiency virus (HIV) evolves with extraordinary rapidity. However, its evolution is constrained by interactions between mutations in its fitness landscape. Here we show that an Ising model describing these interactions, inferred from sequence data obtained prior to the use of antiretroviral drugs, can be used to identify clinically significant sites of resistance mutations. Successful predictions of the resistance sites indicate progress in the development of successful models of real viral evolution at the single residue level and suggest that our approach may be applied to help design new therapies that are less prone to failure even where resistance data are not yet available.
Ragon Institute of MGH, MIT and Harvard
National Science Foundation (U.S.) (Grant PHY11-25915)
National Science Foundation (U.S.) (Grant DMR-12-06323)