title: Identification of drug resistance mutations in HIV from constraints on natural evolution.
abstract: 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.
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Butler
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.|Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02139, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Barton
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Mehran
authors.initials: M
authors.lastname: Kardar
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.|Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02139, USA.|Departments of Chemistry and Biological Engineering, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Arup K
authors.initials: AK
authors.lastname: Chakraborty
mesh_terms: D004347:Drug Interactions; D024882:Drug Resistance, Viral / Q000235:genetics*; D019143:Evolution, Molecular; D006678:HIV / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D006801:Humans; D009154:Mutation
chemical_list: D017320:HIV Protease Inhibitors; D016333:HIV Protease