Identification of drug resistance mutations in HIV from constraints on natural evolution
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 antiretro...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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American Physical Society
2016
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| Online Access: | http://hdl.handle.net/1721.1/101231 https://orcid.org/0000-0003-1467-421X https://orcid.org/0000-0003-1268-9602 https://orcid.org/0000-0002-1112-5912 |
| _version_ | 1826193978150617088 |
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| author | Barton, John P. Kardar, Mehran Butler, Thomas Charles Chakraborty, Arup K |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Barton, John P. Kardar, Mehran Butler, Thomas Charles Chakraborty, Arup K |
| author_sort | Barton, John P. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:48:39Z |
| format | Article |
| id | mit-1721.1/101231 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:48:39Z |
| publishDate | 2016 |
| publisher | American Physical Society |
| record_format | dspace |
| spelling | mit-1721.1/1012312022-09-26T13:52:40Z Identification of drug resistance mutations in HIV from constraints on natural evolution Barton, John P. Kardar, Mehran Butler, Thomas Charles Chakraborty, Arup K 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 Chemistry Massachusetts Institute of Technology. Department of Physics Ragon Institute of MGH, MIT and Harvard Butler, Thomas C. Barton, John P. Kardar, Mehran Chakraborty, Arup K. 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) 2016-02-22T16:14:26Z 2016-02-22T16:14:26Z 2016-02 2015-12 2016-02-19T23:00:03Z Article http://purl.org/eprint/type/JournalArticle 2470-0045 2470-0053 http://hdl.handle.net/1721.1/101231 Butler, Thomas C., John P. Barton, Mehran Kardar, and Arup K. Chakraborty. “Identification of Drug Resistance Mutations in HIV from Constraints on Natural Evolution.” Phys. Rev. E 93, no. 2 (February 19, 2016). © 2016 American Physical Society https://orcid.org/0000-0003-1467-421X https://orcid.org/0000-0003-1268-9602 https://orcid.org/0000-0002-1112-5912 en http://dx.doi.org/10.1103/PhysRevE.93.022412 Physical Review E 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. American Physical Society application/pdf American Physical Society American Physical Society |
| spellingShingle | Barton, John P. Kardar, Mehran Butler, Thomas Charles Chakraborty, Arup K Identification of drug resistance mutations in HIV from constraints on natural evolution |
| title | Identification of drug resistance mutations in HIV from constraints on natural evolution |
| title_full | Identification of drug resistance mutations in HIV from constraints on natural evolution |
| title_fullStr | Identification of drug resistance mutations in HIV from constraints on natural evolution |
| title_full_unstemmed | Identification of drug resistance mutations in HIV from constraints on natural evolution |
| title_short | Identification of drug resistance mutations in HIV from constraints on natural evolution |
| title_sort | identification of drug resistance mutations in hiv from constraints on natural evolution |
| url | http://hdl.handle.net/1721.1/101231 https://orcid.org/0000-0003-1467-421X https://orcid.org/0000-0003-1268-9602 https://orcid.org/0000-0002-1112-5912 |
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