{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T11:48:07Z","timestamp":1759664887222},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1490,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Due to the high mutation rate of human immunodeficiency virus (HIV), drug-resistant-variants emerge frequently. Therefore, researchers are constantly searching for new ways to attack the virus. One new class of anti-HIV drugs is the class of coreceptor antagonists that block cell entry by occupying a coreceptor on CD4 cells. This type of drug just has an effect on the subset of HIVs that use the inhibited coreceptor. A good prediction of whether the viral population inside a patient is susceptible to the treatment is hence very important for therapy decisions and pre-requisite to administering the respective drug. The first prediction models were based on data from Sanger sequencing of the V3 loop of HIV. Recently, a method based on next-generation sequencing (NGS) data was introduced that predicts labels for each read separately and decides on the patient label through a percentage threshold for the resistant viral minority.<\/jats:p>\n               <jats:p>Results: We model the prediction problem on the patient level taking the information of all reads from NGS data jointly into account. This enables us to improve prediction performance for NGS data, but we can also use the trained model to improve predictions based on Sanger sequencing data. Therefore, also laboratories without NGS capabilities can benefit from the improvements. Furthermore, we show which amino acids at which position are important for prediction success, giving clues on how the interaction mechanism between the V3 loop and the particular coreceptors might be influenced.<\/jats:p>\n               <jats:p>Availability: A webserver is available at http:\/\/coreceptor.bioinf.mpi-inf.mpg.de.<\/jats:p>\n               <jats:p>Contact: \u00a0nico.pfeifer@mpi-inf.mpg.de<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts373","type":"journal-article","created":{"date-parts":[[2012,9,7]],"date-time":"2012-09-07T20:35:22Z","timestamp":1347050122000},"page":"i589-i595","source":"Crossref","is-referenced-by-count":20,"title":["Improving HIV coreceptor usage prediction in the clinic using hints from next-generation sequencing data"],"prefix":"10.1093","volume":"28","author":[{"given":"Nico","family":"Pfeifer","sequence":"first","affiliation":[{"name":"Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Campus E1 4, 66123 Saarbr\u00fccken, Germany"}]},{"given":"Thomas","family":"Lengauer","sequence":"additional","affiliation":[{"name":"Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Campus E1 4, 66123 Saarbr\u00fccken, Germany"}]}],"member":"286","published-online":{"date-parts":[[2012,9,3]]},"reference":[{"key":"2023012513060471800_B1","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1126\/science.6189183","article-title":"Isolation of a t-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (aids)","volume":"220","author":"Barr-Sinoussi","year":"1983","journal-title":"Science"},{"key":"2023012513060471800_B2","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1089\/aid.1996.12.1401","article-title":"Covariability of V3 loop amino acids","volume":"12","author":"Bickel","year":"1996","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"2023012513060471800_B3","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/BF00994018","article-title":"Support-vector networks","volume":"20","author":"Cortes","year":"1995","journal-title":"Mach. Learn."},{"key":"2023012513060471800_B4","doi-asserted-by":"crossref","first-page":"e1000743","DOI":"10.1371\/journal.pcbi.1000743","article-title":"Prediction of coreceptor usage of HIV-1 from genotype","volume":"6","author":"Dybowski","year":"2010","journal-title":"PLoS Comput. Biol."},{"key":"2023012513060471800_B5","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"Edgar","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2023012513060471800_B6","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1056\/NEJMoa0803154","article-title":"Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection","volume":"359","author":"F\u00e4tkenheuer","year":"2008","journal-title":"New Engl. J. Med."},{"key":"2023012513060471800_B7","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1089\/aid.2008.0174","article-title":"Development of a panel of well-characterized human immunodeficiency virus type 1 isolates from newly diagnosed patients including acute and recent infections","volume":"25","author":"Fern\u00e1ndez-Garc\u00eda","year":"2009","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"2023012513060471800_B8","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1126\/science.6200936","article-title":"Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS","volume":"224","author":"Gallo","year":"1984","journal-title":"Science"},{"key":"2023012513060471800_B9","first-page":"179","article-title":"Multi-instance kernels","volume-title":"Proceedings 19th International Conference on Machine Learning","author":"G\u00e4rtner","year":"2002"},{"key":"2023012513060471800_B10","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1056\/NEJMoa0803152","article-title":"Maraviroc for Previously Treated Patients with R5 HIV-1 Infection","volume":"359","author":"Gulick","year":"2008","journal-title":"New Engl. J. Med."},{"key":"2023012513060471800_B11","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1186\/1471-2105-11-531","article-title":"BALL-biochemical algorithms library 1.3","volume":"11","author":"Hildebrandt","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2023012513060471800_B12","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1126\/science.1145373","article-title":"Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4","volume":"317","author":"Huang","year":"2007","journal-title":"Science"},{"key":"2023012513060471800_B13","doi-asserted-by":"crossref","first-page":"13376","DOI":"10.1128\/JVI.77.24.13376-13388.2003","article-title":"Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env V3 loop sequences","volume":"77","author":"Jensen","year":"2003","journal-title":"J. Virol."},{"key":"2023012513060471800_B14","doi-asserted-by":"crossref","first-page":"7176","DOI":"10.1073\/pnas.90.15.7176","article-title":"Covariation of mutations in the V3 loop of human immunodeficiency virus type 1 envelope protein: an information theoretic analysis","volume":"90","author":"Korber","year":"1993","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012513060471800_B15","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/nbt1371","article-title":"Bioinformatics prediction of hiv coreceptor usage","volume":"25","author":"Lengauer","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"2023012513060471800_B16","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/sj.emboj.7600947","article-title":"HIV and the chemokine system: 10 years later","volume":"25","author":"Lusso","year":"2006","journal-title":"EMBO J."},{"key":"2023012513060471800_B17","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1086\/589289","article-title":"Reviews of anti-infective agents: maraviroc: the first of a new class of antiretroviral agents","volume":"47","author":"MacArthur","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"2023012513060471800_B18","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/1471-2105-5-169","article-title":"Oligo kernels for datamining on biological sequences: a case study on prokaryotic translation initiation sites","volume":"5","author":"Meinicke","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"2023012513060471800_B19","doi-asserted-by":"crossref","first-page":"7096","DOI":"10.1073\/pnas.82.20.7096","article-title":"3\u2032-azido-3\u2032-deoxythymidine (bw a509u): an antiviral agent that inhibits the infectivity and cytopathic effect of human t-lymphotropic virus type iii\/lymphadenopathy-associated virus in vitro","volume":"82","author":"Mitsuya","year":"1985","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012513060471800_B20","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1080\/14786440109462720","article-title":"On lines and planes of closest fit to systems of points in space","volume":"2","author":"Pearson","year":"1901","journal-title":"Philos. Mag."},{"key":"2023012513060471800_B21","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/ng1847","article-title":"Principal components analysis corrects for stratification in genome-wide association studies","volume":"38","author":"Price","year":"2006","journal-title":"Nat. Genet."},{"key":"2023012513060471800_B22","article-title":"An enhanced version of the Trofile HIV coreceptor tropism assay predicts emergence of CXCR4 use in ACTG5211 vicriviroc trial samples","volume-title":"15th CROI [abstract 869]","author":"Reeves","year":"2008"},{"key":"2023012513060471800_B23","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/COH.0b013e328322f973","article-title":"Current tests to evaluate hiv-1 coreceptor tropism","volume":"4","author":"Rose","year":"2009","journal-title":"Curr. Opin. HIV AIDS"},{"key":"2023012513060471800_B24","doi-asserted-by":"crossref","first-page":"e58","DOI":"10.1371\/journal.pcbi.0030058","article-title":"Structural descriptors of gp120 v3 loop for the prediction of hiv-1 coreceptor usage","volume":"3","author":"Sander","year":"2007","journal-title":"PLoS Comput. Biol."},{"key":"2023012513060471800_B25","volume-title":"Learning with Kernels: Support Vector Machines, Regularization, Optimization, and Beyond","author":"Sch\u00f6lkopf","year":"2001"},{"key":"2023012513060471800_B26","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1177\/135965350701200709","article-title":"Predicting HIV coreceptor usage on the basis of genetic and clinical covariates","volume":"12","author":"Sing","year":"2007","journal-title":"Antivir. Ther."},{"key":"2023012513060471800_B27","doi-asserted-by":"crossref","first-page":"i6","DOI":"10.1093\/bioinformatics\/btn170","article-title":"POIMs: positional oligomer importance matrices\u2013understanding support vector machine-based signal detectors","volume":"24","author":"Sonnenburg","year":"2008","journal-title":"Bioinformatics"},{"key":"2023012513060471800_B28","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1093\/infdis\/jiq030","article-title":"Deep sequencing to infer HIV-1 coreceptor usage: application to three clinical trials of maraviroc in treatment-experienced patients","volume":"203","author":"Swenson","year":"2011","journal-title":"J. Infect. Dis."},{"key":"2023012513060471800_B29","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s00894-001-0058-5","article-title":"New quantitative descriptors of amino acids based on multidimensional scaling of a large number of physical-chemical properties","volume":"7","author":"Venkatarajan","year":"2001","journal-title":"J. Mol. Model."},{"key":"2023012513060471800_B30","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1128\/AAC.00853-06","article-title":"Development and characterization of a novel single-cycle recombinant-virus assay to determine human immunodeficiency virus type 1 coreceptor tropism","volume":"51","author":"Whitcomb","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"2023012513060471800_B31","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/1471-2105-12-119","article-title":"ShoRAH: estimating the genetic diversity of a mixed sample from next-generation sequencing data","volume":"12","author":"Zagordi","year":"2011","journal-title":"BMC Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/18\/i589\/48879426\/bioinformatics_28_18_i589.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/18\/i589\/48879426\/bioinformatics_28_18_i589.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T18:58:36Z","timestamp":1674673116000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/28\/18\/i589\/244384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,3]]},"references-count":31,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2012,9,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bts373","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2012,9,15]]},"published":{"date-parts":[[2012,9,3]]}}}