{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T03:58:38Z","timestamp":1772078318046,"version":"3.50.1"},"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T00:00:00Z","timestamp":1414627200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1003878","type":"journal-article","created":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T17:58:49Z","timestamp":1414691929000},"page":"e1003878","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":32,"title":["The Route of HIV Escape from Immune Response Targeting Multiple Sites Is Determined by the Cost-Benefit Tradeoff of Escape Mutations"],"prefix":"10.1371","volume":"10","author":[{"given":"Rebecca","family":"Batorsky","sequence":"first","affiliation":[]},{"given":"Rinat A.","family":"Sergeev","sequence":"additional","affiliation":[]},{"given":"Igor M.","family":"Rouzine","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2014,10,30]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1126\/science.283.5403.857","article-title":"Control of Viremia in Simian Immunodeficiency Virus Infection by CD8+ Lymphocytes","volume":"283","author":"JE Schmitz","year":"1999","journal-title":"Science"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1084\/jem.189.6.991","article-title":"Dramatic rise in plasma viremia after CD8+ T cell depletion in simian immunodeficiency virus\u2013infected macaques","volume":"189","author":"X Jin","year":"1999","journal-title":"The Journal of experimental medicine"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.cell.2006.01.034","article-title":"Anti-Immunology: Evasion of the Host Immune System by Bacterial and Viral Pathogens","volume":"124","author":"BB Finlay","year":"2006","journal-title":"Cell"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"10758","DOI":"10.1073\/pnas.96.19.10758","article-title":"Linkage disequilibrium test implies a large effective population number for HIV in vivo","volume":"96","author":"IM Rouzine","year":"1999","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"7131","DOI":"10.4049\/jimmunol.0803658","article-title":"Kinetics of Expansion of Epitope-Specific T Cell Responses during Primary HIV-1 Infection","volume":"182","author":"EL Turnbull","year":"2009","journal-title":"The Journal of Immunology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"e225","DOI":"10.1371\/journal.pone.0000225","article-title":"Sequential broadening of CTL responses in early HIV-1 infection is associated with viral escape","volume":"2","author":"AC Karlsson","year":"2007","journal-title":"PLoS ONE"},{"key":"ref7","first-page":"380","article-title":"Vertical T cell immunodominance and epitope entropy determine HIV-1 escape","volume":"123","author":"MKP Liu","year":"2012","journal-title":"J Clin Invest"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1084\/jem.20041455","article-title":"Transmission and accumulation of ctl escape variants drive negative associations between hiv polymorphisms and hla","volume":"201","author":"A Leslie","year":"2005","journal-title":"Journal of Experimental Medicine"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nm998","article-title":"Reversion of ctl escape\u2013variant immunodeficiency viruses in vivo","volume":"10","author":"TC Friedrich","year":"2004","journal-title":"Nat Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"e1000365","DOI":"10.1371\/journal.ppat.1000365","article-title":"Variable Fitness Impact of HIV-1 Escape Mutations to Cytotoxic T Lymphocyte (CTL) Response","volume":"5","author":"RM Troyer","year":"2009","journal-title":"PLoS Pathogens"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"e15639","DOI":"10.1371\/journal.pone.0015639","article-title":"Dynamics of viral evolution and ctl responses in hiv-1 infection","volume":"6","author":"Y Liu","year":"2011","journal-title":"PLoS ONE"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"10518","DOI":"10.1128\/JVI.00655-11","article-title":"Fitness Costs and Diversity of the Cytotoxic T Lymphocyte (CTL) Response Determine the Rate of CTL Escape during Acute and Chronic Phases of HIV Infection","volume":"85","author":"VV Ganusov","year":"2011","journal-title":"Journal of Virology"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e1002529","DOI":"10.1371\/journal.ppat.1002529","article-title":"Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection","volume":"8","author":"MR Henn","year":"2012","journal-title":"PLoS Pathogens"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"e1000103","DOI":"10.1371\/journal.pcbi.1000103","article-title":"Dynamics of immune escape during hiv\/siv infection","volume":"4","author":"CL Althaus","year":"2008","journal-title":"PLoS Computational Biology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"e16052","DOI":"10.1371\/journal.pone.0016052","article-title":"The Role of Recombination for the Coevolutionary Dynamics of HIV and the Immune Response","volume":"6","author":"R Mostowy","year":"2011","journal-title":"PLoS ONE"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.4049\/jimmunol.1300962","article-title":"The Rate of Immune Escape Vanishes When Multiple Immune Responses Control a HIV Infection","volume":"191","author":"HWM van Deutekom","year":"2013","journal-title":"J Immunol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1128\/JVI.01960-08","article-title":"Human Immunodeficiency Virus Type 1 Population Genetics and Adaptation in Newly Infected Individuals","volume":"83","author":"M Kearney","year":"2009","journal-title":"Journal of Virology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"e1001196","DOI":"10.1371\/journal.ppat.1001196","article-title":"Modelling the evolution and spread of HIV immune escape mutants","volume":"6","author":"HR Fryer","year":"2010","journal-title":"PLoS Pathogens"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1084\/jem.193.3.375","article-title":"Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses","volume":"193","author":"AD Kelleher","year":"2001","journal-title":"The Journal of experimental medicine"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1128\/JVI.01879-10","article-title":"The Hypervariable HIV-1 Capsid Protein Residues Comprise HLA-Driven CD8+ T-Cell Escape Mutations and Covarying HLA-Independent Polymorphisms","volume":"85","author":"H Crawford","year":"2011","journal-title":"Journal of Virology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-4690-9-89","article-title":"Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted\/founder genome","volume":"9","author":"H Song","year":"2012","journal-title":"Retrovirology"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"3952","DOI":"10.1128\/JVI.03233-12","article-title":"Frequent and variable cytotoxic-T-lymphocyte escape-associated fitness costs in the human immunodeficiency virus type 1 subtype B Gag proteins","volume":"87","author":"CL Boutwell","year":"2013","journal-title":"Journal of Virology"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"e15639","DOI":"10.1371\/journal.pone.0015639","article-title":"Dynamics of Viral Evolution and CTL Responses in HIV-1 Infection","volume":"6","author":"Y Liu","year":"2011","journal-title":"PLoS ONE"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"3746","DOI":"10.1128\/JVI.02420-10","article-title":"Epitope-specific cd8+ t lymphocytes cross-recognize mutant simian immunodeficiency virus (siv) sequences but fail to contain very early evolution and eventual fixation of epitope escape mutations during siv infection","volume":"85","author":"EM Cale","year":"2011","journal-title":"Journal of Virology"},{"key":"ref25","unstructured":"Ganusov VV, De Boer RJ (2005) Estimating Costs and Benefits of CTL Escape Mutations in SIV\/HIV Infection. PLoS Computational Biology preprint: e24."},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e1002525","DOI":"10.1371\/journal.pcbi.1002525","article-title":"Estimating the fitness cost of escape from HLA presentation in HIV-1 protease and reverse transcriptase","volume":"8","author":"R Mostowy","year":"2012","journal-title":"PLoS Computational Biology"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"5594","DOI":"10.1128\/JVI.02356-07","article-title":"Structural and functional constraints limit options for cytotoxic T-lymphocyte escape in the immunodominant HLA-B27-restricted epitope in human immunodeficiency virus type 1 capsid","volume":"82","author":"A Schneidewind","year":"2008","journal-title":"Journal of Virology"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/nature07746","article-title":"Adaptation of HIV-1 to human leukocyte antigen class I","volume":"458","author":"Y Kawashima","year":"2009","journal-title":"Nature"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"12643","DOI":"10.1128\/JVI.01381-12","article-title":"Differential Clade-Specific HLA-B*3501 Association with HIV-1 Disease Outcome Is Linked to Immunogenicity of a Single Gag Epitope","volume":"86","author":"PC Matthews","year":"2012","journal-title":"Journal of Virology"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1084\/jem.20090365","article-title":"The first t cell response to transmitted\/founder virus contributes to the control of acute viremia in hiv-1 infection","volume":"206","author":"N Goonetilleke","year":"2009","journal-title":"Journal of Experimental Medicine"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e12303","DOI":"10.1371\/journal.pone.0012303","article-title":"Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape Revealed by Ultra-Deep Sequencing","volume":"5","author":"W Fischer","year":"2010","journal-title":"PLoS ONE"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"P01009","DOI":"10.1088\/1742-5468\/2013\/01\/P01009","article-title":"The quantitative theory of within-host viral evolution","volume":"2013","author":"IM Rouzine","year":"2013","journal-title":"Journal of Statistical Mechanics: Theory and Experiment"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"7131","DOI":"10.4049\/jimmunol.0803658","article-title":"Kinetics of expansion of epitope-specific t cell responses during primary hiv-1 infection","volume":"182","author":"EL Turnbull","year":"2009","journal-title":"The Journal of Immunology"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.tim.2006.10.001","article-title":"Stochastic or deterministic: what is the effective population size of HIV-1?","volume":"14","author":"RD Kouyos","year":"2006","journal-title":"Trends in microbiology"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Pennings P, Kryazhimskiy S, Wakeley J (2014) PLOS Genetics: Loss and Recovery of Genetic Diversity in Adapting Populations of HIV. PLoS Genetics.","DOI":"10.1371\/journal.pgen.1004000"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1128\/JVI.68.3.1660-1666.1994","article-title":"Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy","volume":"68","author":"DD Richman","year":"1994","journal-title":"Journal of Virology"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.virol.2005.11.036","article-title":"Waiting times for the appearance of cytotoxic T-lymphocyte escape mutants in chronic HIV-1 infection","volume":"347","author":"Y Liu","year":"2006","journal-title":"Virology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S1368-7646(02)00123-1","article-title":"Fitness of drug resistant HIV-1: methodology and clinical implications","volume":"5","author":"ME Qui\u00f1ones-Mateu","year":"2002","journal-title":"Drug Resistance Updates"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1126\/science.1101786","article-title":"Evidence for Positive Epistasis in HIV-1","volume":"306","author":"S Bonhoeffer","year":"2004","journal-title":"Science"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/ng.795","article-title":"A systems analysis of mutational effects in HIV-1 protease and reverse transcriptase","volume":"43","author":"T Hinkley","year":"2011","journal-title":"Nature Genetics"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1093\/molbev\/msp289","article-title":"Phylogenetic Analysis of Population-Based and Deep Sequencing Data to Identify Coevolving Sites in the nef Gene of HIV-1","volume":"27","author":"AFY Poon","year":"2010","journal-title":"Molecular Biology and Evolution"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"8167","DOI":"10.1128\/JVI.73.10.8167-8178.1999","article-title":"Search for the mechanism of genetic variation in the pro gene of human immunodeficiency virus","volume":"73","author":"IM Rouzine","year":"1999","journal-title":"Journal of Virology"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"e1000981","DOI":"10.1371\/journal.pcbi.1000981","article-title":"Quantifying the Impact of Human Immunodeficiency Virus-1 Escape From Cytotoxic T-Lymphocytes","volume":"6","author":"UD Kadolsky","year":"2010","journal-title":"PLoS Computational Biology"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1146\/annurev-med-080709-124959","article-title":"Early Events in Sexual Transmission of HIV and SIV and Opportunities for Interventions","volume":"62","author":"AT Haase","year":"2011","journal-title":"Annual review of medicine"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1126\/science.279.5359.2103","article-title":"Quantitation of HIV-1-Specific Cytotoxic T Lymphocytes and Plasma Load of Viral RNA","volume":"279","author":"GS Ogg","year":"1998","journal-title":"Science"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"5127","DOI":"10.4049\/jimmunol.162.9.5127","article-title":"Emergence of CTL coincides with clearance of virus during primary simian immunodeficiency virus infection in rhesus monkeys","volume":"162","author":"MJ Kuroda","year":"1999","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jtbi.2009.11.003","article-title":"Model with two types of CTL regulation and experiments on CTL dynamics","volume":"263","author":"RA Sergeev","year":"2010","journal-title":"Journal of Theoretical Biology"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"5661","DOI":"10.1073\/pnas.1102036108","article-title":"Estimate of effective recombination rate and average selection coefficient for HIV in chronic infection","volume":"108","author":"R Batorsky","year":"2011","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1534\/genetics.109.109009","article-title":"Rate of Adaptation in Large Sexual Populations","volume":"184","author":"RA Neher","year":"2010","journal-title":"Genetics"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"e1003534","DOI":"10.1371\/journal.pcbi.1003534","article-title":"Rates of CTL Killing in Persistent Viral Infection In Vivo","volume":"10","author":"M Elemans","year":"2014","journal-title":"PLoS Computational Biology"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"e1003656","DOI":"10.1371\/journal.ppat.1003656","article-title":"Can non-lytic CD8+ T cells drive HIV-1 escape?","volume":"9","author":"NK Seich Al Basatena","year":"2013","journal-title":"PLoS Pathogens"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/373123a0","article-title":"Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection","volume":"373","author":"D Ho","year":"1995","journal-title":"Nature"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1126\/science.271.5255.1582","article-title":"Hiv-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time","volume":"271","author":"A Perelson","year":"1996","journal-title":"Science"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"5037","DOI":"10.1128\/JVI.77.8.5037-5038.2003","article-title":"A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo","volume":"77","author":"M Markowitz","year":"2003","journal-title":"Journal of Virology"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"e1000747","DOI":"10.1371\/journal.ppat.1000747","article-title":"CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells","volume":"6","author":"NR Klatt","year":"2010","journal-title":"PLoS Pathogens"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"e1000748","DOI":"10.1371\/journal.ppat.1000748","article-title":"In Vivo CD8+ T-Cell Suppression of SIV Viremia Is Not Mediated by CTL Clearance of Productively Infected Cells","volume":"6","author":"JK Wong","year":"2010","journal-title":"PLoS Pathogens"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"15323","DOI":"10.1073\/pnas.93.26.15323","article-title":"Cytotoxic T lymphocytes and viral turnover in HIV type 1 infection","volume":"93","author":"P Klenerman","year":"1996","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1073\/pnas.0510016103","article-title":"Two types of cytotoxic lymphocyte regulation explain kinetics of immune response to human immunodeficiency virus","volume":"103","author":"IM Rouzine","year":"2006","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"4832","DOI":"10.1073\/pnas.0711372105","article-title":"Decay dynamics of HIV-1 depend on the inhibited stages of the viral life cycle","volume":"105","author":"AR Sedaghat","year":"2008","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"e16468","DOI":"10.1371\/journal.pone.0016468","article-title":"Implications of CTL-Mediated Killing of HIV-Infected Cells during the Non-Productive Stage of Infection","volume":"6","author":"C Althaus","year":"2011","journal-title":"PLoS ONE"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"e1002200","DOI":"10.1371\/journal.pcbi.1002200","article-title":"Why Don&apos;t CD8+ T Cells Reduce the Lifespan of SIV-Infected Cells In Vivo?","volume":"7","author":"M Elemans","year":"2011","journal-title":"PLoS Computational Biology"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/4716","article-title":"In vivo migration and function of transferred HIV-1-specific cytotoxic T cells","volume":"5","author":"SJ Brodie","year":"1999","journal-title":"Nature Medicine"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"13579","DOI":"10.1128\/JVI.79.21.13579-13586.2005","article-title":"How many human immunodeficiency virus type 1-infected target cells can a cytotoxic T-lymphocyte kill?","volume":"79","author":"WD Wick","year":"2005","journal-title":"Journal of Virology"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1371\/journal.pbio.0040090","article-title":"Inefficient Cytotoxic T Lymphocyte\u2013Mediated Killing of HIV-1\u2013Infected Cells In Vivo","volume":"4","author":"B Asquith","year":"2006","journal-title":"PLoS Biology"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jtbi.2009.12.018","article-title":"Interpreting the effect of vaccination on steady state infection in animals challenged with Simian immunodeficiency virus","volume":"263","author":"RA Sergeev","year":"2010","journal-title":"Journal of Theoretical Biology"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"11749","DOI":"10.1128\/JVI.01128-08","article-title":"Estimating In Vivo Death Rates of Targets due to CD8 T-Cell-Mediated Killing","volume":"82","author":"VV Ganusov","year":"2008","journal-title":"Journal of Virology"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1038\/cr.2013.74","article-title":"Restrictions to HIV-1 replication in resting CD4+ T lymphocytes","volume":"23","author":"X Pan","year":"2013","journal-title":"Cell research"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1038\/nature03513","article-title":"Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells","volume":"434","author":"Q Li","year":"2005","journal-title":"Nature"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"5127","DOI":"10.4049\/jimmunol.162.9.5127","article-title":"Emergence of CTL coincides with clearance of virus during primary simian immunodeficiency virus infection in rhesus monkeys","volume":"162","author":"MJ Kuroda","year":"1999","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1128\/JVI.73.1.797-800.1999","article-title":"Decay kinetics of human immunodeficiency virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy","volume":"73","author":"GS Ogg","year":"1999","journal-title":"Journal of Virology"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003878","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T18:30:21Z","timestamp":1689618621000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003878"}},"subtitle":[],"editor":[{"given":"Christian L.","family":"Althaus","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2014,10,30]]},"references-count":70,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,10,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1003878","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,30]]}}}