{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T18:07:52Z","timestamp":1759774072559,"version":"3.37.3"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1091919"],"award-info":[{"award-number":["OPP1091919"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000913","name":"James S. McDonnell Foundation","doi-asserted-by":"publisher","award":["21st Century Science Initiative Collaborative Award in Understanding Dynamic and Multi-scale Systems"],"award-info":[{"award-number":["21st Century Science Initiative Collaborative Award in Understanding Dynamic and Multi-scale Systems"]}],"id":[{"id":"10.13039\/100000913","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["Postgraduate Scholarship-Doctoral"],"award-info":[{"award-number":["Postgraduate Scholarship-Doctoral"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RAPIDD program of the Science and Technology Directorate Department of Homeland Security and the Fogarty International Center"],"award-info":[{"award-number":["RAPIDD program of the Science and Technology Directorate Department of Homeland Security and the Fogarty International Center"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1007892","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T17:23:58Z","timestamp":1593105838000},"page":"e1007892","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Implications of localized charge for human influenza A H1N1 hemagglutinin evolution: Insights from deep mutational scans"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2217-3071","authenticated-orcid":true,"given":"Chadi M.","family":"Saad-Roy","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0412-150X","authenticated-orcid":true,"given":"Nimalan","family":"Arinaminpathy","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7384-2821","authenticated-orcid":true,"given":"Ned S.","family":"Wingreen","sequence":"additional","affiliation":[]},{"given":"Simon A.","family":"Levin","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4411-1330","authenticated-orcid":true,"given":"Joshua M.","family":"Akey","sequence":"additional","affiliation":[]},{"given":"Bryan T.","family":"Grenfell","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"issue":"5953","key":"pcbi.1007892.ref001","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1126\/science.1178258","article-title":"Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift","volume":"326","author":"SE Hensley","year":"2009","journal-title":"Science"},{"issue":"12","key":"pcbi.1007892.ref002","doi-asserted-by":"crossref","first-page":"e15674","DOI":"10.1371\/journal.pone.0015674","article-title":"Dynamics of Glycoprotein Charge in the Evolutionary History of Human Influenza","volume":"5","author":"N Arinaminpathy","year":"2010","journal-title":"PLOS One"},{"issue":"1","key":"pcbi.1007892.ref003","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/irv.12486","article-title":"Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness","volume":"12","author":"MA Rolfes","year":"2018","journal-title":"Influenza and Other Respiratory Viruses"},{"issue":"1","key":"pcbi.1007892.ref004","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1128\/MMBR.56.1.152-179.1992","article-title":"Evolution and ecology of influenza A viruses","volume":"56","author":"RG Webster","year":"1992","journal-title":"Microbiological Reviews"},{"issue":"37","key":"pcbi.1007892.ref005","doi-asserted-by":"crossref","first-page":"28403","DOI":"10.1074\/jbc.R110.129809","article-title":"Influenza Hemagglutinin and Neuraminidase Membrane Glycoproteins","volume":"285","author":"SJ Gamblin","year":"2010","journal-title":"Journal of Biological Chemistry"},{"issue":"7","key":"pcbi.1007892.ref006","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/S0169-5347(02)02502-8","article-title":"Ecology and evolution of the flu","volume":"17","author":"DJD Earn","year":"2002","journal-title":"Trends in Ecology & Evolution"},{"key":"pcbi.1007892.ref007","doi-asserted-by":"crossref","first-page":"D49","DOI":"10.1016\/j.vaccine.2008.07.039","article-title":"The biology of influenza viruses","volume":"26","author":"NM Bouvier","year":"2008","journal-title":"Vaccine"},{"issue":"2","key":"pcbi.1007892.ref008","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/0092-8674(82)90135-0","article-title":"The antigenic structure of the influenza virus A\/PR\/8\/34 hemagglutinin (H1 subtype)","volume":"31","author":"AJ Caton","year":"1982","journal-title":"Cell"},{"key":"pcbi.1007892.ref009","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.coviro.2016.12.004","article-title":"Immune history and influenza virus susceptibility","volume":"22","author":"S Cobey","year":"2017","journal-title":"Current Opinion in Virology"},{"key":"pcbi.1007892.ref010","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/ni.3680","article-title":"Defining B cell immunodominance to viruses","volume":"18","author":"D Angeletti","year":"2017","journal-title":"Nature Immunology"},{"key":"pcbi.1007892.ref011","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.1172\/JCI122895","article-title":"Antigenic sites in influenza H1 hemagglutinin display species-specific immunodominance","volume":"128","author":"STH Liu","year":"2018","journal-title":"Journal of Clinical Investigation"},{"key":"pcbi.1007892.ref012","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1126\/science.1244730","article-title":"Substitutions near the receptor binding site determine major antigenic change during influenza virus evolution","volume":"342","author":"BF Koel","year":"2013","journal-title":"Science"},{"key":"pcbi.1007892.ref013","doi-asserted-by":"crossref","first-page":"e1004940","DOI":"10.1371\/journal.ppat.1004940","article-title":"Geometric constrains dominate the antigenic evolution of influenza H3N2 hemagglutinin","volume":"11","author":"AG Meyer","year":"2015","journal-title":"PLoS Pathogens"},{"issue":"5656","key":"pcbi.1007892.ref014","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1126\/science.1090727","article-title":"Unifying the Epidemiological and Evolutionary Dynamics of Pathogens","volume":"303","author":"BT Grenfell","year":"2004","journal-title":"Science"},{"key":"pcbi.1007892.ref015","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1093\/infdis\/jiz044","article-title":"Dynamic Perspectives on the Search for a Universal Influenza Vaccine","volume":"219","author":"CM Saad-Roy","year":"2019","journal-title":"The Journal of Infectious Diseases"},{"issue":"2","key":"pcbi.1007892.ref016","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00204-19","article-title":"Human Influenza A Virus Hemagglutinin Glycan Evolution Follows a Temporal Pattern to a Glycan Limit","volume":"10","author":"MO Altman","year":"2019","journal-title":"mBio"},{"issue":"7","key":"pcbi.1007892.ref017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0040422","article-title":"Compensatory Evolution of Net-Charge in Influenza A Virus Hemagglutinin","volume":"7","author":"Y Kobayashi","year":"2012","journal-title":"PLOS ONE"},{"issue":"2","key":"pcbi.1007892.ref018","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1006\/viro.1998.9274","article-title":"Differences in the biological phenotype of low-yielding (L) and high-yielding (H) variants of swine influenza virus A\/NJ\/11\/76 are associated with their different receptor-binding activity","volume":"247","author":"AS Gambaryan","year":"1998","journal-title":"Virology"},{"key":"pcbi.1007892.ref019","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s00239-010-9405-4","article-title":"Selective pressure to increase charge in immunodominant epitopes of the H3 hemagglutinin influenza protein","volume":"72","author":"K Pan","year":"2011","journal-title":"Journal of Molecular Evolution"},{"key":"pcbi.1007892.ref020","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1529\/biophysj.105.071050","article-title":"Salting the charged surface: pH and salt dependence of protein G B1 stability","volume":"90","author":"S Lindman","year":"2006","journal-title":"Biophysical Journal"},{"issue":"9","key":"pcbi.1007892.ref021","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.tibtech.2011.04.003","article-title":"Deep mutational scanning: assessing protein function on a massive scale","volume":"29","author":"CL Araya","year":"2011","journal-title":"Trends in Biotechnology"},{"key":"pcbi.1007892.ref022","article-title":"Accurate measurement of the effect of all amino-acid mutations on influenza hemagglutinin","volume":"155","author":"MB Doud","year":"2016","journal-title":"Viruses"},{"key":"pcbi.1007892.ref023","unstructured":"Schr\u00f6dinger, LLC. The PyMOL Molecular Graphics System, Version 2.2.0; 2018."},{"issue":"5665","key":"pcbi.1007892.ref024","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1126\/science.1093155","article-title":"The Structure and Receptor Binding Properties of the 1918 Influenza Hemagglutinin","volume":"303","author":"SJ Gamblin","year":"2004","journal-title":"Science"},{"issue":"2","key":"pcbi.1007892.ref025","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1089\/vim.2017.0129","article-title":"Antibody Immunodominance: The Key to Understanding Influenza Virus Antigenic Drift","volume":"31","author":"MO Altman","year":"2018","journal-title":"Viral Immunology"},{"issue":"1","key":"pcbi.1007892.ref026","doi-asserted-by":"crossref","first-page":"10432","DOI":"10.1038\/s41598-018-28706-1","article-title":"The influenza virus hemagglutinin head evolves faster than the stalk domain","volume":"8","author":"E Kirkpatrick","year":"2018","journal-title":"Scientific Reports"},{"issue":"9","key":"pcbi.1007892.ref027","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1093\/molbev\/msh194","article-title":"Comparison of site-specific rate-inference methods for protein sequences: empirical Bayesian methods are superior","volume":"21","author":"I Mayrose","year":"2004","journal-title":"Molecular Biology and Evolution"},{"key":"pcbi.1007892.ref028","doi-asserted-by":"crossref","first-page":"D466","DOI":"10.1093\/nar\/gkw857","article-title":"Influenza Research Database: an integrated bioinformatics resource for influenza virus research","volume":"45","author":"Y Zhang","year":"2017","journal-title":"Nucleic Acids Research"},{"issue":"1","key":"pcbi.1007892.ref029","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s12859-015-0590-4","article-title":"Software for the analysis and visualization of deep mutational scanning data","volume":"16","author":"JD Bloom","year":"2015","journal-title":"BMC bioinformatics"},{"key":"pcbi.1007892.ref030","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-21706-2","volume-title":"Modern Applied Statistics with S","author":"WN Venables","year":"2002"},{"key":"pcbi.1007892.ref031","unstructured":"R Core Team. R: A Language and Environment for Statistical Computing; 2018. Available from: https:\/\/www.R-project.org\/."},{"issue":"301","key":"pcbi.1007892.ref032","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1080\/01621459.1963.10500845","article-title":"Hierarchical grouping to optimize an objective function","volume":"58","author":"JH Ward","year":"1963","journal-title":"Journal of the American Statistical Association"},{"key":"pcbi.1007892.ref033","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s00357-014-9161-z","article-title":"Ward\u2019s herarchical agglomerative clustering method: which algorithms implement Ward\u2019s criterion?","volume":"31","author":"F Murtagh","year":"2014","journal-title":"Journal of Classification"},{"key":"pcbi.1007892.ref034","article-title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","author":"JM Lee","year":"2018","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"pcbi.1007892.ref035","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nature14460","article-title":"Global circulation patterns of seasonal influenza viruses vary with antigenic drift","author":"T Bedford","year":"2015","journal-title":"Nature"},{"key":"pcbi.1007892.ref036","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0022-5193(66)90013-0","article-title":"The measurement of diversity in different types of biological collections","volume":"13","author":"EC Pielou","year":"1966","journal-title":"Journal of Theoretical Biology"},{"issue":"10","key":"pcbi.1007892.ref037","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1093\/molbev\/msu220","article-title":"An Experimentally Informed Evolutionary Model Improves Phylogenetic Fit to Divergent Lactamase Homologs","volume":"31","author":"JD Bloom","year":"2014","journal-title":"Molecular Biology and Evolution"},{"key":"pcbi.1007892.ref038","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.12688\/f1000research.17456.1","article-title":"pdb-tools: a swiss army knife for molecular structures","volume":"7","author":"JPGLM Rodrigues","year":"2018","journal-title":"F1000Research"},{"issue":"11","key":"pcbi.1007892.ref039","doi-asserted-by":"crossref","first-page":"6363","DOI":"10.1074\/jbc.271.11.6363","article-title":"The Amino Acid at the X Position of an Asn-X-Ser Sequon Is an Important Determinant of N-Linked Core-glycosylation Efficiency","volume":"271","author":"SH Shakin-Eshleman","year":"1996","journal-title":"Journal of Biological Chemistry"},{"key":"pcbi.1007892.ref040","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-98141-3","volume-title":"ggplot2: Elegant Graphics for Data Analysis","author":"H Wickham","year":"2009"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1007892","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T17:24:29Z","timestamp":1593105869000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1007892"}},"subtitle":[],"editor":[{"given":"Rustom","family":"Antia","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2020,6,25]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1007892","relation":{},"ISSN":["1553-7358"],"issn-type":[{"type":"electronic","value":"1553-7358"}],"subject":[],"published":{"date-parts":[[2020,6,25]]}}}