{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T09:28:39Z","timestamp":1740130119003,"version":"3.37.3"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"D1","license":[{"start":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T00:00:00Z","timestamp":1634601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"ERDF","doi-asserted-by":"publisher","award":["CGL2017-89160P"],"award-info":[{"award-number":["CGL2017-89160P"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"AGAUR","doi-asserted-by":"publisher","award":["2017SGR-1379"],"award-info":[{"award-number":["2017SGR-1379"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Secretaria d\u2019Universitats i Recerca de la Generalitat de Catalunya and the European Social Fund","award":["2020FI_B-01045"],"award-info":[{"award-number":["2020FI_B-01045"]}]},{"name":"Departament de Gen\u00e8tica i de Microbiologia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Adaptive challenges that\u00a0humans faced as they\u00a0expanded across the globe left specific molecular footprints that can be decoded in our today's genomes. Different sets of metrics are used to identify genomic regions that have undergone selection. However, there are fewer methods capable of pinpointing the allele ultimately responsible for this selection. Here, we present PopHumanVar, an interactive online application that is designed to facilitate the exploration and thorough analysis of candidate genomic regions by integrating both functional and population genomics data currently available. PopHumanVar generates useful summary reports of prioritized variants that are putatively causal of recent selective sweeps. It compiles data and graphically represents different layers of information, including natural selection statistics, as well as functional annotations and genealogical estimations of variant age, for biallelic single nucleotide variants (SNVs) of the 1000 Genomes Project phase 3. Specifically, PopHumanVar amasses SNV-based information from GEVA, SnpEFF, GWAS Catalog, ClinVar, RegulomeDB\u00a0and DisGeNET databases, as well as accurate estimations of iHS, nSL\u00a0and iSAFE statistics. Notably, PopHumanVar can successfully identify known causal variants of frequently reported candidate selection regions, including EDAR in East-Asians, ACKR1 (DARC) in Africans\u00a0and LCT\/MCM6 in Europeans. PopHumanVar is open and freely available at https:\/\/pophumanvar.uab.cat.<\/jats:p>","DOI":"10.1093\/nar\/gkab925","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T20:48:32Z","timestamp":1633034912000},"page":"D1069-D1076","source":"Crossref","is-referenced-by-count":1,"title":["PopHumanVar: an interactive application for the functional characterization and prioritization of adaptive genomic variants in humans"],"prefix":"10.1093","volume":"50","author":[{"given":"Aina","family":"Colomer-Vilaplana","sequence":"first","affiliation":[{"name":"Department of Genetics and Microbiology, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Barcelona\u00a008193, Spain"}]},{"given":"Jes\u00fas","family":"Murga-Moreno","sequence":"additional","affiliation":[{"name":"Department of Genetics and Microbiology, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Barcelona\u00a008193, Spain"},{"name":"Institute of Biotechnology and Biomedicine, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Barcelona\u00a008193, Spain"}]},{"given":"Aleix","family":"Canalda-Baltrons","sequence":"additional","affiliation":[{"name":"Department of Genetics and Microbiology, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Barcelona\u00a008193, Spain"}]},{"given":"Clara","family":"Inserte","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology and Biomedicine, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Barcelona\u00a008193, Spain"}]},{"given":"Daniel","family":"Soto","sequence":"additional","affiliation":[{"name":"Department of Genetics and Microbiology, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Barcelona\u00a008193, Spain"}]},{"given":"Marta","family":"Coronado-Zamora","sequence":"additional","affiliation":[{"name":"Department of Genetics and Microbiology, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Barcelona\u00a008193, Spain"},{"name":"Institute of Biotechnology and Biomedicine, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Barcelona\u00a008193, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0374-1475","authenticated-orcid":false,"given":"Antonio","family":"Barbadilla","sequence":"additional","affiliation":[{"name":"Department of Genetics and Microbiology, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Barcelona\u00a008193, Spain"},{"name":"Institute of Biotechnology and Biomedicine, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Barcelona\u00a008193, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8191-0062","authenticated-orcid":false,"given":"S\u00f2nia","family":"Casillas","sequence":"additional","affiliation":[{"name":"Department of Genetics and Microbiology, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Barcelona\u00a008193, Spain"},{"name":"Institute of Biotechnology and Biomedicine, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Barcelona\u00a008193, Spain"}]}],"member":"286","published-online":{"date-parts":[[2021,10,19]]},"reference":[{"key":"2022010507414750100_B1","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nature21347","article-title":"Tracing the peopling of the world through genomics","volume":"541","author":"Nielsen","year":"2017","journal-title":"Nature"},{"key":"2022010507414750100_B2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1126\/science.aaf5098","article-title":"Going global by adapting local: a review of recent human adaptation","volume":"354","author":"Fan","year":"2016","journal-title":"Science"},{"key":"2022010507414750100_B3","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1126\/science.1105436","article-title":"Whole-genome patterns of common DNA variation in three human populations","volume":"307","author":"Hinds","year":"2005","journal-title":"Science"},{"key":"2022010507414750100_B4","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/nature04226","article-title":"A haplotype map of the human genome","volume":"437","author":"Altshuler","year":"2005","journal-title":"Nature"},{"key":"2022010507414750100_B5","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nature09298","article-title":"Integrating common and rare genetic variation in diverse human populations","volume":"467","author":"Altshuler","year":"2010","journal-title":"Nature"},{"key":"2022010507414750100_B6","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1093\/molbev\/msy006","article-title":"Estimating time to the common ancestor for a beneficial allele","volume":"35","author":"Smith","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"2022010507414750100_B7","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1038\/s41588-019-0484-x","article-title":"A method for genome-wide genealogy estimation for thousands of samples","volume":"51","author":"Speidel","year":"2019","journal-title":"Nat. Genet."},{"key":"2022010507414750100_B8","doi-asserted-by":"crossref","first-page":"3497","DOI":"10.1093\/molbev\/msab174","article-title":"Inferring population histories for ancient genomes using genome-wide genealogies","volume":"38","author":"Speidel","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"2022010507414750100_B9","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41586-021-03244-5","article-title":"Origins of modern human ancestry","volume":"590","author":"Bergstr\u00f6m","year":"2021","journal-title":"Nature"},{"key":"2022010507414750100_B10","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1038\/s41588-019-0483-y","article-title":"Inferring whole-genome histories in large population datasets","volume":"51","author":"Kelleher","year":"2019","journal-title":"Nat. Genet."},{"key":"2022010507414750100_B11","doi-asserted-by":"crossref","first-page":"e1004342","DOI":"10.1371\/journal.pgen.1004342","article-title":"Genome-wide inference of ancestral recombination graphs","volume":"10","author":"Rasmussen","year":"2014","journal-title":"PLoS Genet."},{"key":"2022010507414750100_B12","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"2022010507414750100_B13","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/s41559-018-0478-6","article-title":"Patterns of shared signatures of recent positive selection across human populations","volume":"2","author":"Johnson","year":"2018","journal-title":"Nat. Ecol. Evol."},{"key":"2022010507414750100_B14","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41467-018-03100-7","article-title":"Localization of adaptive variants in human genomes using averaged one-dependence estimation","volume":"9","author":"Sugden","year":"2018","journal-title":"Nat. Commun."},{"key":"2022010507414750100_B15","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1126\/science.1124309","article-title":"Positive natural selection in the human lineage","volume":"312","author":"Sabeti","year":"2006","journal-title":"Science"},{"key":"2022010507414750100_B16","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/nature06250","article-title":"Genome-wide detection and characterization of positive selection in human populations","volume":"449","author":"Sabeti","year":"2007","journal-title":"Nature"},{"key":"2022010507414750100_B17","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.tig.2006.06.005","article-title":"Genomic insights into positive selection","volume":"22","author":"Biswas","year":"2006","journal-title":"Trends Genet."},{"key":"2022010507414750100_B18","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1101\/gr.086652.108","article-title":"Constructing genomic maps of positive selection in humans: where do we go from here?","volume":"19","author":"Akey","year":"2009","journal-title":"Genome Res."},{"key":"2022010507414750100_B19","doi-asserted-by":"crossref","first-page":"D1080","DOI":"10.1093\/nar\/gky959","article-title":"PopHumanScan: the online catalog of human genome adaptation","volume":"47","author":"Murga-Moreno","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2022010507414750100_B20","doi-asserted-by":"crossref","first-page":"W603","DOI":"10.1093\/nar\/gkab410","article-title":"snpXplorer: a web application to explore human SNP-associations and annotate SNP-sets","volume":"49","author":"Tesi","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2022010507414750100_B21","doi-asserted-by":"crossref","first-page":"e72","DOI":"10.1371\/journal.pbio.0040072","article-title":"A map of recent positive selection in the human genome","volume":"4","author":"Voight","year":"2006","journal-title":"PLOS Biol."},{"key":"2022010507414750100_B22","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1093\/molbev\/msu077","article-title":"On detecting incomplete soft or hard selective sweeps using haplotype structure","volume":"31","author":"Ferrer-Admetlla","year":"2014","journal-title":"Mol. Biol. Evol."},{"key":"2022010507414750100_B23","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nmeth.4606","article-title":"Identifying the favored mutation in a positive selective sweep","volume":"15","author":"Akbari","year":"2018","journal-title":"Nat. Methods"},{"key":"2022010507414750100_B24","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms","volume":"6","author":"Cingolani","year":"2012","journal-title":"SnpEff. Fly (Austin)"},{"key":"2022010507414750100_B25","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1101\/gr.137323.112","article-title":"Annotation of functional variation in personal genomes using RegulomeDB","volume":"22","author":"Boyle","year":"2012","journal-title":"Genome Res"},{"key":"2022010507414750100_B26","doi-asserted-by":"crossref","first-page":"D980","DOI":"10.1093\/nar\/gkt1113","article-title":"ClinVar: public archive of relationships among sequence variation and human phenotype","volume":"42","author":"Landrum","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2022010507414750100_B27","doi-asserted-by":"crossref","first-page":"D896","DOI":"10.1093\/nar\/gkw1133","article-title":"The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog)","volume":"45","author":"MacArthur","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2022010507414750100_B28","first-page":"D845","article-title":"The DisGeNET knowledge platform for disease genomics: 2019 update","volume":"48","author":"Pi\u00f1ero","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2022010507414750100_B29","doi-asserted-by":"crossref","first-page":"e3000586","DOI":"10.1371\/journal.pbio.3000586","article-title":"Dating genomic variants and shared ancestry in population-scale sequencing data","volume":"18","author":"Albers","year":"2020","journal-title":"PLOS Biol."},{"key":"2022010507414750100_B30","doi-asserted-by":"crossref","first-page":"D1003","DOI":"10.1093\/nar\/gkx943","article-title":"PopHuman: the human population genomics browser","volume":"46","author":"Casillas","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2022010507414750100_B31","doi-asserted-by":"crossref","first-page":"e2209","DOI":"10.1371\/journal.pone.0002209","article-title":"Positive selection in fast Asians for an EDAR allele that enhances NF-\u03baB activation","volume":"3","author":"Bryk","year":"2008","journal-title":"PLoS One"},{"key":"2022010507414750100_B32","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/ng826","article-title":"Identification of a variant associated with adult-type hypolactasia","volume":"30","author":"Enattah","year":"2002","journal-title":"Nat. Genet."},{"key":"2022010507414750100_B33","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.cell.2013.01.016","article-title":"Modeling recent human evolution in mice by expression of a selected EDAR variant","volume":"152","author":"Kamberov","year":"2013","journal-title":"Cell"},{"key":"2022010507414750100_B34","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/jhg.2012.60","article-title":"Effects of an Asian-specific nonsynonymous EDAR variant on multiple dental traits","volume":"57","author":"Park","year":"2012","journal-title":"J. Hum. Genet."},{"key":"2022010507414750100_B35","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41439-018-0024-8","article-title":"Long-range haplotype analysis of the malaria parasite receptor gene ACKR1 in an East-African population","volume":"5","author":"Yin","year":"2018","journal-title":"Hum. Genome Var."},{"key":"2022010507414750100_B36","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1111\/j.1537-2995.2011.03431.x","article-title":"DARC alleles and Duffy phenotypes in African Americans","volume":"52","author":"Schmid","year":"2012","journal-title":"Transfusion (Paris)"},{"key":"2022010507414750100_B37","doi-asserted-by":"crossref","first-page":"e1006560","DOI":"10.1371\/journal.pgen.1006560","article-title":"Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans","volume":"13","author":"McManus","year":"2017","journal-title":"PLOS Genet."},{"key":"2022010507414750100_B38","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/ng1946","article-title":"Convergent adaptation of human lactase persistence in Africa and Europe","volume":"39","author":"Tishkoff","year":"2007","journal-title":"Nat. Genet."},{"key":"2022010507414750100_B39","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00439-008-0593-6","article-title":"Lactose digestion and the evolutionary genetics of lactase persistence","volume":"124","author":"Ingram","year":"2009","journal-title":"Hum. Genet."},{"key":"2022010507414750100_B40","doi-asserted-by":"crossref","first-page":"17453","DOI":"10.1038\/srep17453","article-title":"High level of inbreeding in final phase of 1000 Genomes Project","volume":"5","author":"Gazal","year":"2015","journal-title":"Sci. Rep."},{"key":"2022010507414750100_B41","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1101\/gr.087577.108","article-title":"Signals of recent positive selection in a worldwide sample of human populations","volume":"19","author":"Pickrell","year":"2009","journal-title":"Genome Res."},{"key":"2022010507414750100_B42","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1093\/molbev\/msu211","article-title":"selscan: an efficient multithreaded program to perform EHH-based scans for positive selection","volume":"31","author":"Szpiech","year":"2014","journal-title":"Mol. Biol. Evol."},{"key":"2022010507414750100_B43","doi-asserted-by":"crossref","first-page":"14994","DOI":"10.1038\/ncomms14994","article-title":"Refined genetic maps reveal sexual dimorphism in human meiotic recombination at multiple scales","volume":"8","author":"Bh\u00e9rer","year":"2017","journal-title":"Nat. Commun."},{"key":"2022010507414750100_B44","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","article-title":"GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor","volume":"23","author":"Davis","year":"2007","journal-title":"Bioinformatics"},{"key":"2022010507414750100_B45","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1126\/science.1105136","article-title":"The ENCODE (ENCyclopedia Of DNA Elements) Project","volume":"306","author":"Consortium","year":"2004","journal-title":"Science"},{"key":"2022010507414750100_B46","doi-asserted-by":"crossref","DOI":"10.22541\/au.160405572.29972398\/v1","article-title":"Detecting selection using Extended Haplotype Homozygosity-based statistics on unphased or unpolarized data","author":"Klassmann","year":"2020"},{"key":"2022010507414750100_B47","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/nrg3522","article-title":"Ecological genomics of local adaptation","volume":"14","author":"Savolainen","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"2022010507414750100_B48","first-page":"509","article-title":"Archaic adaptive introgression in TBX15\/WARS2","volume":"34","author":"Racimo","year":"2017","journal-title":"Mol. Biol. Evol."},{"key":"2022010507414750100_B49","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1093\/hmg\/ddm355","article-title":"A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness","volume":"17","author":"Fujimoto","year":"2008","journal-title":"Hum. Mol. Genet."},{"author":"Chang","key":"2022010507414750100_B50","article-title":"2021) shiny: Web Application Framework for R"},{"volume-title":"R: A Language and Environment for Statistical Computing R Foundation for Statistical Computing","year":"2020","author":"Core\u00a0Team","key":"2022010507414750100_B51"},{"key":"2022010507414750100_B52","doi-asserted-by":"crossref","DOI":"10.1201\/9780429447273","volume-title":"Interactive Web-Based Data Visualization with R, plotly, and shiny Chapman and Hall\/CRC","author":"Sievert","year":"2020"},{"volume-title":"DT: A Wrapper of the JavaScript Library \u2018DataTables\u2019","year":"2021","author":"Xie","key":"2022010507414750100_B53"},{"key":"2022010507414750100_B54","doi-asserted-by":"crossref","DOI":"10.1093\/bioinformatics\/btab459","article-title":"JBrowseR: an R interface to the JBrowse 2 genome browser","author":"Hershberg","year":"2021","journal-title":"Bioinformatics"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/50\/D1\/D1069\/42058598\/gkab925.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/50\/D1\/D1069\/42058598\/gkab925.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T08:24:03Z","timestamp":1641371043000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/50\/D1\/D1069\/6401894"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,19]]},"references-count":54,"journal-issue":{"issue":"D1","published-online":{"date-parts":[[2021,10,19]]},"published-print":{"date-parts":[[2022,1,7]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkab925","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"type":"print","value":"0305-1048"},{"type":"electronic","value":"1362-4962"}],"subject":[],"published-other":{"date-parts":[[2022,1,7]]},"published":{"date-parts":[[2021,10,19]]}}}