{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:18:42Z","timestamp":1793395122462,"version":"4.5.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:00:00Z","timestamp":1590710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Key Technologies Research and Development Program of China","award":["2018YFC1003500"],"award-info":[{"award-number":["2018YFC1003500"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671510"],"award-info":[{"award-number":["81671510"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rare coding variants have been proven to be one of the significant factors contributing to spermatogenic failure in patients with non-obstructive azoospermia (NOA) and severe oligospermia (SO). To delineate the molecular characteristics of idiopathic NOA and SO, we performed whole-exome sequencing of 314 unrelated patients of Chinese Han origin and verified our findings by comparing to 400 fertile controls. We detected six pathogenic\/likely pathogenic variants and four variants of unknown significance, in genes known to cause NOA\/SO, and 9 of which had not been earlier reported. Additionally, we identified 20 novel NOA candidate genes affecting 25 patients. Among them, five (BRDT, CHD5, MCM9, MLH3 and ZFX) were considered as strong candidates based on the evidence obtained from murine functional studies and human single-cell (sc)RNA-sequencing data. These genetic findings provide insight into the aetiology of human NOA\/SO and pave the way for further functional analysis and molecular diagnosis of male infertility.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa101","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T11:09:05Z","timestamp":1590491345000},"page":"2451-2459","source":"Crossref","is-referenced-by-count":78,"title":["Whole-exome sequencing of a large Chinese azoospermia and severe oligospermia cohort identifies novel infertility causative variants and genes"],"prefix":"10.1093","volume":"29","author":[{"given":"Shitao","family":"Chen","sequence":"first","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai, 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guishuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoguo","family":"Zheng","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai, 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunna","family":"Ge","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai, 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubing","family":"Dai","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai, 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ping","sequence":"additional","affiliation":[{"name":"Department of Urology, Shanghai Human Sperm Bank, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Shanghai Human Sperm Bank, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Andrology, Reproductive Medicine Research Center, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Andrology, Reproductive Medicine Research Center, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Reproduction, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Male Reproduction and Genetics, National Health and Family Planning Commission, Family Planning Research Institute of Guangdong Province, Guangzhou, 510031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Zhong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Male Reproduction and Genetics, National Health and Family Planning Commission, Family Planning Research Institute of Guangdong Province, Guangzhou, 510031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongtong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Reproductive Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingjun","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Reproductive Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghan","family":"Huang","sequence":"additional","affiliation":[{"name":"The First People's Hospital of Foshan, Sun Yat-sen University, Foshan, 528000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Assisted Reproductive Medicine, The Sixth Medical Center of PLA General Hospital, Beijing, 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changli","family":"Shen","sequence":"additional","affiliation":[{"name":"Reproductive Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Yuan","sequence":"additional","affiliation":[{"name":"Peking University First Hospital Andrology Center & Urology Department, Beijing, 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Guangdong Province Hospital of Chinese Medicine, Guangzhou, 510140, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuying","family":"Pei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medicine, Ningxia Medical University, Yinchuan, 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Yan","family":"Cheng","sequence":"additional","affiliation":[{"name":"The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Sun","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai, 200030, China"},{"name":"Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,29]]},"reference":[{"key":"2020081306365277900_ref1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12958-015-0032-1","article-title":"A unique view on male infertility around the globe","volume":"13","author":"Agarwal","year":"2015","journal-title":"Reprod. Biol. Endocrinol."},{"key":"2020081306365277900_ref2","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/humupd\/dmp048","article-title":"World Health Organization reference values for human semen characteristics","volume":"16","author":"Cooper","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"2020081306365277900_ref3","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.fertnstert.2018.09.012","article-title":"Management of nonobstructive azoospermia: a committee opinion","volume":"110","author":"Practice Committee of the American Society for Reproductive Medicine","year":"2018","journal-title":"Fertil. Steril."},{"key":"2020081306365277900_ref4","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41585-018-0003-3","article-title":"Genetics of male infertility","volume":"15","author":"Krausz","year":"2018","journal-title":"Nat. Rev. Urol."},{"key":"2020081306365277900_ref5","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00439-019-01974-1","article-title":"New insights into the genetics of spermatogenic failure: a review of the literature","volume":"138","author":"Cannarella","year":"2019","journal-title":"Hum. Genet."},{"key":"2020081306365277900_ref6","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.aju.2017.12.003","article-title":"A systematic review on the genetics of male infertility in the era of next-generation sequencing","volume":"16","author":"Robay","year":"2018","journal-title":"Arab. J. Urol."},{"key":"2020081306365277900_ref7","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.fertnstert.2019.03.036","article-title":"Where are we going with gene screening for male infertility?","volume":"111","author":"Thirumavalavan","year":"2019","journal-title":"Fertil. Steril."},{"key":"2020081306365277900_ref8","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/gim.2018.10","article-title":"Point-of-care whole-exome sequencing of idiopathic male infertility","volume":"20","author":"Fakhro","year":"2018","journal-title":"Genet. Med."},{"key":"2020081306365277900_ref9","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1002\/humu.23312","article-title":"Validation and application of a novel integrated genetic screening method to a cohort of 1,112 men with idiopathic azoospermia or severe oligozoospermia","volume":"38","author":"Oud","year":"2017","journal-title":"Hum. Mutat."},{"key":"2020081306365277900_ref10","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nature13127","article-title":"Guidelines for investigating causality of sequence variants in human disease","volume":"508","author":"MacArthur","year":"2014","journal-title":"Nature"},{"key":"2020081306365277900_ref11","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/ng.1040","article-title":"A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia","volume":"44","author":"Hu","year":"2011","journal-title":"Nat. Genet."},{"key":"2020081306365277900_ref12","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"2020081306365277900_ref13","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41422-018-0099-2","article-title":"The adult human testis transcriptional cell atlas","volume":"28","author":"Guo","year":"2018","journal-title":"Cell Res."},{"key":"2020081306365277900_ref14","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/ejhg.2015.107","article-title":"STAG3 truncating variant as the cause of primary ovarian insufficiency","volume":"24","author":"Le Quesne Stabej","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"2020081306365277900_ref15","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1172\/JCI118930","article-title":"A novel missense mutation in the amino-terminal domain of the human androgen receptor gene in a family with partial androgen insensitivity syndrome causes reduced efficiency of protein translation","volume":"98","author":"Choong","year":"1996","journal-title":"J. Clin. Invest."},{"key":"2020081306365277900_ref16","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa1406192","article-title":"X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men","volume":"372","author":"Yatsenko","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"2020081306365277900_ref17","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/humupd\/dmp023","article-title":"Male infertility and the involvement of the X chromosome","volume":"15","author":"Stouffs","year":"2009","journal-title":"Hum. Reprod. Update"},{"key":"2020081306365277900_ref18","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00412-005-0346-4","article-title":"Mei1 is epistatic to Dmc1 during mouse meiosis","volume":"114","author":"Reinholdt","year":"2005","journal-title":"Chromosoma"},{"key":"2020081306365277900_ref19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ucl.2013.08.013","article-title":"Obstructive azoospermia","volume":"41","author":"Wosnitzer","year":"2014","journal-title":"Urol. Clin. North Am."},{"key":"2020081306365277900_ref20","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/86927","article-title":"An abundance of X-linked genes expressed in spermatogonia","volume":"27","author":"Wang","year":"2001","journal-title":"Nat. Genet."},{"key":"2020081306365277900_ref21","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/ng931","article-title":"Meiotic arrest and aneuploidy in MLH3-deficient mice","volume":"31","author":"Lipkin","year":"2002","journal-title":"Nat. Genet."},{"key":"2020081306365277900_ref22","doi-asserted-by":"publisher","DOI":"10.1101\/517748","article-title":"Mutation of MLH3 endonuclease motif reveals integration between crossover pathways in Mammalian meiosis","author":"Toledo","year":"2019","journal-title":"bioRxiv"},{"key":"2020081306365277900_ref23","doi-asserted-by":"crossref","first-page":"3809\u20133820","DOI":"10.1038\/emboj.2012.233","article-title":"Bromodomain-dependent stage-specific male genome programming by Brdt","volume":"31","author":"Gaucher","year":"2012","journal-title":"EMBO J"},{"key":"2020081306365277900_ref24","doi-asserted-by":"crossref","first-page":"e1007209","DOI":"10.1371\/journal.pgen.1007209","article-title":"BRDT is an essential epigenetic regulator for proper chromatin organization, silencing of sex chromosomes and crossover formation in male meiosis","volume":"14","author":"Manterola","year":"2018","journal-title":"PLoS Genet."},{"key":"2020081306365277900_ref25","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1242\/dev.004481","article-title":"The first bromodomain of Brdt, a testis-specific member of the BET sub-family of double-bromodomain-containing proteins, is essential for male germ cell differentiation","volume":"134","author":"Shang","year":"2007","journal-title":"Development"},{"key":"2020081306365277900_ref26","doi-asserted-by":"crossref","first-page":"19914","DOI":"10.18632\/oncotarget.15251","article-title":"Whole-exome sequencing identified a homozygous BRDT mutation in a patient with acephalic spermatozoa","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"2020081306365277900_ref27","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1038\/ncomms4812","article-title":"Chd5 orchestrates chromatin remodelling during sperm development","volume":"5","author":"Li","year":"2014","journal-title":"Nat. Commun."},{"key":"2020081306365277900_ref28","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.molcel.2012.05.048","article-title":"MCM8- and MCM9-deficient mice reveal gametogenesis defects and genome instability due to impaired homologous recombination","volume":"47","author":"Lutzmann","year":"2012","journal-title":"Mol. Cell"},{"key":"2020081306365277900_ref29","first-page":"576","article-title":"MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency","volume":"102","author":"Desai","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2020081306365277900_ref30","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1242\/dev.124.11.2275","article-title":"Zfx mutation results in small animal size and reduced germ cell number in male and female mice","volume":"124","author":"Luoh","year":"1997","journal-title":"Development"},{"key":"2020081306365277900_ref31","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/ng.367","article-title":"A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation","volume":"41","author":"Tarpey","year":"2009","journal-title":"Nat. Genet."},{"key":"2020081306365277900_ref32","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1101\/gad.315978.118","article-title":"Localized protein biotinylation at DNA damage sites identifies ZPET, a repressor of homologous recombination","volume":"33","author":"Moquin","year":"2019","journal-title":"Genes Dev."},{"key":"2020081306365277900_ref33","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/gim.2016.225","article-title":"A familial study of azoospermic men identifies three novel causative mutations in three new human azoospermia genes","volume":"19","author":"Gershoni","year":"2017","journal-title":"Genet. Med."},{"key":"2020081306365277900_ref34","doi-asserted-by":"crossref","first-page":"4982","DOI":"10.1073\/pnas.0505123103","article-title":"TEX14 is essential for intercellular bridges and fertility in male mice","volume":"103","author":"Greenbaum","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2020081306365277900_ref35","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1083\/jcb.200709057","article-title":"Mouse TEX15 is essential for DNA double-strand break repair and chromosomal synapsis during male meiosis","volume":"180","author":"Yang","year":"2008","journal-title":"J. Cell Biol."},{"key":"2020081306365277900_ref36","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2020081306365277900_ref37","doi-asserted-by":"crossref","first-page":"e103","DOI":"10.1093\/nar\/gkx193","article-title":"NGSCheckMate: software for validating sample identity in next-generation sequencing studies within and across data types","volume":"45","author":"Lee","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2020081306365277900_ref38","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with burrows-wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2020081306365277900_ref39","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat. Genet."},{"key":"2020081306365277900_ref40","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2020081306365277900_ref41","doi-asserted-by":"crossref","first-page":"D853","DOI":"10.1093\/nar\/gky1095","article-title":"The UCSC genome browser database: 2019 update","volume":"47","author":"Haeussler","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2020081306365277900_ref42","doi-asserted-by":"crossref","first-page":"D865","DOI":"10.1093\/nar\/gkt1059","article-title":"Current status and new features of the consensus coding sequence database","volume":"42","author":"Farrell","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2020081306365277900_ref43","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"1000 Genomes Project Consortium","year":"2015","journal-title":"Nature"},{"key":"2020081306365277900_ref44","doi-asserted-by":"publisher","DOI":"10.1101\/531210","article-title":"Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes","author":"Karczewski","year":"2019","journal-title":"bioRxiv"},{"key":"2020081306365277900_ref45","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1038\/gim.2017.26","article-title":"Using high-resolution variant frequencies to empower clinical genome interpretation","volume":"19","author":"Whiffin","year":"2017","journal-title":"Genet. Med."},{"key":"2020081306365277900_ref46","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ajhg.2017.01.004","article-title":"InterVar: clinical interpretation of genetic variants by the 2015 ACMG-AMP guidelines","volume":"100","author":"Li","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"2020081306365277900_ref47","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"Rentzsch","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2020081306365277900_ref48","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"2020081306365277900_ref49","doi-asserted-by":"crossref","first-page":"W452","DOI":"10.1093\/nar\/gks539","article-title":"SIFT web server: predicting effects of amino acid substitutions on proteins","volume":"40","author":"Sim","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2020081306365277900_ref50","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"Mutation Taster2: mutation prediction for the deep-sequencing age","volume":"11","author":"Schwarz","year":"2014","journal-title":"Nat. Methods"},{"key":"2020081306365277900_ref51","doi-asserted-by":"crossref","first-page":"e1001025","DOI":"10.1371\/journal.pcbi.1001025","article-title":"Identifying a high fraction of the human genome to be under selective constraint using GERP++","volume":"6","author":"Davydov","year":"2010","journal-title":"PLoS Comput. Biol."},{"key":"2020081306365277900_ref52","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat. Biotechnol."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddaa101\/33413109\/ddaa101.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/29\/14\/2451\/33637601\/ddaa101.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/29\/14\/2451\/33637601\/ddaa101.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T22:55:51Z","timestamp":1666652151000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/29\/14\/2451\/5848267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,29]]},"references-count":52,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2020,5,29]]},"published-print":{"date-parts":[[2020,8,11]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddaa101","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,7,15]]},"published":{"date-parts":[[2020,5,29]]}}}