{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T08:20:22Z","timestamp":1774599622440,"version":"3.50.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"W1","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100503"],"award-info":[{"award-number":["32100503"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170637"],"award-info":[{"award-number":["32170637"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong project","award":["2017GC010644"],"award-info":[{"award-number":["2017GC010644"]}]},{"DOI":"10.13039\/501100007162","name":"Department of Science and Technology of Guangdong Province","doi-asserted-by":"publisher","award":["2018B030322006"],"award-info":[{"award-number":["2018B030322006"]}],"id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Most complex disease-associated loci mapped by genome-wide association studies (GWAS) are located in non-coding regions. It remains elusive which genes the associated loci regulate and in which tissues\/cell types the regulation occurs. Here, we present PCGA (https:\/\/pmglab.top\/pcga), a comprehensive web server for jointly estimating both associated tissues\/cell types and susceptibility genes for complex phenotypes by GWAS summary statistics. The web server is built on our published method, DESE, which represents an effective method to mutually estimate driver tissues and genes by integrating GWAS summary statistics and transcriptome data. By collecting and processing extensive bulk\u00a0and single-cell RNA sequencing datasets, PCGA has included expression profiles of 54 human tissues, 2,214 human cell types and 4,384 mouse cell types, which provide the basis for estimating associated tissues\/cell types and genes for complex phenotypes. We develop a framework to sequentially estimate associated tissues and cell types of a complex phenotype according to their hierarchical relationships we curated. Meanwhile, we construct a phenotype-cell-gene association landscape by estimating the associated tissues\/cell types and genes of 1,871 public GWASs. The association landscape is generally consistent with biological knowledge and can be searched and browsed at the PCGA website.<\/jats:p>","DOI":"10.1093\/nar\/gkac425","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T11:22:40Z","timestamp":1652181760000},"page":"W568-W576","source":"Crossref","is-referenced-by-count":18,"title":["PCGA: a comprehensive web server for phenotype-cell-gene association analysis"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3481-4224","authenticated-orcid":false,"given":"Chao","family":"Xue","sequence":"first","affiliation":[{"name":"Program in Bioinformatics, Zhongshan School of Medicine and The Fifth Affiliated Hospital, Sun Yat-sen University , Guangzhou \u00a0510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences , Guangzhou \u00a0510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics, Zhongshan School of Medicine and The Fifth Affiliated Hospital, Sun Yat-sen University , Guangzhou \u00a0510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qihan","family":"Long","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics, Zhongshan School of Medicine and The Fifth Affiliated Hospital, Sun Yat-sen University , Guangzhou \u00a0510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics, Zhongshan School of Medicine and The Fifth Affiliated Hospital, Sun Yat-sen University , Guangzhou \u00a0510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangyi","family":"Li","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics, Zhongshan School of Medicine and The Fifth Affiliated Hospital, Sun Yat-sen University , Guangzhou \u00a0510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjie","family":"Peng","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics, Zhongshan School of Medicine and The Fifth Affiliated Hospital, Sun Yat-sen University , Guangzhou \u00a0510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Yang","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics, Zhongshan School of Medicine and The Fifth Affiliated Hospital, Sun Yat-sen University , Guangzhou \u00a0510080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4733-0109","authenticated-orcid":false,"given":"Miaoxin","family":"Li","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics, Zhongshan School of Medicine and The Fifth Affiliated Hospital, Sun Yat-sen University , Guangzhou \u00a0510080, China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University) , Ministry of Education, Guangzhou \u00a0510080, China"},{"name":"Center for Precision Medicine, Sun Yat-sen University , Guangzhou \u00a0510080, China"},{"name":"Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University , Zhuhai 519000 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"2022070500002680500_B1","doi-asserted-by":"crossref","first-page":"5900","DOI":"10.1038\/s41467-020-19653-5","article-title":"15 years of genome-wide association studies and no signs of slowing down","volume":"11","author":"Loos","year":"2020","journal-title":"Nat. Commun."},{"key":"2022070500002680500_B2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41576-019-0200-9","article-title":"Mechanisms of tissue and cell-type specificity in heritable traits and diseases","volume":"21","author":"Hekselman","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"2022070500002680500_B3","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1038\/ng.3981","article-title":"Estimating the causal tissues for complex traits and diseases","volume":"49","author":"Ongen","year":"2017","journal-title":"Nat. Genet."},{"key":"2022070500002680500_B4","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/ng.3404","article-title":"Partitioning heritability by functional annotation using genome-wide association summary statistics","volume":"47","author":"Finucane","year":"2015","journal-title":"Nat. Genet."},{"key":"2022070500002680500_B5","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.1093\/bioinformatics\/btz138","article-title":"deTS: tissue-specific enrichment analysis to decode tissue specificity","volume":"35","author":"Pei","year":"2019","journal-title":"Bioinformatics"},{"key":"2022070500002680500_B6","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/s41588-018-0081-4","article-title":"Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types","volume":"50","author":"Finucane","year":"2018","journal-title":"Nat. Genet."},{"key":"2022070500002680500_B7","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.ajhg.2017.09.009","article-title":"Inferring relevant cell types for complex traits by using single-cell gene expression","volume":"101","author":"Calderon","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"2022070500002680500_B8","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1038\/s41467-019-11181-1","article-title":"Genetic mapping of cell type specificity for complex traits","volume":"10","author":"Watanabe","year":"2019","journal-title":"Nat. Commun."},{"key":"2022070500002680500_B9","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1186\/s13059-019-1801-5","article-title":"DESE: estimating driver tissues by selective expression of genes associated with complex diseases or traits","volume":"20","author":"Jiang","year":"2019","journal-title":"Genome Biol."},{"key":"2022070500002680500_B10","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/nbt.4131","article-title":"Boosting the power of single-cell analysis","volume":"36","author":"Wen","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"2022070500002680500_B11","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.trecan.2018.02.003","article-title":"Single-Cell transcriptomic analysis of tumor heterogeneity","volume":"4","author":"Levitin","year":"2018","journal-title":"Trends Cancer"},{"key":"2022070500002680500_B12","doi-asserted-by":"crossref","first-page":"e8046","DOI":"10.15252\/msb.20178046","article-title":"Using single-cell genomics to understand developmental processes and cell fate decisions","volume":"14","author":"Griffiths","year":"2018","journal-title":"Mol. Syst. Biol."},{"key":"2022070500002680500_B13","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/nbt.4103","article-title":"Simultaneous single-cell profiling of lineages and cell types in the vertebrate brain","volume":"36","author":"Raj","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"2022070500002680500_B14","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41586-020-2157-4","article-title":"Construction of a human cell landscape at single-cell level","volume":"581","author":"Han","year":"2020","journal-title":"Nature"},{"key":"2022070500002680500_B15","doi-asserted-by":"crossref","first-page":"baz046","DOI":"10.1093\/database\/baz046","article-title":"PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data","volume":"2019","author":"Franzen","year":"2019","journal-title":"Database (Oxford)"},{"key":"2022070500002680500_B16","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The genotype-tissue expression (GTEx) project","volume":"45","author":"Lonsdale","year":"2013","journal-title":"Nat. Genet."},{"key":"2022070500002680500_B17","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41586-020-2157-4","article-title":"Construction of a human cell landscape at single-cell level","volume":"581","author":"Han","year":"2020","journal-title":"Nature"},{"key":"2022070500002680500_B18","doi-asserted-by":"crossref","first-page":"D996","DOI":"10.1093\/nar\/gks1042","article-title":"Allen brain atlas: an integrated spatio-temporal portal for exploring the central nervous system","volume":"41","author":"Sunkin","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2022070500002680500_B19","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2010-11-3-r25","article-title":"A scaling normalization method for differential expression analysis of RNA-seq data","volume":"11","author":"Robinson","year":"2010","journal-title":"Genome Biol."},{"key":"2022070500002680500_B20","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1038\/nprot.2009.97","article-title":"Mapping identifiers for the integration of genomic datasets with the R\/Bioconductor package biomaRt","volume":"4","author":"Durinck","year":"2009","journal-title":"Nat. Protoc."},{"key":"2022070500002680500_B21","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1038\/s41588-018-0248-z","article-title":"An atlas of genetic associations in UK biobank","volume":"50","author":"Canela-Xandri","year":"2018","journal-title":"Nat. Genet."},{"key":"2022070500002680500_B22","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1038\/s41588-019-0481-0","article-title":"A global overview of pleiotropy and genetic architecture in complex traits","volume":"51","author":"Watanabe","year":"2019","journal-title":"Nat. Genet."},{"key":"2022070500002680500_B23","first-page":"D807","article-title":"CAUSALdb: a database for disease\/trait causal variants identified using summary statistics of genome-wide association studies","volume":"48","author":"Wang","year":"2020","journal-title":"Nucleic. Acids. Res."},{"key":"2022070500002680500_B24","doi-asserted-by":"crossref","first-page":"D799","DOI":"10.1093\/nar\/gku1202","article-title":"GRASP v2.0: an update on the genome-wide repository of associations between SNPs and phenotypes","volume":"43","author":"Eicher","year":"2015","journal-title":"Nucleic. Acids. Res."},{"key":"2022070500002680500_B25","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1093\/bioinformatics\/bty682","article-title":"A powerful conditional gene-based association approach implicated functionally important genes for schizophrenia","volume":"35","author":"Li","year":"2019","journal-title":"Bioinformatics"},{"key":"2022070500002680500_B26","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":"2022070500002680500_B27","volume-title":"Architectural styles and the design of network-based software architectures","author":"Fielding","year":"2000"},{"key":"2022070500002680500_B28","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41586-018-0590-4","article-title":"Single-cell transcriptomics of 20 mouse organs creates a tabula muris","volume":"562","author":"Schaum","year":"2018","journal-title":"Nature"},{"key":"2022070500002680500_B29","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.immuni.2009.08.007","article-title":"Regulatory t cells in asthma","volume":"31","author":"Lloyd","year":"2009","journal-title":"Immunity"},{"key":"2022070500002680500_B30","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/nri2870","article-title":"Functions of t cells in asthma: more than just T(H)2 cells","volume":"10","author":"Lloyd","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"2022070500002680500_B31","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1136\/bmj.332.7554.1369","article-title":"Diagnosis and management of thyrotoxicosis","volume":"332","author":"Pearce","year":"2006","journal-title":"BMJ"},{"key":"2022070500002680500_B32","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1097\/MOO.0b013e3283533632","article-title":"Role of innate immunity in the pathogenesis of allergic rhinitis","volume":"20","author":"Melvin","year":"2012","journal-title":"Curr. Opin. Otolaryngol. Head Neck Surg."},{"key":"2022070500002680500_B33","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41590-020-00816-x","article-title":"The immunology of rheumatoid arthritis","volume":"22","author":"Weyand","year":"2021","journal-title":"Nat. Immunol."},{"key":"2022070500002680500_B34","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.intimp.2014.06.033","article-title":"Role of immune system in type 1 diabetes mellitus pathogenesis","volume":"22","author":"Szablewski","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"2022070500002680500_B35","first-page":"150","article-title":"The role of the immune system and cytokines involved in the pathogenesis of autoimmune thyroid disease (AITD)","volume":"65","author":"Mikos","year":"2014","journal-title":"Endokrynol. Pol."},{"key":"2022070500002680500_B36","doi-asserted-by":"crossref","first-page":"e1004219","DOI":"10.1371\/journal.pcbi.1004219","article-title":"MAGMA: generalized gene-set analysis of GWAS data","volume":"11","author":"de\u00a0Leeuw","year":"2015","journal-title":"PLoS Comput. Biol."},{"key":"2022070500002680500_B37","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.3389\/fphar.2019.01568","article-title":"Role of endothelial dysfunction in cardiovascular diseases: the link between inflammation and hydrogen sulfide","volume":"10","author":"Sun","year":"2019","journal-title":"Front Pharmacol"},{"key":"2022070500002680500_B38","first-page":"441","article-title":"Endothelial function and inflammation in coronary artery disease","volume":"92","author":"Tousoulis","year":"2006","journal-title":"Heart"},{"key":"2022070500002680500_B39","first-page":"521","article-title":"Depression as a glial-based synaptic dysfunction","volume":"9","author":"Rial","year":"2015","journal-title":"Front Cell Neurosci"},{"key":"2022070500002680500_B40","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fncel.2016.00163","article-title":"Editorial: glial plasticity in depression","volume":"10","author":"Oliveira","year":"2016","journal-title":"Front Cell Neurosci"},{"key":"2022070500002680500_B41","first-page":"S4","article-title":"The central role of t cells in rheumatoid arthritis","volume":"25","author":"Cope","year":"2007","journal-title":"Clin. Exp. Rheumatol."},{"key":"2022070500002680500_B42","doi-asserted-by":"crossref","first-page":"622306","DOI":"10.3389\/fimmu.2021.622306","article-title":"The role of natural killer cells in autoimmune diseases","volume":"12","author":"Kucuksezer","year":"2021","journal-title":"Front. Immunol."},{"key":"2022070500002680500_B43","doi-asserted-by":"crossref","first-page":"491974","DOI":"10.1100\/2012\/491974","article-title":"Natural killer cells and their role in rheumatoid arthritis: friend or foe?","volume":"2012","author":"Shegarfi","year":"2012","journal-title":"ScientificWorldJournal"},{"key":"2022070500002680500_B44","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/ar1010","article-title":"Roles of b cells in rheumatoid arthritis","volume":"5","author":"Silverman","year":"2003","journal-title":"Arthritis Res. Ther."},{"key":"2022070500002680500_B45","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.7150\/ijbs.49871","article-title":"Role of smooth muscle cells in cardiovascular disease","volume":"16","author":"Zhuge","year":"2020","journal-title":"Int J Biol Sci"},{"key":"2022070500002680500_B46","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3390\/biom9090472","article-title":"Fibroblasts and their pathological functions in the fibrosis of aortic valve sclerosis and atherosclerosis","volume":"9","author":"Singh","year":"2019","journal-title":"Biomolecules"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/50\/W1\/W568\/44379329\/gkac425.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/50\/W1\/W568\/44379329\/gkac425.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:05:33Z","timestamp":1656979533000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/50\/W1\/W568\/6593560"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,26]]},"references-count":46,"journal-issue":{"issue":"W1","published-online":{"date-parts":[[2022,5,26]]},"published-print":{"date-parts":[[2022,7,5]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkac425","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,7,5]]},"published":{"date-parts":[[2022,5,26]]}}}