{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:57:53Z","timestamp":1785448673015,"version":"3.56.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007225","name":"MOST","doi-asserted-by":"publisher","award":["111-2221-E-002-166-MY3"],"award-info":[{"award-number":["111-2221-E-002-166-MY3"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"NSTC","doi-asserted-by":"publisher","award":["112-2221-E-002-184-MY3"],"award-info":[{"award-number":["112-2221-E-002-184-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>The Killer-cell Immunoglobulin-like Receptor (KIR) is a highly polymorphic region in the human genome, associated with autoimmune diseases and organ transplantation. The sequences of KIR genes are highly similar among star alleles as well as in between individual genes, with the copy number of each KIR gene typically ranging from 0 to 4. In this study, we introduce Graph-KIR, a tool designed to estimate gene copy numbers and predict full-resolution (7-digit, encompassing both coding and non-coding sequence variations) from a whole genome sequencing (WGS) sample.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Graph-KIR is capable of independently typing KIR alleles per sample with no reliance on the distribution of any framework gene in a cohort. In a set of 100 simulated samples, Graph-KIR demonstrated 99.2% accuracy in copy number estimation and high F1-score of allele typing: 91.79% at 7-digit resolution, 97.37% at 5-digit resolution, and 97.11% at 3-digit resolution. Graph-KIR outperforms existing tools such as Geny (96.39% F1-score), PING\u2019s WGS version (92.77% F1-score), and T1K (90.44% F1-score) at 5-digit resolution. By analyzing the results on 44 HPRC samples, Graph-KIR achieves better F1-score than Geny and PING at 7-digit resolution. The release of Graph-KIR adds another valuable tool to assist users in accurately estimating copy numbers and calling alleles of KIR genes from WGS samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The Graph-KIR and paper-related pipeline codes are available at https:\/\/github.com\/linnil1\/KIR_graph.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag521","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T11:39:52Z","timestamp":1784374792000},"source":"Crossref","is-referenced-by-count":0,"title":["Graph-KIR: graph-based KIR copy number estimation and allele calling using short-read sequencing data"],"prefix":"10.1093","volume":"42","author":[{"given":"Hong-Ye","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Biomechatronics Engineering, National Taiwan University , Taipei 10617,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomechatronics Engineering, National Taiwan University , Taipei 10617,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Yu","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Genomics and Proteomics, National Taiwan University , Taipei 10055,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Wen","family":"Chuang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Genomics and Proteomics, National Taiwan University , Taipei 10055,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Kai","family":"Hung","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Genomics and Proteomics, National Taiwan University , Taipei 10055,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Jim","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University , Taipei 10617,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob Shujui","family":"Hsu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Genomics and Proteomics, National Taiwan University , Taipei 10055,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7447-8045","authenticated-orcid":false,"given":"Chia-Lang","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Medical Research, National Taiwan University Hospital , Taipei 10002,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Chien","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine , Taipei 10051,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Lung","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Genomics and Proteomics, National Taiwan University , Taipei 10055,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6940-6389","authenticated-orcid":false,"given":"Chien-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomechatronics Engineering, National Taiwan University , Taipei 10617,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"2026073017011906600_btag521-B1","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":"2026073017011906600_btag521-B2","doi-asserted-by":"crossref","first-page":"5222","DOI":"10.4049\/jimmunol.175.8.5222","article-title":"KIR3DL1 polymorphisms that affect NK cell inhibition by HLA-Bw4 ligand","volume":"175","author":"Carr","year":"2005","journal-title":"J Immunol"},{"key":"2026073017011906600_btag521-B3","doi-asserted-by":"crossref","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"Gigascience"},{"key":"2026073017011906600_btag521-B5","doi-asserted-by":"crossref","first-page":"btae622","DOI":"10.1093\/bioinformatics\/btae622","article-title":"Biologically-informed killer cell immunoglobulin-like receptor gene annotation tool","volume":"40","author":"Ford","year":"2024","journal-title":"Bioinformatics"},{"key":"2026073017011906600_btag521-B6","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/bioinformatics\/btr708","article-title":"ART: a next-generation sequencing read simulator","volume":"28","author":"Huang","year":"2012","journal-title":"Bioinformatics"},{"key":"2026073017011906600_btag521-B7","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1101\/gr.278358.123","article-title":"Genetic complexity of killer-cell immunoglobulin-like receptor genes in human pangenome assemblies","volume":"34","author":"Hung","year":"2024","journal-title":"Genome Res"},{"key":"2026073017011906600_btag521-B8","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1101\/gr.137976.112","article-title":"Copy number variation leads to considerable diversity for B but not a haplotypes of the human KIR genes encoding NK cell receptors","volume":"22","author":"Jiang","year":"2012","journal-title":"Genome Res"},{"key":"2026073017011906600_btag521-B9","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat Biotechnol"},{"key":"2026073017011906600_btag521-B10","doi-asserted-by":"crossref","first-page":"D1115","DOI":"10.1093\/nar\/gkab959","article-title":"The UCSC genome browser database: 2022 update","volume":"50","author":"Lee","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2026073017011906600_btag521-B11","author":"Li","year":"2013"},{"key":"2026073017011906600_btag521-B12","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","article-title":"Minimap2: pairwise alignment for nucleotide sequences","volume":"34","author":"Li","year":"2018","journal-title":"Bioinformatics"},{"key":"2026073017011906600_btag521-B13","doi-asserted-by":"crossref","first-page":"e1008904","DOI":"10.1371\/journal.pcbi.1008904","article-title":"High-throughput interpretation of killer-cell immunoglobulin-like receptor short-read sequencing data with PING","volume":"17","author":"Marin","year":"2021","journal-title":"PLoS Comput Biol"},{"key":"2026073017011906600_btag521-B14","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1111\/tan.14949","article-title":"Software update: interpreting killer-cell immunoglobulin-like receptors from whole genome sequence data with PING","volume":"101","author":"Marin","year":"2023","journal-title":"HLA"},{"key":"2026073017011906600_btag521-B15","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1007\/s00251-003-0571-z","article-title":"Killer-cell immunoglobulin-like receptor (KIR) nomenclature report, 2002","volume":"55","author":"Marsh","year":"2003","journal-title":"Immunogenetics"},{"key":"2026073017011906600_btag521-B16","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ajhg.2016.06.023","article-title":"Defining KIR and HLA class I genotypes at highest resolution via high-throughput sequencing","volume":"99","author":"Norman","year":"2016","journal-title":"Am J Hum Genet"},{"key":"2026073017011906600_btag521-B17","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.3389\/fimmu.2019.01179","article-title":"Killer Ig-like receptors (KIRs): their role in NK cell modulation and developments leading to their clinical exploitation","volume":"10","author":"Pende","year":"2019","journal-title":"Front Immunol"},{"key":"2026073017011906600_btag521-B18","author":"Poplin","year":"2017"},{"key":"2026073017011906600_btag521-B19","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative genomics viewer","volume":"29","author":"Robinson","year":"2011","journal-title":"Nat Biotechnol"},{"key":"2026073017011906600_btag521-B20","doi-asserted-by":"crossref","first-page":"D1234","DOI":"10.1093\/nar\/gks1140","article-title":"IPD\u2014the immuno polymorphism database","volume":"41","author":"Robinson","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2026073017011906600_btag521-B21","doi-asserted-by":"crossref","first-page":"583013","DOI":"10.3389\/fimmu.2020.583013","article-title":"Accurate and efficient KIR gene and haplotype inference from genome sequencing reads with novel K-mer signatures","volume":"11","author":"Roe","year":"2020","journal-title":"Front Immunol"},{"key":"2026073017011906600_btag521-B22","doi-asserted-by":"crossref","first-page":"100101","DOI":"10.1016\/j.xgen.2022.100101","article-title":"Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method","volume":"2","author":"Sakaue","year":"2022","journal-title":"Cell Genom"},{"key":"2026073017011906600_btag521-B23","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1101\/gr.277585.122","article-title":"Efficient and accurate KIR and HLA genotyping with massively parallel sequencing data","volume":"33","author":"Song","year":"2023","journal-title":"Genome Res"},{"key":"2026073017011906600_btag521-B24","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1093\/bioinformatics\/btv112","article-title":"Unified representation of genetic variants","volume":"31","author":"Tan","year":"2015","journal-title":"Bioinformatics"},{"key":"2026073017011906600_btag521-B25","first-page":"42","article-title":"GNU parallel\u2014the command-line power tool","volume":"36","author":"Tange","year":"2011","journal-title":"Login USENIX Mag"},{"key":"2026073017011906600_btag521-B26","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.ajhg.2015.09.005","article-title":"Imputation of KIR types from SNP variation data","volume":"97","author":"Vukcevic","year":"2015","journal-title":"Am J Hum Genet"},{"key":"2026073017011906600_btag521-B27","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41586-022-04601-8","article-title":"The human pangenome project: a global resource to map genomic diversity","volume":"604","author":"Wang","year":"2022","journal-title":"Nature"},{"key":"2026073017011906600_btag521-B28","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1084\/jem.20051884","article-title":"Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function","volume":"203","author":"Yawata","year":"2006","journal-title":"J Exp Med"},{"key":"2026073017011906600_btag521-B29","doi-asserted-by":"crossref","first-page":"1494995","DOI":"10.3389\/fimmu.2024.1494995","article-title":"Geny: a genotyping tool for allelic decomposition of killer cell immunoglobulin-like receptor genes","volume":"15","author":"Zhou","year":"2024","journal-title":"Front Immunol"},{"key":"2026073017011906600_btag521-B30","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1101\/gr.278985.124","article-title":"Full-resolution HLA and KIR gene annotations for human genome assemblies","volume":"34","author":"Zhou","year":"2024","journal-title":"Genome Res"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btag521\/69682281\/btag521.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/42\/7\/btag521\/69682281\/btag521.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/42\/7\/btag521\/69682281\/btag521.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:01:25Z","timestamp":1785445285000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btag521\/8739079"}},"subtitle":[],"editor":[{"given":"Can","family":"Alkan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":29,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7,2]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btag521","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,7]]},"article-number":"btag521"}}