{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T21:10:38Z","timestamp":1777065038960,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1008904","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000}}],"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"national institutes of health","doi-asserted-by":"publisher","award":["NIH-R01AI128775"],"award-info":[{"award-number":["NIH-R01AI128775"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"national institutes of health","doi-asserted-by":"publisher","award":["NIH-R01AI128775"],"award-info":[{"award-number":["NIH-R01AI128775"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH-R01AI128775"],"award-info":[{"award-number":["NIH-R01AI128775"]}],"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"],"abstract":"<jats:p>\n                    The\n                    <jats:italic>killer-cell immunoglobulin-like receptor<\/jats:italic>\n                    (\n                    <jats:italic>KIR)<\/jats:italic>\n                    complex on chromosome 19 encodes receptors that modulate the activity of natural killer cells, and variation in these genes has been linked to infectious and autoimmune disease, as well as having bearing on pregnancy and transplant outcomes. The medical relevance and high variability of\n                    <jats:italic>KIR<\/jats:italic>\n                    genes makes short-read sequencing an attractive technology for interrogating the region, providing a high-throughput, high-fidelity sequencing method that is cost-effective. However, because this gene complex is characterized by extensive nucleotide polymorphism, structural variation including gene fusions and deletions, and a high level of homology between genes, its interrogation at high resolution has been thwarted by bioinformatic challenges, with most studies limited to examining presence or absence of specific genes. Here, we present the PING (Pushing Immunogenetics to the Next Generation) pipeline, which incorporates empirical data, novel alignment strategies and a custom alignment processing workflow to enable high-throughput\n                    <jats:italic>KIR<\/jats:italic>\n                    sequence analysis from short-read data. PING provides\n                    <jats:italic>KIR<\/jats:italic>\n                    gene copy number classification functionality for all\n                    <jats:italic>KIR<\/jats:italic>\n                    genes through use of a comprehensive alignment reference. The gene copy number determined per individual enables an innovative genotype determination workflow using genotype-matched references. Together, these methods address the challenges imposed by the structural complexity and overall homology of the\n                    <jats:italic>KIR<\/jats:italic>\n                    complex. To determine copy number and genotype determination accuracy, we applied PING to European and African validation cohorts and a synthetic dataset. PING demonstrated exceptional copy number determination performance across all datasets and robust genotype determination performance. Finally, an investigation into discordant genotypes for the synthetic dataset provides insight into misaligned reads, advancing our understanding in interpretation of short-read sequencing data in complex genomic regions. PING promises to support a new era of studies of KIR polymorphism, delivering high-resolution\n                    <jats:italic>KIR<\/jats:italic>\n                    genotypes that are highly accurate, enabling high-quality, high-throughput\n                    <jats:italic>KIR<\/jats:italic>\n                    genotyping for disease and population studies.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1008904","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T13:40:26Z","timestamp":1627911626000},"page":"e1008904","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":32,"title":["High-throughput Interpretation of Killer-cell Immunoglobulin-like Receptor Short-read Sequencing Data with PING"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2334-0396","authenticated-orcid":true,"given":"Wesley 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G.","family":"Augusto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tasneem","family":"Yusufali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4730-5165","authenticated-orcid":true,"given":"Bianca","family":"Heyn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3397-2514","authenticated-orcid":true,"given":"Jan","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6442-9573","authenticated-orcid":true,"given":"Vinzenz","family":"Lange","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8485-2945","authenticated-orcid":true,"given":"J\u00fcrgen","family":"Sauter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Norman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill A.","family":"Hollenbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,8,2]]},"reference":[{"key":"pcbi.1008904.ref001","first-page":"428","volume-title":"Immunology Today","author":"M Colonna","year":"2000"},{"issue":"17","key":"pcbi.1008904.ref002","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1182\/blood-2012-03-416867","article-title":"CD8 T cells express randomly selected KIRs with distinct specificities compared with NK cells","volume":"120","author":"NK Bj\u00f6rkstr\u00f6m","year":"2012","journal-title":"Blood"},{"issue":"6","key":"pcbi.1008904.ref003","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1182\/blood-2009-09-245746","article-title":"Education of human natural killer cells by activating killer cell 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