{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T19:38:28Z","timestamp":1786995508690,"version":"build-2736575974"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Killer cell immunoglobulin-like receptors (KIRs) are polymorphic immune regulators that modulate natural killer and T cell responses via interactions with human leukocyte antigen (HLA) class I ligands. High combinatorial diversity of KIR and HLA influences infection, autoimmunity, cancer, transplantation, and reproductive success. Although comprehensive KIR genotyping is achievable through targeted sequencing, complex genomic architecture hampers large-scale disease studies using genome wide data. Here, we introduce PONG2.0, a computational framework that accurately imputes high-resolution genotypes for all KIR that interact with HLA, directly from SNP-array data. We trained multi-ancestry models using matched SNP and KIR alleles from a subset of the 1000 Genomes Project (EUR\u2009=\u2009187, AMR\u2009=\u200993, SAS\u2009=\u2009102, AFR\u2009=\u2009102, EAS\u2009=\u2009102), achieving 92\u201399% overall accuracy. Validation against targeted sequencing of 267 independent samples confirmed robust per-locus concordance (92.1\u201397.7%). Population-level benchmarking of &amp;gt;\u20098000 individuals showed strong agreement with targeted sequencing (R2 up to 0.999; median deviation 0.6\u20136.8%), demonstrating reliable genotyping of samples that were independent from the model-building data. PONG2.0 is implemented as an open-source R package with pre-trained models, providing an efficient and scalable solution for KIR immunogenetics in large-scale biobanks and cohort studies. https:\/\/github.com\/NormanLabUCD\/PONG2<\/jats:p>","DOI":"10.1093\/hmg\/ddag075","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:18:52Z","timestamp":1785323932000},"source":"Crossref","is-referenced-by-count":0,"title":["PONG 2.0: allele imputation for the killer cell immunoglobulin-like receptors"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9944-571X","authenticated-orcid":false,"given":"Suraju A","family":"Sadeeq","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, Anschutz Health Science Building, 1890 N. Revere Court, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A","family":"Leaton","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Anschutz Health Science Building, 1890 N. Revere Court, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine M","family":"Kichula","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Anschutz Health Science Building, 1890 N. Revere Court, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ticiana D J","family":"Farias","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Anschutz Health Science Building, 1890 N. Revere Court, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neus","family":"Font-Porterias","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Anschutz Health Science Building, 1890 N. Revere Court, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas R","family":"Pollock","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Anschutz Health Science Building, 1890 N. Revere Court, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Colorado Center for Personalized Medicine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E","family":"Collora","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Anschutz Health Science Building, 1890 N. Revere Court, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick C","family":"Castelli","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, S\u00e3o Paulo State University (Unesp) , Botucatu - SP,","place":["18618-687, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9728-6567","authenticated-orcid":false,"given":"Christopher R","family":"Gignoux","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Anschutz Health Science Building, 1890 N. Revere Court, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8370-7703","authenticated-orcid":false,"given":"Paul J","family":"Norman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Anschutz Health Science Building, 1890 N. Revere Court, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["United States"]},{"name":"Department of Immunology and Microbiology, Research I North, 12800 East 19th Avenue, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["United States"]},{"name":"Department of Orthopedics, Academic Office One, 12631 East 17th Avenue, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"2026081715104671100_ref1","doi-asserted-by":"publisher","volume":"44","DOI":"10.1016\/j.blre.2020.100678"},{"key":"2026081715104671100_ref2","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/nri1570","article-title":"MHC class I molecules and KIRS in human history, health and survival","volume":"5","author":"Parham","year":"2005","journal-title":"Nat Rev 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of killer immunoglobulin-like receptor and human leukocyte antigen loci: a population-based case-control study","volume":"213","author":"Goedert","year":"2016","journal-title":"J Infect Dis"},{"key":"2026081715104671100_ref7","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-13-405","article-title":"KIR3DS1\/L1 and HLA-Bw4-80I are associated with HIV disease progression among HIV typical progressors and long-term nonprogressors","volume":"13","author":"Jiang","year":"2013","journal-title":"BMC Infect Dis"},{"key":"2026081715104671100_ref8","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1007\/s00439-015-1579-9","article-title":"KIR and HLA under pressure: evidences of coevolution across worldwide populations","volume":"134","author":"Augusto","year":"2015","journal-title":"Hum Genet"},{"key":"2026081715104671100_ref9","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1002\/iid3.178","article-title":"KIR2DS5 allotypes that recognize the C2 epitope of HLA-C are 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