{"doi":"10.1371/journal.pcbi.1009059","title":"Allele imputation for the killer cell immunoglobulin-like receptor KIR3DL1/S1","abstract":"Highly polymorphic interaction of KIR3DL1 and KIR3DS1 with HLA class I ligands modulates the effector functions of natural killer (NK) cells and some T cells. This genetically determined diversity affects severity of infections, immune-mediated diseases, and some cancers, and impacts the course of immunotherapies, including transplantation. KIR3DL1 is an inhibitory receptor, and KIR3DS1 is an activating receptor encoded by the KIR3DL1/S1 gene that has more than 200 diverse and divergent alleles. Determination of KIR3DL1/S1 genotypes for medical application is hampered by complex sequence and structural variation, requiring targeted approaches to generate and analyze high-resolution allele data. To overcome these obstacles, we developed and optimized a model for imputing KIR3DL1/S1 alleles at high-resolution from whole-genome SNP data. We designed the model to represent a substantial component of human genetic diversity. Our Global imputation model is effective at genotyping KIR3DL1/S1 alleles with an accuracy ranging from 88% in Africans to 97% in East Asians, with mean specificity of 99% and sensitivity of 95% for alleles >1% frequency. We used the established algorithm of the HIBAG program, in a modification named Pulling Out Natural killer cell Genomics (PONG). Because HIBAG was designed to impute HLA alleles also from whole-genome SNP data, PONG allows combinatorial diversity of KIR3DL1/S1 with HLA-A and -B to be analyzed using complementary techniques on a single data source. The use of PONG thus negates the need for targeted sequencing data in very large-scale association studies where such methods might not be tractable.","journal":"PLoS Computational Biology","year":2022,"id":280675,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9475,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":816883,"name":"Laura Ann Leaton","orcid":"0000-0002-0650-5830","position":1,"is_corresponding":false},{"id":817408,"name":"Erica A. Harrison","orcid":null,"position":2,"is_corresponding":false},{"id":774981,"name":"Katherine M. Kichula","orcid":"0000-0002-9817-3043","position":3,"is_corresponding":false},{"id":576875,"name":"Marte K. Viken","orcid":"0000-0002-3917-9269","position":4,"is_corresponding":false},{"id":11239,"name":"Jonathan A. Shortt","orcid":"0000-0002-7980-5420","position":5,"is_corresponding":false},{"id":11360,"name":"Christopher R. Gignoux","orcid":"0000-0001-9728-6567","position":6,"is_corresponding":false},{"id":673474,"name":"Benedicte A. Lie","orcid":"0000-0002-1159-7004","position":7,"is_corresponding":false},{"id":51082,"name":"Damjan Vukcevic","orcid":"0000-0001-7780-9586","position":8,"is_corresponding":false},{"id":29691,"name":"Stephen Leslie","orcid":"0000-0003-3511-3470","position":9,"is_corresponding":false},{"id":19722,"name":"Paul J. Norman","orcid":"0000-0001-8370-7703","position":10,"is_corresponding":false},{"id":564883,"name":"Genelle F. Harrison","orcid":"0000-0003-3386-8159","position":0,"is_corresponding":true}],"reference_count":109,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:29:03.247347Z","pmid":"35192601","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}