{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:48:58Z","timestamp":1771634938571,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009131","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000}}],"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Human immunogenetic variation in the form of HLA and KIR types has been shown to be strongly associated with a multitude of immune-related phenotypes. However, association studies involving immunogenetic loci most commonly involve simple analyses of classical HLA allelic diversity, resulting in limitations regarding the interpretability and reproducibility of results. We here present MiDAS, a comprehensive R package for immunogenetic data transformation and statistical analysis. MiDAS recodes input data in the form of HLA alleles and KIR types into biologically meaningful variables, allowing HLA amino acid fine mapping, analyses of HLA evolutionary divergence as well as experimentally validated HLA-KIR interactions. Further, MiDAS enables comprehensive statistical association analysis workflows with phenotypes of diverse measurement scales. MiDAS thus closes the gap between the inference of immunogenetic variation and its efficient utilization to make relevant discoveries related to immune and disease biology. It is freely available under a MIT license.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009131","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T17:42:17Z","timestamp":1625593337000},"page":"e1009131","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["MiDAS\u2014Meaningful Immunogenetic Data at Scale"],"prefix":"10.1371","volume":"17","author":[{"given":"Maciej","family":"Migdal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4598-0199","authenticated-orcid":true,"given":"Dan Fu","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William F.","family":"Forrest","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir","family":"Horowitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4548-7548","authenticated-orcid":true,"given":"Christian","family":"Hammer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,7,6]]},"reference":[{"key":"pcbi.1009131.ref001","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nri.2017.143","article-title":"HLA variation and disease","volume":"18","author":"CA Dendrou","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"pcbi.1009131.ref002","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":"D Pende","year":"2019","journal-title":"Front Immunol"},{"key":"pcbi.1009131.ref003","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":"D Vukcevic","year":"2015","journal-title":"Am J Hum Genetics"},{"key":"pcbi.1009131.ref004","doi-asserted-by":"crossref","first-page":"e0172444","DOI":"10.1371\/journal.pone.0172444","article-title":"Comparison of HLA allelic imputation programs.","volume":"12","author":"JH Karnes","year":"2017","journal-title":"Plos One."},{"key":"pcbi.1009131.ref005","first-page":"bbaa223","article-title":"In silico tools for accurate HLA and KIR inference from clinical sequencing data empower immunogenetics on individual-patient and population scales","author":"J Chen","year":"2020","journal-title":"Brief Bioinform"},{"key":"pcbi.1009131.ref006","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13073-020-00790-x","article-title":"The landscape of host genetic factors involved in immune response to common viral infections","volume":"12","author":"L Kachuri","year":"2020","journal-title":"Genome Med."},{"key":"pcbi.1009131.ref007","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/ng.1076","article-title":"Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis","volume":"44","author":"S Raychaudhuri","year":"2012","journal-title":"Nat Genet"},{"key":"pcbi.1009131.ref008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2172-9-1","article-title":"HLA class I supertypes: a revised and updated classification","volume":"9","author":"J Sidney","year":"2008","journal-title":"Bmc Immunol"},{"key":"pcbi.1009131.ref009","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1093\/infdis\/jiv127","article-title":"HLA Class I Supertype Associations With Clinical Outcome of Secondary Dengue Virus Infections in Ethnic Thais","volume":"212","author":"S Vejbaesya","year":"2015","journal-title":"J Infect Dis"},{"key":"pcbi.1009131.ref010","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s00251-017-1003-9","article-title":"The role of KIR and HLA interactions in pregnancy complications","volume":"69","author":"F. Colucci","year":"2017","journal-title":"Immunogenetics"},{"key":"pcbi.1009131.ref011","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1399-0039.2010.01466.x","article-title":"Nomenclature for factors of the HLA system, 2010.","volume":"75","author":"SGE Marsh","year":"2010","journal-title":"Tissue Antigens"},{"key":"pcbi.1009131.ref012","unstructured":"HLA G group definitions. n.d. [cited 4 Jan 2021]. Available: http:\/\/hla.alleles.org\/alleles\/g_groups.html"},{"key":"pcbi.1009131.ref013","first-page":"D783","article-title":"Allele frequency net database (AFND) 2020 update: gold-standard data classification, open access genotype data and new query tools.","volume":"48","author":"FF Gonzalez-Galarza","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1009131.ref014","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/jhg.2008.5","article-title":"The HLA genomic loci map: expression, interaction, diversity and disease","volume":"54","author":"T Shiina","year":"2009","journal-title":"J Hum Genet"},{"key":"pcbi.1009131.ref015","first-page":"D948","article-title":"IPD-IMGT\/HLA Database.","volume":"48","author":"J Robinson","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1009131.ref016","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1126\/science.283.5408.1748","article-title":"HLA and HIV-1: Heterozygote Advantage and B*35-Cw*04 Disadvantage","volume":"283","author":"M Carrington","year":"1999","journal-title":"Science"},{"key":"pcbi.1009131.ref017","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1093\/molbev\/msz249","article-title":"HLA Heterozygote Advantage against HIV-1 Is Driven by Quantitative and Qualitative Differences in HLA Allele-Specific Peptide Presentation","volume":"37","author":"J Arora","year":"2019","journal-title":"Mol Biol Evol"},{"key":"pcbi.1009131.ref018","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1038\/s41591-019-0639-4","article-title":"Evolutionary divergence of HLA class I genotype impacts efficacy of cancer immunotherapy","volume":"25","author":"D Chowell","year":"2019","journal-title":"Nat Med"},{"key":"pcbi.1009131.ref019","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00251-015-0849-y","article-title":"Zooming into the binding groove of HLA molecules: which positions and which substitutions change peptide binding most?","volume":"67","author":"HWM van Deutekom","year":"2015","journal-title":"Immunogenetics"},{"key":"pcbi.1009131.ref020","doi-asserted-by":"crossref","first-page":"e0195778","DOI":"10.1371\/journal.pone.0195778","article-title":"Association between KIR-HLA combination and ulcerative colitis and Crohn\u2019s disease in a Japanese population.","volume":"13","author":"H Saito","year":"2018","journal-title":"Plos One"},{"key":"pcbi.1009131.ref021","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.bbmt.2017.11.029","article-title":"Homozygous HLA-C1 is Associated with Reduced Risk of Relapse after HLA-Matched Transplantation in Patients with Myeloid Leukemia","volume":"24","author":"N Arima","year":"2018","journal-title":"Biol Blood Marrow Tr"},{"key":"pcbi.1009131.ref022","doi-asserted-by":"crossref","first-page":"298348","DOI":"10.1155\/2011\/298348","article-title":"KIR\/HLA Interactions and Pathogen Immunity","volume":"2011","author":"KM Jamil","year":"2011","journal-title":"J Biomed Biotechnol"},{"key":"pcbi.1009131.ref023","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.bbmt.2015.01.018","article-title":"Role of Donor Activating KIR\u2013HLA Ligand\u2013Mediated NK Cell Education Status in Control of Malignancy in Hematopoietic Cell Transplant Recipients.","volume":"21","author":"J Nowak","year":"2015","journal-title":"Biol Blood Marrow Tr"},{"key":"pcbi.1009131.ref024","doi-asserted-by":"crossref","first-page":"33","DOI":"10.4049\/jimmunol.178.1.33","article-title":"Cutting Edge: Allele-Specific and Peptide-Dependent Interactions between KIR3DL1 and HLA-A and HLA-B","volume":"178","author":"H Thananchai","year":"2007","journal-title":"J Immunol"},{"key":"pcbi.1009131.ref025","doi-asserted-by":"crossref","first-page":"6198","DOI":"10.4049\/jimmunol.1300464","article-title":"Allelic Variation in KIR2DL3 Generates a KIR2DL2-like Receptor with Increased Binding to its HLA-C Ligand","volume":"190","author":"WR Frazier","year":"2013","journal-title":"J Immunol"},{"key":"pcbi.1009131.ref026","doi-asserted-by":"crossref","first-page":"4268","DOI":"10.1093\/hmg\/ddv158","article-title":"Epigenetic regulation of differential HLA-A allelic expression levels","volume":"24","author":"V Ramsuran","year":"2015","journal-title":"Hum Mol Genet"},{"key":"pcbi.1009131.ref027","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.humimm.2017.06.195","article-title":"P135 New frequent HLA-DPB1\/DPA1 haplotypes in low resolution typing","volume":"78","author":"P Rao","year":"2017","journal-title":"Hum Immunol"},{"key":"pcbi.1009131.ref028","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1126\/science.185.4154.862","article-title":"Amino Acid Difference Formula to Help Explain Protein Evolution","volume":"185","author":"R. Grantham","year":"1974","journal-title":"Science"},{"key":"pcbi.1009131.ref029","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1093\/molbev\/msy116","article-title":"Divergent allele advantage at human MHC genes: signatures of past and ongoing selection","volume":"35","author":"F Pierini","year":"2018","journal-title":"Mol Biol Evol"},{"key":"pcbi.1009131.ref030","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-immunol-042617-053149","article-title":"Genetics of Natural Killer Cells in Human Health, Disease, and Survival","volume":"36","author":"P Parham","year":"2018","journal-title":"Annu Rev Immunol"},{"key":"pcbi.1009131.ref031","doi-asserted-by":"crossref","first-page":"D1234","DOI":"10.1093\/nar\/gks1140","article-title":"IPD\u2014the Immuno Plymorphism Database","volume":"41","author":"J Robinson","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1009131.ref032","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/gene.2015.44","article-title":"KIR haplotypes are associated with late-onset type 1 diabetes in European\u2013American families","volume":"17","author":"JA Traherne","year":"2016","journal-title":"Genes Immun"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1009131","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1009131","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T17:51:20Z","timestamp":1626457880000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1009131"}},"subtitle":[],"editor":[{"given":"Mihaela","family":"Pertea","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,7,6]]},"references-count":32,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1009131","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1009131","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,6]]}}}