title: Charting improvements in US registry HLA typing ambiguity using a typing resolution score.
abstract: Unrelated stem cell registries have been collecting HLA typing of volunteer bone marrow donors for over 25years. Donor selection for hematopoietic stem cell transplantation is based primarily on matching the alleles of donors and patients at five polymorphic HLA loci. As HLA typing technologies have continually advanced since the beginnings of stem cell transplantation, registries have accrued typings of varied HLA typing ambiguity. We present a new typing resolution score (TRS), based on the likelihood of self-match, that allows the systematic comparison of HLA typings across different methods, data sets and populations. We apply the TRS to chart improvement in HLA typing within the Be The Match Registry of the United States from the initiation of DNA-based HLA typing to the current state of high-resolution typing using next-generation sequencing technologies. In addition, we present a publicly available online tool for evaluation of any given HLA typing. This TRS objectively evaluates HLA typing methods and can help define standards for acceptable recruitment HLA typing.
authors.affiliation: Bioinformatics Research, National Marrow Donor Program, 3001 Broadway Street N.E., Suite 100, Minneapolis, MN 55413-1753, USA. Electronic address: vpaunic@nmdp.org.
authors.forename: Vanja
authors.initials: V
authors.lastname: Paunić
authors.affiliation: Bioinformatics Research, National Marrow Donor Program, 3001 Broadway Street N.E., Suite 100, Minneapolis, MN 55413-1753, USA. Electronic address: lgragert@nmdp.org.
authors.forename: Loren
authors.initials: L
authors.lastname: Gragert
authors.affiliation: Bioinformatics Research, National Marrow Donor Program, 3001 Broadway Street N.E., Suite 100, Minneapolis, MN 55413-1753, USA. Electronic address: jschneid@nmdp.org.
authors.forename: Joel
authors.initials: J
authors.lastname: Schneider
authors.affiliation: Zentrales Knochenmarkspender Register für Deutschland, Helmholtzstraße 10, 89081 Ulm, Germany. Electronic address: carlheinz.mueller@zkrd.de.
authors.forename: Carlheinz
authors.initials: C
authors.lastname: Müller
authors.affiliation: Bioinformatics Research, National Marrow Donor Program, 3001 Broadway Street N.E., Suite 100, Minneapolis, MN 55413-1753, USA. Electronic address: mmaiers@NMDP.ORG.
authors.forename: Martin
authors.initials: M
authors.lastname: Maiers
mesh_terms: D046148:Donor Selection; D005006:Ethnicity; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D016013:Likelihood Functions; D012042:Registries; D012107:Research Design; D014019:Tissue Donors; D014481:United States; D014838:Volunteers
keywords: Be The Match Registry; HLA typing; Human leukocyte antigen; Typing ambiguity; Typing resolution score