PMID- 37867095
OWN - NLM
STAT- MEDLINE
DCOM- 20231204
LR  - 20240206
IS  - 1879-1166 (Electronic)
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 84
IP  - 12
DP  - 2023 Dec
TI  - Combined imputation of HLA genotype and self-identified race leads to better 
      donor-recipient matching.
PG  - 110721
LID - S0198-8859(23)00351-8 [pii]
LID - 10.1016/j.humimm.2023.110721 [doi]
AB  - Allogeneic Hematopoietic Cell Transplantation (HCT) is a curative therapy for 
      hematologic disorders and often requires human leukocyte antigen (HLA)-matched 
      donors. Donor registries have recruited donors utilizing evolving technologies of 
      HLA genotyping methods. This necessitates in-silico ambiguity resolution and 
      statistical imputation based on haplotype frequencies estimated from donor data 
      stratified by self-identified race and ethnicity (SIRE). However, SIRE has 
      limited genetic validity and presents a challenge for individuals with unknown or 
      mixed SIRE. We present MR-GRIMM "Multi-Race Graph IMputation and Matching" that 
      simultaneously imputes the race/ethnic category and HLA genotype using a SIRE 
      based prior. Additionally, we propose a novel method to impute HLA typing 
      inconsistent with current haplotype frequencies. The performance of MR-GRIMM was 
      validated using a dataset of 170,000 donor-recipient pairs. MR-GRIMM has an 
      average 20 % lower matching error (1-AUC) than single-race imputation. The recall 
      metric (sensitivity) of the race/ethnic category imputation from HLA was measured 
      by comparing the imputed donor race with the donor-provided SIRE. Accuracies of 
      0.74 and 0.55 were obtained for the prediction of 5 broad and 21 detailed US 
      population groups respectively. The operational implementation of this algorithm 
      in a registry search could help improve match predictions and access to 
      HLA-matched donors.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Israeli, Sapir
AU  - Israeli S
AD  - Department of Mathematics, Bar-Ilan University, Ramat Gan, Israel.
FAU - Gragert, Loren
AU  - Gragert L
AD  - Department of Pathology and Laboratory Medicine, Tulane University School of 
      Medicine, New Orleans, LA, United States.
FAU - Madbouly, Abeer
AU  - Madbouly A
AD  - National Marrow Donor Program/Be The Match, Minneapolis, MN, United States; 
      Center for International Blood and Marrow Transplant Research, Minneapolis, MN, 
      United States.
FAU - Bashyal, Pradeep
AU  - Bashyal P
AD  - National Marrow Donor Program/Be The Match, Minneapolis, MN, United States; 
      Center for International Blood and Marrow Transplant Research, Minneapolis, MN, 
      United States.
FAU - Schneider, Joel
AU  - Schneider J
AD  - National Marrow Donor Program/Be The Match, Minneapolis, MN, United States.
FAU - Maiers, Martin
AU  - Maiers M
AD  - National Marrow Donor Program/Be The Match, Minneapolis, MN, United States; 
      Center for International Blood and Marrow Transplant Research, Minneapolis, MN, 
      United States.
FAU - Louzoun, Yoram
AU  - Louzoun Y
AD  - Department of Mathematics, Bar-Ilan University, Ramat Gan, Israel. Electronic 
      address: louzouy@math.biu.ac.il.
LA  - eng
GR  - R01 AI128775/AI/NIAID NIH HHS/United States
GR  - R01 AI173095/AI/NIAID NIH HHS/United States
GR  - U01 AI152960/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20231021
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Humans
MH  - Genotype
MH  - *HLA Antigens/genetics
MH  - Haplotypes
MH  - Tissue Donors
MH  - *Hematopoietic Stem Cell Transplantation/methods
MH  - Histocompatibility Antigens Class II/genetics
MH  - Histocompatibility Testing/methods
MH  - Registries
PMC - PMC10842039
MID - NIHMS1941505
OTO - NOTNLM
OT  - EM
OT  - Ethnic groups
OT  - HLA
OT  - HSCT
OT  - Imputation
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/10/23 00:43
MHDA- 2023/12/04 12:43
PMCR- 2024/12/01
CRDT- 2023/10/22 22:04
PHST- 2023/03/17 00:00 [received]
PHST- 2023/09/05 00:00 [revised]
PHST- 2023/10/14 00:00 [accepted]
PHST- 2024/12/01 00:00 [pmc-release]
PHST- 2023/12/04 12:43 [medline]
PHST- 2023/10/23 00:43 [pubmed]
PHST- 2023/10/22 22:04 [entrez]
AID - S0198-8859(23)00351-8 [pii]
AID - 10.1016/j.humimm.2023.110721 [doi]
PST - ppublish
SO  - Hum Immunol. 2023 Dec;84(12):110721. doi: 10.1016/j.humimm.2023.110721. Epub 2023 
      Oct 21.