PMID- 37180102
OWN - NLM
STAT- MEDLINE
DCOM- 20230921
LR  - 20240310
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - Prediction of HLA genotypes from single-cell transcriptome data.
PG  - 1146826
LID - 10.3389/fimmu.2023.1146826 [doi]
LID - 1146826
AB  - The human leukocyte antigen (HLA) locus plays a central role in adaptive immune 
      function and has significant clinical implications for tissue transplant 
      compatibility and allelic disease associations. Studies using bulk-cell RNA 
      sequencing have demonstrated that HLA transcription may be regulated in an 
      allele-specific manner and single-cell RNA sequencing (scRNA-seq) has the 
      potential to better characterize these expression patterns. However, 
      quantification of allele-specific expression (ASE) for HLA loci requires 
      sample-specific reference genotyping due to extensive polymorphism. While 
      genotype prediction from bulk RNA sequencing is well described, the feasibility 
      of predicting HLA genotypes directly from single-cell data is unknown. Here we 
      evaluate and expand upon several computational HLA genotyping tools by comparing 
      predictions from human single-cell data to gold-standard, molecular genotyping. 
      The highest 2-field accuracy averaged across all loci was 76% by arcasHLA and 
      increased to 86% using a composite model of multiple genotyping tools. We also 
      developed a highly accurate model (AUC 0.93) for predicting HLA-DRB345 copy 
      number in order to improve genotyping accuracy of the HLA-DRB locus. Genotyping 
      accuracy improved with read depth and was reproducible at repeat sampling. Using 
      a metanalytic approach, we also show that HLA genotypes from PHLAT and OptiType 
      can generate ASE ratios that are highly correlated (R(2) = 0.8 and 0.94, 
      respectively) with those derived from gold-standard genotyping.
CI  - Copyright (c) 2023 Solomon, Zheng, Dillon, Goldman, Hourigan, Heath and Khatri.
FAU - Solomon, Benjamin D
AU  - Solomon BD
AD  - Department of Pediatrics, Stanford University, Palo Alto, CA, United States.
FAU - Zheng, Hong
AU  - Zheng H
AD  - Institute for Immunity, Transplantation and Infection, School of Medicine, 
      Stanford University, Stanford, CA, United States.
AD  - Center for Biomedical Informatics Research, Department of Medicine, School of 
      Medicine, Stanford University, Stanford, CA, United States.
FAU - Dillon, Laura W
AU  - Dillon LW
AD  - Laboratory of Myeloid Malignancies, National Heart Lung and Blood Institute, 
      Bethesda, MD, United States.
FAU - Goldman, Jason D
AU  - Goldman JD
AD  - Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, 
      United States.
AD  - Providence St. Joseph Health, Renton, WA, United States.
AD  - Division of Allergy & Infectious Diseases, University of Washington, Seattle, WA, 
      United States.
FAU - Hourigan, Christopher S
AU  - Hourigan CS
AD  - Laboratory of Myeloid Malignancies, National Heart Lung and Blood Institute, 
      Bethesda, MD, United States.
FAU - Heath, James R
AU  - Heath JR
AD  - Institute for Systems Biology, Seattle, WA, United States.
AD  - Department of Bioengineering, University of Washington, Seattle, WA, United 
      States.
FAU - Khatri, Purvesh
AU  - Khatri P
AD  - Institute for Immunity, Transplantation and Infection, School of Medicine, 
      Stanford University, Stanford, CA, United States.
AD  - Center for Biomedical Informatics Research, Department of Medicine, School of 
      Medicine, Stanford University, Stanford, CA, United States.
LA  - eng
GR  - R01 CA264090/CA/NCI NIH HHS/United States
GR  - U19 AI109662/AI/NIAID NIH HHS/United States
GR  - U19 AI167903/AI/NIAID NIH HHS/United States
GR  - R38 HL143615/HL/NHLBI NIH HHS/United States
GR  - U19 AI057229/AI/NIAID NIH HHS/United States
GR  - R01 AI125197/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20230425
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Humans
MH  - *Transcriptome
MH  - Sequence Analysis, DNA
MH  - *HLA Antigens/genetics
MH  - Histocompatibility Antigens Class I/genetics
MH  - Genotype
MH  - Histocompatibility Antigens Class II/genetics
PMC - PMC10167300
OTO - NOTNLM
OT  - HLA genotype
OT  - HLA typing algorithm
OT  - allele specific expression
OT  - human leukocyte antigen (HLA)
OT  - major histocompatibility (MHC)
OT  - next-generation sequencing data (NGS)
OT  - single-cell sequencing (scRNA-seq)
COIS- PK is a shareholder and a consultant to Inflammatix, Inc. JH is founder and board 
      member of Isoplexis and PACT Pharma. JG declared contracted research with Gilead, 
      Lilly, and Regeneron. The remaining authors declare that the research was 
      conducted in the absence of any commercial or financial relationships that could 
      be construed as a potential conflict of interest.
EDAT- 2023/05/14 13:10
MHDA- 2023/05/16 06:42
PMCR- 2023/01/01
CRDT- 2023/05/14 12:01
PHST- 2023/01/17 00:00 [received]
PHST- 2023/04/04 00:00 [accepted]
PHST- 2023/05/14 13:10 [pubmed]
PHST- 2023/05/16 06:42 [medline]
PHST- 2023/05/14 12:01 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1146826 [doi]
PST - epublish
SO  - Front Immunol. 2023 Apr 25;14:1146826. doi: 10.3389/fimmu.2023.1146826. 
      eCollection 2023.