PMID- 25040134
OWN - NLM
STAT- MEDLINE
DCOM- 20150515
LR  - 20211203
IS  - 1399-0039 (Electronic)
IS  - 0001-2815 (Linking)
VI  - 84
IP  - 3
DP  - 2014 Sep
TI  - Validation of statistical imputation of allele-level multilocus phased genotypes 
      from ambiguous HLA assignments.
PG  - 285-92
LID - 10.1111/tan.12390 [doi]
AB  - Genetic matching for loci in the human leukocyte antigen (HLA) region between a 
      donor and a patient in hematopoietic stem cell transplantation (HSCT) is critical 
      to outcome; however, methods for HLA genotyping of donors in unrelated stem cell 
      registries often yield results with allelic and phase ambiguity and/or do not 
      query all clinically relevant loci. We present and evaluate a statistical method 
      for in silico imputation of HLA alleles and haplotypes in large ambiguous 
      population data from the Be The Match((R)) Registry. Our method builds on haplotype 
      frequencies estimated from registry populations and exploits patterns of linkage 
      disequilibrium (LD) across HLA haplotypes to infer high resolution HLA 
      assignments. We performed validation on simulated and real population data from 
      the Registry with non-trivial ambiguity content. While real population datasets 
      caused some predictions to deviate from expectation, validations still showed 
      high percent recall for imputed results with average recall >76% when imputing 
      HLA alleles from registry data. We simulated ambiguity generated by several HLA 
      genotyping methods to evaluate the imputation performance on several levels of 
      typing resolution. On average, imputation percent recall of allele-level HLA 
      haplotypes was >95% for allele-level typing, >92% for intermediate resolution 
      typing and >58% for serology (low-resolution) typing. Thus, allele-level HLA 
      assignments can be imputed through the application of a set of statistical and 
      population genetics inferences and with knowledge of haplotype frequencies and 
      self-identified race and ethnicities.
CI  - (c) 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Madbouly, A
AU  - Madbouly A
AD  - Bioinformatics Research, National Marrow Donor Program, Minneapolis, MN, USA.
FAU - Gragert, L
AU  - Gragert L
FAU - Freeman, J
AU  - Freeman J
FAU - Leahy, N
AU  - Leahy N
FAU - Gourraud, P-A
AU  - Gourraud PA
FAU - Hollenbach, J A
AU  - Hollenbach JA
FAU - Kamoun, M
AU  - Kamoun M
FAU - Fernandez-Vina, M
AU  - Fernandez-Vina M
FAU - Maiers, M
AU  - Maiers M
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Validation Study
DEP - 20140711
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Alleles
MH  - Computer Simulation/statistics & numerical data
MH  - *Ethnicity
MH  - Gene Frequency
MH  - Genetic Loci/genetics
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - Haplotypes
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Histocompatibility Testing/*methods/statistics & numerical data
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Models, Genetic
MH  - Registries
MH  - Tissue Donors
MH  - United States
OTO - NOTNLM
OT  - expectation maximization
OT  - human leukocyte antigen
OT  - imputation
OT  - maximum likelihood
OT  - typing ambiguity
OT  - typing resolution
EDAT- 2014/07/22 06:00
MHDA- 2015/05/16 06:00
CRDT- 2014/07/22 06:00
PHST- 2013/08/15 00:00 [received]
PHST- 2014/03/28 00:00 [revised]
PHST- 2014/05/12 00:00 [accepted]
PHST- 2014/07/22 06:00 [entrez]
PHST- 2014/07/22 06:00 [pubmed]
PHST- 2015/05/16 06:00 [medline]
AID - 10.1111/tan.12390 [doi]
PST - ppublish
SO  - Tissue Antigens. 2014 Sep;84(3):285-92. doi: 10.1111/tan.12390. Epub 2014 Jul 11.