PMID- 23849067
OWN - NLM
STAT- MEDLINE
DCOM- 20140127
LR  - 20191210
IS  - 1399-0039 (Electronic)
IS  - 0001-2815 (Linking)
VI  - 82
IP  - 2
DP  - 2013 Aug
TI  - Comparative validation of computer programs for haplotype frequency estimation 
      from donor registry data.
PG  - 93-105
LID - 10.1111/tan.12160 [doi]
AB  - Estimation of human leukocyte antigen (HLA) haplotype frequencies from unrelated 
      stem cell donor registries presents a challenge because of large sample sizes and 
      heterogeneity of HLA typing data. For the 14th International HLA and 
      Immunogenetics Workshop, five bioinformatics groups initiated the 'Registry 
      Diversity Component' aiming to cross-validate and improve current haplotype 
      estimation tools. Five datasets were derived from different donor registries and 
      then used as input for five different computer programs for haplotype frequency 
      estimation. Because of issues related to heterogeneity and complexity of HLA 
      typing data identified in the initial phase, the same five implementations, and 
      two new ones, were used on simulated datasets in a controlled experiment where 
      the correct results were known a priori. These datasets contained various 
      fractions of missing HLA-DR modeled after European haplotype frequencies. We 
      measured the contribution of sampling fluctuation and estimation error to the 
      deviation of the frequencies from their true values, finding equivalent 
      contributions of each for the chosen samples. Because of patient-directed 
      activities, selective prospective typing strategies and the variety and evolution 
      of typing technology, some donors have more complete and better HLA data. In this 
      setting, we show that restricting estimation to fully typed individuals 
      introduces biases that could be overcome by including all donors in frequency 
      estimation. Our study underlines the importance of critical review and validation 
      of tools in registry-related activity and provides a sustainable framework for 
      validating the computational tools used. Accurate frequencies are essential for 
      match prediction to improve registry operations and to help more patients 
      identify suitably matched donors.
CI  - (c) 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Eberhard, H-P
AU  - Eberhard HP
AD  - Zentrales Knochenmarkspender-Register Deutschland (ZKRD), Ulm, Germany.
FAU - Madbouly, A S
AU  - Madbouly AS
FAU - Gourraud, P A
AU  - Gourraud PA
FAU - Balere, M L
AU  - Balere ML
FAU - Feldmann, U
AU  - Feldmann U
FAU - Gragert, L
AU  - Gragert L
FAU - Torres, H Maldonado
AU  - Torres HM
FAU - Pingel, J
AU  - Pingel J
FAU - Schmidt, A H
AU  - Schmidt AH
FAU - Steiner, D
AU  - Steiner D
FAU - van der Zanden, H G M
AU  - van der Zanden HG
FAU - Oudshoorn, M
AU  - Oudshoorn M
FAU - Marsh, S G E
AU  - Marsh SG
FAU - Maiers, M
AU  - Maiers M
FAU - Muller, C R
AU  - Muller CR
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Validation Study
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Gene Frequency
MH  - HLA Antigens/genetics/*immunology
MH  - Haplotypes/*immunology
MH  - Histocompatibility Testing/methods/*standards/statistics & numerical data
MH  - Humans
MH  - *Models, Statistical
MH  - *Registries
MH  - Software/*standards
MH  - *Stem Cell Transplantation
MH  - Unrelated Donors/statistics & numerical data
OTO - NOTNLM
OT  - donor registry
OT  - expectation-maximization
OT  - haplotype frequency estimation
OT  - hematopoietic stem-cell transplant
OT  - human leukocyte antigen
OT  - typing ambiguity
EDAT- 2013/07/16 06:00
MHDA- 2014/01/28 06:00
CRDT- 2013/07/16 06:00
PHST- 2013/01/14 00:00 [received]
PHST- 2013/04/15 00:00 [revised]
PHST- 2013/05/31 00:00 [accepted]
PHST- 2013/07/16 06:00 [entrez]
PHST- 2013/07/16 06:00 [pubmed]
PHST- 2014/01/28 06:00 [medline]
AID - 10.1111/tan.12160 [doi]
PST - ppublish
SO  - Tissue Antigens. 2013 Aug;82(2):93-105. doi: 10.1111/tan.12160.