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1.
HLA ; 87(6): 439-48, 2016 06.
Article in English | MEDLINE | ID: mdl-27219013

ABSTRACT

The accuracy of human leukocyte antigen (HLA)-matching algorithms is a prerequisite for the correct and efficient identification of optimal unrelated donors for patients requiring hematopoietic stem cell transplantation. The goal of this World Marrow Donor Association study was to validate established matching algorithms from different international donor registries by challenging them with simulated input data and subsequently comparing the output. This experiment addressed three specific aspects of HLA matching using different data sets for tasks of increasing complexity. The first two tasks targeted the traditional matching approach identifying discrepancies between patient and donor HLA genotypes by counting antigen and allele differences. Contemporary matching procedures predicting the probability for HLA identity using haplotype frequencies were addressed by the third task. In each task, the identified disparities between the results of the participating computer programs were analyzed, classified and quantified. This study led to a deep understanding of the algorithms participating and finally produced virtually identical results. The unresolved discrepancies total to less than 1%, 4% and 2% for the three tasks and are mostly because of individual decisions in the design of the programs. Based on these findings, reference results for the three input data sets were compiled that can be used to validate future matching algorithms and thus improve the quality of the global donor search process.


Subject(s)
Algorithms , Alleles , Cord Blood Stem Cell Transplantation , HLA Antigens/genetics , Hematopoietic Stem Cell Transplantation , Registries , Datasets as Topic , Gene Frequency , HLA Antigens/classification , HLA Antigens/immunology , Haplotypes , Histocompatibility Testing , Humans , Transplant Recipients , Transplantation, Homologous , Unrelated Donors
2.
Tissue Antigens ; 82(2): 93-105, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23849067

ABSTRACT

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.


Subject(s)
HLA Antigens/immunology , Haplotypes/immunology , Histocompatibility Testing/standards , Models, Statistical , Registries , Software/standards , Stem Cell Transplantation , Gene Frequency , HLA Antigens/genetics , Histocompatibility Testing/methods , Histocompatibility Testing/statistics & numerical data , Humans , Unrelated Donors/statistics & numerical data
3.
Int J Immunogenet ; 40(1): 66-71, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23280139

ABSTRACT

This project has the goal to validate bioinformatics methods and tools for HLA haplotype frequency analysis specifically addressing unique issues of haematopoietic stem cell registry data sets. In addition to generating new methods and tools for the analysis of registry data sets, the intent is to produce a comprehensive analysis of HLA data from 20 million donors from the Bone Marrow Donors Worldwide (BMDW) database. This report summarizes the activity on this project as of the 16IHIW meeting in Liverpool.


Subject(s)
Genetic Variation , HLA Antigens , Haplotypes , Computational Biology , Gene Frequency , HLA Antigens/genetics , HLA Antigens/immunology , Haplotypes/genetics , Haplotypes/immunology , Humans , Registries , Tissue Donors
4.
Tissue Antigens ; 76(5): 352-61, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20604895

ABSTRACT

The human leukocyte antigen (HLA) distribution in donor registry data is typically nonrandom as, mostly for economical reasons, typing additional loci or resolving ambiguities is selectively performed based on the previously known HLA type. Analyzing a sample of over 1 million German stem cell donors, we practically show the extent of the bias caused by the restriction of the input data for HLA haplotype frequency (HF) estimation to subsets selected according to their higher HLA typing resolution and, conversely, the correctness of estimates based on unselected data with a methodology suitable for heterogeneous resolution. We discuss algorithmic aspects of this approach and, also because of the sample size, provide some new insights into the distribution of HLA-DRB1 alleles in the German population and the application of HFs in unrelated donor search.


Subject(s)
HLA Antigens/genetics , Hematopoietic Stem Cell Transplantation , Tissue Donors , Algorithms , Alleles , Female , Gene Frequency , Genes, MHC Class I , Genes, MHC Class II , Germany , HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Haplotypes , Humans , Male , Registries/statistics & numerical data
5.
Bone Marrow Transplant ; 45(5): 839-42, 2010 May.
Article in English | MEDLINE | ID: mdl-20190838

ABSTRACT

Nearly half of the unrelated hematopoietic SCTs facilitated worldwide involves an exchange of products between countries. The process is information intensive and requires coordination through regional hubs of complex data transactions of demographic, clinical and genetic information, laboratory samples and results. Each registry has developed its own unique systems for representing data and process leading to transplantation. The WMDA Information Technology Working Group was formed in the autumn of 2001 as a forum to discuss and develop standards for information technology (IT) in support of hematopoietic stem cell registries. Its membership includes experts in IT from the WMDA member registries. The group has focused its standardization efforts on three areas: Standardized reference data sets for validation and plausibility controls for HLA and other data domains. Matching algorithm standards for determining histocompatibility. Communication standards between registries.


Subject(s)
Computer Communication Networks/standards , Hematopoietic Stem Cell Transplantation/standards , Tissue Donors , Tissue and Organ Procurement/organization & administration , Tissue and Organ Procurement/standards , Humans , Registries/standards , Transplantation, Homologous
6.
Bone Marrow Transplant ; 43(10): 771-8, 2009 May.
Article in English | MEDLINE | ID: mdl-19060930

ABSTRACT

Allogeneic haematopoietic SCT is a standard therapy for many patients with haematological diseases. A major aim of public umbilical cord blood (UCB) banking is to establish an inventory with a large HLA diversity. Few studies have compared HLA diversity between UCB banks and volunteer unrelated donor (VUD) registries and examined whether UCB banks indeed collect more units with rare alleles and haplotypes. This study compares HLA-A/B/DRB1 allele frequencies and inferred A/B/DRB1-haplotypes in 1602 UCB units and 3093 VUD from two centres in distinct recruitment areas in Switzerland. The results show that the frequencies of HLA-DRB1 alleles as well as of the HLA-A/B/DRB1 haplotypes differ between UCB and VUD. Ten DRB1 alleles occurred at a 2- to 12-fold higher relative frequency in UCB than in VUD and 27 rare alleles were identified in UCB. Out of these 27 alleles, 15 were absent in the entire VUD data set of the national registry. This difference in allele frequencies was found only by intermediate/high-resolution typing. Targeted recruitment of UCB units from non-Caucasian donors could further increase HLA allele and haplotype diversity of available donors. Intermediate or high-resolution DNA typing is essential to identify rare alleles or allele groups.


Subject(s)
Blood Banking/methods , Fetal Blood , HLA Antigens/genetics , Alleles , Fetal Blood/immunology , Gene Frequency , Hematopoietic Stem Cells/immunology , Humans , Registries , Switzerland
7.
Ann Hematol ; 79(8): 437-43, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10985363

ABSTRACT

To improve the infrastructure of hemopoietic stem-cell transplantations in our country, the German Registry for Hemopoietic Stem-Cell Transplantations (DRST) was established in 1998. The present paper summarizes the current status of the DRST and gives a survey of transplant activities in Germany in 1998 in terms of transplant units, transplant types, transplant frequencies and underlying diseases.


Subject(s)
Hematopoietic Stem Cell Transplantation/statistics & numerical data , Blood Cells/transplantation , Child , Data Collection , Fetal Blood , Germany/epidemiology , Humans , Multicenter Studies as Topic , Registries , Reoperation/statistics & numerical data , Transplantation, Autologous
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