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Hap-E搜索2.0:基于单倍型频率的概率性供体-受体匹配算法性能提升

Hap-E Search 2.0: Improving the Performance of a Probabilistic Donor-Recipient Matching Algorithm Based on Haplotype Frequencies.

作者信息

Urban Christine, Schmidt Alexander H, Hofmann Jan Andreas

机构信息

DKMS, Tübingen, Germany.

出版信息

Front Med (Lausanne). 2020 Feb 18;7:32. doi: 10.3389/fmed.2020.00032. eCollection 2020.

DOI:10.3389/fmed.2020.00032
PMID:32133364
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7040233/
Abstract

In the setting of hematopoietic stem cell transplantation, donor-patient HLA matching is the prime donor selection criterion. Matching algorithms provide ordered lists of donors where the probability of a donor to be an HLA match is calculated in cases where either donor or patient HLA typing information is ambiguous or incomplete. While providing important information for the selection of suitable donors, these algorithms are computationally demanding and often need several minutes up to hours to generate search results. Here, we present a new search kernel implementation for Hap-E Search, the haplotype frequency-based matching algorithm of DKMS. The updated search kernel uses pre-calculated information on donor genotypes to speed up the search process. The new algorithm reliably provides search results in <1 min for a large donor database (>9 Mio donors) including matching and mismatching donors, even for frequent or incomplete patient HLA data where the matching list contains several thousand donors. In these cases, the search process is accelerated by factors of 10 and more compared to the old Hap-E Search implementation. The predicted matching probabilities of the new algorithm were validated with data from verification typing requests of 67,550 donor-patient pairs.

摘要

在造血干细胞移植的背景下,供体与患者的HLA配型是主要的供体选择标准。匹配算法提供供体的有序列表,在供体或患者的HLA分型信息不明确或不完整的情况下,计算供体成为HLA匹配的概率。虽然这些算法为选择合适的供体提供了重要信息,但它们对计算要求很高,通常需要几分钟到几小时才能生成搜索结果。在此,我们展示了一种用于Hap-E Search的新搜索内核实现方式,Hap-E Search是DKMS基于单倍型频率的匹配算法。更新后的搜索内核使用预先计算的供体基因型信息来加速搜索过程。新算法能够在不到1分钟的时间内,为包含匹配和不匹配供体的大型供体数据库(超过900万个供体)可靠地提供搜索结果,即使对于匹配列表包含数千个供体的常见或不完整的患者HLA数据也是如此。在这些情况下,与旧的Hap-E Search实现方式相比,搜索过程加速了10倍甚至更多。新算法的预测匹配概率通过67550对供体-患者对的验证分型请求数据进行了验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1b/7040233/7af63bdcf61a/fmed-07-00032-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1b/7040233/ca8c8e3be9ee/fmed-07-00032-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1b/7040233/9b3d631ed90d/fmed-07-00032-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1b/7040233/88a6db0d8d7a/fmed-07-00032-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1b/7040233/3264cc846f0b/fmed-07-00032-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1b/7040233/7af63bdcf61a/fmed-07-00032-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1b/7040233/ca8c8e3be9ee/fmed-07-00032-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1b/7040233/9b3d631ed90d/fmed-07-00032-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1b/7040233/88a6db0d8d7a/fmed-07-00032-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1b/7040233/3264cc846f0b/fmed-07-00032-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1b/7040233/7af63bdcf61a/fmed-07-00032-g0005.jpg

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本文引用的文献

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Blood. 2019 Sep 19;134(12):924-934. doi: 10.1182/blood.2019001212. Epub 2019 Jul 10.
2
HapLogic: A Predictive Human Leukocyte Antigen-Matching Algorithm to Enhance Rapid Identification of the Optimal Unrelated Hematopoietic Stem Cell Sources for Transplantation.HapLogic:一种预测性人类白细胞抗原匹配算法,用于加强对移植最佳无关造血干细胞来源的快速识别。
Biol Blood Marrow Transplant. 2016 Nov;22(11):2038-2046. doi: 10.1016/j.bbmt.2016.07.022. Epub 2016 Aug 2.
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A comparative reference study for the validation of HLA-matching algorithms in the search for allogeneic hematopoietic stem cell donors and cord blood units.
用于验证 HLA 匹配算法的比较参考研究,以寻找同种异体造血干细胞供体和脐血单位。
HLA. 2016 Jun;87(6):439-48. doi: 10.1111/tan.12817. Epub 2016 May 24.
4
Using EasyMatch® to anticipate the identification of an HLA identical unrelated donor: A validated efficient time and cost saving method.使用EasyMatch®预测人类白细胞抗原(HLA)全相合无关供者的识别:一种经验证的高效省时且节省成本的方法。
Hum Immunol. 2016 Nov;77(11):1008-1015. doi: 10.1016/j.humimm.2016.02.004. Epub 2016 Feb 20.
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HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry.美国注册中心造血干细胞移植供者 HLA 配型概率。
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