Despite its demonstrated importance in hematopoietic cell transplantation, the HLA-DPB1 locus is only typed in one in five unrelated donors in the United States. Addressing this issue, we developed a DPB1 Prediction Service that leverages seven-locus haplotype frequencies (HLA-A ∼ C ∼ B ∼ DRB3/4/5 ∼ DRB1 ∼ DQB1 ∼ DPB1) to extend the imputation of six-locus HLA typing (HLA-A ∼ C ∼ B ∼ DRB3/4/5 ∼ DRB1 ∼ DQB1) to the HLA-DPB1 locus, including the novel prediction of HLA-DPB1 TCE groups to calculate donor-recipient TCE permissive match probabilities. Simulations of current-day patient searches reveal the service can fill in missing gaps for another four in five donors that appears on lists. To validate its performance, samples of 206,328 registered donors and 5,218 donor-recipient pairs with known high-resolution HLA-DPB1 typing were used for predicted-versus-observed comparisons. These comparisons demonstrated that the predictions were correct for 11.9–19.7% of HLA-DPB1 genotypes, 64.9–70.0% of TCE groups, and 61.0% of permissive match categories. Although HLA-DPB1 match predictions must be confirmed by additional typing, knowledge of TCE match probabilities facilitates rapid and improved identification of best donor options, especially for populations of color. Thus, we developed the TCE Prediction Tool user interface for a pilot program with several transplant centers to preview the accuracy and utility of this prediction framework, which provides valuable upfront optimization of donor selection.

尽管HLA-DPB1基因座在造血细胞移植中的重要性已得到证实，但在美国只有五分之一的无关供体中被分型。为了解决这个问题，我们开发了一个 DPB1 预测服务，它利用七位点单倍型频率 ( HLA-A  ∼  C  ∼  B  ∼  DRB3/4/5  ∼  DRB1  ∼  DQB1 ∼ DPB1 ) 来扩展六位点 HLA 分型 ( HLA -A  ~  C  ~  B  ~  DRB3/4/5  ~  DRB1  ~  DQB1）到HLA-DPB1基因座，包括新的预测HLA-DPB1 TCE 组计算供体-受体 TCE 允许匹配概率。对当前患者搜索的模拟显示，该服务可以为出现在名单上的另外五分之四的捐赠者填补缺失的空白。为了验证其性能，使用了 206,328 名注册捐赠者和 5,218 对已知高分辨率HLA-DPB1分型的捐赠者-接受者对的样本进行预测与观察比较。这些比较表明，11.9-19.7% 的HLA-DPB1基因型、64.9-70.0% 的 TCE 组和 61.0% 的允许匹配类别的预测是正确的。虽然HLA-DPB1匹配预测必须通过额外的打字来确认，TCE 匹配概率的知识有助于快速和改进识别最佳供体选择，特别是对于有色人种。因此，我们为与多个移植中心的试点项目开发了 TCE 预测工具用户界面，以预览该预测框架的准确性和实用性，从而为供体选择提供有价值的前期优化。