论文标题
基于家庭的HLA归类和单位相同移植的优化
Family based HLA imputation and optimization of haplo-identical transplants
论文作者
论文摘要
最近,具有多个HLA不匹配的单倍体相同的移植已成为系统细胞移植的可行选择。单倍型共享检测需要捐助者和接受者的插补。我们表明,即使在所有等位基因均已知道时,在高分辨率键入中,单倍型相位的错误率也有15%,在低分辨率键入中甚至更多。同样,在相关的捐助者中,应估算父母的单倍型,以确定每个孩子遗传的单倍型。我们将语法(基于图形的Familly插定)提出,以在家庭谱系HLA键入数据和母犯血单位对中的相位等位基因。我们表明,当有血统数据可用时,语法实际上没有分阶段错误。我们将语法应用于具有不同键入分辨率以及配对的绳索键入的模拟,并显示出非常高的相位准确性,并提高了等位基因的准确性。我们使用语法来检测重组事件,并表明模拟中错误检测到的重组事件的速率(假阳性率)非常低。然后,我们将重组检测应用于打字家庭,以估计以色列和澳大利亚人口数据集的重组率。估计的重组率的上限为每个家族10-20%(每个人1-4%)。 Gramm可在以下网址提供:https://gramm.math.biu.ac.il/。
Recently, haplo-identical transplantation with multiple HLA mismatches has become a viable option for system cell transplants. Haplotype sharing detection requires imputation of donor and recipient. We show that even in high-resolution typing when all alleles are known, there is a 15% error rate in haplotype phasing, and even more in low resolution typings. Similarly, in related donors, parents haplotypes should be imputed to determine what haplotype each child inherited. We propose GRAMM (GRaph bAsed FaMilly iMputation) to phase alleles in family pedigree HLA typing data, and in mother-cord blood unit pairs. We show that GRAMM has practically no phasing errors when pedigree data are available. We apply GRAMM to simulations with different typing resolutions as well as paired cord-mother typings, and show very high phasing accuracy, and improved alleles imputation accuracy. We use GRAMM to detect recombination events and show that the rate of falsely detected recombination events (False Positive Rate) in simulations is very low. We then apply recombination detection to typed families to estimate the recombination rate in Israeli and Australian population datasets. The estimated recombination rate has an upper bound of 10-20% per family (1-4% per individual). GRAMM is available at: https://gramm.math.biu.ac.il/.