EDS files (raw data) from QuantStudio for Validation of Single Nucleotide Variant Assays for Human Leukocyte Antigen Haplotypes HLA-B*15:02 and HLA-A*31:01 Across Diverse Ancestral Backgrounds

The human leukocyte antigen haplotypes <i>HLA-B*15:02</i> and <i>HLA-A*31:01</i> have been linked to life-threatening adverse drug reactions to the anticonvulsants carbamazepine and oxcarbazepine. Identification of these haplotypes via pharmacogenetic techniques facilitates implementation of precision medicine to prevent such reactions. Using reference samples from diverse ancestral origins, we investigated the test analytical validity (i.e., ability to detect whether or not the haplotypes were present or absent) of TaqMan assays for single nucleotide variants previously identified as potentially being able to “tag” these haplotypes. A TaqMan custom assay for rs10484555 and an inventoried assay for rs17179220 and were able to identify with 100% sensitivity and 100% specificity <i>HLA-B*15:02</i> and <i>HLA-A*31:01</i> respectively. A custom assay for rs144012689 that takes into account a neighboring single nucleotide variant with manual calling was also able to identify <i>HLA-B*15:02</i> with 100% sensitivity and 100% specificity. A custom assay for rs106235 identified <i>HLA-A*31:01</i> with 100% sensitivity and 95% specificity. The slight reduction in specificity for the latter was owing to another haplotype (<i>HLA-A*33:03</i>) also being detected. While any positive call using the rs106235 assay could therefore be further investigated, as the presence of the <i>HLA-A*31:01</i> haplotype confers adverse drug reaction risk, the absence of false negatives (indexed by sensitivity) is more important than false positives. In summary, we present validated TaqMan assay methodology for efficient detection of HLA haplotypes <i>HLA-B*15:02 </i>and <i>HLA-A*31:01</i>. Our data are relevant for other genotyping technologies that identify, or have the potential to identify, these haplotypes using single nucleotide variants. <b></b><br>These data files are the output from QuantStudio, the raw data from this study.

人类白细胞抗原（human leukocyte antigen, HLA）单倍型HLA-B*15:02与HLA-A*31:01，已被证实与抗惊厥药卡马西平、奥卡西平诱导的危及生命的药物不良反应相关。通过药物遗传学技术鉴定此类单倍型，可推动精准医学的落地应用，从而有效预防此类不良反应的发生。本研究采用源自不同祖先群体的参考样本，针对此前被认为可“标记”上述单倍型的单核苷酸变异，评估了TaqMan检测法的分析有效性（即检测该单倍型存在与否的能力）。
针对rs10484555的定制TaqMan检测法，以及针对rs17179220的商品化TaqMan检测法，可分别以100%灵敏度和100%特异性准确鉴定HLA-B*15:02与HLA-A*31:01。一种针对rs144012689的定制TaqMan检测法，在纳入邻近单核苷酸变异信息并采用人工判读的前提下，同样可实现以100%灵敏度和100%特异性鉴定HLA-B*15:02。针对rs106235的定制TaqMan检测法可用于鉴定HLA-A*31:01，其灵敏度为100%，特异性为95%。该检测法特异性略有下降的原因在于，其可同时检出另一种单倍型HLA-A*33:03。
因此，针对rs106235检测法的阳性结果可进一步开展复核验证；鉴于HLA-A*31:01单倍型的存在会增加药物不良反应风险，相较于假阳性结果，无假阴性（以灵敏度为评价指标）更为关键。综上，本研究验证了可高效检测HLA单倍型HLA-B*15:02与HLA-A*31:01的TaqMan检测方法学。本研究数据对于其他可通过单核苷酸变异识别或潜在可识别此类单倍型的基因分型技术，均具有参考价值。
本研究的原始数据文件均为QuantStudio系统的输出结果。