Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea.
Genes (Basel). 2021 Aug 25;12(9):1308. doi: 10.3390/genes12091308.
Neurofibromatosis type 1, characterized by neurofibromas and café-au-lait macules, is one of the most common genetic disorders caused by pathogenic variants. Because of the high proportion of splicing mutations in , identifying variants that alter splicing may be an essential issue for laboratories. Here, we investigated the sensitivity and specificity of SpliceAI, a recently introduced splicing prediction algorithm in conjunction with other tools. We evaluated 285 variants identified from 653 patients. The effect on variants on splicing alteration was confirmed by complementary DNA sequencing followed by genomic DNA sequencing. For prediction of splicing effects, we used SpliceAI, MaxEntScan (MES), and Splice Site Finder-like (SSF). The sensitivity and specificity of SpliceAI were 94.5% and 94.3%, respectively, with a cut-off value of Δ Score > 0.22. The area under the curve of SpliceAI was 0.975 ( < 0.0001). Combined analysis of MES/SSF showed a sensitivity of 83.6% and specificity of 82.5%. The concordance rate between SpliceAI and MES/SSF was 84.2%. SpliceAI showed better performance for the prediction of splicing alteration for variants compared with MES/SSF. As a convenient web-based tool, SpliceAI may be helpful in clinical laboratories conducting DNA-based sequencing.
神经纤维瘤病 1 型，其特征为神经纤维瘤和咖啡牛奶斑，是由致病性变异引起的最常见的遗传疾病之一。由于剪接突变在 中所占比例较高，因此鉴定改变剪接的变异可能是实验室的一个重要问题。在这里，我们研究了 SpliceAI 的灵敏度和特异性，SpliceAI 是一种最近引入的剪接预测算法，并结合了其他工具。我们评估了从 653 名患者中鉴定出的 285 个变体。通过互补 DNA 测序和基因组 DNA 测序确认了变体对剪接改变的影响。为了预测剪接效应，我们使用了 SpliceAI、MaxEntScan (MES) 和 Splice Site Finder-like (SSF)。SpliceAI 的灵敏度和特异性分别为 94.5%和 94.3%，截断值为ΔScore>0.22。SpliceAI 的曲线下面积为 0.975（<0.0001）。MES/SSF 的联合分析显示灵敏度为 83.6%，特异性为 82.5%。SpliceAI 与 MES/SSF 的一致性率为 84.2%。与 MES/SSF 相比，SpliceAI 对 变体剪接改变的预测性能更好。作为一种方便的基于网络的工具，SpliceAI 可能有助于进行基于 DNA 的 测序的临床实验室。
