Genomics Institute, UC Santa Cruz, Santa Cruz, California.
FaBiT Department, Biocomputing Group, University of Bologna, Bologna, Italy.
Hum Mutat. 2019 Sep;40(9):1546-1556. doi: 10.1002/humu.23861. Epub 2019 Aug 23.
Testing for variation in BRCA1 and BRCA2 (commonly referred to as BRCA1/2), has emerged as a standard clinical practice and is helping countless women better understand and manage their heritable risk of breast and ovarian cancer. Yet the increased rate of BRCA1/2 testing has led to an increasing number of Variants of Uncertain Significance (VUS), and the rate of VUS discovery currently outpaces the rate of clinical variant interpretation. Computational prediction is a key component of the variant interpretation pipeline. In the CAGI5 ENIGMA Challenge, six prediction teams submitted predictions on 326 newly-interpreted variants from the ENIGMA Consortium. By evaluating these predictions against the new interpretations, we have gained a number of insights on the state of the art of variant prediction and specific steps to further advance this state of the art.
BRCA1 和 BRCA2（通常称为 BRCA1/2）的变异检测已经成为一种标准的临床实践，它帮助无数女性更好地了解和管理其遗传性乳腺癌和卵巢癌风险。然而，BRCA1/2 检测率的增加导致了越来越多的意义不确定的变异（VUS）的发现，目前 VUS 的发现率超过了临床变异解释的速度。计算预测是变异解释管道的关键组成部分。在 CAGI5 ENIGMA 挑战赛中，六个预测团队对 ENIGMA 联盟的 326 个新解释的变体提交了预测。通过将这些预测与新的解释进行评估，我们对变异预测的最新技术水平以及进一步提高这一技术水平的具体步骤有了一些深入的了解。
