近年来二代测序技术发展迅速,在精准医疗和遗传诊断上得到日益广泛的应用。对二代测序数据进行分析的一个核心环节是对遗传变异位点的识别和注释。基于此,本课题组开发了一个能高效对全基因组单核苷酸多态位点进行功能注释的软件——BIG-Annotator。该软件以JAVA语言编写,且提供多线程运行模式,运行更为高效,比现有的同类软件或流程提速10多倍,适用于人群队列研究、大样本全基因组关联分析等数据量庞大、时效性要求高的分析需求。同时,该软件还集成了目前常用的二代测序遗传变异注释数据库,以及临床数据解读与报告的标准指南(2015 ACMG-AMP《解读报告标准指南》),并且增加了针对肿瘤组织遗传变异注释的信息。最后,通过两个研究实例具体说明该软件在遗传诊断中的应用。

The next generation sequencing (NGS) technology has been playing important roles in genetic diagnosis of diseases in recent years, and serving as a technological basis of precision medicine. In analyzing NGS data, the variant annotation is an important step. In this study, we developed a computationally efficient software (BIG-Annotator) to perform functional annotation for whole-genome single nucleotide polymorphisms. BIG-Annotator integrates the widely used databases and pipelines for variant annotation of genetic diseases and tumors, and follows the 2015 ACMG-AMP Standard Guide for Interpretation and Reporting of Clinical Variants. BIG-Annotator is ten times faster than the existing software, and suitable for annotating genomic sequencing data from large samples. Here we present two analysis cases of genetic diagnosis using BIG-Annotator to show its applications.