GRIDSS, PURPLE, LINX: Unscrambling the tumor genome via integrated analysis of structural variation and copy number

We have developed a novel, integrated and comprehensive purity, ploidy, structural variant and copy number somatic analysis toolkit for whole genome sequencing data of paired tumor/normal samples. We show that the combination of using GRIDSS for somatic structural variant calling and PURPLE for somatic copy number alteration calling allows highly sensitive, precise and consistent copy number and structural variant determination, as well as providing novel insights for short structural variants and regions of complex local topology. LINX, an interpretation tool, leverages the integrated structural variant and copy number calling to cluster individual structural variants into higher order events and chains them together to predict local derivative chromosome structure. LINX classifies and extensively annotates genomic rearrangements including simple and reciprocal breaks, LINE, viral and pseudogene insertions, and complex events such as chromothripsis. LINX also comprehensively calls genic fusions including chained fusions. Finally, our toolkit provides novel visualisation methods providing insight into complex genomic rearrangements.EGA study EGAS00001004034

我们研发了一款新型整合式综合体细胞分析工具包，可针对配对肿瘤/正常样本的全基因组测序数据，开展纯度、倍性、结构变异与拷贝数维度的全面体细胞分析。研究表明，将用于体细胞结构变异检出的GRIDSS与用于体细胞拷贝数变异检出的PURPLE相结合，可实现灵敏度高、精确度强且一致性佳的拷贝数与结构变异鉴定，同时还能为短结构变异及复杂局部拓扑区域提供全新的分析视角。基因组变异解读工具LINX依托整合后的结构变异与拷贝数检出结果，将单个结构变异聚类为高阶事件并进行串联，以此预测局部衍生染色体的结构特征。LINX可对基因组重排进行分类与全方位注释，涵盖简单断裂与相互易位、LINE插入、病毒插入及假基因插入等类型，同时也可识别染色体碎裂等复杂基因组事件。LINX还可全面检出基因融合事件，包括串联融合在内。最后，该工具包提供了新型可视化方法，可辅助解析复杂基因组重排事件。EGA研究EGAS00001004034