Analysis pipelines for cancer genome sequencing in mice
Analysis pipelines for cancer genome sequencing in mice
复制标题
DOI：
10.1038/s41596-019-0234-7
复制
发表时间：
2020-01-06
期刊：
影响因子：
14.8
通讯作者：
Rad, Roland
中科院分区：
文献类型：
--
作者：
Lange, Sebastian;Engleitner, Thomas;Rad, Roland
人类癌症的小鼠模型已经改变了我们将遗传学、分子机制和表型联系起来的能力。通过下一代测序（NGS）的进展，小鼠的反向和正向遗传学目前都在获得动力。然而，分析测序数据的方法是为人类开发的，因此不能解释基因组结构和实验设置中的物种特异性差异。在这里，我们描述了专门针对小鼠基因组数据分析的标准化计算管道。我们提出了新的工具和工作流程，用于检测不同的改变类型，包括单核苷酸变异（SNV），小插入和缺失（indels），拷贝数变异（CNV），杂合性丢失（洛）和复杂的重排，如在chromothripsis。工作流程已使用多种方法进行了广泛验证和交叉比较。我们还提供有关执行单个分析类型的分步指导，提供有关数据解释的建议，并在线提供完整的代码。该协议需要2-7天，这取决于所需的分析。在这里，作者提出了专门针对小鼠癌症基因组测序数据分析的标准化计算管道。该协议能够检测单核苷酸变异，插入缺失，拷贝数变异，杂合性丢失和复杂的重排，如chromothripsis。
Mouse models of human cancer have transformed our ability to link genetics, molecular mechanisms and phenotypes. Both reverse and forward genetics in mice are currently gaining momentum through advances in next-generation sequencing (NGS). Methodologies to analyze sequencing data were, however, developed for humans and hence do not account for species-specific differences in genome structures and experimental setups. Here, we describe standardized computational pipelines specifically tailored to the analysis of mouse genomic data. We present novel tools and workflows for the detection of different alteration types, including single-nucleotide variants (SNVs), small insertions and deletions (indels), copy-number variations (CNVs), loss of heterozygosity (LOH) and complex rearrangements, such as in chromothripsis. Workflows have been extensively validated and cross-compared using multiple methodologies. We also give step-by-step guidance on the execution of individual analysis types, provide advice on data interpretation and make the complete code available online. The protocol takes 2-7 d, depending on the desired analyses.Here, the authors present standardized computational pipelines tailored specifically to the analysis of cancer genome sequencing data from mice. The protocol enables detection of single-nucleotide variants, indels, copy-number variations, loss of heterozygosity and complex rearrangements such as those of chromothripsis.