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.

人类癌症的小鼠模型改变了我们将遗传学、分子机制和表型联系起来的能力。目前，通过下一代测序（NGS）的进步，小鼠的反向和正向遗传学正在获得动力。然而，分析测序数据的方法是为人类开发的，因此没有考虑基因组结构和实验设置的物种特异性差异。在这里，我们描述了专门为小鼠基因组数据分析而定制的标准化计算管道。我们提出了用于检测不同改变类型的新颖工具和工作流程，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（LOH）和复杂重排，例如如染色体碎裂症。工作流程已使用多种方法进行了广泛验证和交叉比较。我们还为执行各个分析类型提供分步指导，提供数据解释建议，并在线提供完整的代码。该方案需要 2-7 天，具体取决于所需的分析。