Sequencing of patient-derived xenograft (PDX) mouse models allows investigation of the molecular mechanisms of human tumor samples engrafted in a mouse host. Thus, both human and mouse genetic material is sequenced. Several methods have been developed to remove mouse sequencing reads from RNA-seq or exome sequencing PDX data and improve the downstream signal. However, for more recent chromatin conformation capture technologies (Hi-C), the effect of mouse reads remains undefined. We evaluated the effect of mouse read removal on the quality of Hi-C data using in silico created PDX Hi-C data with 10% and 30% mouse reads. Additionally, we generated two experimental PDX Hi-C datasets using different library preparation strategies. We evaluated three alignment strategies (Direct, Xenome, Combined) and three processing pipelines (Juicer, HiC-Pro, HiCExplorer) on the quality of Hi-C data. Removal of mouse reads had little-to-no effect on data quality than the results obtained with Direct alignment strategy. Juicer pipeline extracted the most useful information from PDX Hi-C data. However, library preparation strategy had the largest effect on all quality metrics. Together, our study presents comprehensive guidelines on PDX Hi-C data processing.

中文翻译：

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患者来源异种移植物的染色质构象捕获（Hi-C）测序：分析指南

患者源性异种移植（PDX）小鼠模型的测序可以研究移植到小鼠宿主中的人类肿瘤样品的分子机制。因此，人类和小鼠遗传物质均被测序。已经开发了几种方法来从RNA-seq或外显子组测序PDX数据中删除小鼠测序读数，并改善下游信号。但是，对于最新的染色质构象捕获技术（Hi-C），鼠标读取的效果仍然不确定。我们使用在计算机上创建的具有10％和30％鼠标读取的PDX Hi-C数据，评估了鼠标读取移除对Hi-C数据质量的影响。此外，我们使用不同的库制备策略生成了两个实验性的PDX Hi-C数据集。我们评估了三种对齐策略（直接，Xenome，组合）和三种处理管道（Juicer，HiC-Pro，HiCExplorer）有关Hi-C数据的质量。与直接比对策略获得的结果相比，删除鼠标读数对数据质量几乎没有影响。榨汁机管道从PDX Hi-C数据中提取了最有用的信息。但是，图书馆准备策略对所有质量指标的影响最大。总之，我们的研究提出了有关PDX Hi-C数据处理的综合指南。