Are special read alignment strategies necessary and cost-effective when handling sequencing reads from patient-derived tumor xenografts?

摘要: Patient-derived tumor xenografts in mice are widely used cancer research and have become important developing personalized therapies. When these subject to DNA sequencing, the samples could contain various amounts of mouse DNA. It has been unclear how reads would affect data analyses. We conducted comprehensive simulations compare three alignment strategies at different mutation rates, read lengths, sequencing error human-mouse mixing ratios sequenced regions. also a nasopharyngeal carcinoma xenograft cell line test work on real data. found "filtering" "combined reference" performed better than aligning directly human reference terms variant calling accuracies. The combined strategy was particularly good reducing false negative variants calls without significantly increasing positive rate. In some scenarios performance gain two special handling too small for be cost-effective, but it crucial when non-synonymous SNVs should minimized, especially exome sequencing. Our study systematically analyzes effects contamination human-in-mouse xenografts. findings provide information designing analysis pipelines