A comparison of next-generation sequencing analysis methods for cancer xenograft samples

Abstract

The application of next-generation sequencing (NGS) technology in cancer is influenced by the quality and purity of tissue samples. This issue is especially critical for patient-derived xenograft (PDX) models, which have proven to be by far the best preclinical tool for investigating human tumor biology, because the sensitivity and specificity of NGS analysis in xenograft samples would be compromised by the contamination of mouse DNA and RNA. This definitely affects downstream analyses by causing inaccurate mutation calling and gene expression estimates. The reliability of NGS data analysis for cancer xenograft samples is therefore highly dependent on whether the sequencing reads derived from the xenograft could be distinguished from those originated from the host. That is, each sequence read needs to be accurately assigned to its original species. Here, we review currently available methodologies in this field, including Xenome, Disambiguate, bamcmp and pdxBlacklist, and provide guidelines for users.

Keywords: Alignment; Host contamination control; Next-generation sequencing; Patient-derived xenograft.