De novo identification of expressed cancer somatic mutations from single-cell RNA sequencing data
Tianyun Zhang, Hanying Jia, Tairan Song, Lin Lv, D. Gulhan, Haishuai Wang, Wei Guo, Ruibin Xi, Hongshan Guo, Ning Shen
Abstract
Identifying expressed somatic mutations from single-cell RNA sequencing data de novo is challenging but highly valuable. We propose RESA - Recurrently Expressed SNV Analysis, a computational framework to identify expressed somatic mutations from scRNA-seq data. RESA achieves an average precision of 0.77 on three in silico spike-in datasets. In extensive benchmarking against existing methods using 19 datasets, RESA consistently outperforms them. Furthermore, we applied RESA to analyze intratumor mutational heterogeneity in a melanoma drug resistance dataset. By enabling high precision detection of expressed somatic mutations, RESA substantially enhances the reliability of mutational analysis in scRNA-seq. RESA is available at https://github.com/ShenLab-Genomics/RESA .