A variational algorithm to detect the clonal copy number substructure of tumors from scRNA-seq data

• Published in: Nature communications Vol. 14; no. 1; pp. 1074 - 13
• Main Authors: De Falco, Antonio, Caruso, Francesca, Su, Xiao-Dong, Iavarone, Antonio, Ceccarelli, Michele
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.02.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/67/2329; 631/67/327; 631/67/69; 639/705; Algorithms; Aneuploidy; Brain cancer; Brain Neoplasms; Brain tumors; Breakpoints; Copy number; DNA Copy Number Variations - genetics; Evolution; Gene sequencing; Heterogeneity; Humanities and Social Sciences; Humans; Inference; multidisciplinary; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Segmentation; Sequence Analysis, RNA - methods; Single-Cell Analysis - methods; Single-Cell Gene Expression Analysis; Tumor microenvironment; Tumor Microenvironment - genetics; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-36790-9

Single-cell RNA sequencing is the reference technology to characterize the composition of the tumor microenvironment and to study tumor heterogeneity at high resolution. Here we report Single CEll Variational ANeuploidy analysis (SCEVAN), a fast variational algorithm for the deconvolution of the clonal substructure of tumors from single-cell RNA-seq data. It uses a multichannel segmentation algorithm exploiting the assumption that all the cells in a given copy number clone share the same breakpoints. Thus, the smoothed expression profile of every individual cell constitutes part of the evidence of the copy number profile in each subclone. SCEVAN can automatically and accurately discriminate between malignant and non-malignant cells, resulting in a practical framework to analyze tumors and their microenvironment. We apply SCEVAN to datasets encompassing 106 samples and 93,322 cells from different tumor types and technologies. We demonstrate its application to characterize the intratumor heterogeneity and geographic evolution of malignant brain tumors. The inference of clonal architectures in cancer using single-cell RNA-seq data remains challenging. Here, the authors develop SCEVAN, a variational algorithm for copy number-based clonal structure inference in single-cell RNA-seq data that can characterise evolution and heterogeneity in the tumour and the microenvironment.