Single-cell RNA and ATAC sequencing technologies enable the examination of gene expression and chromatin accessibility in individual cells, providing insights into cellular phenotypes. In cancer research, it is important to consistently analyze these states within an evolutionary context on genetic clones. Here we present CONGAS+, a Bayesian model to map single-cell RNA and ATAC profiles onto the latent space of copy number clones. CONGAS+ clusters cells into tumour subclones with similar ploidy, rendering straightforward to compare their expression and chromatin profiles. The framework, implemented on GPU and tested on real and simulated data, scales to analyse seamlessly thousands of cells, demonstrating better performance than single-molecule models, and supporting new multi-omics assays. In prostate cancer, lymphoma and basal cell carcinoma, CONGAS+ successfully identifies complex subclonal architectures while providing a coherent mapping between ATAC and RNA, facilitating the study of genotype-phenotype maps and their connection to genomic instability.
Copyright: © 2023 Patruno et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.