Inferring Phenotypes of Copy Number Clones in Cancer Populations Using TreeAlign

Somatic copy number changes modify gene expression and drive cancer development and progression. Single-cell techniques now allow for the profiling of both gene expression and copy number, opening the possibility of linking expression changes with copy number changes at a single-cell level. However, joint measurement of both expression and copy number from the same cell is not commonplace, and thus joint analysis of expression and copy number requires computational integration of the two modalities. TreeAlign is a method for matching cells in single-cell RNA (scRNA) data to clones inferred from single-cell whole genome sequence (scWGS) data. TreeAlign is phylogeny aware and capable of robustly modeling the effect of gene dosage on gene expression. In this chapter, we provide a practical guide for using TreeAlign to jointly analyze copy number and gene expression from single-cell whole genome sequencing and single-cell RNA sequencing datasets.