SlideCNA: Spatial copy number alteration detection from Slide-seq-like spatial transcriptomics data

Solid tumors are spatially heterogeneous in their genetic, molecular and cellular composition, and this variation can be meaningful for diagnosis, prognosis and therapy. Recent spatial profiling studies have mostly charted genetic and RNA variation in tumors separately. To leverage the potential of RNA to identify copy number alterations (CNAs), we developed SlideCNA, a computational tool to extract sparse spatial CNA signals from spatial transcriptomics data, using expression-aware spatial binning. We test SlideCNA on simulated and real Slide-seq data of metastatic breast cancer (MBC) and demonstrate its potential for spatial sub-clone detection. ### Competing Interest Statement A.R. is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas, and was an SAB member of ThermoFisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics and Asimov until July 31, 2020. O.R.R and A.R. are employees of Genentech from August 1, 2020 and October 19, 2020, respectively, and have equity in Roche. O.R.R. and A.R. are named inventors on multiple patents filed by the Broad Institute in the area of single cell and spatial genomics. S.R. has received research support from KITE/Gilead and Bristol-Myers-Squibb and is on the SAB of Immunitas Therapeutics.