scAbsolute: measuring single-cell ploidy and replication status
Michael P Schneider, Amy E Cullen, Justina Pangonyte, Jason Skelton, Harvey Major, Elke Van Oudenhove, María J. García, Blas Chaves-Urbano, Anna Piskorz, James D. Brenton, Geoff Macintyre, Florian Markowetz
Abstract
Cancer cells often exhibit DNA copy number aberrations and can vary widely in their ploidy. Correct estimation of the ploidy of single-cell genomes is paramount for downstream analysis. Based only on single-cell DNA sequencing information, scAbsolute achieves accurate and unbiased measurement of single-cell ploidy and replication status, including whole-genome duplications. We demonstrate scAbsolute's capabilities using experimental cell multiplets, a FUCCI cell cycle expression system, and a benchmark against state-of-the-art methods. scAbsolute provides a robust foundation for single-cell DNA sequencing analysis across different technologies and has the potential to enable improvements in a number of downstream analyses.