scAbsolute: measuring single-cell ploidy and replication status

Abstract

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.

Keywords

• Single-cell DNA sequencing
• Singe-cell genomics
• Ploidy estimation
• Whole-genome doubling
• Whole-genome duplication
• Cell cycle stage