SCCNAInfer: a robust and accurate tool to infer the absolute copy number on scDNA-seq data

Abstract

Abstract Motivation Copy number alterations (CNAs) play an important role in disease progression, especially in cancer. Single-cell DNA sequencing (scDNA-seq) facilitates the detection of CNAs of each cell that is sequenced at a shallow and uneven coverage. However, the state-of-the-art CNA detection tools based on scDNA-seq are still subject to genome-wide errors due to the wrong estimation of the ploidy. Results We developed SCCNAInfer, a computational tool that utilizes the subclonal signal inside the tumor cells to more accurately infer each cell’s ploidy and CNAs. Given the segmentation result of an existing CNA detection method, SCCNAInfer clusters the cells, infers the ploidy of each subclone, refines the read count by bin clustering, and accurately infers the CNAs for each cell. Both simulated and real datasets show that SCCNAInfer consistently improves upon the state-of-the-art CNA detection tools such as Aneufinder, Ginkgo, SCOPE, and SeCNV. Availability and implementation SCCNAInfer is freely available at https://github.com/compbio-mallory/SCCNAInfer.