scLongTree: an accurate computational tool to infer the longitudinal tree for scDNAseq data

Abstract

Longitudinal single-cell DNA sequencing (scDNA-seq) refers to single-cell data sequenced at different time points providing more knowledge of the order of mutations than scDNA-seq taken at only one time point. The technique can facilitate the inference of subclonal trees that depict the evolution of cancer cells and facilitate understanding of how cancer grows, with implications for prognosis and treatment. There is currently a scarcity of tools that can infer subclonal trees based on longitudinal scDNA-seq, and existing tools are limited in accuracy and scale. We therefore introduce scLongTree, a computational tool that can accurately infer a subclonal tree based on longitudinal scDNA-seq. ScLongTree is scalable to hundreds of mutations, and outperforms state-of-the-art tools such as LACE, SCITE, and SiCloneFit on a comprehensive simulated dataset. Tests on a real dataset, SA501, showed that scLongTree can more accurately interpret the progressive growth of the tumor than LACE, and is more robust to different numbers of mutations being used. Tests on a large AML dataset AML107, which has 4,617 cells, show that scLongTree is scalable to thousands of cells. ScLongTree is freely available on https://github.com/compbio-mallory/sc_longitudinal_infer. Key pointsO_LIWe propose scLongTree that can infer the subclonal longitudinal tree for cancer given single-cell DNA sequencing data, and thus can facilitate the study of cancer evolution given the dataset from multiple time points. C_LIO_LIMultiple simulated data show that scLongTree is more accurate than existing state-of-the-art methods such as LACE, SCITE and SiCloneFit. C_LIO_LIScLongTree has been shown to have a higher scalability than LACE and thus can be applicable to the datasets that have hundreds of mutations. C_LIO_LIThe experiment on a real SA501 shows that scLongTree is more robust to the number of mutations than LACE. It consistently generates the same longitudinal tree even under different sets of mutations. C_LIO_LIThe experiment on AML107 shows that scLongTree is scalable to thousands of cells. C_LI