BiTSC^2: Bayesian inference of Tumor clonal Tree by joint analysis of Single-Cell SNV and CNA data
Chen, Z.; Gong, F.; Wan, L.; Ma, L.
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The rapid development of single-cell DNA sequencing (scDNA-seq) technology has greatly enhanced the resolution of tumor cell profiling, providing an unprecedented perspective in characterizing intra-tumoral heterogeneity and understanding tumor progression and metastasis. However, prominent algorithms for constructing tumor phylogeny based on scDNA-seq data usually only take single nucleotide variations (SNVs) as markers, failing to consider the effect caused by copy number alterations (CNAs). Here, we propose BiTSC2, Bayesian inference of Tumor clonal Tree by joint analysis of Single-Cell SNV and CNA data. BiTSC2 takes raw reads from scDNA-seq as input, accounts for sequencing errors, models dropout rate and assigns single cells into subclones. By applying Markov Chain Monte Carlo (MCMC) sampling, BiTSC2 can simultaneously estimate the subclonal scCNA and scSNV genotype matrices, sub-clonal assignments and tumor subclonal evolutionary tree. In comparison with existing methods on synthetic and real tumor data, BiTSC2 shows high accuracy in genotype recovery and sub-clonal assignment. BiTSC2 also performs robustly in dealing with scDNA-seq data with low sequencing depth and variant dropout rate.
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