Chantada, D. | bioRxiv Science

bioRxiv2025

Single-cell phylodynamics reveal rapid late-stage colorectal cancer expansions

Single-cell whole-genome sequencing of 335 cells from seven colorectal cancers, coupled with Bayesian phylodynamic modeling, revealed tumors often originate decades before diagnosis, remain indolent, and expand rapidly within two years. Strong spatial structuring with minimal interregional mixing was observed, while substitution rates varied widely and were decoupled from growth. Our findings highlight extended evolutionary stasis and sudden expansion, informing strategies for early detection and intervention.

evolutionary biology↗

bioRxiv2022

SIEVE: joint inference of single-nucleotide variants and cell phylogeny from single-cell DNA sequencing data

Single-cell DNA sequencing (scDNA-seq) has enabled the identification of single nucleotide somatic variants and the reconstruction of cell phylogenies. However, statistical phylogenetic models for cell phylogeny reconstruction from raw sequencing data are still in their infancy. Here we present SIEVE (SIngle-cell EVolution Explorer), a statistical method for the joint inference of somatic variants and cell phylogeny under the finite-sites assumption from scDNA-seq reads. SIEVE leverages raw read counts for all nucleotides at candidate variant sites, and corrects the acquisition bias of branch lengths. In our simulations, SIEVE outperforms other methods both in phylogenetic accuracy and variant calling accuracy. We apply SIEVE to three scDNA-seq datasets, for colorectal (CRC) and triple-negative breast cancer (TNBC), one of them generated by us. On simulated data, SIEVE reliably infers homo-and heterozygous somatic variants. The analysis of real data uncovers that double mutant genotypes are rare in CRC but unexpectedly frequent in TNBC samples.

bioinformatics↗