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

Genome Biol. 2022 Nov 30;23(1):248. doi: 10.1186/s13059-022-02813-9.

Abstract

We present SIEVE, a statistical method for the joint inference of somatic variants and cell phylogeny under the finite-sites assumption from single-cell DNA sequencing. SIEVE leverages raw read counts for all nucleotides and corrects the acquisition bias of branch lengths. In our simulations, SIEVE outperforms other methods in phylogenetic reconstruction and variant calling accuracy, especially in the inference of homozygous variants. Applying SIEVE to three datasets, one for triple-negative breast (TNBC), and two for colorectal cancer (CRC), we find that double mutant genotypes are rare in CRC but unexpectedly frequent in the TNBC samples.

Keywords: Acquisition bias correction; Cell phylogeny reconstruction; Finite-sites assumption; Single-cell DNA sequencing; Somatic variant calling; Statistical phylogenetic models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA
  • Humans
  • Nucleotides
  • Phylogeny
  • Sequence Analysis, DNA
  • Triple Negative Breast Neoplasms*

Substances

  • DNA
  • Nucleotides