COMPASS: joint copy number and mutation phylogeny reconstruction from amplicon single-cell sequencing data

Area of Science:

• Oncology
• Genomics
• Computational Biology

Background:

• Understanding tumor evolution and treatment resistance relies on reconstructing somatic DNA alterations.
• Single-cell DNA sequencing (scDNAseq) offers insights into clonal heterogeneity and phylogenetic relationships.
• Existing phylogenetic methods often struggle with combined SNV/CNA analysis or targeted sequencing data.

Purpose of the Study:

• To develop a computational method, COMPASS, for inferring joint phylogeny of SNVs and CNAs from targeted scDNAseq data.
• To address limitations of current phylogenetic tools for complex scDNAseq data.

Main Methods:

• Development of COMPASS, a novel computational approach.
• Application and validation on simulated datasets.
• Testing on real-world scDNAseq data from acute myeloid leukemia patients.

Main Results:

• COMPASS successfully infers joint phylogeny of SNVs and CNAs from targeted scDNAseq.
• Identified clonal CNAs validated by bulk data.
• Detected subclonal CNAs requiring single-cell resolution, revealing convergent evolution patterns.

Conclusions:

• COMPASS provides a robust method for analyzing combined SNV and CNA evolution in tumors.
• Enables deeper understanding of tumor heterogeneity and evolutionary trajectories.
• Facilitates discovery of novel evolutionary mechanisms like convergent evolution.