MEDALT: single-cell copy number lineage tracing enabling gene discovery

We present a Minimal Event Distance Aneuploidy Lineage Tree (MEDALT) algorithm that infers the evolution history of a cell population based on single-cell copy number (SCCN) profiles, and a statistical routine named lineage speciation analysis (LSA), whichty facilitates discovery of fitness-associated alterations and genes from SCCN lineage trees. MEDALT appears more accurate than phylogenetics approaches in reconstructing copy number lineage. From data from 20 triple-negative breast cancer patients, our approaches effectively prioritize genes that are essential for breast cancer cell fitness and predict patient survival, including those implicating convergent evolution. The source code of our study is available at https://github.com/KChen-lab/MEDALT.

Automated summary

The MEDALT algorithm and LSA statistical routine accurately infer the evolutionary history of cell populations based on SCCN lineage trees to discover fitness-associated genes. By analyzing data from triple-negative breast cancer patients, essential genes for breast cancer fitness and patient survival can be effectively predicted.