Paper ID: 2311.12917

Orchard: building large cancer phylogenies using stochastic combinatorial search

E. Kulman, R. Kuang, Q. Morris

Phylogenies depicting the evolutionary history of genetically heterogeneous subpopulations of cells from the same cancer i.e., cancer phylogenies, provide useful insights about cancer development and inform treatment. Cancer phylogenies can be reconstructed using data obtained from bulk DNA sequencing of multiple tissue samples from the same cancer. We introduce Orchard, a fast algorithm that reconstructs cancer phylogenies using point mutations detected in bulk DNA sequencing data. Orchard constructs cancer phylogenies progressively, one point mutation at a time, ultimately sampling complete phylogenies from a posterior distribution implied by the bulk DNA data. Orchard reconstructs more plausible phylogenies than state-of-the-art cancer phylogeny reconstruction methods on 90 simulated cancers and 14 B-progenitor acute lymphoblastic leukemias (B-ALLs). These results demonstrate that Orchard accurately reconstructs cancer phylogenies with up to 300 mutations. We then introduce a simple graph based clustering algorithm that uses a reconstructed phylogeny to infer unique groups of mutations i.e., mutation clusters, that characterize the genetic differences between cancer cell populations, and show that this approach is competitive with state-of-the-art mutation clustering methods.

Submitted: Nov 21, 2023