BitPhylogeny: a probabilistic framework for reconstructing intra-tumor phylogenies.
Bottom Line: Here, we present BitPhylogenyBitPhylogeny, a probabilistic framework to reconstruct intra-tumor evolutionary pathways.Using a full Bayesian approach, we jointly estimate the number and composition of clones in the sample as well as the most likely tree connecting them.We validate our approach in the controlled setting of a simulation study and compare it against several competing methods.
Cancer has long been understood as a somatic evolutionary process, but many details of tumor progression remain elusive. Here, we present BitPhylogenyBitPhylogeny, a probabilistic framework to reconstruct intra-tumor evolutionary pathways. Using a full Bayesian approach, we jointly estimate the number and composition of clones in the sample as well as the most likely tree connecting them. We validate our approach in the controlled setting of a simulation study and compare it against several competing methods. In two case studies, we demonstrate how BitPhylogeny BitPhylogeny reconstructs tumor phylogenies from methylation patterns in colon cancer and from single-cell exomes in myeloproliferative neoplasm.
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Mentions: Figure 7A presents the results of the BitPhylogeny analysis. It shows a tree structure with a major clone (labeled as clone c) containing 33 out of all 58 cells. This clone is the most progressed clone since it has the longest total branch length from the root clone. One distinct feature of the reconstructed tree is that it captures both clonal progression (e.g., clone b to c) and binary branching with unobserved common ancestors (e.g., clones d and e). As a validation, genotypes from both bulk-sequenced normal and cancer cells are included in the analysis. The normal genotype is correctly identified as the root of the tree (clone a in Figure 7A). The genotype of the bulk-sequenced tumor is assigned to the most progressed clone c. While the analysis of the data with classical phylogenetic models in the original study only showed evidence for monoclonal evolution, BitPhylogeny reveals an additional structure of the tumor phylogeny involving in total half of all cells analyzed.Figure 7