Deciphering Tumor Evolution with PhyloSub Algorithm
Explore the PhyloSub algorithm for inferring tumor phylogenies from single nucleotide variants (SNVs) in genetically diverse subclonal populations of cells. Discover the assumptions, rules, and ordering methods used in reconstructing the evolutionary history of tumors. Uncover the potential of infinite sites assumption and topological constraint rules in tumor phylogeny inference with PhyloSub.
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Presentation Transcript
PhyloSub Jiao et. al. BMC Bioinformatics 2014, 15:35
Background Genetically-diverse subclonal populations of cells in tumors Can reconstruct evolutionary history of tumor SNV s (single nucleotide variants) Limitation: frequencies measured independently
Method Infinite sites assumption Topological constraint rules PhyloSub infers tumor phylogenies from SNV allele frequency Partial order plot
Assumptions and Rules of Model Clonal evolution theory Infinite sites assumption Need at least two tumor samples to rule out a linear phylogeny
Ordering Rule Given the following frequencies: fA, fBand fC Rule: If fB> fC, the phylogeny can be parallel OR B can be an ancestor of C Frequencies of A, B and C give constraint alone
Dirichlet Process 3 hyper parameters: 0, and 0 and = # of nodes (subclones) in tree = height of tree = # of siblings in tree -> width of tree
Partial Order Plot Data from Jan et. al paper found coexistence of multiple subclonal lineages in HSC from AML samples Single assay provided ground truth tree Samples: SU048 and SU070
