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Patient-Specific Phylogenetic and Pathway Analysis of Tumor Evolution (306681)Jinpeng of Liu, University of Kentucky
Arnold Stromberg, University of Kentucky
Chi Wang, University of Kentucky
*Tingting Zhai, University of Kentucky
Keywords: Tumor evolution, Phylogenetic analysis, Gene expression
Studying tumor evolution is a major task to understand the biological mechanism of carcinogenesis, develop new cancer therapies, and prevent drug resistance. We focus on two important questions in tumor evolution. The first question is to quantify intra-tumor heterogeneity, where multiple subclones of tumor cells with distinct genomic and transcriptomic profiles arise during tumor evolution. Although many bioinformatics methods based on gene mutation data have been proposed to estimate intra-tumor heterogeneity, there are limited methods for inferring subclonal structures from gene expression data. Another question is to estimate the temporal order of alteration of key cancer pathways during tumor evolution. Current methods are population-based, inferring the order for a group of patients. To our knowledge, no method has been developed to infer the order of pathway alteration for an individual patient. We present a new statistical method to 1) reconstruct the evolutionary history and population frequency of the subclonal lineages of tumor cells and 2) infer temporal order of pathway alterations in tumor evolution for each individual patient based on RNA-seq data.