Georgia Institute of Technology College of Sciences

Inference of evolutionary dynamics of heterogeneous cancer and viral populations Abstract: Genetic diversity of cancer cell populations and intra-host viral populations is one of the major factors influencing disease progression and treatment outcome. However, evolutionary dynamics of such populations remain poorly understood. Quantification of selection is a key step to understanding evolutionary mechanisms driving cancer and viral diseases. We will introduce a mathematical model and an algorithmic framework for inference of fitness landscapes of heterogeneous populations from genomic data. It is based on a maximal likelihood approach, whose objective is to estimate a vector of clone/strain fitnesses which better fits the observed tumor phylogeny, observed population structure and the dynamical system describing evolution of the population as a branching process. We will discuss our approach to solve the problem by transforming the original continuous maximum likelihood problem into a discrete optimization problem, which could be considered as a variant of scheduling problem with precedent constraints and with non-linear cumulative cost function.