Inferring the Evolutionary History of Tumors

Abstract:

Bulk sequencing of tumor DNA is a popular strategy for uncovering information about the spectrum of mutations arising in the tumor, and is often supplemented by multi-region sequencing, which provides a view of tumor heterogeneity. The statistical issues arise from the fact that bulk sequencing makes the determination of sub-clonal frequencies, and other quantities of interest, difficult. In this talk I will discuss this problem, beginning with its setting in population genetics. The data provide an estimate of the site frequency spectrum (SFS) of the mutations in the tumor, which is used as the basis for inference. I will describe how Approximate Bayesian Computation can be used for inference in problems like this one in which likelihoods are intractable. I will also describe a model for selective clonal sweeps that estimates the number of subclones that have arisen in the tumor; here the inference is based on a method of moments using the SFS. Time permitting, I will describe some novel experimental methods we are developing to understand the 3D structure of tumors, paving the way for some challenging inferential problems that will require engagement from data scientists and others.

Biography:

Simon Tavaré joined Columbia University in 2018 as the Herbert and Florence Irving Director of the Irving Institute for Cancer Dynamics and a professor in the Departments of Statistics and Biological Sciences. From 1978 to 2003, Simon worked in the USA and from 2003, he was a professor in the Department of Applied Mathematics and Theoretical Physics and the Department of Oncology at the University of Cambridge, England. From February 2013 to January 2018, he was director of the Cancer Research UK Cambridge Institute, which had become a department of the University of Cambridge in January 2013. His research focuses on statistical bioinformatics and computational biology, particularly evolutionary approaches to understanding cancer biology. Dr. Tavaré is an elected fellow of the Academy of Medical Sciences and of the Royal Society, and a member of the European Molecular Biology Organization. He was president of the London Mathematical Society from 2015 to 2017 and was elected a fellow of the American Mathematical Society and a foreign associate of the U.S. National Academy of Sciences in 2018.

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The MIT Statistics and Data Science Center hosts guest lecturers from around the world in this weekly seminar.