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ZIH-Kolloquium: Statistical Inference of growth and mutation patterns of tumors based on genomic data

Datum
13.12.2019
Zeit
14:00 - 15:00
Sprecher
Marek Kimmel
Zugehörigkeit
Rice University and Silesian University of Technology
Serie
TUD ZIH Kolloquium
Sprache
en
Hauptthema
Informatik
Andere Themen
Informatik
Beschreibung

Statistical Inference of growth and mutation patterns of tumors based on genomic data

We present a mathematical model of growth of secondary clones in cancer cell populations, anchored in the coalescence theory. Recent years have seen considerable work on inference about cancer evolution from mutations identified in cancer samples. Much of the modeling work has been based on classical models of population genetics, generalized to accommodate time-varying cell population size. Reverse-time, genealogical views of such models, have been used to infer aspects of the past of growing populations. Another approach is to use branching processes, the simplest scenario being the classical linear birth-death process. Inference from evolutionary models of DNA often exploits summary statistics of the sequence data, a common one being the so-called Site Frequency Spectrum (SFS). In a bulk tumor sequencing experiment we can estimate for each site at which a novel somatic point mutation has arisen, the proportion of cells that carry that mutation. These numbers are then grouped into collections of sites which have similar mutant fractions. We examine how the SFS based on birth-death processes differs from those based on the coalescent model. This may stem from the different sampling mechanisms in the two approaches. However, we also show that despite this, they are quantitatively comparable for the range of parameters typical for tumor cell populations. We also present a model of tumor evolution with selective sweeps, and demonstrate how it may help in understanding the history of a tumor as well as the influence of data pre-processing. Based on the model, we describe difficulties in reconstructing past demography of tumors. Considerations are illustrated by analysis of site frequency spectra of tumors from The Cancer Genome Atlas.

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Letztmalig verändert: 06.12.2019, 00:05:42

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TUD Andreas-Pfitzmann-Bau (Informatik) (APB 1096)Nöthnitzer Straße4601069Dresden
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E-Mail
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