Local Adaptive Mapping of Karyotype Fitness Landscapes

Author:

Beck Richard J,Andor Noemi

Abstract

AbstractAneuploidy occurs in most solid tumors and has the potential to dramatically modify cellular phenotype and fitness. Despite the importance of aneuploidy in tumor evolution, quantitative understanding of the evolutionary landscape of aneuploidy is lacking. To address this question, we developed a method to infer the fitness landscape of either arm-level or whole-chromosome level karyotypes. Our method takes longitudinal single cell sequencing data from an evolving cell population as input, then estimates the fitness of thousands of karyotypes located near to the input data in karyotype space. The predictive ability of the method was validated using artificial data generated from an agent based model, as well as data from a selection of in vitro and in vivo passaged cell lines. We applied our pipeline to an in vitro dataset of serially passaged cells and - based on topological analysis of the fitness landscape around diploid and tetraploid karyotypes - found support for the hypothesis that whole genome doubling benefits tumour cells by conferring robustness against missegregations.

Publisher

Cold Spring Harbor Laboratory

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