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- W3013452103 abstract "The distribution of fitness effects (DFE) defines how new mutations spread through an evolving population. The ratio of non-synonymous to synonymous mutations (dN/dS) has become a popular method to detect selection in somatic cells. However the link, in somatic evolution, between dN/dS values and fitness coefficients is missing. Here we present a quantitative model of somatic evolutionary dynamics that determines the selective coefficients of individual driver mutations from dN/dS estimates. We then measure the DFE for somatic mutant clones in ostensibly normal oesophagus and skin. We reveal a broad distribution of fitness effects, with the largest fitness increases found for TP53 and NOTCH1 mutants (proliferative bias 1-5%). This study provides the theoretical link between dN/dS values and selective coefficients in somatic evolution, and measures the DFE of mutations in human tissues." @default.
- W3013452103 created "2020-04-03" @default.
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- W3013452103 date "2020-03-30" @default.
- W3013452103 modified "2023-10-06" @default.
- W3013452103 title "Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios" @default.
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- W3013452103 doi "https://doi.org/10.7554/elife.48714" @default.
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