dc.contributor.author | Williams, MJ | |
dc.contributor.author | Zapata, L | |
dc.contributor.author | Werner, B | |
dc.contributor.author | Barnes, CP | |
dc.contributor.author | Sottoriva, A | |
dc.contributor.author | Graham, TA | |
dc.date.accessioned | 2020-06-01T14:44:32Z | |
dc.date.available | 2020-03-09 | |
dc.date.available | 2020-06-01T14:44:32Z | |
dc.date.issued | 2020-03-30 | |
dc.identifier.citation | eLife 2020;9:e48714 DOI: 10.7554/eLife.48714 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/64534 | |
dc.description.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. | en_US |
dc.language | eng | |
dc.language.iso | en | en_US |
dc.publisher | eLife Sciences Publications Ltd | en_US |
dc.relation.ispartof | Elife | |
dc.rights | Creative Commons Attribution License | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | cancer evolution | en_US |
dc.subject | computational biology | en_US |
dc.subject | distribution of fitness effects | en_US |
dc.subject | dn/ds | en_US |
dc.subject | genetics | en_US |
dc.subject | genomics | en_US |
dc.subject | human | en_US |
dc.subject | population genetics | en_US |
dc.subject | somatic evolution | en_US |
dc.subject | systems biology | en_US |
dc.title | Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios. | en_US |
dc.type | Article | en_US |
dc.rights.holder | (c) Williams et al. | |
dc.identifier.doi | 10.7554/eLife.48714 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/32223898 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 9 | en_US |
dcterms.dateAccepted | 2020-03-09 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |