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 | 2020-04-17T09:54:28Z | |
dc.date.issued | 2020-03-30 | |
dc.identifier.citation | eLife, 2020, 9 | |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3594 | |
dc.identifier.eissn | 2050-084X | |
dc.identifier.doi | 10.7554/elife.48714 | |
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. | |
dc.format | Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELIFE SCIENCES PUBLICATIONS LTD | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-03-09 | |
rioxxterms.versionofrecord | 10.7554/elife.48714 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-03-30 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | eLife | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR | |
pubs.publication-status | Published | |
pubs.volume | 9 | |
pubs.embargo.terms | Not known | |
dc.contributor.icrauthor | Zapata Ortiz, Luis | |
dc.contributor.icrauthor | Sottoriva, Andrea | |
dc.contributor.icrauthor | Graham, Trevor | |