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dc.contributor.authorWilliams, MJ
dc.contributor.authorZapata, L
dc.contributor.authorWerner, B
dc.contributor.authorBarnes, CP
dc.contributor.authorSottoriva, A
dc.contributor.authorGraham, TA
dc.date.accessioned2020-04-17T09:54:28Z
dc.date.issued2020-03-30
dc.identifier.citationeLife, 2020, 9
dc.identifier.issn2050-084X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3594
dc.identifier.eissn2050-084X
dc.identifier.doi10.7554/elife.48714
dc.description.abstractThe 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.formatElectronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleMeasuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios.
dc.typeJournal Article
dcterms.dateAccepted2020-03-09
rioxxterms.versionofrecord10.7554/elife.48714
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-03-30
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfeLife
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.publication-statusPublished
pubs.volume9
pubs.embargo.termsNot known
dc.contributor.icrauthorSottoriva, Andreaen


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