dc.contributor.author | Lord, CJ | |
dc.contributor.author | Quinn, N | |
dc.contributor.author | Ryan, CJ | |
dc.date.accessioned | 2020-07-08T10:13:04Z | |
dc.date.issued | 2020-05-28 | |
dc.identifier.citation | eLife, 2020, 9 | |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3823 | |
dc.identifier.eissn | 2050-084X | |
dc.identifier.doi | 10.7554/elife.58925 | |
dc.description.abstract | Genetic interactions, including synthetic lethal effects, can now be systematically identified in cancer cell lines using high-throughput genetic perturbation screens. Despite this advance, few genetic interactions have been reproduced across multiple studies and many appear highly context-specific. Here, by developing a new computational approach, we identified 220 robust driver-gene associated genetic interactions that can be reproduced across independent experiments and across non-overlapping cell line panels. Analysis of these interactions demonstrated that: (i) oncogene addiction effects are more robust than oncogene-related synthetic lethal effects; and (ii) robust genetic interactions are enriched among gene pairs whose protein products physically interact. Exploiting the latter observation, we used a protein-protein interaction network to identify robust synthetic lethal effects associated with passenger gene alterations and validated two new synthetic lethal effects. Our results suggest that protein-protein interaction networks can be used to prioritise therapeutic targets that will be more robust to tumour heterogeneity. | |
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 | Integrative analysis of large-scale loss-of-function screens identifies robust cancer-associated genetic interactions. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-05-18 | |
rioxxterms.versionofrecord | 10.7554/elife.58925 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-05-28 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | eLife | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function | |
pubs.publication-status | Published | |
pubs.volume | 9 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Gene Function | |
dc.contributor.icrauthor | Lord, Christopher | |