Differentiating between cancer and normal tissue samples using multi-hit combinations of genetic mutations

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dc.contributor.authorDash, Sajalen
dc.contributor.authorKinney, N.A.en
dc.contributor.authorVarghese, Ronnieen
dc.contributor.authorGarner, Harold R.en
dc.contributor.authorFeng, Wu-chunen
dc.contributor.authorAnandakrishnan, Ramuen
dc.contributor.departmentElectrical and Computer Engineeringen
dc.contributor.departmentComputer Scienceen
dc.date.accessioned2019-03-29T13:05:27Zen
dc.date.available2019-03-29T13:05:27Zen
dc.date.issued2019-01-30en
dc.description.abstractCancer is known to result from a combination of a small number of genetic defects. However, the specific combinations of mutations responsible for the vast majority of cancers have not been identified. Current computational approaches focus on identifying driver genes and mutations. Although individually these mutations can increase the risk of cancer they do not result in cancer without additional mutations. We present a fundamentally different approach for identifying the cause of individual instances of cancer: we search for combinations of genes with carcinogenic mutations (multi-hit combinations) instead of individual driver genes or mutations. We developed an algorithm that identified a set of multi-hit combinations that differentiate between tumor and normal tissue samples with 91% sensitivity (95% Confidence Interval (CI) = 89–92%) and 93% specificity (95% CI = 91–94%) on average for seventeen cancer types. We then present an approach based on mutational profile that can be used to distinguish between driver and passenger mutations within these genes. These combinations, with experimental validation, can aid in better diagnosis, provide insights into the etiology of cancer, and provide a rational basis for designing targeted combination therapies. © 2019, The Author(s).en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-018-37835-6en
dc.identifier.issn20452322en
dc.identifier.issue1en
dc.identifier.other1005en
dc.identifier.pmid30700767en
dc.identifier.urihttp://hdl.handle.net/10919/88747en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleDifferentiating between cancer and normal tissue samples using multi-hit combinations of genetic mutationsen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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