FI
F Iorio
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2 records found
1
Journal article
(2016)
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Daniel J. Vis, Lorenzo Bombardelli, Howard Lightfoot, Francesco Iorio, MJ Garnett, Lodewyk Wessels
Aim: Experimental variation in dose–response data of drugs tested on cell lines result in inaccuracies in the estimate of a key drug sensitivity characteristic: the IC50. We aim to improve the precision of the half-limiting dose (IC50) estimates by simultaneously employing all dose–responses across all cell lines and drugs, rather than using a single drug–cell line response.
Materials & methods: We propose a multilevel mixed effects model that takes advantage of all available dose–response data.
Results: The new estimates are highly concordant with the currently used Bayesian model when the data are well behaved. Otherwise, the multilevel model is clearly superior.
Conclusion: The multilevel model yields a significant reduction of extreme IC50 estimates, an increase in precision and it runs orders of magnitude faster.
...
Aim: Experimental variation in dose–response data of drugs tested on cell lines result in inaccuracies in the estimate of a key drug sensitivity characteristic: the IC50. We aim to improve the precision of the half-limiting dose (IC50) estimates by simultaneously employing all dose–responses across all cell lines and drugs, rather than using a single drug–cell line response.
Materials & methods: We propose a multilevel mixed effects model that takes advantage of all available dose–response data.
Results: The new estimates are highly concordant with the currently used Bayesian model when the data are well behaved. Otherwise, the multilevel model is clearly superior.
Conclusion: The multilevel model yields a significant reduction of extreme IC50 estimates, an increase in precision and it runs orders of magnitude faster.
Journal article
(2016)
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Francesco Iorio, Theo A. Knijnenburg, More Authors..., Daniel J. Vis, Graham R. Bignell, Michael P. Menden, Michael Schubert, Nanne Aben, Emanuel Gonçalves, Syd Barthorpe, Lodewyk Wessels
Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature of cancer. Using this information to guide the development and application of therapies in the clinic is challenging. Here, we report how cancerdriven alterations identified in 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation, and gene expression) can be mapped onto 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs. We find that cell lines faithfully
recapitulate oncogenic alterations identified in tumors, find that many of these associate with drug sensitivity/resistance, and highlight the importance
of tissue lineage in mediating drug response. Logicbased modeling uncovers combinations of alterations that sensitize to drugs, while machine learning
demonstrates the relative importance of different data types in predicting drug response. Our analysis and datasets are rich resources to link genotypes with cellular phenotypes and to identify therapeutic options for selected cancer sub-populations. ...
recapitulate oncogenic alterations identified in tumors, find that many of these associate with drug sensitivity/resistance, and highlight the importance
of tissue lineage in mediating drug response. Logicbased modeling uncovers combinations of alterations that sensitize to drugs, while machine learning
demonstrates the relative importance of different data types in predicting drug response. Our analysis and datasets are rich resources to link genotypes with cellular phenotypes and to identify therapeutic options for selected cancer sub-populations. ...
Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature of cancer. Using this information to guide the development and application of therapies in the clinic is challenging. Here, we report how cancerdriven alterations identified in 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation, and gene expression) can be mapped onto 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs. We find that cell lines faithfully
recapitulate oncogenic alterations identified in tumors, find that many of these associate with drug sensitivity/resistance, and highlight the importance
of tissue lineage in mediating drug response. Logicbased modeling uncovers combinations of alterations that sensitize to drugs, while machine learning
demonstrates the relative importance of different data types in predicting drug response. Our analysis and datasets are rich resources to link genotypes with cellular phenotypes and to identify therapeutic options for selected cancer sub-populations.
recapitulate oncogenic alterations identified in tumors, find that many of these associate with drug sensitivity/resistance, and highlight the importance
of tissue lineage in mediating drug response. Logicbased modeling uncovers combinations of alterations that sensitize to drugs, while machine learning
demonstrates the relative importance of different data types in predicting drug response. Our analysis and datasets are rich resources to link genotypes with cellular phenotypes and to identify therapeutic options for selected cancer sub-populations.