Abstract
In 2013, we published a comparative analysis of mutation and gene expression profiles and drug sensitivity measurements for 15 drugs characterized in the 471 cancer cell lines screened in the Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE). While we found good concordance in gene expression profiles, there was substantial inconsistency in the drug responses reported by the GDSC and CCLE projects. We received extensive feedback on the comparisons that we performed. This feedback, along with the release of new data, prompted us to revisit our initial analysis. We present a new analysis using these expanded data, where we address the most significant suggestions for improvements on our published analysis — that targeted therapies and broad cytotoxic drugs should have been treated differently in assessing consistency, that consistency of both molecular profiles and drug sensitivity measurements should be compared across cell lines, and that the software analysis tools provided should have been easier to run, particularly as the GDSC and CCLE released additional data.Our re-analysis supports our previous finding that gene expression data are significantly more consistent than drug sensitivity measurements. Using new statistics to assess data consistency allowed identification of two broad effect drugs and three targeted drugs with moderate to good consistency in drug sensitivity data between GDSC and CCLE. For three other targeted drugs, there were not enough sensitive cell lines to assess the consistency of the pharmacological profiles. We found evidence of inconsistencies in pharmacological phenotypes for the remaining eight drugs.Overall, our findings suggest that the drug sensitivity data in GDSC and CCLE continue to present challenges for robust biomarker discovery. This re-analysis provides additional support for the argument that experimental standardization and validation of pharmacogenomic response will be necessary to advance the broad use of large pharmacogenomic screens.
Highlights
The goal of precision medicine is the identification of the best therapy for each patient and their own unique manifestation of a disease
This inconsistency can be clearly seen by plotting drug response reported for each of the 15 drugs provided in both Genomics of Drug Sensitivity in Cancer (GDSC) and Cell Line Encyclopedia (CCLE) for the 471 cell lines assayed by both studies7–10
Consistent with the results reported by the CCLE2, the vast majority of cell lines had highly concordant fingerprints (462 out of 470 cell lines with single nucleotide polymorphism (SNP) profiles available in both GDSC and CCLE; Dataset 1)
Summary
The goal of precision medicine is the identification of the best therapy for each patient and their own unique manifestation of a disease. The gene expression data showed reasonable consistency between the two studies, the drug sensitivity measurements were surprisingly inconsistent This inconsistency can be clearly seen by plotting drug response reported for each of the 15 drugs provided in both GDSC and CCLE for the 471 cell lines assayed by both studies. Since the publication of our comparative analysis, we received a great deal of constructive feedback from the scientific community regarding multiple aspects of the analysis we reported, including suggestions for analytical methods that might uncover greater consistency between the studies Both GDSC and CCLE have released new drug sensitivity and molecular profiling data, allowing us to revisit our initial analysis, and to extend it using these new data
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
