doi: 10.1038/nature20580.
Drug response consistency in CCLE and CGP
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- PMID: 27905419
- PMCID: PMC5554885
- DOI: 10.1038/nature20580
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Drug response consistency in CCLE and CGP
Nature.
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No abstract available
Figures
This document was given to manual curators as example dose–response curves. These idealized data represent various dose–response curves one might encounter in CCLE and/or CGP and indicate how they should be classified.
This is one page, as an example, from the data given to manual curators, which they were instructed to rate as either sensitive or insensitive.
a, Slope (ms; left) or area under the curve (AUCs; right) of the dose–response curves for all overlapping drug/cell line pairs (2,520) in CCLE and CGP, considering only the shared dose range (denoted by subscript s). All ms and AUCs values were normalized based on the respective drug dose range, to facilitate comparison across drugs (see Supplementary Methods). Colour indicates density of dots. The black dashed line is x = y. In example dose–response curves, stars represent the shared dose range. b, Relationship between ms and AUCs for each database (inset m and AUC defined with the entire dose range as opposed to the shared dose range). The SVM classifier decision boundary divides the plot into sensitive and insensitive drug/cell line pairs, as indicated by the black dashed line. Slope and y-intercept of boundary line for CCLEs: m = −1.32, b = −0.01; CGPs: m = −1.31, b = −0.06. Colour of dots indicates the mean of the binary classifications from eight manual curators; blue indicates a unanimous sensitivity rating, green a very uncertain rating, and red a unanimous insensitivity rating. c, Consistency (left) and inconsistency (right) of classification methods broken down by drug. Far left plot shows manual curation consistency between CCLE and CGP. Middle left plot shows consistency between the manual curation data from CCLE and the CCLE SVM classifier. Middle right plot shows consistency between the manual curation data from CGP and the CGP SVM classifier. Far right plot shows consistency between the CCLE SVM classifier used to classify CGP data and the CGP SVM classifier used to classify CCLE data. Colour indicates percentage consistency as denoted by the colour bar. Numbers denote number of observations, black for consistent, white for inconsistent. d, Inconsistent drug/cell line pairs based on manual curation results. Histograms bin the Euclidian distance between each discrepantly classified drug/cell line pair (that is, called sensitive in one database and insensitive in the other) and the decision boundary (black dashed line) in the AUCs versus ms plots for CCLE (left) or CGP (right). In inset, coloured dots indicate drug/cell line pairs that were classified discrepantly in CCLE and CGP. Colour corresponds to density of dots. Black dashed line indicates the decision boundary for the SVM classifier. Grey dashed lines indicate a Euclidian distance of 0.1 from the decision boundary in either direction e, IC50 values from all sensitive cell line/drug combinations as determined by SVM classifier in CCLE or CGP. The black dashed line is x = y. f, IC50 values from all sensitive cell line/drug pairs (same as in Fig. 1e) stratified by drug, for drugs having at least 5 points. All correlation coefficients are Pearson.