Cancer Therapeutics Response Signatures
These transcriptomic signatures were made using data from the Cancer Therapeutics Response Portal (CTRP) project. The data includes 860 cancer cell lines and combines basal (untreated) gene expression with measurements of sensitivity to 481 anti-cancer compounds. Drug sensitivity was measured as cell viability (ATP levels measured by CellTiter-Glo®) over a sixteen-point concentration-response curve (two-fold dilution) in duplicate after 72 hours of treatment with each compound and summarized as the area under the concentration-response curve (AUC). Signatures were created separately for each tissue/cell lineage noted in the dataset. Signatures were also created with the data from all tissues combined and with the data from all of the solid tumor cell lines combined (called “non-hl” because they exclude cells categorized as “haematopoietic and lymphoid tissue”). More information about the CTRP project can be found at http://portals.broadinstitute.org/ctrp.
The signature creation method was as follows:
1) Subset the CTRP data to only cell lines of a given tissue/cell lineage. 2) For each compound: select cell lines that are sensitive to treatment (5 lowest AUCs) and resistant to treatment (5 highest AUCs), where AUC is area under cell viability curve after treatment with that drug. 3) Construct signature by finding average log fold change in (untreated) gene expression between these two groups of cell lines (i.e. log fold change = average log2 expression in resistant cell lines - average log2 expression in sensitive cell lines)
Note: Weights for each gene are given by the log fold change in expression, so a positive weight represents a gene that has higher expression in resistant cell lines, i.e. a gene that could be considered a marker of drug resistance. Alternatively, a negative weight represents a gene that has higher expression in sensitive cell lines and may be related to drug sensitivity. p-values for each fold change were computed from a two-sided t-test.Keywords: CTRP | drug response | cancer | BROAD | signatures |