CancerDR: Cancer Drug Resistance Database

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General about CancerDR

CancerDR is the compilation of mutation data and pharmacological drug profiles from Catalogue Of Somatic Mutations (COSMIC)and Cancer Cell Line Encyclopedia (CCLE). In COSMIC, 138 anticancer drugs targeting a wide range of therapeutic targets were screened on 275-507 cell lines and in case of CCLE, 24 anticancer drugs were screened on more than 500 cell lines. We have compiled both of these data on a single platform in user-friendly format to make out some useful conclusions on cancer drug resistance. Methods of drug screening on cancer cell lines are available on COSMIC and CCLE websites respectively.

We obtained the mutational status of 116 unique drug targets in cell lines form the parallel sequencing data available at CCLE website. Then we tried to correlate the mutation status of targets with IC50 values of the drugs.

Along with this, we have been predicted the structures of these therapeutic targets. To correlate the effect of mutation on target structure, we predicted the tertiary structures of all mutants reported in CCLE for 116 drug targets. In addition to this, structural alignments of wild type drug targets with their mutants are generated and covered in the CancerDR.

For sequence alignment purpose, all the given mutations were mapped on the target sequence. Then alignment of wild type and their mutants were generated. These sequences can also be used for the alignment of short reads to find out the mutations in a given target gene. After sequence alignment, we generated the phylogenetic trees of mutants to show the distance between them.

We also tried to cluster the cell lines on the basis of IC50 values of anticancer drugs assayed on them. This will help to identify the most sensitive or most resistant cell lines for a particular drug. Similarly, we cluster the drugs to identify which drug is most effective or less effective on a particular cell line.