Rafael Irizarry, IDI-BD2K partner, has submitted this problem for the Heathcare Innovation Replicathon.
In 2012, two studies (Garnett et al and Barretina et al) attempted to correlate large numbers of gene expression, mutation, and copy number measurements in hundreds of cancer cell lines with sensitivities to hundreds of different drugs, with the goal of finding genes or mutations that might indicate certain kinds of cancers with vulnerabilities to specific drugs. However, a subsequent study (Haibe-Kains et al 2013), attempting to replicate the initial findings, found major inconsistencies in the results of the two studies. We can review the papers, download the data and analyze it ourselves to form our own conclusions.
Readings for project:
- Haibe-Kains, B. et al. Inconsistency in large pharmacogenomic
studies. Nature 504, 389–393 (2013).
- Barretina, J. et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603–607 (2012).
- Garnett, M. J. et al. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature 483, 570–575 (2012).
- Safikhani, Z. et al. Assessment of pharmacogenomic agreement. bioRxiv 48470 (2016). doi:10.1101/048470
- Smirnov, P. et al. PharmacoGx: an R package for analysis of large pharmacogenomic datasets. Bioinformatics 32, 1244–1246 (2016).