## Replication Study: Systematic identification of genomic markers of drug sensitivity in cancer cells <br> **Abstract:** In 2016, as part of the [Reproducibility Project: Cancer Biology][1], we published a Registered Report ([Vanden Heuvel et al., 2016][2]), that described how we intended to replicate selected experiments from the paper "Systematic identification of genomic markers of drug sensitivity in cancer cells" ([Garnett et al., 2012][3]). Here we report the results. We found Ewing’s sarcoma cell lines, overall, were more sensitive to the PARP inhibitor olaparib than osteosarcoma cell lines; however, while the effect was in the same direction as the original study (Figure 4C; [Garnett et al., 2012][3]), it was not statistically significant. Further, mouse mesenchymal cells transformed with either the EWS-FLI1 or FUS-CHOP rearrangement displayed similar sensitivities to olaparib, whereas the Ewing’s sarcoma cell line SK-N-MC had increased olaparib sensitivity. In the original study, mouse mesenchymal cells transformed with the EWS-FLI1 rearrangement and SK-N-MC cells were found to have similar sensitivities to olaparib, whereas mesenchymal cells transformed with the FUS-CHOP rearrangement displayed a reduced sensitivity to olaparib (Figure 4E; [Garnett et al., 2012][3]). We also studied another Ewing’s sarcoma cell line, A673: A673 cells depleted of EWS-FLI1 or a negative control both displayed similar sensitivities to olaparib, whereas the original study reported a decreased sensitivity to olaparib when EWS-FLI1 was depleted (Figure 4F; [Garnett et al., 2012][3]). Differences between the original study and this replication attempt, such as the use of different sarcoma cell lines and level of knockdown efficiency, are factors that might have influenced the outcomes. Finally, where possible, we report meta-analyses for each result. ---------- ### Contents **Reports:** Read the [Replication Study][4] or view the [preprint versions][5]. **Note**: In order to successfully run and knit the Replication Study Manuscript R Markdown file, you must install a series of necessary R packages. Review the necessary packages and noted versions on the R Markdown file [here][6], or run and knit the r markdown file below and they will be downloaded automatically. To reproduce the Replication Study manuscript text run this in [R Studio][7] (note: downloads [R markdown file][8] directly from osf.io: <br> library(httr) library(pandoc) library(rmarkdown) GET("https://osf.io/x28wg/?action=download",write_disk("Replication_Study_37.Rmd", overwrite = T)) render("Replication_Study_37.Rmd", output_format = "word_document") <br> Also, explore the Registered Report and materials related to the Registered Report [here][2]. **Data and Material Availability:** All associated data, protocols, analysis scripts, and other digital materials are available within this OSF project. **Experiments replicated**: Reproduce and explore the figures, analyses, data, and methods generated in this replication attempt. <br> - [Sensitivity of Ewing’s sarcoma cell lines to PARP inhibition][9] <br> -Replication of Figure 4C and Supplemental Figure 16 of Garnett et al., 2012 - [Sensitivity to olaparib in cells transformed with the EWS-FLI1 rearrangement][10] <br> -Replication of Figure 4E of Garnett et al., 2012 - [Olaparib sensitivity after depletion of EWS-FLI1 from A673 cells][11] <br> -Replication of Figure 4F and Supplemental Figure 20 Garnett et al., 2012 **Meta-analysis**: As a measure of evaluating reproducibility a meta-analysis of each effect was performed. The forest plots, analyses, and data are available [here][12]. <br> Questions about the project can be directed to [contact+rpcb@cos.io.][13] [1]: https://osf.io/e81xl/wiki/home/ [2]: https://elifesciences.org/articles/13620 [3]: https://www.nature.com/articles/nature11005 [4]: https://doi.org/10.7554/eLife.29747 [5]: https://osf.io/m8629/ [6]: https://osf.io/x28wg/ [7]: https://www.rstudio.com [8]: https://osf.io/x28wg/ [9]: https://osf.io/zy3s5/wiki/home/ [10]: https://osf.io/t3dm6/wiki/home/ [11]: https://osf.io/2w22x/wiki/home/ [12]: https://osf.io/whs6e/wiki/home/ [13]: mailto:contact+rpcb@cos.io