## Replication Study: Discovery and Preclinical Validation of Drug Indications Using Compendia of Public Gene Expression Data <br> **Abstract:** In 2015, as part of the [Reproducibility Project: Cancer Biology][1], we published a Registered Report ([Kandela et al., 2015][2]), that described how we intended to replicate selected experiments from the paper “Discovery and Preclinical Validation of Drug Indications Using Compendia of Public Gene Expression Data“ ([Sirota et al., 2011][3]). Here we report the results of those experiments. We found that cimetidine treatment in a xenograft model using A549 lung adenocarcinoma cells resulted in decreased tumor volume compared to vehicle control; however, while the effect was in the same direction as the original study (Figure 4C; [Sirota et al., 2011][4]), it was not statistically significant. Whereas, cimetidine treatment in a xenograft model using ACHN renal cell carcinoma cells did not differ from vehicle control treatment, similar to the original study (Supplemental Figure 1; [Sirota et al., 2011][5]). Doxorubicin treatment in a xenograft model using A549 lung adenocarcinoma cells did not result in a statistically significant difference compared to vehicle control despite tumor volume being reduced to levels similar to those reported in the original study (Figure 4C; [Sirota et al., 2011][6]). Finally, we report a random effects meta-analysis for each result. These meta-analyses show that the inhibition of A549 derived tumors by cimetidine resulted in a statistically significant effect, as did the inhibition of A549 derived tumors by doxorubicin. The effect of cimetidine on ACHN derived tumors was not statistically significant, as predicted. ---------- ### Contents **Reports:** Read the [Replication Study][7], or view the [preprint versions][8]. To reproduce the Replication Study manuscript text run this in [R Studio][9] (note: downloads [R markdown file][10] directly from osf.io): library(httr) library(rmarkdown) GET("https://osf.io/ywphk/?action=download", write_disk("Replication_Study_21.Rmd", overwrite = T)) render("Replication_Study_21.Rmd", output_format = "word_document") <br> Also, explore the [Registered Report][11] and materials related to the Registered Report [here][12]. <br> **Experiments replicated:** Reproduce and explore the figures, analyses, data, and methods generated in this replication attempt. - [Assessing the effect of cimetidine treatment on tumor growth][13] - Replication of Figure 4C and Supplemental Figure 1 in Sirota et al., 2011. <br> **Meta-analyses:** As a measure of evaluating reproducibility a meta-analysis of each effect was performed. The forest plots, analyses, and data are available [here][14]. <br> Questions about the project can be directed to [contact+rpcb@cos.io][15]. [1]: https://osf.io/e81xl/wiki/home/ [2]: http://elifesciences.org/content/4/e06847v1 [3]: http://stm.sciencemag.org/content/3/96/96ra77 [4]: http://stm.sciencemag.org/content/3/96/96ra77 [5]: http://stm.sciencemag.org/content/3/96/96ra77 [6]: http://stm.sciencemag.org/content/3/96/96ra77 [7]: http://dx.doi.org/10.7554/eLife.17044 [8]: https://osf.io/x5qy2/ [9]: https://www.rstudio.com [10]: https://osf.io/ywphk/ [11]: https://elifesciences.org/content/4/e06847 [12]: https://osf.io/uazfe/wiki/home/ [13]: https://osf.io/fh6gn/wiki/home/ [14]: https://osf.io/jcghv/wiki/home/ [15]: mailto:contact+rpcb@cos.io