## Replication Study: Discovery and Preclinical Validation of Drug Indications Using Compendia of Public Gene Expression Data
In 2015, as part of the [Reproducibility Project: Cancer Biology], we published a Registered Report ([Kandela et al., 2015]), 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]). 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]), 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]). 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]). 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.
**Reports:** Read the [Replication Study], or view the [preprint versions].
To reproduce the Replication Study manuscript text run this in [R Studio] (note: downloads [R markdown file] directly from osf.io):
GET("https://osf.io/ywphk/?action=download", write_disk("Replication_Study_21.Rmd", overwrite = T))
render("Replication_Study_21.Rmd", output_format = "word_document")
Also, explore the [Registered Report] and materials related to the Registered Report [here].
**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]
- Replication of Figure 4C and Supplemental Figure 1 in Sirota et al., 2011.
**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].
Questions about the project can be directed to [firstname.lastname@example.org].