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<h2>Replication Study: Discovery and Preclinical Validation of Drug Indications Using Compendia of Public Gene Expression Data</h2> <p><br> <strong>Abstract:</strong></p> <p>In 2015, as part of the <a href="https://osf.io/e81xl/wiki/home/" rel="nofollow">Reproducibility Project: Cancer Biology</a>, we published a Registered Report (<a href="http://elifesciences.org/content/4/e06847v1" rel="nofollow">Kandela et al., 2015</a>), 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“ (<a href="http://stm.sciencemag.org/content/3/96/96ra77" rel="nofollow">Sirota et al., 2011</a>). 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; <a href="http://stm.sciencemag.org/content/3/96/96ra77" rel="nofollow">Sirota et al., 2011</a>), 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; <a href="http://stm.sciencemag.org/content/3/96/96ra77" rel="nofollow">Sirota et al., 2011</a>). 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; <a href="http://stm.sciencemag.org/content/3/96/96ra77" rel="nofollow">Sirota et al., 2011</a>). 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.</p> <hr> <h3>Contents</h3> <p><strong>Reports:</strong> Read the <a href="http://dx.doi.org/10.7554/eLife.17044" rel="nofollow">Replication Study</a>, or view the <a href="https://osf.io/x5qy2/" rel="nofollow">preprint versions</a>. </p> <p>To reproduce the Replication Study manuscript text run this in <a href="https://www.rstudio.com" rel="nofollow">R Studio</a> (note: downloads <a href="https://osf.io/ywphk/" rel="nofollow">R markdown file</a> directly from <a href="http://osf.io" rel="nofollow">osf.io</a>):</p> <pre class="highlight"><code>library(httr) library(rmarkdown) GET(&quot;<a href="https://osf.io/ywphk/?action=download" rel="nofollow">https://osf.io/ywphk/?action=download</a>&quot;, write_disk(&quot;Replication_Study_21.Rmd&quot;, overwrite = T)) render(&quot;Replication_Study_21.Rmd&quot;, output_format = &quot;word_document&quot;)</code></pre> <p><br> Also, explore the <a href="https://elifesciences.org/content/4/e06847" rel="nofollow">Registered Report</a> and materials related to the Registered Report <a href="https://osf.io/uazfe/wiki/home/" rel="nofollow">here</a>.</p> <p><br> <strong>Experiments replicated:</strong> Reproduce and explore the figures, analyses, data, and methods generated in this replication attempt.</p> <ul> <li><a href="https://osf.io/fh6gn/wiki/home/" rel="nofollow">Assessing the effect of cimetidine treatment on tumor growth</a></li> <li>Replication of Figure 4C and Supplemental Figure 1 in Sirota et al., 2011.</li> </ul> <p><br> <strong>Meta-analyses:</strong> As a measure of evaluating reproducibility a meta-analysis of each effect was performed. The forest plots, analyses, and data are available <a href="https://osf.io/jcghv/wiki/home/" rel="nofollow">here</a>.</p> <p><br> Questions about the project can be directed to <a href="mailto:contact+rpcb@cos.io">contact+rpcb@cos.io</a>.</p>
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