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<h2>Registered Report: Discovery and Preclinical Validation of Drug Indications Using Compendia of Public Gene Expression Data</h2> <p><br> <strong>Abstract:</strong></p> <p>The <a href="https://osf.io/e81xl/wiki/home/" rel="nofollow">Reproducibility Project: Cancer Biology</a> seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered report describes the proposed replication plan of key experiments from ‘Discovery and Preclinical Validation of Drug Indications Using Compendia of Public Gene Expression Data’ by Sirota et al., published in <em>Science Translational Medicine</em> in 2011 (<a href="http://stm.sciencemag.org/content/3/96/96ra77" rel="nofollow">Sirota et al., 2011</a>). The key experiments being replicated include Figure 4C and D and Supplemental Figure 1. In these figures, Sirota and colleagues. tested a proof of concept experiment validating their prediction that cimetidine, a histamine-2 (H2) receptor agonist commonly used to treat peptic ulcers (<a href="http://dx.doi.org/10.1016/j.ejps.2011.02.004" rel="nofollow">Kubecova et al., 2011</a>), would be effective against lung adenocarcinoma (Figure 4C and D). As a control they also tested the effects of cimetidine against renal carcinoma, for which it was not predicted to be efficacious (Supplemental Figure 1). The Reproducibility Project: Cancer Biology is a collaboration between the <a href="https://cos.io/" rel="nofollow">Center for Open Science</a> and <a href="https://www.scienceexchange.com/" rel="nofollow">Science Exchange</a>, and the results of the replications will be published by <a href="https://elifesciences.org/" rel="nofollow"><em>eLife</em></a>.</p> <hr> <h3>Contents</h3> <p>This component contains additional materials relating to the Registered Report for Study 21: Sirota et al., 2011 (<em>Science Translational Medicine</em>).</p> <p>The published Registered Report can be found <a href="https://elifesciences.org/content/4/e06847" rel="nofollow">here</a>. </p> <p><strong>Registered Report Initial Draft</strong>:</p> <ul> <li>This document represents the first draft of the selected experimental protocols. It contains the information that the Core team, with help from scientist volunteers, was able to glean from the original publication and its supplemental materials before the original authors were contacted for their input.<ul> <li><a href="https://osf.io/zirw7/" rel="nofollow">Study 21 Registered Report initial draft</a></li> </ul> </li> </ul> <p><strong>Data Estimation</strong>:</p> <ul> <li>When original data was unable to be obtained, or original qualitative data was quantified (for example, Western blots), the estimated data is contained here. Examples include densitometric quantification of Western blot bands, or estimations of means and variances from published graphs.<ul> <li><a href="https://osf.io/bv5pk/" rel="nofollow">Study 21 estimated data.xlsx</a></li> <li><a href="https://osf.io/aw87h/" rel="nofollow">Study 21 Figure 4C estimating datapoints.pptx</a></li> <li><a href="https://osf.io/kcsf6/" rel="nofollow">Study 21 Supp Fig 1 estimating datapoints.pptx</a></li> </ul> </li> </ul> <p><strong>Power Calculations</strong>:</p> <ul> <li>These documents contain details about how power calculations were performed, and include spreadsheets documenting statistical tests as well as any PRISM files, R scripts or additional materials used. Note: AUC = area under the curve.<ul> <li><a href="https://osf.io/myia7/" rel="nofollow">Study 21 Power Calculations.xlxs</a></li> <li><a href="https://osf.io/fxurm/" rel="nofollow">Study 21 2-way ANOVA.R</a></li> <li><a href="https://osf.io/krpmz/" rel="nofollow">Study 21 2-way ANOVA_SEM.R</a></li> <li><a href="https://osf.io/36a4y/" rel="nofollow">Study 21 2-way ANOVA_less comparisons.R</a></li> <li><a href="https://osf.io/jy8np/" rel="nofollow">Study 21 AUC.R</a></li> <li><a href="https://osf.io/2sqwa/" rel="nofollow">Study 21 AUC_SEM.R</a><ul> <li>Area under the curve calculations were performed for the initial submission of the Registered Report, but were then removed at the request of the reviewers.</li> </ul> </li> </ul> </li> </ul>
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