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<h2>Registered report: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate</h2> <p><br> <strong>Abstract</strong> 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 selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of <a href="https://osf.io/e81xl/wiki/studies/" rel="nofollow">citations and Altmetric scores</a> (<a href="https://elifesciences.org/content/3/e04333" rel="nofollow">Errington et al., 2014</a>). This Registered Report describes the proposed replication plan of key experiments from “The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate” by Ward and colleagues, published in <em>Cancer Cell</em> in 2010 (<a href="http://www.cell.com/cancer-cell/abstract/S1535-6108%2810%2900036-X" rel="nofollow">Ward et al., 2010</a>). The experiments that will be replicated are those reported in Figures 2, 3 and 5. Ward and colleagues demonstrate the mutations in isocitrate dehydrogenase 2 (<em>IDH2</em>), commonly found in acute myeloid leukemia (AML), abrogate the enzyme’s wild-type activity and confer to the mutant neomorphic activity that produces the oncometabolite 2-hydroxyglutarate (2-HG) (Figures 2 and 3). They then show that elevated levels of 2-HG are correlated with mutations in <em>IDH1</em> and <em>IDH2</em> in AML patient samples (Figure 5). 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 16: Ward et al., 2010 (<em>Cancer Cell</em>).</p> <p>The published Registered Report can be found <a href="http://elifesciences.org/content/5/e12626v1" 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/g4wpj/" rel="nofollow">Study 16 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/7gvqa/" rel="nofollow">Study 16 Figure 2A data estimation</a></li> <li><a href="https://osf.io/ys2xf/" rel="nofollow">Study 16 Figure 2B data estimation</a></li> <li><a href="https://osf.io/vfr5s/" rel="nofollow">Study 16 Figure 5C data estimation</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.<ul> <li><a href="https://osf.io/6uxp4/" rel="nofollow">Study 16 power calculations summarized.xlsx</a></li> <li><a href="https://osf.io/v8tu9/" rel="nofollow">Study 16 Figure2A.R</a></li> <li><a href="https://osf.io/63rxp/" rel="nofollow">Study 16 Figure2B.R</a></li> <li><a href="https://osf.io/hfn3j/" rel="nofollow">Study 16 Figure5C.R</a></li> <li><a href="https://osf.io/qu62c/" rel="nofollow">Study 16 Figure3D Simulation.R</a></li> <li><a href="https://osf.io/v9n5k/" rel="nofollow">Study 16 Figure3D.pzf</a></li> </ul> </li> </ul>
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