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<title>BUHMBOX</title>

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<h1 class="about"> BUHMBOX: Distinguishing pleiotropy and heterogeneity</h1>

            <p>BUHMBOX is a tool to distinguish pleiotropy and heterogeneitiy.
                Suppose that 
                we collect disease A cases.
                Then we observe that known disease B risk alleles are enriched within disease A cases.
                Is this because disease A and B have pleiotropy, or because disease A patients have a subset that shows genetic characteristics of disease B? 
                BUHMBOX (Breaking Up Heterogeneous Mixture Based On Cross-locus correlations) is a tool to distinguish these two situations.</p>

	    <p>
	    <img src="images/buhmbox.png" width="600" style="display: block; margin-left: auto; margin-right: auto; box-shadow:3px 3px 3px #888888;"/>
	    </p>

	      
	    <p>The intuition under BUHMBOX is that we will observe weak positive correlations between disease-B-loci in disease A cases, if it were due to heterogeneity, because of the subgrouping. Thus BUHMBOX aggregrates the correlations into one statistic. To strictly control for false positives, BUHMBOX uses pruning, PCs, and comparison to controls.</p>

            <p>BUHMBOX is developed by Buhm Han in
	      the labs of <a href="/personal/soumya/">
		Soumya Raychaudhuri </a> and <a href="/personal/debakker/">
		Paul de Bakker </a> at the <a href="www.brighamandwomens.org/">Brigham and Women's 
		Hospital</a> and <a href="http://hms.harvard.edu">Harvard Medical
        School</a>, and the <a href="http://www.broadinstitute.org">Broad Institute<a/>.</p>

<h2>Links</h2>
	    <ul>
              <li><a href="data/buhmbox_v0.38/buhmbox.R" onClick="javascript: pageTracker._trackPageview('/downloads/Rfile');">
                  Download: BUHMBOX v0.38 (R script)</a> &lt;--- right click and download </li>
              <li><a href="data/buhmbox_powercalc_v0.1/buhmbox_powercalc.R">
                  Download: BUHMBOX power calculation code (R script)</a> &lt;--- right click and download </li>
              <li><a href="buhmbox_manual.html">
		  Manual: BUHMBOX 
		  </a></li>
              <li><a href="buhmbox_powercalc_manual.html">
		  Manual: BUHMBOX Power calculation
		  </a></li>
	    </ul>
<p></p>

<h2>Reference</h2>
<p>
<a href="http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3572.html">
Buhm Han¶*, Jennie G Pouget*, Kamil Slowikowski, Eli Stahl, Cue Hyunkyu Lee, Dorothee Diogo, Xinli Hu, Yu Rang Park, Eunji Kim, Peter K Gregersen, Solbritt Rantapää Dahlqvist, Jane Worthington, Javier Martin, Steve Eyre, Lars Klareskog, Tom Huizinga, Wei-Min Chen, Suna Onengut-Gumuscu, Stephen S Rich, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Naomi R Wray, Soumya Raychaudhuri¶ "A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases." Nature Genetics. In Press
doi:10.1038/ng.3572
</a>
</p>

<p>
Also was at Biorxiv:
<a href="http://biorxiv.org/content/early/2015/11/06/030783" target="_blank">http://biorxiv.org/content/early/2015/11/06/030783</a>
</p>

<h2>Any questions?</h2>
<p>You can contact us at buhmhan AT amc DOT seoul DOT kr</p>

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