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Then examine the <span class="math inline">\(p\)</span>-values in order.</p> <p>Step 1: If <span class="math inline">\(p_{(1)} \leq \alpha/n\)</span> reject <span class="math inline">\(H_{(1)}\)</span> and go to Step 2. Otherwise, accept <span class="math inline">\(H_{(1)}, H_{(2)}, \ldots, H_{(n)}\)</span> and stop.</p> <p>……</p> <p>Step <span class="math inline">\(i\)</span>: If <span class="math inline">\(p_{(i)} \leq \alpha / (n − i + 1)\)</span> reject <span class="math inline">\(H_{(i)}\)</span> and go to step <span class="math inline">\(i + 1\)</span>. Otherwise, accept <span class="math inline">\(H_{(i)}, H_{(i + 1)}, \ldots, H_{(n)}\)</span> and stop.</p> <p>……</p> <p>Step <span class="math inline">\(n\)</span>: If <span class="math inline">\(p_{(n)} \leq \alpha\)</span>, reject <span class="math inline">\(H_{(n)}\)</span>. Otherwise, accept <span class="math inline">\(H_{(n)}\)</span>.</p> <p>Hence the procedure starts with the most extreme (smallest) <span class="math inline">\(p\)</span>-value and stops the first time <span class="math inline">\(p_{(i)}\)</span> exceeds the critical value <span class="math inline">\(\alpha_i = \alpha/(n − i + 1)\)</span>.</p> <p><strong>It can be shown that Holm’s procedure conservatively controls the FWER in the strong sense, under arbitrary correlation among <span class="math inline">\(p\)</span>-values.</strong></p> </div> <div id="hochbergs-step-up-procedure-start-from-the-largest-p-value" class="section level2"> <h2>Hochberg’s step-up procedure: start from the largest <span class="math inline">\(p\)</span>-value</h2> <p><em>It can be shown that Hochberg’s procedure conservatively controls the FWER in the strong sense, when <span class="math inline">\(p\)</span>-values are independent.</em></p> <p>First, order the <span class="math inline">\(p\)</span>-values</p> <p><span class="math display">\[ p_{(1)} \leq p_{(2)} \leq \cdots \leq p_{(n)} \]</span></p> <p>and let <span class="math inline">\(H_{(1)}, H_{(2)}, \ldots, H_{(n)}\)</span> be the corresponding hypotheses. Then examine the <span class="math inline">\(p\)</span>-values in order.</p> <p>Step 1: If <span class="math inline">\(p_{(n)} \leq \alpha\)</span> reject <span class="math inline">\(H_{(1)}, \ldots, H_{(n)}\)</span> and stop. Otherwise, accept <span class="math inline">\(H_{(n)}\)</span> and go to step 2.</p> <p>……</p> <p>Step <span class="math inline">\(i\)</span>: If <span class="math inline">\(p_{(n - i + 1)} \leq \alpha / i\)</span> reject <span class="math inline">\(H_{(1)}, \ldots, H_{(n - i + 1)}\)</span> and stop. Otherwise, accept <span class="math inline">\(H_{(n - i + 1)}\)</span> and go to step <span class="math inline">\(i + 1\)</span>.</p> <p>……</p> <p>Step <span class="math inline">\(n\)</span>: If <span class="math inline">\(p_{(1)} \leq \alpha / n\)</span>, reject <span class="math inline">\(H_{(1)}\)</span>. Otherwise, accept <span class="math inline">\(H_{(1)}\)</span>.</p> <p>Hence the procedure starts with the least extreme (largest) <span class="math inline">\(p\)</span>-value and stops the first time <span class="math inline">\(p_{(i)}\)</span> falls below the critical value <span class="math inline">\(\alpha_i = \alpha/(n − i + 1)\)</span>.</p> <p><strong>It can be shown that Hochberg’s procedure conservatively controls the FWER in the strong sense, when <span class="math inline">\(p\)</span>-values are independent.</strong></p> <p><strong><a href="https://projecteuclid.org/euclid.aos/1028144846">Sarkar 1998</a> also pointed out that Hochberg’s procedure can control the FWER strongly under certain dependency among the test statistics, such as a multivariate normal with a common marginal distribution and positive correlations.</strong></p> <p><strong>Holm’s procedure is based on Bonferroni correction, whereas Hochberg’s on Sime’s inequality. Both use exactly the same thresholds, comparing <span class="math inline">\(p_{(i)}\)</span> with <span class="math inline">\(\alpha/(n − i + 1)\)</span>, yet Holm’s starts from the smallest <span class="math inline">\(p\)</span>-value, and Hochberg’s from the largest. Hochberg’s is thus strictly more powerful than Holm’s.</strong></p> </div> <div id="result" class="section level2"> <h2>Result</h2> <p>Now we apply the two procedures to the simulated, correlated null data.</p> <pre class="r"><code>p1 = read.table("../output/p_null_liver.txt") p2 = read.table("../output/p_null_liver_777.txt") p = rbind(p1, p2) m = nrow(p) holm = hochberg = matrix(nrow = m, ncol = ncol(p)) for(i in 1:m){ holm[i, ] = p.adjust(p[i, ], method = "holm") # p-values adjusted by Holm (1979) hochberg[i, ] = p.adjust(p[i, ], method = "hochberg") # p_values adjusted by Hochberg (1988) }</code></pre> <pre class="r"><code>## calculate empirical FWER at 100 nominal FWER's alpha = seq(0, 0.15, length = 100) fwer_holm = fwer_hochberg = c() for (i in 1:length(alpha)) { fwer_holm[i] = mean(apply(holm, 1, function(x) {min(x) <= alpha[i]})) fwer_hochberg[i] = mean(apply(hochberg, 1, function(x) {min(x) <= alpha[i]})) } fwer_holm_se = sqrt(fwer_holm * (1 - fwer_holm) / m) fwer_hochberg_se = sqrt(fwer_hochberg * (1 - fwer_hochberg) / m)</code></pre> <p>Here at each nominal FWER from <span class="math inline">\(0\)</span> to <span class="math inline">\(0.15\)</span>, we plot the empirical FWER, calculated from <span class="math inline">\(m = 2000\)</span> independent simulation trials. Dotted lines indicate one standard error computed from binomial model <span class="math inline">\(= \sqrt{\hat{\text{FWER}}(1 - \hat{\text{FWER}}) / m}\)</span>.</p> <pre class="r"><code>plot(alpha, fwer_holm, pch = 1, xlab = "nominal FWER", ylab = "empirical FWER", xlim = c(0, max(alpha)), ylim = c(0, max(alpha)), cex = 0.75) points(alpha, fwer_hochberg, col = "blue", pch = 19, cex = 0.25) lines(alpha, fwer_holm - fwer_holm_se, lty = 3) lines(alpha, fwer_holm + fwer_holm_se, lty = 3) lines(alpha, fwer_hochberg + fwer_hochberg_se, lty = 3, col = "blue") lines(alpha, fwer_hochberg - fwer_hochberg_se, lty = 3, col = "blue") abline(0, 1, lty = 3, col = "red") legend("topleft", c("Holm", "Hochberg"), col = c(1, "blue"), pch = c(1, 19))</code></pre> <p><img src="figure/StepDown.Rmd/unnamed-chunk-3-1.png" width="672" style="display: block; margin: auto;" /></p> <p>The results from Holm’s step-down and Hochberg’s step-up are almost the same for this simulated data set. They both give almost the same discoveries, although in theory Hochberg’s should be strictly more powerful than Holm’s. <em>The agreement of both procedures may indicate that test statistics are indeed inflated for moderate observations but not extreme observations.</em></p> </div> <div id="session-information" class="section level2"> <h2>Session Information</h2> <pre class="r"><code>sessionInfo()</code></pre> <pre><code>R version 3.4.2 (2017-09-28) Platform: x86_64-apple-darwin15.6.0 (64-bit) Running under: macOS Sierra 10.12.6 Matrix products: default BLAS: /Library/Frameworks/R.framework/Versions/3.4/Resources/lib/libRblas.0.dylib LAPACK: /Library/Frameworks/R.framework/Versions/3.4/Resources/lib/libRlapack.dylib locale: [1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8 attached base packages: [1] stats graphics grDevices utils datasets methods base loaded via a namespace (and not attached): [1] compiler_3.4.2 backports_1.1.1 magrittr_1.5 rprojroot_1.2 [5] tools_3.4.2 htmltools_0.3.6 yaml_2.1.14 Rcpp_0.12.13 [9] stringi_1.1.5 rmarkdown_1.6 knitr_1.17 git2r_0.19.0 [13] stringr_1.2.0 digest_0.6.12 workflowr_0.7.0 evaluate_0.10.1</code></pre> </div> <hr> <p> This <a href="http://rmarkdown.rstudio.com">R Markdown</a> site was created with <a href="https://github.com/jdblischak/workflowr">workflowr</a> </p> <hr> <!-- To enable disqus, uncomment the section below and provide your disqus_shortname --> <!-- disqus <div id="disqus_thread"></div> <script type="text/javascript"> /* * * CONFIGURATION VARIABLES: EDIT BEFORE PASTING INTO YOUR WEBPAGE * * */ var disqus_shortname = 'rmarkdown'; // required: replace example with your forum shortname /* * * DON'T EDIT BELOW THIS LINE * * */ (function() { var dsq = document.createElement('script'); dsq.type = 'text/javascript'; dsq.async = true; dsq.src = '//' + disqus_shortname + '.disqus.com/embed.js'; (document.getElementsByTagName('head')[0] || document.getElementsByTagName('body')[0]).appendChild(dsq); })(); </script> <noscript>Please enable JavaScript to view the <a href="http://disqus.com/?ref_noscript">comments powered by Disqus.</a></noscript> <a href="http://disqus.com" class="dsq-brlink">comments powered by <span class="logo-disqus">Disqus</span></a> --> </div> </div> </div> <script> // add bootstrap table styles to pandoc tables function bootstrapStylePandocTables() { $('tr.header').parent('thead').parent('table').addClass('table table-condensed'); } $(document).ready(function () { bootstrapStylePandocTables(); }); </script> <!-- dynamically load mathjax for compatibility with self-contained --> <script> (function () { var script = document.createElement("script"); script.type = "text/javascript"; script.src = "https://mathjax.rstudio.com/latest/MathJax.js?config=TeX-AMS-MML_HTMLorMML"; document.getElementsByTagName("head")[0].appendChild(script); })(); </script> </body> </html>