In this set of simulations, we consider settings with both null and non-null tests with an informative and uninformative covariate. The informative covariate is sampled uniformly from the interval [0, 1], and the conditional probability of a test being non-null is a smooth (cubic) function of the covariate. The uninformative covariate is simply uninformly sampled independently from the interval [0, 1]. The uninformative covariate is included as a baseline to compare the informative covariate against. We include simulation results again with Gaussian, t-distributed, and Chi-Squared distributed test statistics.
library(dplyr) library(ggplot2) library(SummarizedBenchmark) library(parallel) ## load helper functions for (f in list.files("../R", "\\.(r|R)$", full.names = TRUE)) { source(f) } ## project data/results folders resdir <- "results" dir.create(resdir, showWarnings = FALSE, recursive = TRUE) ## intermediary files we create below gauss_file <- file.path(resdir, "informative-cubic-benchmark-gaussian.rds") tdist_file <- file.path(resdir, "informative-cubic-benchmark-t5.rds") tdist11_file <- file.path(resdir, "informative-cubic-benchmark-t11.rds") chisq_file <- file.path(resdir, "informative-cubic-benchmark-chisq4.rds") ## number of cores for parallelization cores <- 20 B <- 100 ## define bechmarking design bd <- initializeBenchDesign()
As described in simulations-null.Rmd
, we include Scott's FDR Regression in the analysis
for simulations with Gaussian or t-distributed test statistics. Again, we include both
nulltype = "empirical"
and nulltype = "theoretical"
.
bdplus <- bd bdplus <- addBMethod(bdplus, "fdrreg-t", FDRreg::FDRreg, function(x) { x$FDR }, z = test_statistic, features = model.matrix( ~ splines::bs(ind_covariate, df = 3) - 1), nulltype = 'theoretical', control = list(lambda = 0.01)) bdplus <- addBMethod(bdplus, "fdrreg-e", FDRreg::FDRreg, function(x) { x$FDR }, z = test_statistic, features = model.matrix( ~ splines::bs(ind_covariate, df = 3) - 1), nulltype = 'empirical', control = list(lambda = 0.01))
All simulation settings will share the following parameters.
m <- 20000 # integer: number of hypothesis tests pi0 <- pi0_cubic(0.90) # numeric: proportion of null hypotheses icovariate <- runif # functional: independent covariate
Simulation results will be presented excluding a subset of methods, and for certain plots (upset plots), a single alpha cutoff will be used.
excludeSet <- c("unadjusted", "bl-df02", "bl-df04", "bl-df05") ualpha <- 0.05
First, we consider the setting with Gaussian test statistics.
es_dist <- rnorm_generator(3) # functional: dist of alternative test stats ts_dist <- rnorm_perturber(1) # functional: sampling dist/noise for test stats null_dist <- rnorm_2pvaluer(1) # functional: dist to calc p-values seed <- 608
We next run the simulations (including Scott's FDR Regression).
if (file.exists(gauss_file)) { res <- readRDS(gauss_file) } else { res <- mclapply(X = 1:B, FUN = simIteration, bench = bdplus, m = m, pi0 = pi0, es_dist = es_dist, icovariate = icovariate, ts_dist = ts_dist, null_dist = null_dist, seed = seed, mc.cores = cores) saveRDS(res, file = gauss_file) } res_i <- lapply(res, `[[`, "informative") res_u <- lapply(res, `[[`, "uninformative")
Here, we show the relationship between the independent covariate and p-values for a single replication of the experiment.
onerun <- simIteration(bdplus, m = m, pi0 = pi0, es_dist = es_dist, ts_dist = ts_dist, icovariate = icovariate, null_dist = null_dist, execute = FALSE)
rank_scatter(onerun, pvalue = "pval", covariate = "ind_covariate")
strat_hist(onerun, pvalue = "pval", covariate = "ind_covariate", maxy = 10, numQ = 3)
We plot the averaged results across r B
replications.
resdf <- plotsim_standardize(res_i, alpha = seq(0.01, 0.10, 0.01)) plotsim_average(resdf, met="rejections", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met="FDR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met="TPR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met="TNR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE)
We also take a look at the distribution of rejects for each method as a function of the effect size and independent covariate.
covariateLinePlot(res_i, alpha = ualpha, covname = "effect_size") covariateLinePlot(res_i, alpha = ualpha, covname = "ind_covariate")
We also look at the FDR as a function of the independent covariate.
covariateLinePlot(res_i, alpha = ualpha, covname = "ind_covariate", metric = "FDR")
Finally, (if enough methods produce rejections at r ualpha
) we take a look at
the overlap of rejections between methods.
if (numberMethodsReject(resdf, alphacutoff = ualpha, filterSet = excludeSet) >= 3) { aggupset(res_i, alpha = ualpha, supplementary = FALSE, return_list = FALSE) } else { message("Not enough methods found rejections at alpha ", ualpha, "; skipping upset plot") }
We also compare the simulation results with and without an informative covariate.
resdfu <- plotsim_standardize(res_u, alpha = seq(0.01, 0.10, 0.01)) resdfiu <- dplyr::full_join(select(resdf, rep, blabel, param.alpha, key, performanceMetric, alpha, value), select(resdfu, rep, blabel, param.alpha, key, performanceMetric, alpha, value), by = c("rep", "blabel", "param.alpha", "key", "performanceMetric", "alpha"), suffix = c(".info", ".uninfo")) resdfiu <- dplyr::mutate(resdfiu, value = value.info - value.uninfo) plotsim_average(resdfiu, met="rejections", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE) plotsim_average(resdfiu, met="FDR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE) plotsim_average(resdfiu, met="TPR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE) plotsim_average(resdfiu, met="TNR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE)
Next, we consider the setting with t-distributed test statistics.
es_dist <- rnorm_generator(3) # functional: dist of alternative test stats ts_dist <- rt_perturber(5) # functional: sampling dist/noise for test stats null_dist <- rt_2pvaluer(5) # functional: dist to calc p-values seed <- 815
For the t-distributed setting, we must specify the number of degrees of freedom
for ASH. We add an additional parameter to the ashq
method with the corresponding
degrees of freedom of the test statistic distribution.
bdplust <- modifyBMethod(bdplus, "ashq", df = 5)
We next run the simulations (including Scott's FDR Regression and ASH with degrees of freedom specified).
if (file.exists(tdist_file)) { res <- readRDS(tdist_file) } else { res <- mclapply(X = 1:B, FUN = simIteration, bench = bdplust, m = m, pi0 = pi0, es_dist = es_dist, icovariate = icovariate, ts_dist = ts_dist, null_dist = null_dist, seed = seed, mc.cores = cores) saveRDS(res, file = tdist_file) } res_i <- lapply(res, `[[`, "informative") res_u <- lapply(res, `[[`, "uninformative")
Here, we show the relationship between the independent covariate and p-values for a single replication of the experiment.
onerun <- simIteration(bdplus, m = m, pi0 = pi0, es_dist = es_dist, ts_dist = ts_dist, icovariate = icovariate, null_dist = null_dist, execute = FALSE)
rank_scatter(onerun, pvalue = "pval", covariate = "ind_covariate")
strat_hist(onerun, pvalue = "pval", covariate = "ind_covariate", maxy = 10, numQ = 3)
We plot the averaged results across r B
replications.
resdf <- plotsim_standardize(res_i, alpha = seq(0.01, 0.10, 0.01)) plotsim_average(resdf, met="rejections", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met="FDR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met="TPR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met="TNR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE)
We also take a look at the distribution of rejects for each method as a function of the effect size and independent covariate.
covariateLinePlot(res_i, alpha = ualpha, covname = "effect_size") covariateLinePlot(res_i, alpha = ualpha, covname = "ind_covariate")
We also look at the FDR as a function of the independent covariate.
covariateLinePlot(res_i, alpha = ualpha, covname = "ind_covariate", metric = "FDR")
Finally, (if enough methods produce rejections at r ualpha
) we take a look at
the overlap of rejections between methods.
if (numberMethodsReject(resdf, alphacutoff = ualpha, filterSet = excludeSet) >= 3) { aggupset(res_i, alpha = ualpha, supplementary = FALSE, return_list = FALSE) } else { message("Not enough methods found rejections at alpha ", ualpha, "; skipping upset plot") }
We also compare the simulation results with and without an informative covariate.
resdfu <- plotsim_standardize(res_u, alpha = seq(0.01, 0.10, 0.01)) resdfiu <- dplyr::full_join(select(resdf, rep, blabel, param.alpha, key, performanceMetric, alpha, value), select(resdfu, rep, blabel, param.alpha, key, performanceMetric, alpha, value), by = c("rep", "blabel", "param.alpha", "key", "performanceMetric", "alpha"), suffix = c(".info", ".uninfo")) resdfiu <- dplyr::mutate(resdfiu, value = value.info - value.uninfo) plotsim_average(resdfiu, met="rejections", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE) plotsim_average(resdfiu, met="FDR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE) plotsim_average(resdfiu, met="TPR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE) plotsim_average(resdfiu, met="TNR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE)
Next, we consider a second setting with t-distributed test statistics.
es_dist <- rnorm_generator(3) # functional: dist of alternative test stats ts_dist <- rt_perturber(11) # functional: sampling dist/noise for test stats null_dist <- rt_2pvaluer(11) # functional: dist to calc p-values seed <- 9158
For the t-distributed setting, we must specify the number of degrees of freedom
for ASH. We add an additional parameter to the ashq
method with the corresponding
degrees of freedom of the test statistic distribution.
bdplust <- modifyBMethod(bdplus, "ashq", df = 11)
We next run the simulations (including Scott's FDR Regression and ASH with degrees of freedom specified).
if (file.exists(tdist11_file)) { res <- readRDS(tdist11_file) } else { res <- mclapply(X = 1:B, FUN = simIteration, bench = bdplust, m = m, pi0 = pi0, es_dist = es_dist, icovariate = icovariate, ts_dist = ts_dist, null_dist = null_dist, seed = seed, mc.cores = cores) saveRDS(res, file = tdist11_file) } res_i <- lapply(res, `[[`, "informative") res_u <- lapply(res, `[[`, "uninformative")
Here, we show the relationship between the independent covariate and p-values for a single replication of the experiment.
onerun <- simIteration(bdplus, m = m, pi0 = pi0, es_dist = es_dist, ts_dist = ts_dist, icovariate = icovariate, null_dist = null_dist, execute = FALSE)
rank_scatter(onerun, pvalue = "pval", covariate = "ind_covariate")
strat_hist(onerun, pvalue = "pval", covariate = "ind_covariate", maxy = 10, numQ = 3)
We plot the averaged results across r B
replications.
resdf <- plotsim_standardize(res_i, alpha = seq(0.01, 0.10, 0.01)) plotsim_average(resdf, met="rejections", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met="FDR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met="TPR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met="TNR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE)
We also take a look at the distribution of rejects for each method as a function of the effect size and independent covariate.
covariateLinePlot(res_i, alpha = ualpha, covname = "effect_size") covariateLinePlot(res_i, alpha = ualpha, covname = "ind_covariate")
We also look at the FDR as a function of the independent covariate.
covariateLinePlot(res_i, alpha = ualpha, covname = "ind_covariate", metric = "FDR")
Finally, (if enough methods produce rejections at r ualpha
) we take a look at
the overlap of rejections between methods.
if (numberMethodsReject(resdf, alphacutoff = ualpha, filterSet = excludeSet) >= 3) { aggupset(res_i, alpha = ualpha, supplementary = FALSE, return_list = FALSE) } else { message("Not enough methods found rejections at alpha ", ualpha, "; skipping upset plot") }
We also compare the simulation results with and without an informative covariate.
resdfu <- plotsim_standardize(res_u, alpha = seq(0.01, 0.10, 0.01)) resdfiu <- dplyr::full_join(select(resdf, rep, blabel, param.alpha, key, performanceMetric, alpha, value), select(resdfu, rep, blabel, param.alpha, key, performanceMetric, alpha, value), by = c("rep", "blabel", "param.alpha", "key", "performanceMetric", "alpha"), suffix = c(".info", ".uninfo")) resdfiu <- dplyr::mutate(resdfiu, value = value.info - value.uninfo) plotsim_average(resdfiu, met="rejections", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE) plotsim_average(resdfiu, met="FDR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE) plotsim_average(resdfiu, met="TPR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE) plotsim_average(resdfiu, met="TNR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE)
Finally, we consider the setting with chi-squared distributed test statistics.
es_dist <- rnorm_generator(15) # functional: dist of alternative test stats ts_dist <- rchisq_perturber(4) # functional: sampling dist/noise for test stats null_dist <- rchisq_pvaluer(4) # functional: dist to calc p-values seed <- 1023
For the chi-squared distributed setting, we must change the "mode" setting for ASH
from the default of 0 to "estimate"
since the mode of null and alternative test statistics
are no longer centered at 0. While both approximate Normality and unimodality of effects are
violated in this simulation setting, by allowing the mode to be estimated, rather than forced
to 0, should return more comparable results.
bdchi <- modifyBMethod(bd, "ashq", mode = "empirical")
We next run the simulations. We do not include FDR Regression because the test statistics are not approximately normally distributed.
if (file.exists(chisq_file)) { res <- readRDS(chisq_file) } else { res <- mclapply(X = 1:B, FUN = simIteration, bench = bdchi, m = m, pi0 = pi0, es_dist = es_dist, icovariate = icovariate, ts_dist = ts_dist, null_dist = null_dist, seed = seed, mc.cores = cores) saveRDS(res, file = chisq_file) } res_i <- lapply(res, `[[`, "informative") res_u <- lapply(res, `[[`, "uninformative")
Here, we show the relationship between the independent covariate and p-values for a single replication of the experiment.
onerun <- simIteration(bdchi, m = m, pi0 = pi0, es_dist = es_dist, ts_dist = ts_dist, icovariate = icovariate, null_dist = null_dist, execute = FALSE)
rank_scatter(onerun, pvalue = "pval", covariate = "ind_covariate")
strat_hist(onerun, pvalue = "pval", covariate = "ind_covariate", maxy = 10, numQ = 3)
We plot the averaged results across r B
replications.
resdf <- plotsim_standardize(res_i, alpha = seq(0.01, 0.10, 0.01)) plotsim_average(resdf, met = "rejections", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met = "FDR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met = "TPR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met = "TNR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE)
Since ashq
is not appropriate when the test statistics are not approximately normal or t,
we also plot the results without this method.
plotsim_average(resdf, met = "rejections", filter_set = c(excludeSet, "ashq"), merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met = "FDR", filter_set = c(excludeSet, "ashq"), merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met = "TPR", filter_set = c(excludeSet, "ashq"), merge_ihw = TRUE, errorBars = TRUE) plotsim_average(resdf, met = "TNR", filter_set = c(excludeSet, "ashq"), merge_ihw = TRUE, errorBars = TRUE)
We also take a look at the distribution of rejects for each method as a function of
the effect size and independent covariate. Again, we plot these without ashq
.
covariateLinePlot(lapply(res_i, function(x) { x[, -which(colnames(x) == "ashq")] }), alpha = ualpha, covname = "effect_size") covariateLinePlot(lapply(res_i, function(x) { x[, -which(colnames(x) == "ashq")] }), alpha = ualpha, covname = "ind_covariate")
We also look at the FDR as a function of the independent covariate.
covariateLinePlot(res_i, alpha = ualpha, covname = "ind_covariate", metric = "FDR")
Finally, (if enough methods produce rejections at r ualpha
) we take a look at
the overlap of rejections between methods. Again, without ashq
.
if (numberMethodsReject(resdf, alphacutoff = ualpha, filterSet = c(excludeSet, "ashq")) >= 3) { aggupset(lapply(res_i, function(x) { x[, -which(colnames(x) == "ashq")] }), alpha = ualpha, supplementary = FALSE, return_list = FALSE) } else { message("Not enough methods found rejections at alpha ", ualpha, "; skipping upset plot") }
We also compare the simulation results with and without an informative covariate.
resdfu <- plotsim_standardize(res_u, alpha = seq(0.01, 0.10, 0.01)) resdfiu <- dplyr::full_join(select(resdf, rep, blabel, param.alpha, key, performanceMetric, alpha, value), select(resdfu, rep, blabel, param.alpha, key, performanceMetric, alpha, value), by = c("rep", "blabel", "param.alpha", "key", "performanceMetric", "alpha"), suffix = c(".info", ".uninfo")) resdfiu <- dplyr::mutate(resdfiu, value = value.info - value.uninfo) plotsim_average(resdfiu, met="rejections", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE) plotsim_average(resdfiu, met="FDR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE) plotsim_average(resdfiu, met="TPR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE) plotsim_average(resdfiu, met="TNR", filter_set = excludeSet, merge_ihw = TRUE, errorBars = TRUE, diffplot = TRUE)
sessionInfo()
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