Summary

In this set of simulations, we consider settings with both null and non-null tests with varying distribution of effect sizes under the non-null (alternative) setting. Both informative and uninformative covariates are included in the setting as described in simulations-informative-cubic.Rmd. The effect sizes for non-null tests are sampled from unimodal distributions composed of a mixture of normal distributions, as described in the original adaptive shrinkage (ASH) manuscript (Stephens, 2016).

Workspace Setup

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
spiky_file <- file.path(resdir, "uasettings-benchmark-spiky.rds")
flattop_file <- file.path(resdir, "uasettings-benchmark-flattop.rds")
skew_file <- file.path(resdir, "uasettings-benchmark-skew.rds")
bimodal_file <- file.path(resdir, "uasettings-benchmark-bimodal.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". Since all settings in this series of simulations use Gaussian test statistics, we include Scott's FDR Regression in all of the comparisons.

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
ts_dist <- rnorm_perturber(1)       # functional: sampling dist/noise for test stats
null_dist <- rnorm_2pvaluer(1)      # functional: dist to calc p-values
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

Spiky Setting

First, we consider the setting where the effect sizes under the alternative are distributed according to a "spiky" unimodal distribution centered around zero, as defined in the ASH simulations.

Data Simulation

es_dist <- function(n) { 2*sampler_spiky(n) }       # functional: dist of alternative test stats
seed <- 778

We next run the simulations.

if (file.exists(spiky_file)) {
    res <- readRDS(spiky_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 = spiky_file)
}
res_i <- lapply(res, `[[`, "informative")
res_u <- lapply(res, `[[`, "uninformative")

Covariate Diagnostics

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)

Benchmark Metrics

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")

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)

Flat-Top Setting

Next, we consider the setting where the effect sizes under the alternative are distributed according to a "flat top" unimodal distribution centered around zero, as defined in the ASH simulations.

Data Simulation

es_dist <- function(n) { 2*sampler_flat_top(n) }       # functional: dist of alternative test stats
seed <- 980

We next run the simulations.

if (file.exists(flattop_file)) {
    res <- readRDS(flattop_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 = flattop_file)
}
res_i <- lapply(res, `[[`, "informative")
res_u <- lapply(res, `[[`, "uninformative")

Covariate Diagnostics

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)

Benchmark Metrics

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")

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)

Skewed Setting

Next, we consider the setting where the effect sizes under the alternative are distributed according to a skewed unimodal distribution not centered at zero, as defined in the ASH simulations.

Data Simulation

es_dist <- function(n) { 2*sampler_skew(n) }       # functional: dist of alternative test stats
seed <- 206

We next run the simulations.

if (file.exists(skew_file)) {
    res <- readRDS(skew_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 = skew_file)
}
res_i <- lapply(res, `[[`, "informative")
res_u <- lapply(res, `[[`, "uninformative")

Covariate Diagnostics

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)

Benchmark Metrics

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")

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)

Bimodal Setting

Finally, we consider the setting where the effect sizes under the alternative are distributed according to a bimodal distribution (equal mixture of two normal distributions centered at -2, 2, with variance 1), again, as defined in the ASH simulations.

Data Simulation

es_dist <- function(n) { 2*sampler_bimodal(n) }        # functional: dist of alternative test stats
seed <- 913

We next run the simulations.

if (file.exists(bimodal_file)) {
    res <- readRDS(bimodal_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 = bimodal_file)
}
res_i <- lapply(res, `[[`, "informative")
res_u <- lapply(res, `[[`, "uninformative")

Covariate Diagnostics

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)

Benchmark Metrics

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")

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)

Session Info

sessionInfo()


stephaniehicks/benchmarkfdrData2019 documentation built on June 20, 2021, 10 a.m.