Last updated: 2021-05-21

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Knit directory: methyl-geneset-testing/

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library(here)
library(minfi)
library(limma)
library(reshape2)
library(missMethyl)
library(ggplot2)
library(glue)
library(tidyverse)
library(patchwork)
library(ChAMPdata)
library(tictoc)
library(IlluminaHumanMethylationEPICanno.ilm10b4.hg19)
library(EnsDb.Hsapiens.v75)
library(ChAMP)
library(ebGSEA)
library(methylGSA)
library(gt)
source(here("code/utility.R"))

Compare run-time of different methods

Setup inputs

Create database for translating gene IDs.

edb <- EnsDb.Hsapiens.v75
transIDs <- genes(edb, columns = c("symbol", "gene_id", "entrezid"), 
                       return.type = "DataFrame")

Measure run-times for different methods

Execute and record run-time for each method (on a single core) for the three different contrasts.

outDir <- here::here("data/cache-runtime")
if (!dir.exists(outDir)) dir.create(outDir)

inFile <- here("data/cache-runtime/run-time-results.rds")

if(!file.exists(inFile)){
    
    data("PathwayList")
    keep <- sapply(PathwayList, function(x) any(x %in% transIDs$symbol))
    symbol <- suppressMessages(lapply(PathwayList[keep], function(x){
        tmp <- unlist(transIDs$symbol[transIDs$symbol %in% x], use.names = FALSE)
        tmp[!is.na(tmp)]
    }))
    entrezid <- suppressMessages(lapply(symbol, function(x){
        tmp <- unlist(transIDs$entrezid[transIDs$symbol %in% x], use.names = FALSE)
        tmp[!is.na(tmp)]
    }))
    
    load(here("data/cache-intermediates/input.RData"))
    bVals <- ilogit2(mVals)
    anno <- minfi::getAnnotation(IlluminaHumanMethylationEPICanno.ilm10b4.hg19)
    timing <- NULL
    
    for(i in 1:ncol(tfit$contrasts)){
        top <- topTreat(tfit, coef = i, number = 5000)
        
        tic("gometh")
        res <- gsameth(sig.cpg = rownames(top), 
                       all.cpg = rownames(tfit$coefficients), collection = entrezid, 
                       array.type = "EPIC", anno = anno)
        toc(log = TRUE, quiet = TRUE)
        tmp <- strsplit2(tic.log(format = TRUE)[[1]], " ")
        log <- data.frame(method = gsub(":", "", tmp[1]), time = tmp[2], 
                          contrast = colnames(tfit$contrasts)[i])
        tic.clearlog()
        timing <- bind_rows(timing, log)
        
        tic("mgsa.glm")
        res <- methylglm(cpg.pval = tfit$p.value[,i],
                         FullAnnot = anno, minsize = minsize, maxsize = maxsize,
                         GS.list = symbol, GS.idtype = "SYMBOL")
        toc(log = TRUE, quiet = TRUE)
        tmp <- strsplit2(tic.log(format = TRUE)[[1]], " ")
        log <- data.frame(method = gsub(":", "", tmp[1]), time = tmp[2], 
                          contrast = colnames(tfit$contrasts)[i])
        tic.clearlog()
        timing <- bind_rows(timing, log)
        
        tic("mgsa.ora")
        res <- methylRRA(cpg.pval = tfit$p.value[,i],
                         method = "ORA", FullAnnot = anno, minsize = minsize,
                         maxsize = maxsize, GS.list = symbol,
                         GS.idtype = "SYMBOL")
        toc(log = TRUE, quiet = TRUE)
        tmp <- strsplit2(tic.log(format = TRUE)[[1]], " ")
        log <- data.frame(method = gsub(":", "", tmp[1]), time = tmp[2], 
                          contrast = colnames(tfit$contrasts)[i])
        tic.clearlog()
        timing <- bind_rows(timing, log)
        
        tic("mgsa.gsea")
        res <- methylRRA(cpg.pval = tfit$p.value[,i],
                         method = "GSEA", FullAnnot = anno, minsize = minsize,
                         maxsize = maxsize, GS.list = symbol,
                         GS.idtype = "SYMBOL")
        toc(log = TRUE, quiet = TRUE)
        tmp <- strsplit2(tic.log(format = TRUE)[[1]], " ")
        log <- data.frame(method = gsub(":", "", tmp[1]), time = tmp[2], 
                          contrast = colnames(tfit$contrasts)[i])
        tic.clearlog()
        timing <- bind_rows(timing, log)
        
        cellType <- names(tfit$contrasts[,i])[tfit$contrasts[,i] != 0]
        tic("ebgsea")
        #tic("champ.ebgsea")
        # ebgs <- champ.ebGSEA(beta = mVals[,targets$CellType %in% cellType],
        #                      pheno = targets$CellType[targets$CellType %in% cellType],
        #                      minN = 5, adjPval=1, arraytype = "EPIC")
        groups <- names(tfit$contrasts[,i])[tfit$contrasts[,i] != 0]
        samps <- as.logical(unname(rowSums(tfit$design[,groups])))
        pheno <- unname(tfit$design[samps, groups][,1])
        
        gtRanks <- doGT(pheno.v = pheno,
                        data.m = bVals[, samps],
                        array = "EPIC",
                        ncores = 1)
        ebgs <- data.frame(doGSEAwt(rankEID.m = gtRanks, ptw.ls = entrezid,
                                    ncores = 1, minN = minsize, adjPVth = 1)$`Rank(P)`)
        
        toc(log = TRUE, quiet = TRUE)
        tmp <- strsplit2(tic.log(format = TRUE)[[1]], " ")
        log <- data.frame(method = gsub(":", "", tmp[1]), time = tmp[2], 
                          contrast = colnames(tfit$contrasts)[i])
        tic.clearlog()
        timing <- bind_rows(timing, log)
        
    }
    saveRDS(timing, file = inFile)
    
} else {
    timing <- readRDS(inFile)
    colnames(timing)[3] <- "contrast"
    
}

Visualise results

Plot run-time results.

timing %>% mutate(time = as.integer(time)) %>%
    mutate(method = unname(dict[method])) -> dat

p1 <- ggplot(dat, aes(x = reorder(method, -time), y = time/60, 
                      fill = contrast)) + 
    geom_bar(position = "dodge", stat = "identity") +
    labs(x = "Method", y = "Run time (minutes)", fill = "Contrast")
p1

Version Author Date
f148103 Jovana Maksimovic 2021-04-20
4c57176 JovMaksimovic 2021-04-13
555069b JovMaksimovic 2020-08-14
inFile <- here("data/cache-runtime/run-time-mcores-ebgsea.rds")

if(!file.exists(inFile)){
    
    data("PathwayList")
    keep <- sapply(PathwayList, function(x) any(x %in% transIDs$symbol))
    symbol <- suppressMessages(lapply(PathwayList[keep], function(x){
        tmp <- unlist(transIDs$symbol[transIDs$symbol %in% x], use.names = FALSE)
        tmp[!is.na(tmp)]
    }))
    entrezid <- suppressMessages(lapply(symbol, function(x){
        tmp <- unlist(transIDs$entrezid[transIDs$symbol %in% x], use.names = FALSE)
        tmp[!is.na(tmp)]
    }))
    
    load(here("data/cache-intermediates/input.RData"))
    bVals <- ilogit2(mVals)
    anno <- minfi::getAnnotation(IlluminaHumanMethylationEPICanno.ilm10b4.hg19)
    multi <- NULL
    
    for(i in 1:ncol(tfit$contrasts)){
        
        tic("ebgsea.10")
        groups <- names(tfit$contrasts[,i])[tfit$contrasts[,i] != 0]
        samps <- as.logical(unname(rowSums(tfit$design[,groups])))
        pheno <- unname(tfit$design[samps, groups][,1])
        
        gtRanks <- doGT(pheno.v = pheno,
                        data.m = bVals[, samps],
                        array = "EPIC",
                        ncores = 10)
        ebgs <- data.frame(doGSEAwt(rankEID.m = gtRanks, ptw.ls = entrezid,
                                    ncores = 10, minN = minsize, adjPVth = 1)$`Rank(P)`)
        toc(log = TRUE, quiet = TRUE)
        tmp <- strsplit2(tic.log(format = TRUE)[[1]], " ")
        log <- data.frame(method = gsub(":", "", tmp[1]), time = tmp[2], 
                          contrast = colnames(tfit$contrasts)[i])
        tic.clearlog()
        multi <- bind_rows(multi, log)
        
        tic("ebgsea.20")
        groups <- names(tfit$contrasts[,i])[tfit$contrasts[,i] != 0]
        samps <- as.logical(unname(rowSums(tfit$design[,groups])))
        pheno <- unname(tfit$design[samps, groups][,1])
        
        gtRanks <- doGT(pheno.v = pheno,
                        data.m = bVals[, samps],
                        array = "EPIC",
                        ncores = 20)
        ebgs <- data.frame(doGSEAwt(rankEID.m = gtRanks, ptw.ls = entrezid,
                                    ncores = 20, minN = minsize, adjPVth = 1)$`Rank(P)`)
        toc(log = TRUE, quiet = TRUE)
        tmp <- strsplit2(tic.log(format = TRUE)[[1]], " ")
        log <- data.frame(method = gsub(":", "", tmp[1]), time = tmp[2], 
                          contrast = colnames(tfit$contrasts)[i])
        tic.clearlog()
        multi <- bind_rows(multi, log)
        
    }
    saveRDS(multi, file = inFile)
    
} else {
    multi <- readRDS(inFile)
    
}

Plot run-time results.

multi %>% mutate(time = as.integer(time)) %>%
    mutate(cores = limma::strsplit2(method, ".", fixed=TRUE)[,2]) -> ebgseaMulti

p2 <- ggplot(ebgseaMulti, aes(x = cores, y = time/60, fill = contrast)) + 
    geom_bar(position = "dodge", stat = "identity") +
    labs(x = "No. cores", y = "Run time (minutes)", fill = "Contrast") +
    ggtitle("Using multiple cores for ebGSEA") 
p2

Version Author Date
8511442 Jovana Maksimovic 2021-05-17
f148103 Jovana Maksimovic 2021-04-20
4c57176 JovMaksimovic 2021-04-13
555069b JovMaksimovic 2020-08-14
inFile <- here("data/cache-runtime/run-time-mcores.rds")

if(!file.exists(inFile)){
    
    data("PathwayList")
    keep <- sapply(PathwayList, function(x) any(x %in% transIDs$symbol))
    symbol <- suppressMessages(lapply(PathwayList[keep], function(x){
        tmp <- unlist(transIDs$symbol[transIDs$symbol %in% x], use.names = FALSE)
        tmp[!is.na(tmp)]
    }))
    
    load(here("data/cache-intermediates/input.RData"))
    bVals <- ilogit2(mVals)
    anno <- minfi::getAnnotation(IlluminaHumanMethylationEPICanno.ilm10b4.hg19)
    multi <- NULL
    
    for(i in 1:ncol(tfit$contrasts)){
        
        tic("mgsa.glm.10")
        res <- methylglm(cpg.pval = tfit$p.value[,i],
                         FullAnnot = anno, minsize = minsize, maxsize = maxsize,
                         GS.list = symbol, GS.idtype = "SYMBOL", parallel = TRUE,
                         BPPARAM = BiocParallel::MulticoreParam(workers = 10))
        toc(log = TRUE, quiet = TRUE)
        tmp <- strsplit2(tic.log(format = TRUE)[[1]], " ")
        log <- data.frame(method = gsub(":", "", tmp[1]), time = tmp[2], 
                          contrast = colnames(tfit$contrasts)[i])
        tic.clearlog()
        multi <- bind_rows(multi, log)
        
        tic("mgsa.glm.20")
        res <- methylglm(cpg.pval = tfit$p.value[,i],
                         FullAnnot = anno, minsize = minsize, maxsize = maxsize,
                         GS.list = symbol, GS.idtype = "SYMBOL", parallel = TRUE,
                         BPPARAM = BiocParallel::MulticoreParam(workers = 20))
        toc(log = TRUE, quiet = TRUE)
        tmp <- strsplit2(tic.log(format = TRUE)[[1]], " ")
        log <- data.frame(method = gsub(":", "", tmp[1]), time = tmp[2], 
                          contrast = colnames(tfit$contrasts)[i])
        tic.clearlog()
        multi <- bind_rows(multi, log)
        
    }
    saveRDS(multi, file = inFile)
    
} else {
    multi <- readRDS(inFile)
}

Plot run-time results.

multi %>% mutate(time = as.integer(time)) %>%
    mutate(cores = limma::strsplit2(method, ".", fixed=TRUE)[,3]) -> mglmMulti

p3 <- ggplot(mglmMulti, aes(x = cores, y = time/60, fill = contrast)) + 
    geom_bar(position = "dodge", stat = "identity") +
    labs(x = "No. cores", y = "Run time (minutes)", fill = "Contrast") +
    ggtitle("Using multiple cores for mGLM") 
p3

Version Author Date
8511442 Jovana Maksimovic 2021-05-17
f148103 Jovana Maksimovic 2021-04-20
4c57176 JovMaksimovic 2021-04-13

Combining single core and multi-core plots.

p1 / (p2 | p3) + plot_layout(guides = "collect") &
  theme(text = element_text(size = 8))

Version Author Date
8511442 Jovana Maksimovic 2021-05-17
f148103 Jovana Maksimovic 2021-04-20
4c57176 JovMaksimovic 2021-04-13

Run-time summary table

timing$cores <- 1
timing$time <- as.integer(timing$time)
ebgseaMulti$cores <- as.integer(ebgseaMulti$cores)
mglmMulti$cores <- as.integer(mglmMulti$cores)
timing <- bind_rows(timing, ebgseaMulti,  mglmMulti)

timing$method[grepl("mgsa.glm",timing$method)] <- "mgsa.glm"
timing$method[grepl("ebgsea",timing$method)] <- "ebgsea"

timing %>% mutate(method = unname(dict[method])) %>% 
    group_by(method, cores) %>%
    mutate(time = as.integer(time)) %>%
    summarise(mean = mean(time)) %>%
    mutate(mins = mean/60) %>%
    dplyr::select(method, cores, mins) %>%
    arrange(cores, mins) %>%
    as_tibble() -> tab
`summarise()` has grouped output by 'method'. You can override using the `.groups` argument.
tab %>% gt() %>%
    fmt_number(columns = vars(mins), decimals = 2) %>%
    cols_label(
        mins = md("**Minutes**"),
        cores = md("**Cores**"),
        method = md("**Method**")
        ) %>%
  tab_header(
    title = md("**Average run-time across all contrasts**"),
    subtitle = md("Using Broad MSigDB gene sets from `ChAMP` package")
    ) %>%
  tab_source_note(md("_*Blade Server: 24 CPUs - Intel(R) Xeon(R) Gold 6126 CPU @ 2.60GHz._"))
Average run-time across all contrasts
Using Broad MSigDB gene sets from ChAMP package
Method Cores Minutes
mRRA (ORA) 1 0.13
GOmeth 1 0.54
mRRA (GSEA) 1 3.04
mGLM 1 47.95
ebGSEA 1 50.12
mGLM 10 16.12
ebGSEA 10 36.07
mGLM 20 9.86
ebGSEA 20 33.79
*Blade Server: 24 CPUs - Intel(R) Xeon(R) Gold 6126 CPU @ 2.60GHz.

sessionInfo()
R version 4.0.3 (2020-10-10)
Platform: x86_64-apple-darwin17.0 (64-bit)
Running under: macOS Mojave 10.14.6

Matrix products: default
BLAS:   /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRblas.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/4.0/Resources/lib/libRlapack.dylib

locale:
[1] en_AU.UTF-8/en_AU.UTF-8/en_AU.UTF-8/C/en_AU.UTF-8/en_AU.UTF-8

attached base packages:
[1] stats4    parallel  stats     graphics  grDevices utils     datasets 
[8] methods   base     

other attached packages:
 [1] gt_0.2.2                                           
 [2] methylGSA_1.8.0                                    
 [3] ebGSEA_0.1.0                                       
 [4] ChAMP_2.20.1                                       
 [5] RPMM_1.25                                          
 [6] cluster_2.1.1                                      
 [7] DT_0.17                                            
 [8] IlluminaHumanMethylationEPICmanifest_0.3.0         
 [9] Illumina450ProbeVariants.db_1.26.0                 
[10] DMRcate_2.4.1                                      
[11] EnsDb.Hsapiens.v75_2.99.0                          
[12] ensembldb_2.14.0                                   
[13] AnnotationFilter_1.14.0                            
[14] GenomicFeatures_1.42.3                             
[15] AnnotationDbi_1.52.0                               
[16] tictoc_1.0                                         
[17] ChAMPdata_2.22.0                                   
[18] patchwork_1.1.1                                    
[19] forcats_0.5.1                                      
[20] stringr_1.4.0                                      
[21] dplyr_1.0.5                                        
[22] purrr_0.3.4                                        
[23] readr_1.4.0                                        
[24] tidyr_1.1.3                                        
[25] tibble_3.1.0                                       
[26] tidyverse_1.3.0                                    
[27] glue_1.4.2                                         
[28] ggplot2_3.3.3                                      
[29] missMethyl_1.24.0                                  
[30] IlluminaHumanMethylationEPICanno.ilm10b4.hg19_0.6.0
[31] IlluminaHumanMethylation450kanno.ilmn12.hg19_0.6.0 
[32] reshape2_1.4.4                                     
[33] limma_3.46.0                                       
[34] minfi_1.36.0                                       
[35] bumphunter_1.32.0                                  
[36] locfit_1.5-9.4                                     
[37] iterators_1.0.13                                   
[38] foreach_1.5.1                                      
[39] Biostrings_2.58.0                                  
[40] XVector_0.30.0                                     
[41] SummarizedExperiment_1.20.0                        
[42] Biobase_2.50.0                                     
[43] MatrixGenerics_1.2.1                               
[44] matrixStats_0.58.0                                 
[45] GenomicRanges_1.42.0                               
[46] GenomeInfoDb_1.26.7                                
[47] IRanges_2.24.1                                     
[48] S4Vectors_0.28.1                                   
[49] BiocGenerics_0.36.0                                
[50] here_1.0.1                                         
[51] workflowr_1.6.2                                    

loaded via a namespace (and not attached):
  [1] Hmisc_4.5-0                               
  [2] Rsamtools_2.6.0                           
  [3] rprojroot_2.0.2                           
  [4] crayon_1.4.1                              
  [5] MASS_7.3-53.1                             
  [6] rhdf5filters_1.2.0                        
  [7] nlme_3.1-152                              
  [8] backports_1.2.1                           
  [9] reprex_2.0.0                              
 [10] sva_3.38.0                                
 [11] impute_1.64.0                             
 [12] GOSemSim_2.16.1                           
 [13] rlang_0.4.10                              
 [14] readxl_1.3.1                              
 [15] DSS_2.38.0                                
 [16] BiocParallel_1.24.1                       
 [17] globaltest_5.44.0                         
 [18] bit64_4.0.5                               
 [19] isva_1.9                                  
 [20] rngtools_1.5                              
 [21] methylumi_2.36.0                          
 [22] DOSE_3.16.0                               
 [23] haven_2.3.1                               
 [24] tidyselect_1.1.0                          
 [25] XML_3.99-0.6                              
 [26] nleqslv_3.3.2                             
 [27] GenomicAlignments_1.26.0                  
 [28] xtable_1.8-4                              
 [29] magrittr_2.0.1                            
 [30] evaluate_0.14                             
 [31] cli_2.4.0                                 
 [32] zlibbioc_1.36.0                           
 [33] rstudioapi_0.13                           
 [34] doRNG_1.8.2                               
 [35] whisker_0.4                               
 [36] bslib_0.2.4                               
 [37] rpart_4.1-15                              
 [38] fastmatch_1.1-0                           
 [39] shiny_1.6.0                               
 [40] xfun_0.22                                 
 [41] askpass_1.1                               
 [42] clue_0.3-58                               
 [43] multtest_2.46.0                           
 [44] tidygraph_1.2.0                           
 [45] interactiveDisplayBase_1.28.0             
 [46] ggrepel_0.9.1                             
 [47] base64_2.0                                
 [48] biovizBase_1.38.0                         
 [49] scrime_1.3.5                              
 [50] dendextend_1.14.0                         
 [51] png_0.1-7                                 
 [52] permute_0.9-5                             
 [53] reshape_0.8.8                             
 [54] withr_2.4.1                               
 [55] ggforce_0.3.3                             
 [56] lumi_2.42.0                               
 [57] bitops_1.0-6                              
 [58] plyr_1.8.6                                
 [59] cellranger_1.1.0                          
 [60] JADE_2.0-3                                
 [61] pillar_1.5.1                              
 [62] cachem_1.0.4                              
 [63] fs_1.5.0                                  
 [64] clusterProfiler_3.18.1                    
 [65] DelayedMatrixStats_1.12.3                 
 [66] vctrs_0.3.7                               
 [67] ellipsis_0.3.1                            
 [68] generics_0.1.0                            
 [69] tools_4.0.3                               
 [70] foreign_0.8-81                            
 [71] tweenr_1.0.2                              
 [72] munsell_0.5.0                             
 [73] fgsea_1.16.0                              
 [74] DelayedArray_0.16.3                       
 [75] fastmap_1.1.0                             
 [76] compiler_4.0.3                            
 [77] httpuv_1.5.5                              
 [78] rtracklayer_1.50.0                        
 [79] geneLenDataBase_1.26.0                    
 [80] ExperimentHub_1.16.0                      
 [81] beanplot_1.2                              
 [82] Gviz_1.34.1                               
 [83] plotly_4.9.3                              
 [84] GenomeInfoDbData_1.2.4                    
 [85] gridExtra_2.3                             
 [86] DNAcopy_1.64.0                            
 [87] edgeR_3.32.1                              
 [88] lattice_0.20-41                           
 [89] utf8_1.2.1                                
 [90] later_1.1.0.1                             
 [91] RobustRankAggreg_1.1                      
 [92] BiocFileCache_1.14.0                      
 [93] jsonlite_1.7.2                            
 [94] affy_1.68.0                               
 [95] scales_1.1.1                              
 [96] sparseMatrixStats_1.2.1                   
 [97] genefilter_1.72.1                         
 [98] lazyeval_0.2.2                            
 [99] promises_1.2.0.1                          
[100] doParallel_1.0.16                         
[101] latticeExtra_0.6-29                       
[102] R.utils_2.10.1                            
[103] goseq_1.42.0                              
[104] checkmate_2.0.0                           
[105] cowplot_1.1.1                             
[106] rmarkdown_2.7                             
[107] nor1mix_1.3-0                             
[108] statmod_1.4.35                            
[109] siggenes_1.64.0                           
[110] downloader_0.4                            
[111] dichromat_2.0-0                           
[112] BSgenome_1.58.0                           
[113] igraph_1.2.6                              
[114] HDF5Array_1.18.1                          
[115] bsseq_1.26.0                              
[116] survival_3.2-10                           
[117] yaml_2.2.1                                
[118] htmltools_0.5.1.1                         
[119] memoise_2.0.0                             
[120] VariantAnnotation_1.36.0                  
[121] graphlayouts_0.7.1                        
[122] quadprog_1.5-8                            
[123] viridisLite_0.3.0                         
[124] digest_0.6.27                             
[125] assertthat_0.2.1                          
[126] commonmark_1.7                            
[127] mime_0.10                                 
[128] rappdirs_0.3.3                            
[129] BiasedUrn_1.07                            
[130] RSQLite_2.2.5                             
[131] data.table_1.14.0                         
[132] blob_1.2.1                                
[133] R.oo_1.24.0                               
[134] preprocessCore_1.52.1                     
[135] labeling_0.4.2                            
[136] fastICA_1.2-2                             
[137] shinythemes_1.2.0                         
[138] splines_4.0.3                             
[139] Formula_1.2-4                             
[140] Rhdf5lib_1.12.1                           
[141] illuminaio_0.32.0                         
[142] AnnotationHub_2.22.0                      
[143] ProtGenerics_1.22.0                       
[144] RCurl_1.98-1.3                            
[145] broom_0.7.6                               
[146] hms_1.0.0                                 
[147] modelr_0.1.8                              
[148] rhdf5_2.34.0                              
[149] colorspace_2.0-0                          
[150] base64enc_0.1-3                           
[151] BiocManager_1.30.12                       
[152] nnet_7.3-15                               
[153] sass_0.3.1                                
[154] GEOquery_2.58.0                           
[155] Rcpp_1.0.6                                
[156] mclust_5.4.7                              
[157] enrichplot_1.10.2                         
[158] fansi_0.4.2                               
[159] R6_2.5.0                                  
[160] grid_4.0.3                                
[161] lifecycle_1.0.0                           
[162] curl_4.3                                  
[163] kpmt_0.1.0                                
[164] affyio_1.60.0                             
[165] jquerylib_0.1.3                           
[166] DO.db_2.9                                 
[167] Matrix_1.3-2                              
[168] qvalue_2.22.0                             
[169] ROC_1.66.0                                
[170] org.Hs.eg.db_3.12.0                       
[171] RColorBrewer_1.1-2                        
[172] IlluminaHumanMethylation450kmanifest_0.4.0
[173] htmlwidgets_1.5.3                         
[174] polyclip_1.10-0                           
[175] biomaRt_2.46.3                            
[176] shadowtext_0.0.7                          
[177] reactome.db_1.74.0                        
[178] marray_1.68.0                             
[179] rvest_1.0.0                               
[180] mgcv_1.8-34                               
[181] openssl_1.4.3                             
[182] htmlTable_2.1.0                           
[183] codetools_0.2-18                          
[184] lubridate_1.7.10                          
[185] GO.db_3.12.1                              
[186] gtools_3.8.2                              
[187] prettyunits_1.1.1                         
[188] dbplyr_2.1.1                              
[189] R.methodsS3_1.8.1                         
[190] gtable_0.3.0                              
[191] DBI_1.1.1                                 
[192] git2r_0.28.0                              
[193] wateRmelon_1.34.0                         
[194] highr_0.8                                 
[195] httr_1.4.2                                
[196] KernSmooth_2.23-18                        
[197] stringi_1.5.3                             
[198] progress_1.2.2                            
[199] farver_2.1.0                              
[200] annotate_1.68.0                           
[201] viridis_0.5.1                             
[202] xml2_1.3.2                                
[203] combinat_0.0-8                            
[204] rvcheck_0.1.8                             
[205] BiocVersion_3.12.0                        
[206] bit_4.0.4                                 
[207] scatterpie_0.1.5                          
[208] jpeg_0.1-8.1                              
[209] ggraph_2.0.5                              
[210] pkgconfig_2.0.3                           
[211] knitr_1.31