Source: https://github.com/markziemann/TODO

Introduction

Here we are establishing the methylation profile of ovarian cancer versus healthy tissue in order to understand whether this signature can be observed in the blood of individuals who will soon be diagnosed with the disease.

suppressPackageStartupMessages({
  library("mitch")
  library("HGNChelper")
  library("IlluminaHumanMethylation450kanno.ilmn12.hg19")
  library("IlluminaHumanMethylationEPICanno.ilm10b4.hg19")
  library("kableExtra")
  library("vioplot")
  library("beeswarm")
  library("RhpcBLASctl")
  library("eulerr")
  library("gplots")
})

RhpcBLASctl::blas_set_num_threads(1)

Load cancer data

dm <- readRDS("GSE133556_limma.rds")

anno <- getAnnotation(IlluminaHumanMethylationEPICanno.ilm10b4.hg19)

myann <- data.frame(anno[,c("UCSC_RefGene_Name","UCSC_RefGene_Group","Islands_Name","Relation_to_Island")])

head(myann)
##            UCSC_RefGene_Name UCSC_RefGene_Group              Islands_Name
## cg18478105            YTHDF1             TSS200   chr20:61846843-61848103
## cg09835024            EIF2S3            TSS1500    chrX:24072558-24073135
## cg14361672              PKN3            TSS1500  chr9:131464843-131465830
## cg01763666            CCDC57               Body                          
## cg12950382         INF2;INF2          Body;Body                          
## cg02115394       CDC16;CDC16      TSS200;TSS200 chr13:115000148-115000874
##            Relation_to_Island
## cg18478105             Island
## cg09835024             Island
## cg14361672            N_Shore
## cg01763666            OpenSea
## cg12950382            OpenSea
## cg02115394             Island
gp <- myann[,"UCSC_RefGene_Name",drop=FALSE]
gp2 <- strsplit(gp$UCSC_RefGene_Name,";")
names(gp2) <- rownames(gp)
gp2 <- lapply(gp2,unique)
gt1 <- stack(gp2)
colnames(gt1) <- c("gene","probe")
gt1$probe <- as.character(gt1$probe)
dim(gt1)
## [1] 684970      2
head(gt1)
##     gene      probe
## 1 YTHDF1 cg18478105
## 2 EIF2S3 cg09835024
## 3   PKN3 cg14361672
## 4 CCDC57 cg01763666
## 5   INF2 cg12950382
## 6  CDC16 cg02115394

Load gene sets

gs1 <- mitch::gmt_import("../../ReactomePathways_2024-12-13.gmt")
gs2 <- mitch::gmt_import("../../c5.go.v2024.1.Hs.symbols.gmt")
names(gs2) <- gsub("_"," ",names(gs2))

gs <- c(gs1,gs2)

gs3 <- mitch::gmt_import("../../go_2024-11.gmt")
gs3 <- gs3[which(lapply(gs3,length)>5)]
length(gs3)
## [1] 6929

Update deprecated gene symbols

new.hgnc.table <- getCurrentHumanMap()
## Using the already downloaded hgnc_complete_set.txt file.
fix <- checkGeneSymbols(gt1$gene,map=new.hgnc.table)
## Warning in checkGeneSymbols(gt1$gene, map = new.hgnc.table): Human gene symbols
## should be all upper-case except for the 'orf' in open reading frames. The case
## of some letters was corrected.
## Warning in checkGeneSymbols(gt1$gene, map = new.hgnc.table): x contains
## non-approved gene symbols
fix2 <- fix[which(fix$x != fix$Suggested.Symbol),]
length(unique(fix2$x))
## [1] 3300
gt1$gene <- fix$Suggested.Symbol
head(gt1)
##     gene      probe
## 1 YTHDF1 cg18478105
## 2 EIF2S3 cg09835024
## 3   PKN3 cg14361672
## 4 CCDC57 cg01763666
## 5   INF2 cg12950382
## 6  CDC16 cg02115394

Run mitch (cancer v normal)

y <- mitch_import(dm,DEtype="limma",geneTable=gt1)
## The input is a single dataframe; one contrast only. Converting
##         it to a list for you.
## Note: Mean no. genes in input = 776521
## Note: no. genes in output = 22227
## Warning in mitch_import(dm, DEtype = "limma", geneTable = gt1): Warning: less than half of the input genes are also in the
##         output
head(y)
##                   x
## A1BG      0.5004944
## A1BG-AS1  0.6143223
## A1CF     -1.8473972
## A2M       1.5320527
## A2M-AS1  -1.3189297
## A2ML1     1.1002124
y <- y[order(y$x),,drop=FALSE]

head(y)
##                   x
## MIR3925   -6.965108
## MIR3186   -6.940750
## ZNG1E     -6.277947
## SNORA64   -6.158418
## MYT1L-AS1 -6.124371
## S100A8    -6.103746
tail(y)
##                   x
## NFIA-AS1   7.839315
## MIR4730    7.858167
## MIR6830    8.317100
## MIR4660    8.329101
## CDKN2A-AS1 8.685757
## ZNF587B    9.595748
res <- mitch_calc(y,gs,priority="effect",cores=12,minsetsize=5)
## Note: Enrichments with large effect sizes may not be
##             statistically significant.
mres <- res$enrichment_result

head(mres,30) %>% kbl() %>% kable_paper("hover", full_width = F)
set setSize pANOVA s.dist p.adjustANOVA
11171 GOMF HEMOGLOBIN ALPHA BINDING 5 0.0003632 -0.9206192 0.0048707
2260 GOBP ANTIGEN PROCESSING AND PRESENTATION ENDOGENOUS LIPID ANTIGEN VIA MHC CLASS IB 5 0.0004808 -0.9014670 0.0060605
11356 GOMF LIPID ANTIGEN BINDING 5 0.0004808 -0.9014670 0.0060605
11615 GOMF ODORANT BINDING 101 0.0000000 -0.8968044 0.0000000
11258 GOMF INHIBITORY MHC CLASS I RECEPTOR ACTIVITY 9 0.0000039 -0.8885988 0.0001079
2555 GOBP CARDIAC SEPTUM CELL DIFFERENTIATION 5 0.0013667 0.8266943 0.0137572
4475 GOBP MESENCHYME MIGRATION 5 0.0017535 0.8079741 0.0166943
11617 GOMF OLFACTORY RECEPTOR ACTIVITY 353 0.0000000 -0.7846647 0.0000000
8245 GOBP REGULATION OF RNA POLYMERASE II TRANSCRIPTION PREINITIATION COMPLEX ASSEMBLY 6 0.0010053 0.7752876 0.0108103
540 Expression and translocation of olfactory receptors 354 0.0000000 -0.7693521 0.0000000
1147 Olfactory Signaling Pathway 361 0.0000000 -0.7557259 0.0000000
11445 GOMF MHC CLASS IB RECEPTOR ACTIVITY 8 0.0002519 -0.7472208 0.0036817
8877 GOBP SENSORY PERCEPTION OF SMELL 379 0.0000000 -0.7363084 0.0000000
720 H139Hfs13* PPM1K causes a mild variant of MSUD 5 0.0045557 0.7325353 0.0349307
943 Maple Syrup Urine Disease 5 0.0045557 0.7325353 0.0349307
12148 GOMF TRACE AMINE RECEPTOR ACTIVITY 7 0.0010289 -0.7163688 0.0109964
10084 GOCC MLL3 4 COMPLEX 10 0.0000948 0.7127515 0.0016323
9882 GOCC FC RECEPTOR COMPLEX 5 0.0061878 -0.7069211 0.0445019
3199 GOBP DISRUPTION OF CELLULAR ANATOMICAL STRUCTURE IN ANOTHER ORGANISM 6 0.0028639 -0.7029237 0.0244616
2533 GOBP CARDIAC FIBROBLAST CELL DIFFERENTIATION 5 0.0074484 0.6910269 0.0514361
9970 GOCC INSULIN LIKE GROWTH FACTOR BINDING PROTEIN COMPLEX 5 0.0082162 0.6824948 0.0552409
2852 GOBP CENTROMERIC SISTER CHROMATID COHESION 10 0.0001955 0.6801278 0.0030050
4401 GOBP MATURE CONVENTIONAL DENDRITIC CELL DIFFERENTIATION 5 0.0084544 -0.6799928 0.0561996
316 Conjugation of salicylate with glycine 8 0.0009418 -0.6751879 0.0102804
7062 GOBP PROTEIN POLYUFMYLATION 5 0.0093898 0.6707407 0.0610311
8516 GOBP RESPONSE TO ACTINOMYCIN D 5 0.0097938 0.6669967 0.0629252
5109 GOBP NEGATIVE REGULATION OF INTRINSIC APOPTOTIC SIGNALING PATHWAY IN RESPONSE TO OSMOTIC STRESS 5 0.0100319 0.6648546 0.0639864
9040 GOBP SPLICEOSOMAL CONFORMATIONAL CHANGES TO GENERATE CATALYTIC CONFORMATION 5 0.0100602 0.6646026 0.0640675
186 Branched-chain ketoacid dehydrogenase kinase deficiency 5 0.0102194 0.6631986 0.0647217
2944 GOBP CITRATE METABOLIC PROCESS 5 0.0104206 0.6614526 0.0656480
updf <- head(subset(mres,p.adjustANOVA<0.05 & s.dist > 0),15)

dndf <- head(subset(mres,p.adjustANOVA<0.05 & s.dist < 0),15)

up <- updf$s.dist
names(up) <- updf$set
dn <- dndf$s.dist
names(dn) <- dndf$set
top <- c(up,dn)
top <- top[order(top)]

par(mar = c(5.1, 28.1, 4.1, 2.1))
barplot(top,horiz=TRUE,las=1,xlab="ES")

alldn <- subset(mres,p.adjustANOVA<0.05 & s.dist < 0)$set

allup <- subset(mres,p.adjustANOVA<0.05 & s.dist > 0)$set

par(mar = c(5.1, 4.1, 4.1, 2.1))

Get incidence data

incid <- readRDS("../../multi_ewas_incid.rds")
incid2 <- incid[,grep("ovarian_cancer",colnames(incid) ),drop=FALSE]
head(incid2)
##          ovarian_cancer
## A1BG       0.0006228232
## A1BG-AS1   0.0006301492
## A1CF      -0.0013322063
## A2M       -0.0010100706
## A2M-AS1   -0.0000064800
## A2ML1     -0.0008099856
ires <- mitch_calc(incid2,genesets=gs,minsetsize=5,cores=12,priority="effect")
## Note: Enrichments with large effect sizes may not be
##             statistically significant.
ires <- ires$enrichment_result

head(ires,30) %>% kbl(caption="incidence") %>% kable_paper("hover", full_width = F)
incidence
set setSize pANOVA s.dist p.adjustANOVA
1155 Organic anion transport 5 0.0008296 -0.8631215 0.0207108
7251 GOBP REGULATION OF AMACRINE CELL DIFFERENTIATION 6 0.0004140 0.8323107 0.0124354
1290 Prostanoid ligand receptors 9 0.0000728 0.7634835 0.0032098
7314 GOBP REGULATION OF BINDING OF SPERM TO ZONA PELLUCIDA 5 0.0031114 -0.7634215 0.0520127
10308 GOCC RADIAL SPOKE HEAD 5 0.0031178 0.7632579 0.0520190
11839 GOMF PROTEIN ARGININE DEIMINASE ACTIVITY 5 0.0040543 -0.7420962 0.0613993
5174 GOBP NEGATIVE REGULATION OF MHC CLASS II BIOSYNTHETIC PROCESS 5 0.0041419 0.7403509 0.0623420
6226 GOBP POSITIVE REGULATION OF ENAMEL MINERALIZATION 5 0.0047651 -0.7288247 0.0689337
9976 GOCC INTRACELLULAR CYCLIC NUCLEOTIDE ACTIVATED CATION CHANNEL COMPLEX 5 0.0050059 -0.7247341 0.0710775
11833 GOMF PROSTANOID RECEPTOR ACTIVITY 11 0.0000908 0.6814131 0.0038330
607 Formation of lateral plate mesoderm 5 0.0090529 0.6739751 0.1036228
11020 GOMF ESTROGEN 2 HYDROXYLASE ACTIVITY 5 0.0090622 -0.6738842 0.1036329
9809 GOCC EARLY ENDOSOME LUMEN 5 0.0094848 0.6698482 0.1069718
7558 GOBP REGULATION OF ENAMEL MINERALIZATION 8 0.0011012 -0.6662007 0.0253265
56 Activation of C3 and C5 6 0.0047960 -0.6648486 0.0690157
9842 GOCC EPSILON DNA POLYMERASE COMPLEX 5 0.0103516 0.6620489 0.1133985
10812 GOMF CCR6 CHEMOKINE RECEPTOR BINDING 5 0.0103852 -0.6617580 0.1133985
11135 GOMF GUANYLATE CYCLASE REGULATOR ACTIVITY 8 0.0012584 -0.6584390 0.0280005
10855 GOMF COENZYME A DIPHOSPHATASE ACTIVITY 5 0.0112135 0.6548496 0.1180155
4400 GOBP MATURE CONVENTIONAL DENDRITIC CELL DIFFERENTIATION 5 0.0117899 0.6503045 0.1220395
10458 GOCC TRANSCRIPTION FACTOR AP 1 COMPLEX 5 0.0118798 0.6496137 0.1226114
9515 GOBP XENOBIOTIC GLUCURONIDATION 6 0.0059100 -0.6488947 0.0784053
10654 GOMF AMMONIA LYASE ACTIVITY 5 0.0119822 -0.6488319 0.1231512
11832 GOMF PROSTAGLANDIN E RECEPTOR ACTIVITY 5 0.0123826 0.6458322 0.1263150
10671 GOMF AP 1 ADAPTOR COMPLEX BINDING 5 0.0131203 0.6405236 0.1304803
314 Conjugation of benzoate with glycine 6 0.0073559 -0.6318198 0.0905267
282 Ciprofloxacin ADME 5 0.0147274 -0.6298155 0.1412103
4044 GOBP INTESTINAL CHOLESTEROL ABSORPTION 18 0.0000038 -0.6294056 0.0002852
7872 GOBP REGULATION OF MESODERMAL CELL DIFFERENTIATION 10 0.0005712 0.6290494 0.0157299
9150 GOBP TELENCEPHALON REGIONALIZATION 13 0.0001065 0.6206518 0.0043173
updf <- head(subset(ires,p.adjustANOVA<0.05 & s.dist > 0),15)

dndf <- head(subset(ires,p.adjustANOVA<0.05 & s.dist < 0),15)

up <- updf$s.dist
names(up) <- updf$set
dn <- dndf$s.dist
names(dn) <- dndf$set
top <- c(up,dn)
top <- top[order(top)]

par(mar = c(5.1, 28.1, 4.1, 2.1))
barplot(top,horiz=TRUE,las=1,xlab="ES")

idn <- subset(ires,p.adjustANOVA<0.05 & s.dist < 0)$set

iup <- subset(ires,p.adjustANOVA<0.05 & s.dist > 0)$set

par(mar = c(5.1, 4.1, 4.1, 2.1))

Intersect sig pw

l <- list("cup"=allup,"cdn"=alldn,"idn"=idn,"iup"=iup)

plot(euler(l),quantities = TRUE)

intersect(allup,iup)
##   [1] "GOCC SIN3 TYPE COMPLEX"                                                                     
##   [2] "Regulation of endogenous retroelements by KRAB-ZFP proteins"                                
##   [3] "ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression"                            
##   [4] "Assembly of the ORC complex at the origin of replication"                                   
##   [5] "Regulation of endogenous retroelements"                                                     
##   [6] "GOBP REGULATION OF ATTACHMENT OF SPINDLE MICROTUBULES TO KINETOCHORE"                       
##   [7] "mRNA Splicing"                                                                              
##   [8] "mRNA Splicing - Major Pathway"                                                              
##   [9] "Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)"                   
##  [10] "Activation of HOX genes during differentiation"                                             
##  [11] "Activation of anterior HOX genes in hindbrain development during early embryogenesis"       
##  [12] "HDACs deacetylate histones"                                                                 
##  [13] "GOCC HISTONE DEACETYLASE COMPLEX"                                                           
##  [14] "Mitochondrial translation elongation"                                                       
##  [15] "Processing of Capped Intron-Containing Pre-mRNA"                                            
##  [16] "GOCC MITOCHONDRIAL LARGE RIBOSOMAL SUBUNIT"                                                 
##  [17] "GOBP RNA SPLICING VIA TRANSESTERIFICATION REACTIONS"                                        
##  [18] "Mitochondrial translation termination"                                                      
##  [19] "Unfolded Protein Response (UPR)"                                                            
##  [20] "HATs acetylate histones"                                                                    
##  [21] "Mitochondrial translation"                                                                  
##  [22] "GOBP SPLEEN DEVELOPMENT"                                                                    
##  [23] "GOBP RNA SPLICING"                                                                          
##  [24] "GOCC ORGANELLAR RIBOSOME"                                                                   
##  [25] "PRC2 methylates histones and DNA"                                                           
##  [26] "GOMF HISTONE ACETYLTRANSFERASE BINDING"                                                     
##  [27] "GOBP ATTACHMENT OF SPINDLE MICROTUBULES TO KINETOCHORE"                                     
##  [28] "Mitochondrial translation initiation"                                                       
##  [29] "GOBP POSITIVE REGULATION OF STEM CELL POPULATION MAINTENANCE"                               
##  [30] "Assembly of the pre-replicative complex"                                                    
##  [31] "DNA Replication Pre-Initiation"                                                             
##  [32] "Positive epigenetic regulation of rRNA expression"                                          
##  [33] "GOBP REGULATION OF CHROMOSOME ORGANIZATION"                                                 
##  [34] "GOBP MITOCHONDRIAL TRANSLATION"                                                             
##  [35] "RNA Polymerase I Promoter Clearance"                                                        
##  [36] "RNA Polymerase I Transcription"                                                             
##  [37] "GOCC ENDOPLASMIC RETICULUM PROTEIN CONTAINING COMPLEX"                                      
##  [38] "GOBP MRNA PROCESSING"                                                                       
##  [39] "Epigenetic regulation of gene expression"                                                   
##  [40] "GOCC NUCLEOSOME"                                                                            
##  [41] "GOCC ATPASE COMPLEX"                                                                        
##  [42] "Chromosome Maintenance"                                                                     
##  [43] "RUNX1 regulates transcription of genes involved in differentiation of HSCs"                 
##  [44] "Metabolism of RNA"                                                                          
##  [45] "Chromatin modifications during the maternal to zygotic transition (MZT)"                    
##  [46] "Transcription-Coupled Nucleotide Excision Repair (TC-NER)"                                  
##  [47] "Ub-specific processing proteases"                                                           
##  [48] "GOBP DNA TEMPLATED TRANSCRIPTION INITIATION"                                                
##  [49] "Nucleotide Excision Repair"                                                                 
##  [50] "GOCC TRANSCRIPTION REPRESSOR COMPLEX"                                                       
##  [51] "GOMF STRUCTURAL CONSTITUENT OF CHROMATIN"                                                   
##  [52] "Telomere Maintenance"                                                                       
##  [53] "GOMF RIBONUCLEOPROTEIN COMPLEX BINDING"                                                     
##  [54] "Global Genome Nucleotide Excision Repair (GG-NER)"                                          
##  [55] "GOBP MITOCHONDRIAL GENE EXPRESSION"                                                         
##  [56] "RNA Polymerase I Promoter Escape"                                                           
##  [57] "GOCC NUCLEAR CHROMOSOME"                                                                    
##  [58] "SUMOylation"                                                                                
##  [59] "GOCC MITOCHONDRIAL PROTEIN CONTAINING COMPLEX"                                              
##  [60] "B-WICH complex positively regulates rRNA expression"                                        
##  [61] "SUMO E3 ligases SUMOylate target proteins"                                                  
##  [62] "GOMF HISTONE DEACETYLASE BINDING"                                                           
##  [63] "GOBP NEGATIVE REGULATION OF RESPONSE TO ENDOPLASMIC RETICULUM STRESS"                       
##  [64] "Respiratory electron transport"                                                             
##  [65] "GOCC CONDENSED CHROMOSOME CENTROMERIC REGION"                                               
##  [66] "Cell Cycle Checkpoints"                                                                     
##  [67] "GOCC LARGE RIBOSOMAL SUBUNIT"                                                               
##  [68] "GOBP PROTEIN DNA COMPLEX ASSEMBLY"                                                          
##  [69] "GOMF CHROMATIN DNA BINDING"                                                                 
##  [70] "GOCC NUCLEAR PROTEIN CONTAINING COMPLEX"                                                    
##  [71] "GOCC CHROMOSOME CENTROMERIC REGION"                                                         
##  [72] "GOBP FORELIMB MORPHOGENESIS"                                                                
##  [73] "GOMF TRANSCRIPTION COACTIVATOR ACTIVITY"                                                    
##  [74] "GOBP REGULATION OF PROTEASOMAL PROTEIN CATABOLIC PROCESS"                                   
##  [75] "GOBP TELOMERE ORGANIZATION"                                                                 
##  [76] "GOCC CHROMOSOMAL REGION"                                                                    
##  [77] "GOBP REGULATION OF PROTEASOMAL UBIQUITIN DEPENDENT PROTEIN CATABOLIC PROCESS"               
##  [78] "GOBP DOUBLE STRAND BREAK REPAIR"                                                            
##  [79] "GOCC CONDENSED CHROMOSOME"                                                                  
##  [80] "GOBP RECOMBINATIONAL REPAIR"                                                                
##  [81] "DNA Double-Strand Break Repair"                                                             
##  [82] "DNA Replication"                                                                            
##  [83] "DNA Repair"                                                                                 
##  [84] "Epigenetic regulation by WDR5-containing histone modifying complexes"                       
##  [85] "Deubiquitination"                                                                           
##  [86] "GOBP REGULATION OF DOUBLE STRAND BREAK REPAIR"                                              
##  [87] "G2/M Checkpoints"                                                                           
##  [88] "GOBP EPIGENETIC REGULATION OF GENE EXPRESSION"                                              
##  [89] "GOCC CHROMOSOME TELOMERIC REGION"                                                           
##  [90] "GOBP PROTEIN DNA COMPLEX ORGANIZATION"                                                      
##  [91] "GOBP EMBRYONIC APPENDAGE MORPHOGENESIS"                                                     
##  [92] "GOBP CHROMATIN REMODELING"                                                                  
##  [93] "Mitotic Anaphase"                                                                           
##  [94] "Senescence-Associated Secretory Phenotype (SASP)"                                           
##  [95] "GOBP APPENDAGE MORPHOGENESIS"                                                               
##  [96] "GOBP RIBONUCLEOPROTEIN COMPLEX BIOGENESIS"                                                  
##  [97] "GOBP RRNA METABOLIC PROCESS"                                                                
##  [98] "GOBP TELOMERE MAINTENANCE"                                                                  
##  [99] "Synthesis of DNA"                                                                           
## [100] "Homology Directed Repair"                                                                   
## [101] "GOCC NUCLEAR SPECK"                                                                         
## [102] "GOCC NUCLEAR BODY"                                                                          
## [103] "GOMF CHROMATIN BINDING"                                                                     
## [104] "GOCC RIBOSOME"                                                                              
## [105] "GOBP CHROMOSOME ORGANIZATION"                                                               
## [106] "GOBP SISTER CHROMATID SEGREGATION"                                                          
## [107] "GOBP REGULATION OF DNA REPAIR"                                                              
## [108] "Oxidative Stress Induced Senescence"                                                        
## [109] "GOBP PROTEASOME MEDIATED UBIQUITIN DEPENDENT PROTEIN CATABOLIC PROCESS"                     
## [110] "GOBP RRNA PROCESSING"                                                                       
## [111] "Aerobic respiration and respiratory electron transport"                                     
## [112] "GOCC RIBOSOMAL SUBUNIT"                                                                     
## [113] "GOCC CATALYTIC COMPLEX"                                                                     
## [114] "GOBP VENTRAL SPINAL CORD DEVELOPMENT"                                                       
## [115] "HDR through Homologous Recombination (HRR)"                                                 
## [116] "GOCC SITE OF DNA DAMAGE"                                                                    
## [117] "GOMF TRANSCRIPTION COREGULATOR BINDING"                                                     
## [118] "HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)"                
## [119] "S Phase"                                                                                    
## [120] "GOMF TRANSCRIPTION FACTOR BINDING"                                                          
## [121] "Regulation of TP53 Activity"                                                                
## [122] "GOBP REGULATION OF RESPONSE TO ENDOPLASMIC RETICULUM STRESS"                                
## [123] "GOBP APPENDAGE DEVELOPMENT"                                                                 
## [124] "GOBP MRNA METABOLIC PROCESS"                                                                
## [125] "HCMV Early Events"                                                                          
## [126] "GOMF RNA POLYMERASE II SPECIFIC DNA BINDING TRANSCRIPTION FACTOR BINDING"                   
## [127] "GOBP PANCREAS DEVELOPMENT"                                                                  
## [128] "GOBP REGULATION OF UBIQUITIN DEPENDENT PROTEIN CATABOLIC PROCESS"                           
## [129] "GOBP METAPHASE CHROMOSOME ALIGNMENT"                                                        
## [130] "GOBP NUCLEOSOME ORGANIZATION"                                                               
## [131] "GOBP CHROMOSOME LOCALIZATION"                                                               
## [132] "GOCC SITE OF DOUBLE STRAND BREAK"                                                           
## [133] "GOBP RIBOSOME BIOGENESIS"                                                                   
## [134] "GOBP REGULATION OF PROTEOLYSIS INVOLVED IN PROTEIN CATABOLIC PROCESS"                       
## [135] "M Phase"                                                                                    
## [136] "Gene expression (Transcription)"                                                            
## [137] "Translation"                                                                                
## [138] "Transcriptional regulation of granulopoiesis"                                               
## [139] "RNA Polymerase II Transcription"                                                            
## [140] "GOBP CELL FATE SPECIFICATION"                                                               
## [141] "GOCC TRANSFERASE COMPLEX"                                                                   
## [142] "GOBP CELL CYCLE CHECKPOINT SIGNALING"                                                       
## [143] "G2/M DNA damage checkpoint"                                                                 
## [144] "GOBP DNA REPAIR"                                                                            
## [145] "GOMF SEQUENCE SPECIFIC DNA BINDING"                                                         
## [146] "Cell Cycle"                                                                                 
## [147] "GOBP ROOF OF MOUTH DEVELOPMENT"                                                             
## [148] "GOMF RRNA BINDING"                                                                          
## [149] "GOMF TRANSCRIPTION COREGULATOR ACTIVITY"                                                    
## [150] "Base Excision Repair"                                                                       
## [151] "Neddylation"                                                                                
## [152] "GOCC PROTEIN DNA COMPLEX"                                                                   
## [153] "rRNA processing"                                                                            
## [154] "GOCC INTRACELLULAR PROTEIN CONTAINING COMPLEX"                                              
## [155] "Cell Cycle, Mitotic"                                                                        
## [156] "GOBP EMBRYONIC DIGIT MORPHOGENESIS"                                                         
## [157] "GOMF DNA BINDING TRANSCRIPTION FACTOR BINDING"                                              
## [158] "GOBP REGULATION OF MITOTIC CELL CYCLE PHASE TRANSITION"                                     
## [159] "GOBP PROTEASOMAL PROTEIN CATABOLIC PROCESS"                                                 
## [160] "Protein ubiquitination"                                                                     
## [161] "GOMF TRANSCRIPTION REGULATOR ACTIVITY"                                                      
## [162] "GOBP DNA DAMAGE RESPONSE"                                                                   
## [163] "Transcriptional regulation by RUNX1"                                                        
## [164] "HCMV Infection"                                                                             
## [165] "GOBP INTRACELLULAR ESTROGEN RECEPTOR SIGNALING PATHWAY"                                     
## [166] "GOBP MITOTIC SISTER CHROMATID SEGREGATION"                                                  
## [167] "Generic Transcription Pathway"                                                              
## [168] "rRNA processing in the nucleus and cytosol"                                                 
## [169] "Major pathway of rRNA processing in the nucleolus and cytosol"                              
## [170] "GOMF CATALYTIC ACTIVITY ACTING ON A NUCLEIC ACID"                                           
## [171] "GOMF STRUCTURAL CONSTITUENT OF RIBOSOME"                                                    
## [172] "GOCC TRANSCRIPTION REGULATOR COMPLEX"                                                       
## [173] "RHO GTPase Effectors"                                                                       
## [174] "GOBP SIGNAL TRANSDUCTION IN RESPONSE TO DNA DAMAGE"                                         
## [175] "GOMF CIS REGULATORY REGION SEQUENCE SPECIFIC DNA BINDING"                                   
## [176] "GOMF DAMAGED DNA BINDING"                                                                   
## [177] "GOBP CELLULAR RESPONSE TO TOPOLOGICALLY INCORRECT PROTEIN"                                  
## [178] "GOBP DNA INTEGRITY CHECKPOINT SIGNALING"                                                    
## [179] "GOMF CATALYTIC ACTIVITY ACTING ON RNA"                                                      
## [180] "GOBP DNA REPLICATION"                                                                       
## [181] "GOCC UBIQUITIN LIGASE COMPLEX"                                                              
## [182] "GOMF DNA BINDING TRANSCRIPTION FACTOR ACTIVITY"                                             
## [183] "GOBP MODIFICATION DEPENDENT MACROMOLECULE CATABOLIC PROCESS"                                
## [184] "GOBP RESPONSE TO TOPOLOGICALLY INCORRECT PROTEIN"                                           
## [185] "GOBP PROTEIN FOLDING"                                                                       
## [186] "GOBP REGULATION OF CELL CYCLE PHASE TRANSITION"                                             
## [187] "GOBP DNA RECOMBINATION"                                                                     
## [188] "GOBP MITOTIC CELL CYCLE PHASE TRANSITION"                                                   
## [189] "GOMF UBIQUITIN LIKE PROTEIN BINDING"                                                        
## [190] "GOBP MITOTIC CELL CYCLE PROCESS"                                                            
## [191] "Transcriptional Regulation by TP53"                                                         
## [192] "GOBP REGULATION OF CELLULAR RESPONSE TO STRESS"                                             
## [193] "GOCC CULLIN RING UBIQUITIN LIGASE COMPLEX"                                                  
## [194] "GOBP NUCLEIC ACID CATABOLIC PROCESS"                                                        
## [195] "Cellular Senescence"                                                                        
## [196] "GOBP POSITIVE REGULATION OF RNA METABOLIC PROCESS"                                          
## [197] "GOMF DNA BINDING TRANSCRIPTION ACTIVATOR ACTIVITY"                                          
## [198] "Cellular responses to stress"                                                               
## [199] "GOBP CELL CYCLE PHASE TRANSITION"                                                           
## [200] "GOBP PROTEIN LOCALIZATION TO ORGANELLE"                                                     
## [201] "GOBP ANTERIOR POSTERIOR PATTERN SPECIFICATION"                                              
## [202] "Antigen processing: Ubiquitination & Proteasome degradation"                                
## [203] "GOBP POSITIVE REGULATION OF TRANSCRIPTION BY RNA POLYMERASE II"                             
## [204] "GOBP NEGATIVE REGULATION OF TRANSCRIPTION BY RNA POLYMERASE II"                             
## [205] "GOBP ESTABLISHMENT OF PROTEIN LOCALIZATION TO ORGANELLE"                                    
## [206] "G2/M Transition"                                                                            
## [207] "GOMF MOLECULAR ADAPTOR ACTIVITY"                                                            
## [208] "GOBP DNA METABOLIC PROCESS"                                                                 
## [209] "GOMF MOLECULAR CARRIER ACTIVITY"                                                            
## [210] "GOBP REGULATION OF CELL CYCLE PROCESS"                                                      
## [211] "GOBP REGULATION OF CELL CYCLE G2 M PHASE TRANSITION"                                        
## [212] "GOCC MITOCHONDRIAL MATRIX"                                                                  
## [213] "GOBP ENDOPLASMIC RETICULUM UNFOLDED PROTEIN RESPONSE"                                       
## [214] "Mitotic G2-G2/M phases"                                                                     
## [215] "Cellular response to chemical stress"                                                       
## [216] "GOBP PROTEOLYSIS INVOLVED IN PROTEIN CATABOLIC PROCESS"                                     
## [217] "GOBP NEGATIVE REGULATION OF RNA BIOSYNTHETIC PROCESS"                                       
## [218] "Cellular responses to stimuli"                                                              
## [219] "GOBP REGULATION OF DNA METABOLIC PROCESS"                                                   
## [220] "Chaperonin-mediated protein folding"                                                        
## [221] "GOBP NEGATIVE REGULATION OF NUCLEOBASE CONTAINING COMPOUND METABOLIC PROCESS"               
## [222] "GOBP VACUOLE ORGANIZATION"                                                                  
## [223] "GOCC TRANSFERASE COMPLEX TRANSFERRING PHOSPHORUS CONTAINING GROUPS"                         
## [224] "Protein folding"                                                                            
## [225] "GOMF UBIQUITIN LIKE PROTEIN LIGASE BINDING"                                                 
## [226] "GOCC ORGANELLE INNER MEMBRANE"                                                              
## [227] "GOBP MITOTIC CELL CYCLE"                                                                    
## [228] "Class I MHC mediated antigen processing & presentation"                                     
## [229] "GOBP REGULATION OF CELL CYCLE"                                                              
## [230] "GOCC RNA POLYMERASE II TRANSCRIPTION REGULATOR COMPLEX"                                     
## [231] "GOBP INTRINSIC APOPTOTIC SIGNALING PATHWAY IN RESPONSE TO DNA DAMAGE"                       
## [232] "GOBP REGULATION OF SIGNAL TRANSDUCTION BY P53 CLASS MEDIATOR"                               
## [233] "GOBP PROTEIN POLYUBIQUITINATION"                                                            
## [234] "GOBP MACROAUTOPHAGY"                                                                        
## [235] "GOBP MITOTIC NUCLEAR DIVISION"                                                              
## [236] "GOBP NEGATIVE REGULATION OF CELL CYCLE PROCESS"                                             
## [237] "GOBP CELL CYCLE PROCESS"                                                                    
## [238] "GOBP REGULATION OF MITOTIC CELL CYCLE"                                                      
## [239] "Signaling by TGFB family members"                                                           
## [240] "Gastrulation"                                                                               
## [241] "GOCC MITOCHONDRIAL ENVELOPE"                                                                
## [242] "GOBP REGULATION OF POST TRANSLATIONAL PROTEIN MODIFICATION"                                 
## [243] "GOBP SIGNAL TRANSDUCTION BY P53 CLASS MEDIATOR"                                             
## [244] "GOMF UBIQUITIN BINDING"                                                                     
## [245] "GOBP MIRNA METABOLIC PROCESS"                                                               
## [246] "GOBP INTRINSIC APOPTOTIC SIGNALING PATHWAY BY P53 CLASS MEDIATOR"                           
## [247] "GOBP CELL CYCLE"                                                                            
## [248] "GOBP INTRACELLULAR TRANSPORT"                                                               
## [249] "GOBP MICROTUBULE CYTOSKELETON ORGANIZATION INVOLVED IN MITOSIS"                             
## [250] "Signaling by Rho GTPases"                                                                   
## [251] "GOBP TRANSLATION"                                                                           
## [252] "GOBP ENDOCRINE SYSTEM DEVELOPMENT"                                                          
## [253] "GOCC SPINDLE"                                                                               
## [254] "Signaling by Rho GTPases, Miro GTPases and RHOBTB3"                                         
## [255] "GOBP INTRACELLULAR PROTEIN TRANSPORT"                                                       
## [256] "GOBP NEGATIVE REGULATION OF CELL CYCLE"                                                     
## [257] "GOBP REGULATION OF PROTEIN CATABOLIC PROCESS"                                               
## [258] "GOBP PROTEIN MODIFICATION BY SMALL PROTEIN CONJUGATION"                                     
## [259] "GOBP PROTEIN CONTAINING COMPLEX ASSEMBLY"                                                   
## [260] "GOBP EMBRYONIC SKELETAL SYSTEM DEVELOPMENT"                                                 
## [261] "GOBP CELLULAR RESPONSE TO STRESS"                                                           
## [262] "GOBP MITOCHONDRION ORGANIZATION"                                                            
## [263] "GOBP MITOTIC SPINDLE ORGANIZATION"                                                          
## [264] "GOCC MITOCHONDRION"                                                                         
## [265] "Viral Infection Pathways"                                                                   
## [266] "GOCC SPINDLE POLE"                                                                          
## [267] "GOBP EMBRYO DEVELOPMENT ENDING IN BIRTH OR EGG HATCHING"                                    
## [268] "GOBP REGULATION OF PROTEIN UBIQUITINATION"                                                  
## [269] "GOCC ORGANELLE ENVELOPE"                                                                    
## [270] "GOBP MACROMOLECULE CATABOLIC PROCESS"                                                       
## [271] "GOBP CELL DIVISION"                                                                         
## [272] "GOBP REGULATION OF ORGANELLE ORGANIZATION"                                                  
## [273] "GOBP CELLULAR RESPONSE TO STEROID HORMONE STIMULUS"                                         
## [274] "GOBP POSITIVE REGULATION OF POST TRANSLATIONAL PROTEIN MODIFICATION"                        
## [275] "GOBP PATTERN SPECIFICATION PROCESS"                                                         
## [276] "GOBP PROTEIN CATABOLIC PROCESS"                                                             
## [277] "GOBP POST TRANSLATIONAL PROTEIN MODIFICATION"                                               
## [278] "Metabolism of proteins"                                                                     
## [279] "SARS-CoV-1 Infection"                                                                       
## [280] "GOBP SKELETAL SYSTEM MORPHOGENESIS"                                                         
## [281] "GOBP REGULATION OF CATABOLIC PROCESS"                                                       
## [282] "GOCC CENTROSOME"                                                                            
## [283] "Membrane Trafficking"                                                                       
## [284] "GOBP RESPONSE TO ENDOPLASMIC RETICULUM STRESS"                                              
## [285] "GOBP NEURAL PRECURSOR CELL PROLIFERATION"                                                   
## [286] "GOBP PROCESS UTILIZING AUTOPHAGIC MECHANISM"                                                
## [287] "GOMF DNA BINDING TRANSCRIPTION REPRESSOR ACTIVITY"                                          
## [288] "GOBP IN UTERO EMBRYONIC DEVELOPMENT"                                                        
## [289] "GOBP CYTOKINESIS"                                                                           
## [290] "GOMF PROTEIN CONTAINING COMPLEX BINDING"                                                    
## [291] "Vesicle-mediated transport"                                                                 
## [292] "GOBP MICROTUBULE ORGANIZING CENTER ORGANIZATION"                                            
## [293] "GOBP EMBRYO DEVELOPMENT"                                                                    
## [294] "GOBP CELL FATE COMMITMENT"                                                                  
## [295] "GOBP SPINDLE ORGANIZATION"                                                                  
## [296] "GOMF ACYLTRANSFERASE ACTIVITY"                                                              
## [297] "GOBP ESTABLISHMENT OF ORGANELLE LOCALIZATION"                                               
## [298] "GOBP CELLULAR COMPONENT DISASSEMBLY"                                                        
## [299] "GOBP ORGANELLE LOCALIZATION"                                                                
## [300] "GOBP ESTABLISHMENT OF PROTEIN LOCALIZATION"                                                 
## [301] "GOBP PROTEIN TRANSPORT"                                                                     
## [302] "GOBP INTRACELLULAR RECEPTOR SIGNALING PATHWAY"                                              
## [303] "GOBP ESTABLISHMENT OF LOCALIZATION IN CELL"                                                 
## [304] "Post-translational protein modification"                                                    
## [305] "GOCC MICROTUBULE ORGANIZING CENTER"                                                         
## [306] "Infectious disease"                                                                         
## [307] "GOBP GENERATION OF PRECURSOR METABOLITES AND ENERGY"                                        
## [308] "GOBP HEAD DEVELOPMENT"                                                                      
## [309] "GOBP CELL SURFACE RECEPTOR PROTEIN SERINE THREONINE KINASE SIGNALING PATHWAY"               
## [310] "GOBP MYELOID CELL HOMEOSTASIS"                                                              
## [311] "GOBP VESICLE ORGANIZATION"                                                                  
## [312] "GOMF AMINOACYLTRANSFERASE ACTIVITY"                                                         
## [313] "GOCC COATED VESICLE"                                                                        
## [314] "SARS-CoV Infections"                                                                        
## [315] "GOCC MICROTUBULE CYTOSKELETON"                                                              
## [316] "GOMF UBIQUITIN LIKE PROTEIN LIGASE ACTIVITY"                                                
## [317] "GOMF PROTEIN DOMAIN SPECIFIC BINDING"                                                       
## [318] "GOBP INTRINSIC APOPTOTIC SIGNALING PATHWAY"                                                 
## [319] "GOBP EMBRYONIC MORPHOGENESIS"                                                               
## [320] "GOBP NEGATIVE REGULATION OF APOPTOTIC SIGNALING PATHWAY"                                    
## [321] "GOBP REGULATION OF INTRINSIC APOPTOTIC SIGNALING PATHWAY"                                   
## [322] "GOBP REGULATION OF PROTEIN CONTAINING COMPLEX ASSEMBLY"                                     
## [323] "GOBP REGULATION OF TRANSMEMBRANE RECEPTOR PROTEIN SERINE THREONINE KINASE SIGNALING PATHWAY"
## [324] "GOBP PROTEIN MATURATION"                                                                    
## [325] "GOMF PROTEIN HETERODIMERIZATION ACTIVITY"                                                   
## [326] "GOBP ENDOMEMBRANE SYSTEM ORGANIZATION"                                                      
## [327] "GOBP FOREBRAIN DEVELOPMENT"                                                                 
## [328] "GOBP CELLULAR RESPONSE TO ORGANIC CYCLIC COMPOUND"                                          
## [329] "GOBP ORGANONITROGEN COMPOUND CATABOLIC PROCESS"                                             
## [330] "GOBP RESPONSE TO STEROID HORMONE"                                                           
## [331] "GOBP NITROGEN COMPOUND TRANSPORT"                                                           
## [332] "GOBP RESPONSE TO OXIDATIVE STRESS"                                                          
## [333] "GOBP CELLULAR RESPONSE TO HORMONE STIMULUS"                                                 
## [334] "Disease"                                                                                    
## [335] "GOBP REGULATION OF MICROTUBULE BASED PROCESS"                                               
## [336] "GOBP GLAND DEVELOPMENT"                                                                     
## [337] "GOBP ORGANONITROGEN COMPOUND BIOSYNTHETIC PROCESS"                                          
## [338] "GOBP MICROTUBULE CYTOSKELETON ORGANIZATION"                                                 
## [339] "GOMF PROTEIN DIMERIZATION ACTIVITY"                                                         
## [340] "GOBP SKELETAL SYSTEM DEVELOPMENT"                                                           
## [341] "GOBP EMBRYONIC ORGAN DEVELOPMENT"                                                           
## [342] "GOBP NEGATIVE REGULATION OF CELL DIFFERENTIATION"                                           
## [343] "GOCC LATE ENDOSOME"                                                                         
## [344] "Interferon Signaling"                                                                       
## [345] "GOBP REGULATION OF CELLULAR COMPONENT BIOGENESIS"                                           
## [346] "GOBP NEURON APOPTOTIC PROCESS"                                                              
## [347] "GOBP EMBRYONIC ORGAN MORPHOGENESIS"                                                         
## [348] "GOBP NEGATIVE REGULATION OF PROTEIN MODIFICATION PROCESS"                                   
## [349] "GOBP CENTRAL NERVOUS SYSTEM DEVELOPMENT"                                                    
## [350] "GOBP APOPTOTIC SIGNALING PATHWAY"                                                           
## [351] "GOBP REGULATION OF APOPTOTIC SIGNALING PATHWAY"                                             
## [352] "GOMF KINASE BINDING"                                                                        
## [353] "GOCC ENDOSOME MEMBRANE"                                                                     
## [354] "GOCC ORGANELLE SUBCOMPARTMENT"                                                              
## [355] "GOBP RESPONSE TO ENDOGENOUS STIMULUS"                                                       
## [356] "GOBP CELLULAR CATABOLIC PROCESS"                                                            
## [357] "GOBP RESPONSE TO HORMONE"                                                                   
## [358] "GOBP NEGATIVE REGULATION OF DEVELOPMENTAL PROCESS"                                          
## [359] "GOBP REGULATION OF PROTEIN MODIFICATION PROCESS"                                            
## [360] "GOCC VACUOLAR MEMBRANE"                                                                     
## [361] "GOBP REGULATION OF CELL DIFFERENTIATION"                                                    
## [362] "GOBP ENZYME LINKED RECEPTOR PROTEIN SIGNALING PATHWAY"                                      
## [363] "GOBP APOPTOTIC PROCESS"                                                                     
## [364] "GOCC NUCLEAR OUTER MEMBRANE ENDOPLASMIC RETICULUM MEMBRANE NETWORK"                         
## [365] "GOBP NEGATIVE REGULATION OF INTRACELLULAR SIGNAL TRANSDUCTION"                              
## [366] "GOMF PROTEIN HOMODIMERIZATION ACTIVITY"                                                     
## [367] "GOBP REGULATION OF PROGRAMMED CELL DEATH"                                                   
## [368] "GOBP ANIMAL ORGAN MORPHOGENESIS"                                                            
## [369] "GOBP MORPHOGENESIS OF AN EPITHELIUM"                                                        
## [370] "GOBP REGULATION OF PROTEOLYSIS"                                                             
## [371] "Adaptive Immune System"                                                                     
## [372] "GOCC ENDOSOME"                                                                              
## [373] "GOBP PROTEOLYSIS"                                                                           
## [374] "GOBP NEGATIVE REGULATION OF PROGRAMMED CELL DEATH"                                          
## [375] "GOBP RESPONSE TO ORGANIC CYCLIC COMPOUND"                                                   
## [376] "GOBP NEGATIVE REGULATION OF SIGNALING"                                                      
## [377] "GOBP POSITIVE REGULATION OF DEVELOPMENTAL PROCESS"                                          
## [378] "GOBP REGULATION OF CELL DEVELOPMENT"                                                        
## [379] "GOBP POSITIVE REGULATION OF PROTEIN METABOLIC PROCESS"                                      
## [380] "GOBP POSITIVE REGULATION OF CELL DIFFERENTIATION"                                           
## [381] "GOBP RESPONSE TO NITROGEN COMPOUND"                                                         
## [382] "GOBP REGULATION OF INTRACELLULAR SIGNAL TRANSDUCTION"                                       
## [383] "GOBP PHOSPHORYLATION"                                                                       
## [384] "GOBP REGULATION OF MULTICELLULAR ORGANISMAL DEVELOPMENT"                                    
## [385] "GOBP REGULATION OF RESPONSE TO STRESS"                                                      
## [386] "GOBP HEMOPOIESIS"                                                                           
## [387] "GOBP ORGANOPHOSPHATE METABOLIC PROCESS"                                                     
## [388] "GOBP GENERATION OF NEURONS"                                                                 
## [389] "GOBP NEGATIVE REGULATION OF RESPONSE TO STIMULUS"                                           
## [390] "GOBP NEUROGENESIS"                                                                          
## [391] "GOBP CELLULAR RESPONSE TO OXYGEN CONTAINING COMPOUND"                                       
## [392] "GOBP REGULATION OF CELL POPULATION PROLIFERATION"                                           
## [393] "GOBP POSITIVE REGULATION OF SIGNALING"                                                      
## [394] "GOBP CELLULAR RESPONSE TO ORGANIC SUBSTANCE"                                                
## [395] "GOBP INTRACELLULAR SIGNALING CASSETTE"
intersect(alldn,idn)
##  [1] "GOMF ODORANT BINDING"                                              
##  [2] "GOMF OLFACTORY RECEPTOR ACTIVITY"                                  
##  [3] "Expression and translocation of olfactory receptors"               
##  [4] "Olfactory Signaling Pathway"                                       
##  [5] "GOBP SENSORY PERCEPTION OF SMELL"                                  
##  [6] "GOBP SENSORY PERCEPTION OF CHEMICAL STIMULUS"                      
##  [7] "GOBP DETECTION OF STIMULUS INVOLVED IN SENSORY PERCEPTION"         
##  [8] "GOBP KERATINIZATION"                                               
##  [9] "Sensory Perception"                                                
## [10] "GOBP DETECTION OF STIMULUS"                                        
## [11] "Keratinization"                                                    
## [12] "GOMF STRUCTURAL CONSTITUENT OF SKIN EPIDERMIS"                     
## [13] "GOCC KERATIN FILAMENT"                                             
## [14] "GOMF G PROTEIN COUPLED RECEPTOR ACTIVITY"                          
## [15] "Initial triggering of complement"                                  
## [16] "Creation of C4 and C2 activators"                                  
## [17] "Antimicrobial peptides"                                            
## [18] "Formation of the cornified envelope"                               
## [19] "GOBP SENSORY PERCEPTION"                                           
## [20] "Aspirin ADME"                                                      
## [21] "GOCC SODIUM CHANNEL COMPLEX"                                       
## [22] "GOMF MOLECULAR TRANSDUCER ACTIVITY"                                
## [23] "GOMF SODIUM CHANNEL ACTIVITY"                                      
## [24] "GOBP INTERMEDIATE FILAMENT ORGANIZATION"                           
## [25] "GOBP G PROTEIN COUPLED RECEPTOR SIGNALING PATHWAY"                 
## [26] "GOBP PLASMA MEMBRANE FUSION"                                       
## [27] "GOBP PHAGOCYTOSIS RECOGNITION"                                     
## [28] "Complement cascade"                                                
## [29] "GOBP COMPLEMENT ACTIVATION"                                        
## [30] "GOCC INTERMEDIATE FILAMENT CYTOSKELETON"                           
## [31] "Class C/3 (Metabotropic glutamate/pheromone receptors)"            
## [32] "GOBP NERVOUS SYSTEM PROCESS"                                       
## [33] "Diseases associated with O-glycosylation of proteins"              
## [34] "GOBP HUMORAL IMMUNE RESPONSE"                                      
## [35] "GOBP INTERMEDIATE FILAMENT BASED PROCESS"                          
## [36] "GOMF GATED CHANNEL ACTIVITY"                                       
## [37] "GOMF SERINE TYPE ENDOPEPTIDASE INHIBITOR ACTIVITY"                 
## [38] "GOBP CELL RECOGNITION"                                             
## [39] "GOMF MONOATOMIC CATION CHANNEL ACTIVITY"                           
## [40] "GOMF SODIUM ION TRANSMEMBRANE TRANSPORTER ACTIVITY"                
## [41] "GOMF ENDOPEPTIDASE REGULATOR ACTIVITY"                             
## [42] "GOCC MONOATOMIC ION CHANNEL COMPLEX"                               
## [43] "GOMF METAL ION TRANSMEMBRANE TRANSPORTER ACTIVITY"                 
## [44] "GOCC CATION CHANNEL COMPLEX"                                       
## [45] "GOMF PASSIVE TRANSMEMBRANE TRANSPORTER ACTIVITY"                   
## [46] "GOBP SODIUM ION TRANSMEMBRANE TRANSPORT"                           
## [47] "GOMF TRANSLATION REPRESSOR ACTIVITY"                               
## [48] "SLC-mediated transmembrane transport"                              
## [49] "GOCC POSTSYNAPTIC MEMBRANE"                                        
## [50] "GOCC SYNAPTIC MEMBRANE"                                            
## [51] "GOCC EXTERNAL ENCAPSULATING STRUCTURE"                             
## [52] "GOCC RNAI EFFECTOR COMPLEX"                                        
## [53] "GOMF INORGANIC MOLECULAR ENTITY TRANSMEMBRANE TRANSPORTER ACTIVITY"
## [54] "GOBP REGULATORY NCRNA MEDIATED GENE SILENCING"                     
## [55] "GOBP MONOATOMIC ION TRANSPORT"                                     
## [56] "GOBP MONOATOMIC ION TRANSMEMBRANE TRANSPORT"                       
## [57] "GOCC PLASMA MEMBRANE REGION"                                       
## [58] "GOBP TRANSMEMBRANE TRANSPORT"

Cancer specific genes

down100 <- rownames(head(y,100))
down200 <- rownames(head(y,200))
down500 <- rownames(head(y,500))
down1000 <- rownames(head(y,1000))
down2000 <- rownames(head(y,2000))
down5000 <- rownames(head(y,5000))

up100 <- rownames(tail(y,100))
up200 <- rownames(tail(y,200))
up500 <- rownames(tail(y,500))
up1000 <- rownames(tail(y,1000))
up2000 <- rownames(tail(y,2000))
up5000 <- rownames(tail(y,5000))

cancer_genes <- list("down100"=down100,"up100"=up100,
  "down200"=down200,"up200"=up200,
  "down500"=down500,"up500"=up500,
  "down1000"=down1000,"up1000"=up1000,
  "down2000"=down2000,"up2000"=up2000,
  "down5000"=down5000,"up5000"=up5000)

ocres <- mitch_calc(incid2,genesets=cancer_genes,minsetsize=5,cores=12,priority="effect")
## Note: Enrichments with large effect sizes may not be
##             statistically significant.
ocres$enrichment_result %>% kbl(caption="cancer gene signature deteted before diagnosis") %>% kable_paper("hover", full_width = F)
cancer gene signature deteted before diagnosis
set setSize pANOVA s.dist p.adjustANOVA
7 down1000 969 0.0000000 -0.3401385 0.0000000
5 down500 480 0.0000000 -0.3389495 0.0000000
3 down200 189 0.0000000 -0.3162478 0.0000000
9 down2000 1940 0.0000000 -0.3083335 0.0000000
11 down5000 4892 0.0000000 -0.2643184 0.0000000
1 down100 93 0.0006743 -0.2039586 0.0008091
12 up5000 4920 0.0000000 0.1759351 0.0000000
10 up2000 1939 0.0000000 0.1547168 0.0000000
8 up1000 960 0.0000000 0.1215266 0.0000000
6 up500 470 0.0005422 0.0931099 0.0007229
2 up100 90 0.1419874 -0.0895520 0.1548954
4 up200 181 0.8198678 0.0098132 0.8198678

Two dimensional analysis

m <- merge(y,incid2,by=0)
rownames(m) <- m$Row.names
m[,1] <- NULL
colnames(m) <- c("cancer","incidence")
head(m)
##              cancer     incidence
## A1BG      0.5004944  0.0006228232
## A1BG-AS1  0.6143223  0.0006301492
## A1CF     -1.8473972 -0.0013322063
## A2M       1.5320527 -0.0010100706
## A2M-AS1  -1.3189297 -0.0000064800
## A2ML1     1.1002124 -0.0008099856
m2 <- mitch_calc(m,genesets=gs,minsetsize=5,cores=12,priority="effect")
## Note: Enrichments with large effect sizes may not be 
##             statistically significant.
m2res <- m2$enrichment_result
m2res$FDR.cancer <- p.adjust(m2res$p.cancer,method="BH")
m2res$FDR.incidence <- p.adjust(m2res$p.incidence,method="BH")

m2resf <- subset(m2res,FDR.cancer < 0.05 | FDR.incidence < 0.05)
dim(m2res)
## [1] 12277    12
dim(m2resf)
## [1] 2028   12
m2resf <- subset(m2resf,p.adjustMANOVA < 0.05)
dim(m2resf)
## [1] 1772   12
head(m2resf,30) %>% kbl(caption="Top hits in 2D analysis") %>% kable_paper("hover", full_width = F)
Top hits in 2D analysis
set setSize pMANOVA s.cancer s.incidence p.cancer p.incidence s.dist SD p.adjustMANOVA FDR.cancer FDR.incidence
10807 GOMF CCR6 CHEMOKINE RECEPTOR BINDING 5 0.0013170 -0.7939499 -0.6622713 0.0021067 0.0103259 1.0339051 0.0931108 0.0128736 0.0192815 0.1122865
11245 GOMF INHIBITORY MHC CLASS I RECEPTOR ACTIVITY 9 0.0000086 -0.8901312 -0.4513860 0.0000037 0.0190270 0.9980395 0.3102397 0.0001905 0.0001044 0.1609926
11602 GOMF ODORANT BINDING 99 0.0000000 -0.8979114 -0.3454686 0.0000000 0.0000000 0.9620777 0.3906361 0.0000000 0.0000000 0.0000004
11159 GOMF HEMOGLOBIN ALPHA BINDING 5 0.0016623 -0.9222339 -0.2493316 0.0003547 0.3342934 0.9553437 0.4758138 0.0152408 0.0047691 0.6715955
8236 GOBP REGULATION OF RNA POLYMERASE II TRANSCRIPTION PREINITIATION COMPLEX ASSEMBLY 6 0.0010989 0.7774533 0.5481231 0.0009730 0.0200622 0.9512479 0.1621609 0.0112897 0.0105524 0.1656382
1155 Organic anion transport 5 0.0031916 -0.3240681 -0.8637587 0.2095085 0.0008223 0.9225504 0.3816189 0.0251657 0.4535595 0.0204359
2260 GOBP ANTIGEN PROCESSING AND PRESENTATION ENDOGENOUS LIPID ANTIGEN VIA MHC CLASS IB 5 0.0019589 -0.9031802 -0.0708765 0.0004690 0.7837336 0.9059569 0.5885276 0.0172891 0.0058929 0.9266973
11343 GOMF LIPID ANTIGEN BINDING 5 0.0019589 -0.9031802 -0.0708765 0.0004690 0.7837336 0.9059569 0.5885276 0.0172891 0.0058929 0.9266973
2555 GOBP CARDIAC SEPTUM CELL DIFFERENTIATION 5 0.0048408 0.8290094 0.3274810 0.0013247 0.2047499 0.8913475 0.3546342 0.0344324 0.0133968 0.5448217
11604 GOMF OLFACTORY RECEPTOR ACTIVITY 338 0.0000000 -0.7956455 -0.3630216 0.0000000 0.0000000 0.8745493 0.3059113 0.0000000 0.0000000 0.0000000
540 Expression and translocation of olfactory receptors 339 0.0000000 -0.7796031 -0.3560589 0.0000000 0.0000000 0.8570642 0.2994910 0.0000000 0.0000000 0.0000000
1147 Olfactory Signaling Pathway 346 0.0000000 -0.7651999 -0.3557125 0.0000000 0.0000000 0.8438378 0.2895514 0.0000000 0.0000000 0.0000000
7248 GOBP REGULATION OF AMACRINE CELL DIFFERENTIATION 6 0.0013650 -0.0163351 0.8326793 0.9447584 0.0004115 0.8328395 0.6003439 0.0131683 0.9794610 0.0124442
316 Conjugation of salicylate with glycine 8 0.0010791 -0.6777745 -0.4691065 0.0009001 0.0215771 0.8242810 0.1475505 0.0111612 0.0098812 0.1731386
8868 GOBP SENSORY PERCEPTION OF SMELL 364 0.0000000 -0.7445761 -0.3496256 0.0000000 0.0000000 0.8225762 0.2792722 0.0000000 0.0000000 0.0000000
432 Digestion of dietary carbohydrate 6 0.0064954 -0.6437458 -0.5101752 0.0063165 0.0304501 0.8213936 0.0944487 0.0433536 0.0450070 0.2107303
4473 GOBP MESENCHYME MIGRATION 5 0.0063642 0.8100652 0.0417667 0.0017058 0.8715153 0.8111413 0.5432691 0.0427204 0.0162593 0.9586591
12134 GOMF TRACE AMINE RECEPTOR ACTIVITY 7 0.0027405 -0.7188488 -0.3616245 0.0009882 0.0975469 0.8046837 0.2525958 0.0224597 0.0106700 0.3867387
5093 GOBP NEGATIVE REGULATION OF INTERLEUKIN 6 MEDIATED SIGNALING PATHWAY 8 0.0000593 0.6601716 -0.4571507 0.0012216 0.0251453 0.8030027 0.7900661 0.0010074 0.0125965 0.1886972
1290 Prostanoid ligand receptors 9 0.0003444 0.2459981 0.7639554 0.2012734 0.0000721 0.8025852 0.3662512 0.0043815 0.4426789 0.0031948
2552 GOBP CARDIAC PACEMAKER CELL DEVELOPMENT 8 0.0020821 0.6631149 0.4093274 0.0011614 0.0449739 0.7792755 0.1794549 0.0181803 0.0121347 0.2603230
1494 Regulation of gene expression in early pancreatic precursor cells 8 0.0031910 0.6479990 0.3763119 0.0015028 0.0653036 0.7493420 0.1921118 0.0251657 0.0147956 0.3175175
11432 GOMF MHC CLASS IB RECEPTOR ACTIVITY 7 0.0025134 -0.7413644 -0.0185326 0.0006811 0.9323339 0.7415960 0.5111192 0.0210772 0.0079037 0.9778979
8864 GOBP SENSORY PERCEPTION OF CHEMICAL STIMULUS 439 0.0000000 -0.6556101 -0.3284941 0.0000000 0.0000000 0.7333028 0.2313059 0.0000000 0.0000000 0.0000000
105 Amino Acid conjugation 9 0.0029275 -0.5454347 -0.4753191 0.0046016 0.0135357 0.7234827 0.0495793 0.0236145 0.0350456 0.1323073
315 Conjugation of carboxylic acids 9 0.0029275 -0.5454347 -0.4753191 0.0046016 0.0135357 0.7234827 0.0495793 0.0236145 0.0350456 0.1323073
11130 GOMF GUANYLATE CYCLASE REGULATOR ACTIVITY 8 0.0005455 0.2867573 -0.6590992 0.1601660 0.0012443 0.7187778 0.6688216 0.0064454 0.3883921 0.0275747
11438 GOMF MHC CLASS I RECEPTOR ACTIVITY 13 0.0001793 -0.6276205 -0.3497649 0.0000890 0.0289896 0.7185006 0.1964736 0.0025124 0.0015410 0.2052511
10075 GOCC MLL3 4 COMPLEX 10 0.0002683 0.7147043 -0.0362541 0.0000907 0.8426418 0.7156232 0.5310078 0.0035740 0.0015642 0.9479382
5997 GOBP POSITIVE REGULATION OF ACROSOME REACTION 11 0.0008414 -0.5939192 -0.3973388 0.0006468 0.0224911 0.7145755 0.1390033 0.0091981 0.0075766 0.1775689
mx <- as.matrix(m2resf[1:30,4:5])

rownames(mx) <- head(m2resf,30)$set
colfunc <- colorRampPalette(c("blue", "white", "red"))
heatmap.2(mx,trace="none",scale="none",mar=c(5,25),cexCol="0.9",col=colfunc)

mitch_report(res=m2,outfile="2dmitch.html",overwrite=TRUE)
## Note: overwriting existing report
## Dataset saved as " /tmp/RtmplxIhLh/2dmitch.rds ".
## 
## 
## processing file: mitch.Rmd
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## 34/34
## output file: /home/mark.ziemann@domain.internal.burnet.edu.au/projects/cancer_biomarkers/ovarian/GSE133556/mitch.knit.md
## /usr/bin/pandoc +RTS -K512m -RTS /home/mark.ziemann@domain.internal.burnet.edu.au/projects/cancer_biomarkers/ovarian/GSE133556/mitch.knit.md --to html4 --from markdown+autolink_bare_uris+tex_math_single_backslash --output /tmp/RtmplxIhLh/mitch_report.html --lua-filter /usr/local/lib/R/site-library/rmarkdown/rmarkdown/lua/pagebreak.lua --lua-filter /usr/local/lib/R/site-library/rmarkdown/rmarkdown/lua/latex-div.lua --self-contained --variable bs3=TRUE --section-divs --template /usr/local/lib/R/site-library/rmarkdown/rmd/h/default.html --no-highlight --variable highlightjs=1 --variable theme=bootstrap --mathjax --variable 'mathjax-url=https://mathjax.rstudio.com/latest/MathJax.js?config=TeX-AMS-MML_HTMLorMML' --include-in-header /tmp/RtmplxIhLh/rmarkdown-str263f447aa7a028.html
## 
## Output created: /tmp/RtmplxIhLh/mitch_report.html
## [1] TRUE

A few top genes

mrank <- m2$ranked_profile

mrank <- as.data.frame(cbind(mrank,rowMedians(mrank)))

mrank <- mrank[order(mrank$V3),]

head(mrank,50) %>% kbl(caption="common hypomethylated genes") %>% kable_paper("hover", full_width = F)
common hypomethylated genes
cancer incidence V3
KCNQ1-AS1 -8921 -10455 -9688.0
OR10J3 -8913 -10402 -9657.5
OR51A7 -8920 -10383 -9651.5
RNU6-48P -8839 -10460 -9649.5
ASAP1-IT2 -8786 -10463 -9624.5
MIR205 -8797 -10414 -9605.5
SNORA65 -8743 -10454 -9598.5
MIR3186 -8928 -10260 -9594.0
ISM1-AS1 -8906 -10272 -9589.0
OR5AC2 -8794 -10384 -9589.0
MIR7113 -8713 -10464 -9588.5
OR10Z1 -8846 -10322 -9584.0
SNORA10 -8914 -10236 -9575.0
ROR1-AS1 -8664 -10458 -9561.0
FGD5P1 -8647 -10443 -9545.0
MIR548I2 -8678 -10397 -9537.5
MIR3176 -8814 -10257 -9535.5
DEFB114 -8829 -10241 -9535.0
KRTAP11-1 -8793 -10261 -9527.0
OR10K2 -8756 -10278 -9517.0
SNORD99 -8657 -10375 -9516.0
MIR411 -8681 -10348 -9514.5
MIR153-2 -8912 -10115 -9513.5
LINC01103 -8599 -10409 -9504.0
KCND3-IT1 -8748 -10252 -9500.0
OR51G2 -8910 -10087 -9498.5
MIR298 -8769 -10222 -9495.5
OR56B1 -8757 -10234 -9495.5
MIR8065 -8665 -10325 -9495.0
MIR4535 -8547 -10429 -9488.0
LINC01085 -8658 -10315 -9486.5
OR52L1 -8606 -10358 -9482.0
CCL7 -8569 -10359 -9464.0
OR8H3 -8915 -9992 -9453.5
PRSS59P -8610 -10280 -9445.0
CCT8L2 -8442 -10445 -9443.5
KRTAP19-5 -8613 -10248 -9430.5
APOC1P1 -8517 -10329 -9423.0
MIR6787 -8614 -10216 -9415.0
OR5A1 -8850 -9972 -9411.0
KPLCE -8386 -10431 -9408.5
LINC01300 -8516 -10288 -9402.0
LINC01618 -8752 -10052 -9402.0
SNORA51 -8507 -10293 -9400.0
DLGAP2-AS1 -8831 -9958 -9394.5
CYP11B2 -8854 -9921 -9387.5
MIR1297 -8314 -10457 -9385.5
MIR7973-2 -8359 -10411 -9385.0
MIR431 -8454 -10311 -9382.5
SPATA8-AS1 -8798 -9961 -9379.5
tail(mrank,50) %>% kbl(caption="common hypermethylated genes") %>% kable_paper("hover", full_width = F)
common hypermethylated genes
cancer incidence V3
CENPBD2P 12817 10817 11817.0
NICN1 12410 11232 11821.0
TMT1A 12932 10719 11825.5
CIMIP2B 12641 11011 11826.0
DLX2-DT 12984 10675 11829.5
MIR6755 12455 11205 11830.0
RPL23AP64 12829 10834 11831.5
MEIS1-AS3 12411 11256 11833.5
STAM-DT 12526 11159 11842.5
DNAJC3-DT 12693 11002 11847.5
MFAP4 12808 10897 11852.5
GBP1 12544 11185 11864.5
MIR4738 12917 10813 11865.0
ITPKB-IT1 12743 11004 11873.5
WFDC10A 12635 11144 11889.5
MIR626 12522 11266 11894.0
LINC01252 12790 11039 11914.5
AGBL5-AS1 12513 11318 11915.5
MIR4258 12885 10946 11915.5
ZNG1B 12461 11388 11924.5
AMT 12715 11147 11931.0
SNORA20 12966 10902 11934.0
LEMD1-AS1 12757 11121 11939.0
HORMAD2 12593 11306 11949.5
LYSMD1 12632 11268 11950.0
SNORA2A 12490 11411 11950.5
MIR5093 12881 11034 11957.5
IFITM3 12702 11221 11961.5
HOXD12 12746 11183 11964.5
OCM 12741 11213 11977.0
TNFSF13 12711 11258 11984.5
LINC00619 12701 11269 11985.0
TPM3P9 12794 11211 12002.5
LINC00398 12880 11130 12005.0
GPR21 12930 11084 12007.0
FAM83A-AS1 12616 11417 12016.5
MIR6736 12813 11242 12027.5
MIR1284 12814 11255 12034.5
LINC01391 12744 11381 12062.5
MIR615 12870 11264 12067.0
FOXD4L1 12947 11218 12082.5
SNORA74B 12968 11238 12103.0
DLG5-AS1 12943 11326 12134.5
PIN4P1 12883 11424 12153.5
MIR6751 12920 11406 12163.0
IPO5P1 12882 11451 12166.5
MIR6843 12894 11439 12166.5
MIR4492 12934 11441 12187.5
MIR4487 12972 11442 12207.0
CDKN2A-AS1 12992 11427 12209.5

Session information

sessionInfo()
## R version 4.4.1 (2024-06-14)
## Platform: x86_64-pc-linux-gnu
## Running under: Ubuntu 22.04.5 LTS
## 
## Matrix products: default
## BLAS:   /usr/lib/x86_64-linux-gnu/blas/libblas.so.3.10.0 
## LAPACK: /usr/lib/x86_64-linux-gnu/lapack/liblapack.so.3.10.0
## 
## locale:
##  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
##  [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
##  [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
##  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
##  [9] LC_ADDRESS=C               LC_TELEPHONE=C            
## [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
## 
## time zone: Australia/Melbourne
## tzcode source: system (glibc)
## 
## attached base packages:
## [1] parallel  stats4    stats     graphics  grDevices utils     datasets 
## [8] methods   base     
## 
## other attached packages:
##  [1] pkgload_1.4.0                                      
##  [2] GGally_2.2.1                                       
##  [3] ggplot2_3.5.1                                      
##  [4] reshape2_1.4.4                                     
##  [5] gtools_3.9.5                                       
##  [6] tibble_3.2.1                                       
##  [7] dplyr_1.1.4                                        
##  [8] echarts4r_0.4.5                                    
##  [9] gplots_3.2.0                                       
## [10] eulerr_7.0.2                                       
## [11] RhpcBLASctl_0.23-42                                
## [12] beeswarm_0.4.0                                     
## [13] vioplot_0.5.0                                      
## [14] zoo_1.8-12                                         
## [15] sm_2.2-6.0                                         
## [16] kableExtra_1.4.0                                   
## [17] IlluminaHumanMethylationEPICanno.ilm10b4.hg19_0.6.0
## [18] IlluminaHumanMethylation450kanno.ilmn12.hg19_0.6.1 
## [19] minfi_1.50.0                                       
## [20] bumphunter_1.46.0                                  
## [21] locfit_1.5-9.10                                    
## [22] iterators_1.0.14                                   
## [23] foreach_1.5.2                                      
## [24] Biostrings_2.72.1                                  
## [25] XVector_0.44.0                                     
## [26] SummarizedExperiment_1.34.0                        
## [27] Biobase_2.64.0                                     
## [28] MatrixGenerics_1.16.0                              
## [29] matrixStats_1.4.1                                  
## [30] GenomicRanges_1.56.2                               
## [31] GenomeInfoDb_1.40.1                                
## [32] IRanges_2.38.1                                     
## [33] S4Vectors_0.42.1                                   
## [34] BiocGenerics_0.50.0                                
## [35] HGNChelper_0.8.15                                  
## [36] mitch_1.19.3                                       
## 
## loaded via a namespace (and not attached):
##   [1] splines_4.4.1             later_1.4.0              
##   [3] BiocIO_1.14.0             bitops_1.0-9             
##   [5] polyclip_1.10-7           preprocessCore_1.66.0    
##   [7] XML_3.99-0.17             lifecycle_1.0.4          
##   [9] lattice_0.22-6            MASS_7.3-61              
##  [11] base64_2.0.2              scrime_1.3.5             
##  [13] magrittr_2.0.3            limma_3.60.6             
##  [15] sass_0.4.9                rmarkdown_2.29           
##  [17] jquerylib_0.1.4           yaml_2.3.10              
##  [19] httpuv_1.6.15             doRNG_1.8.6              
##  [21] askpass_1.2.1             DBI_1.2.3                
##  [23] RColorBrewer_1.1-3        abind_1.4-8              
##  [25] zlibbioc_1.50.0           quadprog_1.5-8           
##  [27] purrr_1.0.2               RCurl_1.98-1.16          
##  [29] GenomeInfoDbData_1.2.12   genefilter_1.86.0        
##  [31] annotate_1.82.0           svglite_2.1.3            
##  [33] DelayedMatrixStats_1.26.0 codetools_0.2-20         
##  [35] DelayedArray_0.30.1       xml2_1.3.6               
##  [37] tidyselect_1.2.1          farver_2.1.2             
##  [39] UCSC.utils_1.0.0          beanplot_1.3.1           
##  [41] illuminaio_0.46.0         GenomicAlignments_1.40.0 
##  [43] jsonlite_1.8.9            multtest_2.60.0          
##  [45] survival_3.7-0            systemfonts_1.1.0        
##  [47] polylabelr_0.3.0          tools_4.4.1              
##  [49] Rcpp_1.0.13-1             glue_1.8.0               
##  [51] gridExtra_2.3             SparseArray_1.4.8        
##  [53] xfun_0.49                 HDF5Array_1.32.1         
##  [55] withr_3.0.2               fastmap_1.2.0            
##  [57] rhdf5filters_1.16.0       fansi_1.0.6              
##  [59] openssl_2.2.2             caTools_1.18.3           
##  [61] digest_0.6.37             R6_2.5.1                 
##  [63] mime_0.12                 colorspace_2.1-1         
##  [65] RSQLite_2.3.8             utf8_1.2.4               
##  [67] tidyr_1.3.1               generics_0.1.3           
##  [69] data.table_1.16.2         rtracklayer_1.64.0       
##  [71] httr_1.4.7                htmlwidgets_1.6.4        
##  [73] S4Arrays_1.4.1            ggstats_0.7.0            
##  [75] pkgconfig_2.0.3           gtable_0.3.6             
##  [77] blob_1.2.4                siggenes_1.78.0          
##  [79] htmltools_0.5.8.1         scales_1.3.0             
##  [81] png_0.1-8                 knitr_1.49               
##  [83] rstudioapi_0.17.1         tzdb_0.4.0               
##  [85] rjson_0.2.23              nlme_3.1-166             
##  [87] curl_6.0.1                cachem_1.1.0             
##  [89] rhdf5_2.48.0              stringr_1.5.1            
##  [91] KernSmooth_2.23-24        AnnotationDbi_1.66.0     
##  [93] restfulr_0.0.15           GEOquery_2.72.0          
##  [95] pillar_1.9.0              grid_4.4.1               
##  [97] reshape_0.8.9             vctrs_0.6.5              
##  [99] promises_1.3.1            xtable_1.8-4             
## [101] evaluate_1.0.1            readr_2.1.5              
## [103] GenomicFeatures_1.56.0    cli_3.6.3                
## [105] compiler_4.4.1            Rsamtools_2.20.0         
## [107] rlang_1.1.4               crayon_1.5.3             
## [109] rngtools_1.5.2            labeling_0.4.3           
## [111] nor1mix_1.3-3             mclust_6.1.1             
## [113] plyr_1.8.9                stringi_1.8.4            
## [115] viridisLite_0.4.2         BiocParallel_1.38.0      
## [117] munsell_0.5.1             Matrix_1.7-1             
## [119] hms_1.1.3                 sparseMatrixStats_1.16.0 
## [121] bit64_4.5.2               Rhdf5lib_1.26.0          
## [123] KEGGREST_1.44.1           statmod_1.5.0            
## [125] shiny_1.9.1               memoise_2.0.1.9000       
## [127] bslib_0.8.0               bit_4.5.0                
## [129] splitstackshape_1.4.8