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
## 1/34
## 2/34 [checklibraries]
## 3/34
## 4/34 [peek]
## 5/34
## 6/34 [metrics]
## 7/34
## 8/34 [scatterplot]
## 9/34
## 10/34 [contourplot]
## 11/34
## 12/34 [input_geneset_metrics1]
## 13/34
## 14/34 [input_geneset_metrics2]
## 15/34
## 16/34 [input_geneset_metrics3]
## 17/34
## 18/34 [echart1d]
## 19/34 [echart2d]
## 20/34
## 21/34 [heatmap]
## 22/34
## 23/34 [effectsize]
## 24/34
## 25/34 [results_table]
## 26/34
## 27/34 [results_table_complete]
## 28/34
## 29/34 [detailed_geneset_reports1d]
## 30/34
## 31/34 [detailed_geneset_reports2d]
## 32/34
## 33/34 [session_info]
## 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
|