Load packages
knitr::opts_chunk$set(dev = "png")
suppressPackageStartupMessages({
library("missMethyl")
library("GEOquery")
library("limma")
library("topconfects")
library("minfi")
library("IlluminaHumanMethylation450kmanifest")
library("IlluminaHumanMethylation450kanno.ilmn12.hg19")
library("DMRcate")
library("mitch")
library("kableExtra")
library("forestplot")
library("RColorBrewer")
library("plyr")
library("R.utils")
library("eulerr")
library("gplots")
library("reshape2")
library("beeswarm")
})
## Warning: package 'locfit' was built under R version 4.1.0
## Warning: replacing previous import 'minfi::getMeth' by 'bsseq::getMeth' when
## loading 'DMRcate'
ann450k <- getAnnotation(IlluminaHumanMethylation450kanno.ilmn12.hg19)
myann <- data.frame(ann450k[,c("UCSC_RefGene_Name","Regulatory_Feature_Group")])
promoters <- grep("Prom",myann$Regulatory_Feature_Group)
Loading functions
These functions provide shortcuts to help with charts and other analysis. They will eventually be shoved into another Rscript or package but can stay here for now.
source("https://raw.githubusercontent.com/markziemann/ART_methylation/master/meth_functions.R")
myranks<-function(x) {
x$score <- sign(x$logFC)/log10(x$adj.P.Val)
y <- x[,"score",drop=FALSE]
y$rn <- x$Row.names
return(y)
}
heatmap_c<-function(dm,name,mx,n, groups) {
my_palette <- colorRampPalette(c("blue", "white", "red"))(25)
topgenes <- rownames(head(dm[order(dm$P.Value),],n))
ss <- mx[which(rownames(mx) %in% topgenes),]
mycols <- colorRampPalette(c("white","yellow", "orange", "red","darkred"))(n = length(groups))
colCols <- mycols[order(groups)]
heatmap.2(ss,scale="row",margin=c(10, 10),cexRow=0.6,trace="none",cexCol=0.4,
ColSideColors=colCols , col=my_palette, main=name)
}
make_heatmap2_c <- function(confects,name,mx,n, groups) {
topgenes <- head(confects$table$name,n)
my_palette <- colorRampPalette(c("blue", "white", "red"))(25)
ss <- mx[which(rownames(mx) %in% topgenes),]
mycols <- colorRampPalette(c("white","yellow", "orange", "red","darkred"))(n = length(groups))
colCols <- mycols[order(groups)]
heatmap.2(ss,scale="row",margin=c(10, 10),cexRow=0.6,trace="none",cexCol=0.4,
ColSideColors=colCols , col=my_palette, main=name)
}
Data import
load("AccesionnumberGSE74548.Rdata")
Enrichment analysis
We will be using the recently published package mitch to perform enrichment analysis, using average promoter methylation change as an indicator of gene activity. Enrichment will be tested with the mitch package.
dma1a (placebo_vs_supplement_followup(sex,age))
dma2ba (placebo_vs_supplement_Baseline(sex,age))
dma3a (hcy_levels(sex,age))
dma4a (folate_levels(sex,age))
dma5a (vitb12 levels(sex,age))
library("mitch")
download.file("https://reactome.org/download/current/ReactomePathways.gmt.zip",
destfile="ReactomePathways.gmt.zip")
unzip("ReactomePathways.gmt.zip",overwrite = TRUE)
genesets <- gmt_import("ReactomePathways.gmt")
One dimensional enrichment analysis with REACTOME gene sets using average promoter methylation t-statistic.
placebo_vs_supplement_followup_sex_age_mitch <- run_mitch_1d(dma= dma1a, name="placebo_vs_supplement_followup(sex,age)_mitch")
## Note: When prioritising by significance (ie: small
## p-values), large effect sizes might be missed.
head(placebo_vs_supplement_followup_sex_age_mitch,50) %>% kbl() %>% kable_paper("hover", full_width = F)
|
set
|
setSize
|
pANOVA
|
s.dist
|
p.adjustANOVA
|
62
|
Assembly of collagen fibrils and other multimeric structures
|
10
|
0.0003459
|
0.6534943
|
0.3947064
|
582
|
Negative regulation of NMDA receptor-mediated neuronal transmission
|
11
|
0.0009702
|
0.5745218
|
0.4802622
|
1119
|
mRNA 3’-end processing
|
28
|
0.0016493
|
-0.3438167
|
0.4802622
|
686
|
Processing of Capped Intron-Containing Pre-mRNA
|
175
|
0.0017206
|
-0.1380200
|
0.4802622
|
689
|
Processing of Intronless Pre-mRNAs
|
14
|
0.0024286
|
-0.4681452
|
0.4802622
|
831
|
Removal of the Flap Intermediate from the C-strand
|
15
|
0.0027331
|
-0.4469522
|
0.4802622
|
153
|
Condensation of Prometaphase Chromosomes
|
10
|
0.0039265
|
-0.5267674
|
0.4802622
|
61
|
Assembly and cell surface presentation of NMDA receptors
|
12
|
0.0039475
|
0.4806398
|
0.4802622
|
832
|
Reproduction
|
43
|
0.0054452
|
-0.2452345
|
0.4802622
|
84
|
Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
|
14
|
0.0054848
|
-0.4287889
|
0.4802622
|
962
|
Signaling by WNT in cancer
|
23
|
0.0055028
|
0.3345609
|
0.4802622
|
824
|
Regulation of mRNA stability by proteins that bind AU-rich elements
|
73
|
0.0055057
|
-0.1882597
|
0.4802622
|
1091
|
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA
|
14
|
0.0056113
|
-0.4276437
|
0.4802622
|
690
|
Processive synthesis on the C-strand of the telomere
|
17
|
0.0070472
|
-0.3776241
|
0.4802622
|
497
|
Meiosis
|
39
|
0.0072387
|
-0.2487675
|
0.4802622
|
254
|
ER to Golgi Anterograde Transport
|
101
|
0.0078083
|
-0.1536073
|
0.4802622
|
552
|
Myogenesis
|
13
|
0.0084440
|
-0.4219999
|
0.4802622
|
504
|
Metabolism of RNA
|
498
|
0.0085719
|
-0.0697885
|
0.4802622
|
1121
|
mRNA Splicing
|
137
|
0.0091133
|
-0.1295283
|
0.4802622
|
400
|
IKK complex recruitment mediated by RIP1
|
17
|
0.0093644
|
-0.3641542
|
0.4802622
|
114
|
Cell Cycle
|
482
|
0.0095721
|
-0.0698591
|
0.4802622
|
561
|
NOD1/2 Signaling Pathway
|
22
|
0.0100526
|
-0.3171801
|
0.4802622
|
864
|
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
|
23
|
0.0102618
|
-0.3093642
|
0.4802622
|
756
|
RNA Polymerase II Transcription Termination
|
35
|
0.0106228
|
-0.2497632
|
0.4802622
|
97
|
COPII-mediated vesicle transport
|
47
|
0.0112911
|
-0.2138664
|
0.4802622
|
1088
|
Transport to the Golgi and subsequent modification
|
124
|
0.0113651
|
-0.1320677
|
0.4802622
|
498
|
Meiotic recombination
|
19
|
0.0118861
|
-0.3334972
|
0.4802622
|
184
|
DNA Double-Strand Break Repair
|
106
|
0.0121241
|
-0.1414273
|
0.4802622
|
1124
|
mRNA decay by 3’ to 5’ exoribonuclease
|
13
|
0.0122065
|
-0.4015516
|
0.4802622
|
463
|
KSRP (KHSRP) binds and destabilizes mRNA
|
14
|
0.0131439
|
-0.3829093
|
0.4903408
|
981
|
Synaptic adhesion-like molecules
|
10
|
0.0133221
|
0.4520945
|
0.4903408
|
20
|
Aberrant regulation of mitotic cell cycle due to RB1 defects
|
29
|
0.0137798
|
0.2644379
|
0.4913365
|
21
|
Aberrant regulation of mitotic exit in cancer due to RB1 defects
|
15
|
0.0158453
|
0.3598945
|
0.5380612
|
1027
|
Telomere Maintenance
|
53
|
0.0170665
|
-0.1896711
|
0.5380612
|
1003
|
TICAM1, RIP1-mediated IKK complex recruitment
|
17
|
0.0170858
|
-0.3342289
|
0.5380612
|
1122
|
mRNA Splicing - Major Pathway
|
129
|
0.0171699
|
-0.1219346
|
0.5380612
|
633
|
PI3K/AKT Signaling in Cancer
|
50
|
0.0174481
|
-0.1945819
|
0.5380612
|
275
|
Extension of Telomeres
|
41
|
0.0183704
|
-0.2130597
|
0.5515947
|
407
|
Inactivation of APC/C via direct inhibition of the APC/C complex
|
16
|
0.0198398
|
0.3364838
|
0.5654945
|
416
|
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components
|
16
|
0.0198398
|
0.3364838
|
0.5654945
|
530
|
Mitochondrial calcium ion transport
|
13
|
0.0203201
|
0.3718001
|
0.5654945
|
155
|
Constitutive Signaling by AKT1 E17K in Cancer
|
23
|
0.0211349
|
-0.2778793
|
0.5741641
|
396
|
Homology Directed Repair
|
84
|
0.0225500
|
-0.1443025
|
0.5983622
|
1025
|
Telomere C-strand (Lagging Strand) Synthesis
|
27
|
0.0249657
|
-0.2494449
|
0.6040367
|
795
|
Regulation of HSF1-mediated heat shock response
|
62
|
0.0250091
|
-0.1648559
|
0.6040367
|
616
|
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
|
37
|
0.0253776
|
-0.2125932
|
0.6040367
|
910
|
Signaling by Erythropoietin
|
19
|
0.0254756
|
0.2962009
|
0.6040367
|
427
|
Integrin signaling
|
16
|
0.0261639
|
-0.3212346
|
0.6040367
|
662
|
Platelet Aggregation (Plug Formation)
|
16
|
0.0261639
|
-0.3212346
|
0.6040367
|
998
|
TBC/RABGAPs
|
39
|
0.0264696
|
-0.2055769
|
0.6040367
|
placebo_vs_supplement_Baseline_sex_age_mitch <- run_mitch_1d(dma= dma2a, name="placebo_vs_supplement_Baseline_(sex,age)_mitch")
## Note: When prioritising by significance (ie: small
## p-values), large effect sizes might be missed.
head(placebo_vs_supplement_Baseline_sex_age_mitch,50) %>% kbl() %>% kable_paper("hover", full_width = F)
|
set
|
setSize
|
pANOVA
|
s.dist
|
p.adjustANOVA
|
769
|
RORA activates gene expression
|
10
|
0.0011338
|
0.5945025
|
0.4356347
|
336
|
GPVI-mediated activation cascade
|
23
|
0.0011549
|
0.3916311
|
0.4356347
|
73
|
BMAL1:CLOCK,NPAS2 activates circadian gene expression
|
14
|
0.0012542
|
0.4981083
|
0.4356347
|
390
|
Heme signaling
|
25
|
0.0015272
|
0.3663958
|
0.4356347
|
140
|
Circadian Clock
|
50
|
0.0022265
|
0.2503106
|
0.4555077
|
910
|
Signaling by Erythropoietin
|
19
|
0.0046361
|
0.3753460
|
0.4555077
|
710
|
RAF activation
|
27
|
0.0059071
|
0.3062762
|
0.4555077
|
1135
|
rRNA processing in the nucleus and cytosol
|
145
|
0.0073218
|
-0.1295323
|
0.4555077
|
1134
|
rRNA processing
|
149
|
0.0077501
|
-0.1268995
|
0.4555077
|
592
|
Neurotransmitter receptors and postsynaptic signal transmission
|
73
|
0.0080317
|
0.1797770
|
0.4555077
|
114
|
Cell Cycle
|
482
|
0.0081778
|
-0.0713072
|
0.4555077
|
812
|
Regulation of TP53 Activity through Phosphorylation
|
74
|
0.0088900
|
-0.1762455
|
0.4555077
|
1103
|
Vasopressin regulates renal water homeostasis via Aquaporins
|
18
|
0.0093115
|
0.3541772
|
0.4555077
|
504
|
Metabolism of RNA
|
498
|
0.0096577
|
-0.0687051
|
0.4555077
|
98
|
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling
|
15
|
0.0097217
|
0.3857114
|
0.4555077
|
32
|
Activation of NMDA receptors and postsynaptic events
|
43
|
0.0103306
|
0.2262815
|
0.4555077
|
639
|
PKA-mediated phosphorylation of CREB
|
11
|
0.0105203
|
0.4455634
|
0.4555077
|
324
|
G1/S DNA Damage Checkpoints
|
57
|
0.0114586
|
-0.1939051
|
0.4555077
|
381
|
HIV Transcription Initiation
|
37
|
0.0114733
|
-0.2403844
|
0.4555077
|
748
|
RNA Polymerase II HIV Promoter Escape
|
37
|
0.0114733
|
-0.2403844
|
0.4555077
|
750
|
RNA Polymerase II Promoter Escape
|
37
|
0.0114733
|
-0.2403844
|
0.4555077
|
753
|
RNA Polymerase II Transcription Initiation
|
37
|
0.0114733
|
-0.2403844
|
0.4555077
|
754
|
RNA Polymerase II Transcription Initiation And Promoter Clearance
|
37
|
0.0114733
|
-0.2403844
|
0.4555077
|
755
|
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening
|
37
|
0.0114733
|
-0.2403844
|
0.4555077
|
811
|
Regulation of TP53 Activity through Methylation
|
16
|
0.0114831
|
-0.3651172
|
0.4555077
|
483
|
M Phase
|
272
|
0.0117768
|
-0.0894121
|
0.4555077
|
1127
|
p53-Dependent G1 DNA Damage Response
|
55
|
0.0128204
|
-0.1942828
|
0.4555077
|
1128
|
p53-Dependent G1/S DNA damage checkpoint
|
55
|
0.0128204
|
-0.1942828
|
0.4555077
|
57
|
Aquaporin-mediated transport
|
19
|
0.0128780
|
0.3297355
|
0.4555077
|
499
|
Meiotic synapsis
|
22
|
0.0130023
|
-0.3060554
|
0.4555077
|
768
|
RND3 GTPase cycle
|
28
|
0.0134530
|
-0.2700437
|
0.4555077
|
1030
|
The NLRP3 inflammasome
|
12
|
0.0137038
|
-0.4110615
|
0.4555077
|
97
|
COPII-mediated vesicle transport
|
47
|
0.0142987
|
-0.2067872
|
0.4555077
|
329
|
G2/M Transition
|
143
|
0.0145713
|
-0.1188035
|
0.4555077
|
1074
|
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template
|
34
|
0.0148485
|
-0.2416161
|
0.4555077
|
766
|
RND1 GTPase cycle
|
29
|
0.0151270
|
-0.2608284
|
0.4555077
|
79
|
Bile acid and bile salt metabolism
|
14
|
0.0156561
|
0.3731826
|
0.4555077
|
349
|
Glucagon signaling in metabolic regulation
|
16
|
0.0162503
|
0.3471532
|
0.4555077
|
894
|
Signal Transduction
|
1263
|
0.0163476
|
0.0417704
|
0.4555077
|
303
|
Formation of TC-NER Pre-Incision Complex
|
45
|
0.0164619
|
-0.2068992
|
0.4555077
|
497
|
Meiosis
|
39
|
0.0166915
|
-0.2217075
|
0.4555077
|
116
|
Cell Cycle, Mitotic
|
390
|
0.0169410
|
-0.0712338
|
0.4555077
|
495
|
Major pathway of rRNA processing in the nucleolus and cytosol
|
140
|
0.0176070
|
-0.1166571
|
0.4555077
|
1111
|
Vpu mediated degradation of CD4
|
43
|
0.0178434
|
-0.2090183
|
0.4555077
|
723
|
RHO GTPases activate PKNs
|
26
|
0.0180000
|
0.2682031
|
0.4555077
|
951
|
Signaling by ROBO receptors
|
146
|
0.0186913
|
-0.1132043
|
0.4555077
|
992
|
Synthesis of bile acids and bile salts
|
13
|
0.0187632
|
0.3765765
|
0.4555077
|
541
|
Mitotic G2-G2/M phases
|
145
|
0.0203578
|
-0.1120456
|
0.4810867
|
672
|
Post NMDA receptor activation events
|
37
|
0.0206602
|
0.2200592
|
0.4810867
|
638
|
PKA activation
|
10
|
0.0216398
|
0.4195152
|
0.4844200
|
hcy_levels_sex_age_mitch <- run_mitch_1d(dma= dma3a, name="hcy_levels(sex,age)_mitch")
## Note: When prioritising by significance (ie: small
## p-values), large effect sizes might be missed.
head(hcy_levels_sex_age_mitch,50) %>% kbl() %>% kable_paper("hover", full_width = F)
|
set
|
setSize
|
pANOVA
|
s.dist
|
p.adjustANOVA
|
114
|
Cell Cycle
|
482
|
0.0000307
|
0.1123523
|
0.0350588
|
1076
|
Transmission across Chemical Synapses
|
93
|
0.0001346
|
-0.2295945
|
0.0533443
|
591
|
Neuronal System
|
127
|
0.0001622
|
-0.1944369
|
0.0533443
|
593
|
Neurotransmitter release cycle
|
18
|
0.0001870
|
-0.5087470
|
0.0533443
|
116
|
Cell Cycle, Mitotic
|
390
|
0.0002692
|
0.1086585
|
0.0547750
|
504
|
Metabolism of RNA
|
498
|
0.0003756
|
0.0944120
|
0.0547750
|
171
|
Cytokine Signaling in Immune system
|
411
|
0.0004086
|
0.1028010
|
0.0547750
|
411
|
Infectious disease
|
507
|
0.0004106
|
0.0929967
|
0.0547750
|
405
|
Immune System
|
1091
|
0.0004321
|
0.0652212
|
0.0547750
|
483
|
M Phase
|
272
|
0.0011051
|
0.1157945
|
0.1260869
|
855
|
SARS-CoV Infections
|
109
|
0.0012608
|
0.1792976
|
0.1307817
|
427
|
Integrin signaling
|
16
|
0.0016644
|
0.4541637
|
0.1320768
|
662
|
Platelet Aggregation (Plug Formation)
|
16
|
0.0016644
|
0.4541637
|
0.1320768
|
58
|
Arachidonic acid metabolism
|
21
|
0.0016686
|
-0.3964353
|
0.1320768
|
32
|
Activation of NMDA receptors and postsynaptic events
|
43
|
0.0017363
|
-0.2763243
|
0.1320768
|
496
|
Maturation of nucleoprotein
|
10
|
0.0025905
|
0.5502384
|
0.1648188
|
792
|
Regulation of FZD by ubiquitination
|
12
|
0.0026060
|
-0.5020459
|
0.1648188
|
136
|
Chromatin modifying enzymes
|
137
|
0.0027446
|
0.1487530
|
0.1648188
|
137
|
Chromatin organization
|
137
|
0.0027446
|
0.1487530
|
0.1648188
|
329
|
G2/M Transition
|
143
|
0.0030462
|
0.1440907
|
0.1737864
|
369
|
HATs acetylate histones
|
53
|
0.0040229
|
0.2287063
|
0.2185770
|
354
|
Glutamate Neurotransmitter Release Cycle
|
11
|
0.0042456
|
-0.4979804
|
0.2185886
|
541
|
Mitotic G2-G2/M phases
|
145
|
0.0044063
|
0.1375310
|
0.2185886
|
129
|
Cellular responses to stress
|
425
|
0.0051997
|
0.0799945
|
0.2472028
|
756
|
RNA Polymerase II Transcription Termination
|
35
|
0.0057747
|
0.2698393
|
0.2635583
|
128
|
Cellular responses to external stimuli
|
430
|
0.0061600
|
0.0779768
|
0.2703291
|
592
|
Neurotransmitter receptors and postsynaptic signal transmission
|
73
|
0.0073119
|
-0.1819166
|
0.3036982
|
1063
|
Transcriptional regulation of granulopoiesis
|
24
|
0.0074844
|
-0.3155578
|
0.3036982
|
636
|
PIP3 activates AKT signaling
|
172
|
0.0077558
|
0.1182396
|
0.3036982
|
385
|
HSP90 chaperone cycle for steroid hormone receptors (SHR)
|
32
|
0.0081954
|
0.2702679
|
0.3036982
|
543
|
Mitotic Prometaphase
|
146
|
0.0083241
|
0.1270156
|
0.3036982
|
392
|
Heparan sulfate/heparin (HS-GAG) metabolism
|
19
|
0.0087367
|
-0.3476356
|
0.3036982
|
672
|
Post NMDA receptor activation events
|
37
|
0.0087836
|
-0.2491698
|
0.3036982
|
373
|
HDACs deacetylate histones
|
26
|
0.0102370
|
0.2911089
|
0.3280580
|
231
|
Dopamine Neurotransmitter Release Cycle
|
10
|
0.0104297
|
-0.4678365
|
0.3280580
|
1119
|
mRNA 3’-end processing
|
28
|
0.0106448
|
0.2790657
|
0.3280580
|
639
|
PKA-mediated phosphorylation of CREB
|
11
|
0.0107763
|
-0.4441063
|
0.3280580
|
819
|
Regulation of expression of SLITs and ROBOs
|
117
|
0.0114286
|
0.1358073
|
0.3280580
|
638
|
PKA activation
|
10
|
0.0117196
|
-0.4603915
|
0.3280580
|
687
|
Processing of Capped Intronless Pre-mRNA
|
21
|
0.0118759
|
0.3172895
|
0.3280580
|
686
|
Processing of Capped Intron-Containing Pre-mRNA
|
175
|
0.0119129
|
0.1107336
|
0.3280580
|
985
|
Synthesis of Leukotrienes (LT) and Eoxins (EX)
|
10
|
0.0120758
|
-0.4584643
|
0.3280580
|
976
|
Stimuli-sensing channels
|
35
|
0.0131532
|
-0.2424068
|
0.3455051
|
856
|
SARS-CoV-1 Infection
|
41
|
0.0133236
|
0.2236219
|
0.3455051
|
644
|
PTEN Regulation
|
105
|
0.0137762
|
0.1395174
|
0.3493033
|
371
|
HCMV Infection
|
67
|
0.0146450
|
0.1727610
|
0.3632600
|
927
|
Signaling by Interleukins
|
256
|
0.0170422
|
0.0872273
|
0.3923026
|
214
|
Disease
|
900
|
0.0172435
|
0.0480752
|
0.3923026
|
447
|
Interleukin-4 and Interleukin-13 signaling
|
47
|
0.0172547
|
0.2010121
|
0.3923026
|
222
|
Diseases of carbohydrate metabolism
|
22
|
0.0175578
|
-0.2926410
|
0.3923026
|
folate_levels_sex_age_mitch <- run_mitch_1d(dma= dma4a, name="folate_levels(sex,age)_mitch")
## Note: When prioritising by significance (ie: small
## p-values), large effect sizes might be missed.
head(folate_levels_sex_age_mitch,50) %>% kbl() %>% kable_paper("hover", full_width = F)
|
set
|
setSize
|
pANOVA
|
s.dist
|
p.adjustANOVA
|
504
|
Metabolism of RNA
|
498
|
0.0000014
|
0.1282046
|
0.0015500
|
542
|
Mitotic Metaphase and Anaphase
|
186
|
0.0000803
|
0.1684906
|
0.0361717
|
539
|
Mitotic Anaphase
|
185
|
0.0001080
|
0.1658729
|
0.0361717
|
1066
|
Translation
|
225
|
0.0001268
|
0.1491903
|
0.0361717
|
564
|
NOTCH3 Activation and Transmission of Signal to the Nucleus
|
15
|
0.0002541
|
0.5456194
|
0.0438017
|
641
|
PLC beta mediated events
|
29
|
0.0002961
|
-0.3884567
|
0.0438017
|
882
|
Selenocysteine synthesis
|
65
|
0.0003846
|
0.2550419
|
0.0438017
|
174
|
DAG and IP3 signaling
|
26
|
0.0003847
|
-0.4024492
|
0.0438017
|
819
|
Regulation of expression of SLITs and ROBOs
|
117
|
0.0004269
|
0.1891245
|
0.0438017
|
922
|
Signaling by GPCR
|
195
|
0.0005234
|
-0.1448175
|
0.0438017
|
649
|
Peptide chain elongation
|
64
|
0.0006067
|
0.2482024
|
0.0438017
|
1134
|
rRNA processing
|
149
|
0.0006227
|
0.1630403
|
0.0438017
|
426
|
Integrin cell surface interactions
|
23
|
0.0006487
|
-0.4109725
|
0.0438017
|
467
|
L13a-mediated translational silencing of Ceruloplasmin expression
|
82
|
0.0006873
|
0.2172992
|
0.0438017
|
535
|
Mitochondrial translation elongation
|
81
|
0.0007401
|
0.2173183
|
0.0438017
|
601
|
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
|
69
|
0.0007444
|
0.2352026
|
0.0438017
|
1135
|
rRNA processing in the nucleus and cytosol
|
145
|
0.0007746
|
0.1623527
|
0.0438017
|
337
|
GTP hydrolysis and joining of the 60S ribosomal subunit
|
83
|
0.0007900
|
0.2135606
|
0.0438017
|
951
|
Signaling by ROBO receptors
|
146
|
0.0009514
|
0.1590537
|
0.0438017
|
865
|
SRP-dependent cotranslational protein targeting to membrane
|
81
|
0.0009549
|
0.2127624
|
0.0438017
|
334
|
GPCR downstream signalling
|
178
|
0.0009574
|
-0.1442089
|
0.0438017
|
892
|
Separation of Sister Chromatids
|
141
|
0.0009657
|
0.1616027
|
0.0438017
|
23
|
Activated NOTCH1 Transmits Signal to the Nucleus
|
19
|
0.0009712
|
0.4372856
|
0.0438017
|
495
|
Major pathway of rRNA processing in the nucleolus and cytosol
|
140
|
0.0009727
|
0.1620707
|
0.0438017
|
563
|
NOTCH2 Activation and Transmission of Signal to the Nucleus
|
12
|
0.0010013
|
0.5486118
|
0.0438017
|
881
|
Selenoamino acid metabolism
|
73
|
0.0011005
|
0.2213148
|
0.0438017
|
185
|
DNA Repair
|
232
|
0.0011390
|
0.1247902
|
0.0438017
|
534
|
Mitochondrial translation
|
86
|
0.0011442
|
0.2033475
|
0.0438017
|
1070
|
Translesion Synthesis by POLH
|
16
|
0.0011840
|
0.4683599
|
0.0438017
|
420
|
Inositol phosphate metabolism
|
29
|
0.0011871
|
-0.3480376
|
0.0438017
|
271
|
Eukaryotic Translation Elongation
|
67
|
0.0011901
|
0.2293684
|
0.0438017
|
537
|
Mitochondrial translation termination
|
80
|
0.0012921
|
0.2085223
|
0.0438223
|
894
|
Signal Transduction
|
1263
|
0.0012983
|
-0.0559473
|
0.0438223
|
600
|
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
|
81
|
0.0013489
|
0.2064458
|
0.0438223
|
602
|
Nonsense-Mediated Decay (NMD)
|
81
|
0.0013489
|
0.2064458
|
0.0438223
|
633
|
PI3K/AKT Signaling in Cancer
|
50
|
0.0013963
|
-0.2615338
|
0.0438223
|
273
|
Eukaryotic Translation Termination
|
66
|
0.0014296
|
0.2273361
|
0.0438223
|
102
|
CaM pathway
|
20
|
0.0015756
|
-0.4083663
|
0.0438223
|
103
|
Calmodulin induced events
|
20
|
0.0015756
|
-0.4083663
|
0.0438223
|
277
|
Extracellular matrix organization
|
75
|
0.0016116
|
-0.2110299
|
0.0438223
|
9
|
APC/C-mediated degradation of cell cycle proteins
|
73
|
0.0016229
|
0.2137411
|
0.0438223
|
825
|
Regulation of mitotic cell cycle
|
73
|
0.0016229
|
0.2137411
|
0.0438223
|
536
|
Mitochondrial translation initiation
|
81
|
0.0017065
|
0.2020489
|
0.0438223
|
516
|
Metabolism of proteins
|
1217
|
0.0017562
|
0.0552935
|
0.0438223
|
47
|
Anti-inflammatory response favouring Leishmania parasite infection
|
51
|
0.0017892
|
-0.2531165
|
0.0438223
|
475
|
Leishmania parasite growth and survival
|
51
|
0.0017892
|
-0.2531165
|
0.0438223
|
547
|
Muscle contraction
|
64
|
0.0018661
|
-0.2252040
|
0.0438223
|
100
|
Ca-dependent events
|
21
|
0.0018735
|
-0.3921415
|
0.0438223
|
8
|
APC-Cdc20 mediated degradation of Nek2A
|
21
|
0.0018901
|
0.3918127
|
0.0438223
|
304
|
Formation of a pool of free 40S subunits
|
73
|
0.0019203
|
0.2103878
|
0.0438223
|
vitb12_levels_sex_age_mitch <- run_mitch_1d(dma= dma5a, name="vitb12 levels(sex,age)_mitch")
## Note: When prioritising by significance (ie: small
## p-values), large effect sizes might be missed.
head(vitb12_levels_sex_age_mitch,50) %>% kbl() %>% kable_paper("hover", full_width = F)
|
set
|
setSize
|
pANOVA
|
s.dist
|
p.adjustANOVA
|
1134
|
rRNA processing
|
149
|
0.0000233
|
0.2015577
|
0.0266050
|
1135
|
rRNA processing in the nucleus and cytosol
|
145
|
0.0000546
|
0.1948467
|
0.0311454
|
495
|
Major pathway of rRNA processing in the nucleolus and cytosol
|
140
|
0.0001389
|
0.1872003
|
0.0528380
|
504
|
Metabolism of RNA
|
498
|
0.0002441
|
0.0973755
|
0.0696268
|
194
|
Defective CFTR causes cystic fibrosis
|
51
|
0.0012008
|
0.2624751
|
0.2187878
|
774
|
RUNX1 regulates transcription of genes involved in differentiation of HSCs
|
55
|
0.0012204
|
0.2524409
|
0.2187878
|
1066
|
Translation
|
225
|
0.0014064
|
0.1243209
|
0.2187878
|
171
|
Cytokine Signaling in Immune system
|
411
|
0.0015340
|
-0.0921528
|
0.2187878
|
811
|
Regulation of TP53 Activity through Methylation
|
16
|
0.0022985
|
0.4403481
|
0.2335804
|
522
|
Metalloprotease DUBs
|
16
|
0.0024063
|
0.4383563
|
0.2335804
|
193
|
Dectin-1 mediated noncanonical NF-kB signaling
|
50
|
0.0024961
|
0.2474957
|
0.2335804
|
951
|
Signaling by ROBO receptors
|
146
|
0.0027676
|
0.1440392
|
0.2335804
|
560
|
NIK–>noncanonical NF-kB signaling
|
49
|
0.0028198
|
0.2469305
|
0.2335804
|
189
|
Deactivation of the beta-catenin transactivating complex
|
27
|
0.0032455
|
0.3274703
|
0.2335804
|
204
|
Degradation of the extracellular matrix
|
26
|
0.0033008
|
-0.3330989
|
0.2335804
|
337
|
GTP hydrolysis and joining of the 60S ribosomal subunit
|
83
|
0.0035154
|
0.1857288
|
0.2335804
|
819
|
Regulation of expression of SLITs and ROBOs
|
117
|
0.0035735
|
0.1564299
|
0.2335804
|
881
|
Selenoamino acid metabolism
|
73
|
0.0042566
|
0.1938616
|
0.2335804
|
91
|
CDT1 association with the CDC6:ORC:origin complex
|
44
|
0.0043894
|
0.2484848
|
0.2335804
|
63
|
Assembly of the pre-replicative complex
|
53
|
0.0045714
|
0.2254809
|
0.2335804
|
882
|
Selenocysteine synthesis
|
65
|
0.0046133
|
0.2035213
|
0.2335804
|
394
|
Hh mutants are degraded by ERAD
|
46
|
0.0046841
|
0.2412793
|
0.2335804
|
641
|
PLC beta mediated events
|
29
|
0.0048176
|
-0.3026493
|
0.2335804
|
595
|
Nicotinamide salvaging
|
10
|
0.0049132
|
-0.5137438
|
0.2335804
|
304
|
Formation of a pool of free 40S subunits
|
73
|
0.0055667
|
0.1880164
|
0.2377549
|
131
|
Chaperone Mediated Autophagy
|
12
|
0.0058416
|
0.4596733
|
0.2377549
|
405
|
Immune System
|
1091
|
0.0059458
|
-0.0509788
|
0.2377549
|
649
|
Peptide chain elongation
|
64
|
0.0061192
|
0.1984702
|
0.2377549
|
1058
|
Transcriptional regulation by RUNX1
|
122
|
0.0065743
|
0.1429326
|
0.2377549
|
1070
|
Translesion Synthesis by POLH
|
16
|
0.0067669
|
0.3911753
|
0.2377549
|
467
|
L13a-mediated translational silencing of Ceruloplasmin expression
|
82
|
0.0069576
|
0.1727827
|
0.2377549
|
1093
|
UCH proteinases
|
69
|
0.0073759
|
0.1868737
|
0.2377549
|
976
|
Stimuli-sensing channels
|
35
|
0.0074324
|
0.2616810
|
0.2377549
|
472
|
Late endosomal microautophagy
|
21
|
0.0077462
|
0.3358381
|
0.2377549
|
187
|
DNA Replication Pre-Initiation
|
66
|
0.0077959
|
0.1897193
|
0.2377549
|
271
|
Eukaryotic Translation Elongation
|
67
|
0.0079325
|
0.1878934
|
0.2377549
|
199
|
Degradation of AXIN
|
46
|
0.0082584
|
0.2253584
|
0.2377549
|
1095
|
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A
|
43
|
0.0083350
|
0.2327759
|
0.2377549
|
1129
|
p53-Independent DNA Damage Response
|
43
|
0.0083350
|
0.2327759
|
0.2377549
|
1130
|
p53-Independent G1/S DNA damage checkpoint
|
43
|
0.0083350
|
0.2327759
|
0.2377549
|
1033
|
The role of GTSE1 in G2/M progression after G2 checkpoint
|
51
|
0.0087507
|
0.2124869
|
0.2435265
|
894
|
Signal Transduction
|
1263
|
0.0092629
|
-0.0452683
|
0.2476525
|
690
|
Processive synthesis on the C-strand of the telomere
|
17
|
0.0094250
|
-0.3638437
|
0.2476525
|
859
|
SCF-beta-TrCP mediated degradation of Emi1
|
46
|
0.0095501
|
0.2211270
|
0.2476525
|
203
|
Degradation of beta-catenin by the destruction complex
|
67
|
0.0100529
|
0.1821681
|
0.2548977
|
564
|
NOTCH3 Activation and Transmission of Signal to the Nucleus
|
15
|
0.0103480
|
0.3824910
|
0.2551152
|
927
|
Signaling by Interleukins
|
256
|
0.0107838
|
-0.0932152
|
0.2551152
|
539
|
Mitotic Anaphase
|
185
|
0.0112013
|
0.1086819
|
0.2551152
|
47
|
Anti-inflammatory response favouring Leishmania parasite infection
|
51
|
0.0113647
|
-0.2051654
|
0.2551152
|
475
|
Leishmania parasite growth and survival
|
51
|
0.0113647
|
-0.2051654
|
0.2551152
|
Run multi-dimensional enrichment analysis
xl <- list("psf"=dma1a,"psb"=dma2a,"hcy"=dma3a,"folate"=dma4a,"vitb12"= dma5a)
xxl <- lapply(X = xl,run_mitch_rank)
xxxl <- lapply(xxl,function(xxl) { xxl$genenames <- rownames(xxl) ; xxl} )
xxll <- join_all(xxxl,by="genenames")
rownames(xxll) <- xxll$genenames
xxll$genenames=NULL
colnames(xxll) <- names(xl)
head(xxll) %>% kbl() %>% kable_paper("hover", full_width = F)
|
psf
|
psb
|
hcy
|
folate
|
vitb12
|
A1BG
|
-0.5657309
|
-1.4174791
|
-0.7558603
|
0.0645071
|
0.0892108
|
AAAS
|
-0.6107363
|
-0.8349572
|
0.2709769
|
0.2348791
|
0.3931456
|
AACS
|
-0.3554806
|
-0.6653036
|
-0.0617422
|
0.4633213
|
0.7147652
|
AAGAB
|
-1.2687914
|
-1.5150322
|
1.3762765
|
-0.8286218
|
0.1746070
|
AAK1
|
-0.4346004
|
-1.0208703
|
-0.2475015
|
1.5236908
|
0.8921750
|
AAMP
|
-1.5657801
|
-0.8688060
|
1.7589146
|
-0.6785549
|
-0.0254100
|
capture.output(
res <- mitch_calc(xxll,genesets = genesets,priority = "significance"),
file = "/dev/null", append = FALSE,
type = c("output", "message"), split = FALSE)
## Note: When prioritising by significance (ie: small
## p-values), large effect sizes might be missed.
head(res$enrichment_result,50) %>% kbl() %>% kable_paper("hover", full_width = F)
|
set
|
setSize
|
pMANOVA
|
s.psf
|
s.psb
|
s.hcy
|
s.folate
|
s.vitb12
|
p.psf
|
p.psb
|
p.hcy
|
p.folate
|
p.vitb12
|
s.dist
|
SD
|
p.adjustMANOVA
|
504
|
Metabolism of RNA
|
498
|
0.0000000
|
-0.0697885
|
-0.0687051
|
0.0944120
|
0.1282046
|
0.0973755
|
0.0085719
|
0.0096577
|
0.0003756
|
0.0000014
|
0.0002441
|
0.2107673
|
0.0972555
|
0.0000000
|
114
|
Cell Cycle
|
482
|
0.0000014
|
-0.0698591
|
-0.0713072
|
0.1123523
|
0.0557405
|
0.0101540
|
0.0095721
|
0.0081778
|
0.0000307
|
0.0387190
|
0.7065268
|
0.1606181
|
0.0798799
|
0.0007757
|
116
|
Cell Cycle, Mitotic
|
390
|
0.0000020
|
-0.0490737
|
-0.0712338
|
0.1086585
|
0.0877162
|
0.0373771
|
0.0999738
|
0.0169410
|
0.0002692
|
0.0032742
|
0.2102537
|
0.1684646
|
0.0803219
|
0.0007757
|
819
|
Regulation of expression of SLITs and ROBOs
|
117
|
0.0000029
|
0.0316131
|
-0.1219789
|
0.1358073
|
0.1891245
|
0.1564299
|
0.5560760
|
0.0231048
|
0.0114286
|
0.0004269
|
0.0035735
|
0.3075065
|
0.1264760
|
0.0008228
|
1134
|
rRNA processing
|
149
|
0.0000043
|
0.0123926
|
-0.1268995
|
0.0626039
|
0.1630403
|
0.2015577
|
0.7948701
|
0.0077501
|
0.1890291
|
0.0006227
|
0.0000233
|
0.2956078
|
0.1302194
|
0.0008753
|
483
|
M Phase
|
272
|
0.0000051
|
-0.0600325
|
-0.0894121
|
0.1157945
|
0.1074240
|
0.0437637
|
0.0908399
|
0.0117768
|
0.0011051
|
0.0024750
|
0.2176937
|
0.1961173
|
0.0944708
|
0.0008753
|
1135
|
rRNA processing in the nucleus and cytosol
|
145
|
0.0000054
|
0.0219109
|
-0.1295323
|
0.0696364
|
0.1623527
|
0.1948467
|
0.6501424
|
0.0073218
|
0.1494244
|
0.0007746
|
0.0000546
|
0.2939925
|
0.1285029
|
0.0008753
|
686
|
Processing of Capped Intron-Containing Pre-mRNA
|
175
|
0.0000072
|
-0.1380200
|
-0.0158566
|
0.1107336
|
0.1234802
|
0.0463992
|
0.0017206
|
0.7188163
|
0.0119129
|
0.0050427
|
0.2920806
|
0.2212761
|
0.1069471
|
0.0010266
|
1066
|
Translation
|
225
|
0.0000083
|
-0.0171916
|
-0.0613936
|
0.0858546
|
0.1491903
|
0.1243209
|
0.6588687
|
0.1148726
|
0.0274549
|
0.0001268
|
0.0014064
|
0.2216962
|
0.0913532
|
0.0010522
|
32
|
Activation of NMDA receptors and postsynaptic events
|
43
|
0.0000107
|
0.1916652
|
0.2262815
|
-0.2763243
|
-0.2296518
|
-0.1577732
|
0.0298455
|
0.0103306
|
0.0017363
|
0.0092474
|
0.0737810
|
0.4918600
|
0.2397095
|
0.0012218
|
542
|
Mitotic Metaphase and Anaphase
|
186
|
0.0000185
|
-0.0286868
|
-0.0546685
|
0.0949508
|
0.1684906
|
0.1069017
|
0.5021271
|
0.2008816
|
0.0263043
|
0.0000803
|
0.0123702
|
0.2294434
|
0.0950945
|
0.0019208
|
495
|
Major pathway of rRNA processing in the nucleolus and cytosol
|
140
|
0.0000221
|
0.0188465
|
-0.1166571
|
0.0718544
|
0.1620707
|
0.1872003
|
0.7013929
|
0.0176070
|
0.1437443
|
0.0009727
|
0.0001389
|
0.2836159
|
0.1219954
|
0.0020450
|
539
|
Mitotic Anaphase
|
185
|
0.0000233
|
-0.0294864
|
-0.0535774
|
0.0951617
|
0.1658729
|
0.1086819
|
0.4914325
|
0.2112250
|
0.0263682
|
0.0001080
|
0.0112013
|
0.2283009
|
0.0944555
|
0.0020450
|
591
|
Neuronal System
|
127
|
0.0000254
|
0.0918258
|
0.1029264
|
-0.1944369
|
-0.1131847
|
-0.0491564
|
0.0749589
|
0.0459315
|
0.0001622
|
0.0281631
|
0.3404874
|
0.2684375
|
0.1292364
|
0.0020684
|
1076
|
Transmission across Chemical Synapses
|
93
|
0.0000475
|
0.0764105
|
0.1252860
|
-0.2295945
|
-0.1158070
|
-0.0533191
|
0.2040239
|
0.0372722
|
0.0001346
|
0.0542095
|
0.3754541
|
0.3008371
|
0.1438222
|
0.0036098
|
882
|
Selenocysteine synthesis
|
65
|
0.0000722
|
0.1117126
|
-0.1438314
|
0.0982550
|
0.2550419
|
0.2035213
|
0.1200093
|
0.0453040
|
0.1714929
|
0.0003846
|
0.0046133
|
0.3863787
|
0.1534818
|
0.0049671
|
649
|
Peptide chain elongation
|
64
|
0.0000776
|
0.1142242
|
-0.1075982
|
0.1252295
|
0.2482024
|
0.1984702
|
0.1146812
|
0.1372853
|
0.0837184
|
0.0006067
|
0.0061192
|
0.3759014
|
0.1363478
|
0.0049671
|
951
|
Signaling by ROBO receptors
|
146
|
0.0000784
|
0.0126730
|
-0.1132043
|
0.0852251
|
0.1590537
|
0.1440392
|
0.7923784
|
0.0186913
|
0.0766766
|
0.0009514
|
0.0027676
|
0.2574578
|
0.1114902
|
0.0049671
|
592
|
Neurotransmitter receptors and postsynaptic signal transmission
|
73
|
0.0000870
|
0.0835091
|
0.1797770
|
-0.1819166
|
-0.1807279
|
-0.1231870
|
0.2182729
|
0.0080317
|
0.0073119
|
0.0077043
|
0.0693446
|
0.3467345
|
0.1660719
|
0.0050750
|
600
|
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
|
81
|
0.0000957
|
0.0980566
|
-0.0574147
|
0.1481809
|
0.2064458
|
0.1299576
|
0.1279686
|
0.3728050
|
0.0214238
|
0.0013489
|
0.0436475
|
0.3072100
|
0.0990018
|
0.0050750
|
602
|
Nonsense-Mediated Decay (NMD)
|
81
|
0.0000957
|
0.0980566
|
-0.0574147
|
0.1481809
|
0.2064458
|
0.1299576
|
0.1279686
|
0.3728050
|
0.0214238
|
0.0013489
|
0.0436475
|
0.3072100
|
0.0990018
|
0.0050750
|
329
|
G2/M Transition
|
143
|
0.0001096
|
-0.0525791
|
-0.1188035
|
0.1440907
|
0.1139516
|
0.0882287
|
0.2796919
|
0.0145713
|
0.0030462
|
0.0191258
|
0.0696695
|
0.2416821
|
0.1143384
|
0.0050750
|
271
|
Eukaryotic Translation Elongation
|
67
|
0.0001102
|
0.1183645
|
-0.0909257
|
0.1282772
|
0.2293684
|
0.1878934
|
0.0944637
|
0.1989314
|
0.0699274
|
0.0011901
|
0.0079325
|
0.3558742
|
0.1234765
|
0.0050750
|
601
|
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
|
69
|
0.0001129
|
0.1156610
|
-0.0747442
|
0.1337445
|
0.2352026
|
0.1642828
|
0.0972871
|
0.2839399
|
0.0551815
|
0.0007444
|
0.0185041
|
0.3451968
|
0.1153602
|
0.0050750
|
1121
|
mRNA Splicing
|
137
|
0.0001133
|
-0.1295283
|
-0.0045752
|
0.1098446
|
0.1325899
|
0.0406440
|
0.0091133
|
0.9266223
|
0.0270098
|
0.0075979
|
0.4132702
|
0.2193088
|
0.1044721
|
0.0050750
|
881
|
Selenoamino acid metabolism
|
73
|
0.0001201
|
0.1113734
|
-0.1332414
|
0.0921539
|
0.2213148
|
0.1938616
|
0.1005956
|
0.0494802
|
0.1742760
|
0.0011005
|
0.0042566
|
0.3538534
|
0.1397118
|
0.0050750
|
337
|
GTP hydrolysis and joining of the 60S ribosomal subunit
|
83
|
0.0001201
|
0.0861890
|
-0.1002613
|
0.1044792
|
0.2135606
|
0.1857288
|
0.1756726
|
0.1151806
|
0.1006706
|
0.0007900
|
0.0035154
|
0.3293935
|
0.1230240
|
0.0050750
|
541
|
Mitotic G2-G2/M phases
|
145
|
0.0001412
|
-0.0505255
|
-0.1120456
|
0.1375310
|
0.1147165
|
0.0970070
|
0.2955979
|
0.0203578
|
0.0044063
|
0.0175490
|
0.0446141
|
0.2378909
|
0.1113799
|
0.0055117
|
467
|
L13a-mediated translational silencing of Ceruloplasmin expression
|
82
|
0.0001432
|
0.0855665
|
-0.0929431
|
0.1111155
|
0.2172992
|
0.1727827
|
0.1814311
|
0.1466183
|
0.0826635
|
0.0006873
|
0.0069576
|
0.3246221
|
0.1189619
|
0.0055117
|
1107
|
Viral mRNA Translation
|
65
|
0.0001449
|
0.1103411
|
-0.1081976
|
0.1425101
|
0.2192386
|
0.1654113
|
0.1246255
|
0.1321162
|
0.0473197
|
0.0022752
|
0.0213216
|
0.3458576
|
0.1260804
|
0.0055117
|
672
|
Post NMDA receptor activation events
|
37
|
0.0001830
|
0.1546247
|
0.2200592
|
-0.2491698
|
-0.2340015
|
-0.1864568
|
0.1039669
|
0.0206602
|
0.0087836
|
0.0138628
|
0.0499139
|
0.4732265
|
0.2272360
|
0.0067346
|
1122
|
mRNA Splicing - Major Pathway
|
129
|
0.0001899
|
-0.1219346
|
-0.0130350
|
0.1209207
|
0.1369307
|
0.0405473
|
0.0171699
|
0.7989424
|
0.0181166
|
0.0074456
|
0.4281623
|
0.2237273
|
0.1057262
|
0.0067694
|
865
|
SRP-dependent cotranslational protein targeting to membrane
|
81
|
0.0001985
|
0.0317143
|
-0.1410293
|
0.1220391
|
0.2127624
|
0.1384361
|
0.6225179
|
0.0285694
|
0.0581573
|
0.0009549
|
0.0316257
|
0.3165770
|
0.1357692
|
0.0068629
|
304
|
Formation of a pool of free 40S subunits
|
73
|
0.0002125
|
0.0769394
|
-0.1186926
|
0.1178843
|
0.2103878
|
0.1880164
|
0.2566796
|
0.0801364
|
0.0822149
|
0.0019203
|
0.0055667
|
0.3369236
|
0.1308441
|
0.0071312
|
639
|
PKA-mediated phosphorylation of CREB
|
11
|
0.0003012
|
0.0031539
|
0.4455634
|
-0.4441063
|
-0.4237629
|
-0.2177834
|
0.9855549
|
0.0105203
|
0.0107763
|
0.0149730
|
0.2112030
|
0.7891588
|
0.3679791
|
0.0098176
|
105
|
Cap-dependent Translation Initiation
|
90
|
0.0003689
|
0.0643874
|
-0.0735431
|
0.1325721
|
0.1773119
|
0.1414869
|
0.2923162
|
0.2290518
|
0.0301276
|
0.0037261
|
0.0206533
|
0.2803350
|
0.0993439
|
0.0113771
|
272
|
Eukaryotic Translation Initiation
|
90
|
0.0003689
|
0.0643874
|
-0.0735431
|
0.1325721
|
0.1773119
|
0.1414869
|
0.2923162
|
0.2290518
|
0.0301276
|
0.0037261
|
0.0206533
|
0.2803350
|
0.0993439
|
0.0113771
|
273
|
Eukaryotic Translation Termination
|
66
|
0.0004031
|
0.0977808
|
-0.0869678
|
0.1244672
|
0.2273361
|
0.1747084
|
0.1703184
|
0.2226400
|
0.0809056
|
0.0014296
|
0.0142779
|
0.3388529
|
0.1194547
|
0.0121040
|
842
|
Response of EIF2AK4 (GCN2) to amino acid deficiency
|
72
|
0.0004943
|
0.1034869
|
-0.1205556
|
0.1128237
|
0.1945692
|
0.1511999
|
0.1297019
|
0.0775236
|
0.0985330
|
0.0043809
|
0.0268254
|
0.3141512
|
0.1221702
|
0.0144602
|
811
|
Regulation of TP53 Activity through Methylation
|
16
|
0.0005365
|
-0.2614305
|
-0.3651172
|
-0.0382878
|
0.3997767
|
0.4403481
|
0.0703430
|
0.0114831
|
0.7909959
|
0.0056458
|
0.0022985
|
0.7462241
|
0.3710475
|
0.0153047
|
129
|
Cellular responses to stress
|
425
|
0.0005735
|
0.0110043
|
0.0042310
|
0.0799945
|
0.0781623
|
0.0398834
|
0.7007328
|
0.8825244
|
0.0051997
|
0.0063264
|
0.1636160
|
0.1193237
|
0.0358499
|
0.0158342
|
516
|
Metabolism of proteins
|
1217
|
0.0005829
|
-0.0185399
|
-0.0151510
|
0.0377194
|
0.0552935
|
0.0352059
|
0.2942698
|
0.3914006
|
0.0328455
|
0.0017562
|
0.0464001
|
0.0793276
|
0.0335625
|
0.0158342
|
641
|
PLC beta mediated events
|
29
|
0.0006067
|
-0.0895010
|
0.0573311
|
-0.1511775
|
-0.3884567
|
-0.3026493
|
0.4045677
|
0.5934116
|
0.1591582
|
0.0002961
|
0.0048176
|
0.5259725
|
0.1758646
|
0.0160984
|
892
|
Separation of Sister Chromatids
|
141
|
0.0006322
|
-0.0593520
|
-0.0727709
|
0.0795204
|
0.1616027
|
0.1047995
|
0.2255775
|
0.1373213
|
0.1044461
|
0.0009657
|
0.0323603
|
0.2285609
|
0.1038003
|
0.0163952
|
582
|
Negative regulation of NMDA receptor-mediated neuronal transmission
|
11
|
0.0007500
|
0.5745218
|
0.1932348
|
-0.4029953
|
-0.1861340
|
-0.2347148
|
0.0009702
|
0.2672900
|
0.0206808
|
0.2852689
|
0.1778278
|
0.7871195
|
0.3933599
|
0.0190173
|
100
|
Ca-dependent events
|
21
|
0.0009395
|
0.0022533
|
0.2836061
|
-0.1912015
|
-0.3921415
|
-0.2983734
|
0.9857476
|
0.0245341
|
0.1295458
|
0.0018735
|
0.0179921
|
0.5998309
|
0.2686950
|
0.0233031
|
638
|
PKA activation
|
10
|
0.0010733
|
0.0035906
|
0.4195152
|
-0.4603915
|
-0.3905873
|
-0.2346688
|
0.9843192
|
0.0216398
|
0.0117196
|
0.0324983
|
0.1989413
|
0.7717474
|
0.3563011
|
0.0258752
|
392
|
Heparan sulfate/heparin (HS-GAG) metabolism
|
19
|
0.0010885
|
0.0622388
|
-0.1690195
|
-0.3476356
|
-0.3031258
|
-0.1695859
|
0.6387955
|
0.2024044
|
0.0087367
|
0.0222333
|
0.2008959
|
0.5233894
|
0.1597053
|
0.0258752
|
922
|
Signaling by GPCR
|
195
|
0.0011797
|
0.0171414
|
0.0709382
|
-0.0533887
|
-0.1448175
|
-0.0975409
|
0.6814921
|
0.0893869
|
0.2011190
|
0.0005234
|
0.0195016
|
0.1966284
|
0.0866568
|
0.0274705
|
194
|
Defective CFTR causes cystic fibrosis
|
51
|
0.0012240
|
-0.0864399
|
-0.1616559
|
0.0427227
|
0.2374151
|
0.2624751
|
0.2862738
|
0.0461141
|
0.5981799
|
0.0033969
|
0.0012008
|
0.4008601
|
0.1893018
|
0.0278252
|
unlink("multi_mitch.pdf")
capture.output(
mitch_plots(res,outfile="multi_mitch.pdf")
, file = "/dev/null", append = FALSE,
type = c("output", "message"), split = FALSE)
## ```
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```
length(which(res$enrichment_result$p.adjustMANOVA<0.05))
## [1] 67
hm<-as.matrix(res$enrichment_result[1:40,4:8])
rownames(hm)<-res$enrichment_result[1:40,1]
heatmap.2(hm,trace ="none",scale = "none",dendrogram = "none",margins = c(7,25),cexCol = 0.7)