Novakovic: Gene Methylation Enrichment Analysis

Introduction

Previously, Mandhri and I analysed the B-PROOF 450K data, trying to understand whether vitamin supplementation caused changes in gene methylation. We used Limma and some basic analyses, which showed no specific probes with FDR<0.05, nor any DMRs.

In this analysis we will use the principle of Gene Set Enrichment Analysis, applying it to many probes belonging to genes. If the probes are trending in concert, then we can make some judgement about the enrichment of those probes. The statistical test used is the Wilcox test, which can be applied to competitive or self contained test types.

library("parallel")
library("dplyr")

## 
## Attaching package: 'dplyr'

## The following objects are masked from 'package:stats':
## 
##     filter, lag

## The following objects are masked from 'package:base':
## 
##     intersect, setdiff, setequal, union

library("kableExtra")

## 
## Attaching package: 'kableExtra'

## The following object is masked from 'package:dplyr':
## 
##     group_rows

library("eulerr")
library("mitch")

## Registered S3 method overwritten by 'GGally':
##   method from   
##   +.gg   ggplot2

## Registered S3 method overwritten by 'gplots':
##   method    from  
##   plot.venn eulerr

library("tictoc")
source("meth_functions.R")

## Warning: replacing previous import 'matrixStats::rowMedians' by
## 'Biobase::rowMedians' when loading 'DSS'

## Warning: replacing previous import 'matrixStats::anyMissing' by
## 'Biobase::anyMissing' when loading 'DSS'

CORES= detectCores()/2

Get array annotation data

anno <- getAnnotation(IlluminaHumanMethylationEPICanno.ilm10b4.hg19)
myann <- data.frame(anno[,c("UCSC_RefGene_Name","Regulatory_Feature_Group","Islands_Name","Relation_to_Island")])
promoters <- grep("Prom",myann$Regulatory_Feature_Group)

Load Novakovic data

nat_vs_fh <- readRDS("novakovic_nat_vs_fh.rds")
fh_vs_fz <- readRDS("novakovic_fh_vs_fz.rds")
GIFT_vs_FX <- readRDS("novakovic_GIFT_vs_FX.rds")
nat_vs_ART <- readRDS("novakovic_nat_vs_ART.rds")
nat_vs_FX <- readRDS("novakovic_nat_vs_FX.rds")
nat_vs_fz <- readRDS("novakovic_nat_vs_fz.rds")
nat_vs_GIFT <- readRDS("novakovic_nat_vs_GIFT.rds")

if ( ! file.exists("ReactomePathways.gmt") ) {
  download.file("https://reactome.org/download/current/ReactomePathways.gmt.zip",
    destfile="ReactomePathways.gmt.zip")
  unzip("ReactomePathways.gmt.zip")
}
file.info("ReactomePathways.gmt")

##                        size isdir mode               mtime               ctime
## ReactomePathways.gmt 897680 FALSE  664 2022-06-08 15:37:39 2022-06-08 15:37:39
##                                    atime  uid  gid uname grname
## ReactomePathways.gmt 2022-10-13 12:46:42 1001 1001   mdz    mdz

genesets <- gmt_import("ReactomePathways.gmt")
length(genesets)

## [1] 2546

Nat vs fh

dm <- nat_vs_fh$dma
head(dm,50) %>% kbl(caption = "Top significant genes with limma") %>% kable_paper("hover", full_width = F)

Top significant genes with limma

	Row.names	UCSC_RefGene_Name	Regulatory_Feature_Group	Islands_Name	Relation_to_Island	logFC	AveExpr	t	P.Value	adj.P.Val	B	unmeth	meth
743573	cg25867694	SELM	Promoter_Associated	chr22:31503236-31503871	Island	-0.3156571	-3.1661768	-6.729198	0e+00	0.0002040	12.209499	T	C
510348	cg16794867	AADACL2;MIR548H2			OpenSea	-0.3216236	-0.8760669	-6.691628	0e+00	0.0002040	12.035598	T	C
564284	cg18789663	PLD5		chr1:242687922-242688682	Island	-0.3309652	-2.7606954	-6.329495	0e+00	0.0006127	10.383460	T	C
11452	cg00352360	RPL23;SNORA21		chr17:37009471-37010118	N_Shore	-0.3858897	-2.6492284	-6.322583	0e+00	0.0006127	10.352368	T	C
213076	cg06826756	NUP153;NUP153;NUP153		chr6:17706292-17707339	S_Shore	-0.2449756	-2.0423482	-6.241619	0e+00	0.0006127	9.989488	T	C
533323	cg17602885	CLSTN1;CLSTN1			OpenSea	0.3462558	5.0637614	6.227899	0e+00	0.0006127	9.928238	T	C
457675	cg14985987	TAF1A;TAF1A	Promoter_Associated	chr1:222763021-222763270	S_Shore	-0.2828882	-3.0383807	-6.188307	0e+00	0.0006127	9.751875	T	C
656385	cg22481606	SUPT4H1	Promoter_Associated	chr17:56429455-56429906	Island	-0.3552426	-2.7086638	-6.181312	0e+00	0.0006127	9.720777	T	C
462248	cg15140743	TXNDC12;TXNDC12;TXNDC12;BTF3L4;BTF3L4;BTF3L4;BTF3L4;BTF3L4;BTF3L4	Promoter_Associated	chr1:52521780-52522296	Island	-0.2571162	-1.5954869	-6.121021	0e+00	0.0006127	9.453510	T	C
666703	cg22883995	CXXC5		chr5:139060555-139060934	N_Shore	0.5267229	3.9847638	6.116856	0e+00	0.0006127	9.435098	T	C
333901	cg10831391	PFKP;PFKP		chr10:3108650-3111419	Island	-0.3389299	-3.7636582	-6.103599	0e+00	0.0006127	9.376538	T	C
200896	cg06438056	AK2;AK2;AK2;AK2	Promoter_Associated	chr1:33502201-33502719	Island	-0.5625219	-1.8362140	-6.103394	0e+00	0.0006127	9.375633	T	C
12931	cg00397324	MX1;MX1	Promoter_Associated_Cell_type_specific	chr21:42798146-42798884	Island	-0.5990851	-4.3424869	-6.087439	0e+00	0.0006127	9.305249	T	C
650316	cg22225892	NOP2;NOP2	Promoter_Associated	chr12:6676999-6677755	Island	-0.3464083	-4.7374195	-6.076667	0e+00	0.0006127	9.257783	T	C
181735	cg05796321	GFI1;GFI1;GFI1	Promoter_Associated	chr1:92945907-92952609	Island	-0.2053724	-2.0603468	-6.068560	0e+00	0.0006127	9.222093	T	C
207281	cg06647562	GFI1;GFI1;GFI1	Promoter_Associated	chr1:92945907-92952609	Island	-0.2713107	-3.5229696	-6.059967	0e+00	0.0006127	9.184291	T	C
639166	cg21772679	ID2-AS1		chr2:8818928-8819586	Island	-0.2251746	-1.9422282	-6.045368	0e+00	0.0006144	9.120130	T	C
196265	cg06280512	PRKD2;PRKD2;PRKD2;PRKD2;PRKD2	Promoter_Associated	chr19:47217161-47217555	Island	-0.3916168	-3.3592068	-6.035368	0e+00	0.0006144	9.076232	T	C
564253	cg18788524	SEC22B	Unclassified	chr1:145096393-145096784	Island	-0.2650087	-2.3317396	-6.003484	0e+00	0.0006802	8.936529	T	C
63985	cg02002231	FGF5;FGF5;FGF5;FGF5		chr4:81187494-81187913	Island	-0.4227779	-3.7840975	-5.991250	0e+00	0.0006859	8.883033	T	C
300305	cg09700085	SLC6A20;SLC6A20;SLC6A20;SLC6A20	Unclassified_Cell_type_specific	chr3:45837480-45838256	Island	0.2107231	-1.0723417	5.978783	0e+00	0.0006862	8.828578	T	C
529461	cg17465697	TRIM11	Promoter_Associated	chr1:228593811-228594713	Island	-0.4949554	-2.3602891	-5.955838	0e+00	0.0006862	8.728523	T	C
651059	cg22254299	CBX8		chr17:77770672-77778468	Island	-0.4960367	-1.9716473	-5.954344	0e+00	0.0006862	8.722019	T	C
524522	cg17295589	SCN4A		chr17:62019023-62019319	Island	0.4933315	2.6981742	5.953709	0e+00	0.0006862	8.719250	T	C
583046	cg19545623	NSUN7;NSUN7	Unclassified	chr4:40751842-40752493	Island	-0.2328398	-3.0663521	-5.942154	0e+00	0.0006967	8.668955	T	C
226991	cg07267166	ZNF323;ZNF323;ZKSCAN3	Promoter_Associated_Cell_type_specific		OpenSea	-0.4816796	-2.0671166	-5.925353	0e+00	0.0007268	8.595920	T	C
188527	cg06016354	GPSM3;NOTCH4	Promoter_Associated	chr6:32163292-32164383	Island	-0.4162617	-2.4582531	-5.897553	0e+00	0.0008007	8.475324	T	C
363209	cg11847929	TXNDC15	Promoter_Associated	chr5:134209887-134210504	Island	-0.4967544	-4.0096838	-5.887171	0e+00	0.0008118	8.430373	T	C
13401	cg00411784				OpenSea	-0.1950095	0.4719783	-5.830756	0e+00	0.0009862	8.186873	T	C
748708	cg26075747	HLA-E	Promoter_Associated	chr6:30457369-30458175	Island	-0.3212548	-3.6510492	-5.830106	0e+00	0.0009862	8.184077	T	C
642103	cg21888603	TFR2			OpenSea	-0.3378916	0.6483929	-5.825605	0e+00	0.0009862	8.164709	T	C
594300	cg19971459	LOC101929626;PIK3R3;PIK3R3;PIK3R3;PIK3R3;PIK3R3;PIK3R3	Promoter_Associated	chr1:46598126-46599129	Island	-0.2146252	-2.8552755	-5.795703	0e+00	0.0010941	8.036252	T	C
89122	cg02799478	ZNF416	Unclassified	chr19:58089801-58090524	Island	-0.2060661	-2.2822022	-5.790911	0e+00	0.0010941	8.015700	T	C
143693	cg04558112	NOB1	Promoter_Associated	chr16:69788469-69788984	Island	-0.4087524	-3.5570578	-5.782916	0e+00	0.0011017	7.981434	T	C
27821	cg00852573	KCNQ5;KCNQ5;KCNQ5;KCNQ5;KCNQ5		chr6:73330942-73333109	Island	-0.2992594	-2.9466658	-5.773004	0e+00	0.0011017	7.938989	T	C
468667	cg15380588		Promoter_Associated	chr6:144605926-144608280	Island	-0.2663634	-2.4974204	-5.767728	1e-07	0.0011017	7.916414	T	C
629157	cg21367838	STAU1;STAU1;STAU1;STAU1;STAU1	Promoter_Associated	chr20:47804353-47805160	Island	-0.2155629	-2.5936361	-5.762770	1e-07	0.0011017	7.895210	T	C
408157	cg13421194			chr21:15451141-15451458	N_Shelf	0.4166263	3.2722010	5.759942	1e-07	0.0011017	7.883121	T	C
548517	cg18176703		Promoter_Associated	chr3:115502725-115503581	Island	-0.4139401	-4.1938864	-5.742026	1e-07	0.0011470	7.806612	T	C
396240	cg13007349	HSPA9	Promoter_Associated	chr5:137910848-137911637	Island	-0.3078975	-4.1574949	-5.740710	1e-07	0.0011470	7.800998	T	C
740169	cg25729922	MUL1;MUL1	Promoter_Associated	chr1:20834416-20834883	Island	-0.5353564	-4.1844641	-5.732110	1e-07	0.0011658	7.764328	T	C
256518	cg08242354				OpenSea	-0.2600209	0.8534739	-5.720203	1e-07	0.0011809	7.713603	T	C
564906	cg18812579				OpenSea	0.4682625	2.4892253	5.715338	1e-07	0.0011809	7.692902	T	C
291118	cg09392940	LOC100287216;SH3RF3		chr2:109744585-109746833	Island	-0.3786845	-3.6626912	-5.714560	1e-07	0.0011809	7.689588	T	C
229639	cg07352757	ATP11A;ATP11A		chr13:113495320-113495738	Island	0.5230214	3.1956058	5.704539	1e-07	0.0012008	7.646974	T	C
81538	cg02561482	TFAP2B		chr6:50813314-50813699	Island	-0.2354908	-2.1458891	-5.701382	1e-07	0.0012008	7.633557	T	C
657166	cg22510362			chr16:87251634-87251840	Island	-0.2135568	1.4375981	-5.697127	1e-07	0.0012008	7.615482	T	C
439620	cg14394617	HNRNPA1;HNRNPA1;HNRPA1L-2;HNRNPA1;HNRNPA1;CBX5	NonGene_Associated	chr12:54673814-54674988	Island	-0.4284246	-1.5783086	-5.674297	1e-07	0.0012474	7.518635	T	C
511513	cg16839093		Unclassified	chr1:8002408-8002699	Island	-0.3939920	-2.1717300	-5.667213	1e-07	0.0012474	7.488631	T	C
379627	cg12422992	ZFAT;ZFAT;ZFAT;ZFAT;ZFAT;ZFAT;ZFAT	Promoter_Associated	chr8:135724770-135725552	Island	-0.3848550	-3.7352118	-5.664269	1e-07	0.0012474	7.476166	T	C

dm <- dm[,c("UCSC_RefGene_Name","t")]
hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc() 

## 105.902 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res,file="novakovic_gmeawg_nat_vs_fh.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
DAB1	173	-0.7561747	-0.7675348	0	16.991971	0.00e+00
PDE4D	255	-0.7017433	-0.7692419	0	16.196671	0.00e+00
HOXC4	127	-0.8721891	-0.9356466	0	13.970310	0.00e+00
IRX4	44	-1.4563607	-1.3795396	0	12.502106	0.00e+00
LPP	219	-0.5388101	-0.5283732	0	12.463135	0.00e+00
PPT2	96	-0.8937976	-0.9328835	0	11.631933	1.00e-07
CSNK2B	74	-0.9428641	-0.8999860	0	11.537384	1.00e-07
PCDHGA1	394	0.4723780	0.5001869	0	11.523368	1.00e-07
SYNE1	130	-0.6739941	-0.6141945	0	11.389167	1.00e-07
PDZRN3	100	-0.8559139	-0.8822877	0	11.307494	1.00e-07
PRDM8	56	-1.6375164	-1.8487935	0	11.294470	1.00e-07
APBB2	159	-0.6674691	-0.7303094	0	11.053203	2.00e-07
KIAA1949	93	-0.9052544	-0.8242630	0	10.956281	3.00e-07
CDK14	84	-1.0380266	-1.0863048	0	10.871946	4.00e-07
PCDHGA2	382	0.4652116	0.4920521	0	10.820661	4.00e-07
SOCS2	55	-1.4750156	-1.5863794	0	10.804677	4.00e-07
MIR548N	124	-0.8216647	-0.7684238	0	10.780181	4.00e-07
EXOC4	123	-0.6880181	-0.8482577	0	10.739778	5.00e-07
CUTA	60	-1.3355563	-1.4699744	0	10.716735	5.00e-07
PBX1	132	-0.6443964	-0.5870391	0	10.619459	6.00e-07
AUTS2	229	-0.5285884	-0.5020331	0	10.605730	6.00e-07
DLG2	197	-0.5525034	-0.5201347	0	10.583888	7.00e-07
GNAS	209	-0.5002971	-0.5543061	0	10.540614	8.00e-07
ZFP36L2	43	-1.5269761	-1.4071801	0	10.447714	9.00e-07
PAX7	100	-0.8532483	-0.8004553	0	10.437886	1.00e-06
GTDC1	80	-0.8449738	-0.9047989	0	10.436876	1.00e-06
PAX6	120	-0.8422864	-0.8181768	0	10.431037	1.00e-06
ADARB2	463	-0.3605081	-0.4417187	0	10.359881	1.10e-06
NOTCH4	182	-0.6036897	-0.5342262	0	10.196789	1.70e-06
ASTN2	115	-0.6834291	-0.7281253	0	10.190540	1.70e-06
TP73	131	-0.7756848	-0.8122595	0	10.053298	2.30e-06
BNC1	37	-1.3749988	-1.6547849	0	9.953335	2.90e-06
SAMD4A	93	-0.7913643	-0.8671069	0	9.932867	3.00e-06
TOX	90	-0.8356485	-0.8686322	0	9.906992	3.20e-06
PTPRN2	1442	-0.1935615	-0.2050650	0	9.904699	3.30e-06
ASCL2	45	-1.1156340	-1.1415771	0	9.887110	3.40e-06
HOXC5	79	-0.9320835	-1.0762134	0	9.817970	4.00e-06
EYA4	85	-0.8170253	-0.9175051	0	9.814879	4.00e-06
HS3ST1	35	-1.3592941	-1.0698244	0	9.773226	4.40e-06
WT1	81	-0.9004545	-0.8486747	0	9.691161	5.30e-06
NKX6-2	34	-1.5617328	-1.6395237	0	9.583387	6.80e-06
AMOTL2	42	-1.4399250	-1.4366533	0	9.530172	7.70e-06
OPCML	201	-0.5242526	-0.4443077	0	9.511845	8.00e-06
BRD2	148	-0.6944009	-0.8509687	0	9.447623	9.30e-06
GALNT9	273	-0.4370200	-0.4500592	0	9.433429	9.60e-06
FYN	109	-0.6521794	-0.8221859	0	9.361522	1.14e-05
EMX2OS	79	-0.8434582	-0.7940333	0	9.353486	1.16e-05
C9orf3	166	-0.5797704	-0.5392472	0	9.313185	1.27e-05
ZNF407	96	-0.6978681	-0.8494332	0	9.280198	1.37e-05
RNF39	80	-0.9295627	-1.0455269	0	9.247670	1.48e-05

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets, priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>% kbl(caption = "Top enriched gene sets with GMEA-Mitch") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch

	set	setSize	pANOVA	s.dist	p.adjustANOVA
441	Folding of actin by CCT/TriC	10	0.0004755	-0.6380107	0.0018631
426	FOXO-mediated transcription of cell cycle genes	16	0.0000134	-0.6283864	0.0001155
781	NOTCH4 Activation and Transmission of Signal to the Nucleus	11	0.0005096	-0.6051042	0.0019578
1124	Repression of WNT target genes	13	0.0004833	-0.5589100	0.0018887
243	Crosslinking of collagen fibrils	10	0.0022855	-0.5569931	0.0068744
955	Processing of Intronless Pre-mRNAs	19	0.0000698	-0.5268697	0.0004073
117	Beta defensins	32	0.0000004	0.5193640	0.0000047
1069	Regulated proteolysis of p75NTR	11	0.0028569	-0.5193041	0.0082211
1426	Transcriptional regulation of testis differentiation	12	0.0020400	-0.5141429	0.0062217
884	POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation	10	0.0049079	-0.5136572	0.0126890
299	Defensins	40	0.0000000	0.5077968	0.0000004
1364	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	14	0.0010869	-0.5042088	0.0035809
325	Diseases associated with glycosylation precursor biosynthesis	15	0.0007208	-0.5041949	0.0025612
1167	SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs	11	0.0038200	-0.5036257	0.0103859
917	Physiological factors	12	0.0025966	-0.5020596	0.0076743
119	Beta-catenin phosphorylation cascade	16	0.0005092	-0.5018080	0.0019578
953	Processing of Capped Intronless Pre-mRNA	28	0.0000055	-0.4958902	0.0000554
339	Disorders of Developmental Biology	11	0.0047711	-0.4913417	0.0123774
340	Disorders of Nervous System Development	11	0.0047711	-0.4913417	0.0123774
676	Loss of function of MECP2 in Rett syndrome	11	0.0047711	-0.4913417	0.0123774

#mitch_report(mres,outfile="gmeawg_mitch_nat_vs_fh.html",overwrite=FALSE)
# Promoter
dm <- nat_vs_fh$dma
dm <- dm[grep("Promoter_Associated",dm$Regulatory_Feature_Group),]
dm <- dm[,c("UCSC_RefGene_Name","t")]
head(dm,50) %>% kbl(caption = "Top significant promoters with limma") %>% kable_paper("hover", full_width = F)

Top significant promoters with limma

	UCSC_RefGene_Name	t
743573	SELM	-6.729198
457675	TAF1A;TAF1A	-6.188307
656385	SUPT4H1	-6.181312
462248	TXNDC12;TXNDC12;TXNDC12;BTF3L4;BTF3L4;BTF3L4;BTF3L4;BTF3L4;BTF3L4	-6.121021
200896	AK2;AK2;AK2;AK2	-6.103394
12931	MX1;MX1	-6.087439
650316	NOP2;NOP2	-6.076667
181735	GFI1;GFI1;GFI1	-6.068560
207281	GFI1;GFI1;GFI1	-6.059967
196265	PRKD2;PRKD2;PRKD2;PRKD2;PRKD2	-6.035368
529461	TRIM11	-5.955838
226991	ZNF323;ZNF323;ZKSCAN3	-5.925353
188527	GPSM3;NOTCH4	-5.897553
363209	TXNDC15	-5.887171
748708	HLA-E	-5.830106
594300	LOC101929626;PIK3R3;PIK3R3;PIK3R3;PIK3R3;PIK3R3;PIK3R3	-5.795703
143693	NOB1	-5.782916
468667		-5.767728
629157	STAU1;STAU1;STAU1;STAU1;STAU1	-5.762770
548517		-5.742026
396240	HSPA9	-5.740710
740169	MUL1;MUL1	-5.732110
379627	ZFAT;ZFAT;ZFAT;ZFAT;ZFAT;ZFAT;ZFAT	-5.664269
599354	THAP1;THAP1	-5.661379
682134	NICN1	-5.651816
596240	AURKAIP1;AURKAIP1;AURKAIP1;AURKAIP1	-5.649047
232993	DERL1;DERL1;DERL1;DERL1	-5.640295
278763	IRF1	-5.638281
240346	ZNF91	-5.637420
402778	SEC1P;DBP	-5.599301
701239	RORA;RORA;RORA;RORA	-5.587982
317989	CDH24;CDH24	-5.584492
140489	OXNAD1;DPH3;DPH3;DPH3;DPH3	-5.582899
533320	SESN2	-5.570999
135434	NBPF3	-5.560405
138167	SETD1A;SETD1A	-5.556512
85093	STK11	-5.547755
257402	MTHFR;CLCN6;MTHFR;CLCN6;CLCN6;CLCN6	-5.536864
621085	SUSD1;SUSD1;SUSD1;SUSD1;SUSD1;SUSD1;MIR3134	-5.536832
157319	S100A6;S100A6	-5.533519
703541	LIMK2	-5.533368
250420	C21orf45	-5.525969
616631	YTHDC1;YTHDC1	-5.514405
90019	ZNF707;ZNF707;ZNF707	-5.511375
34987	CCT3;C1orf182;CCT3;CCT3	-5.509115
152843	PNRC2	-5.500155
183968		-5.491291
421250	LOC389791;PTGES2;PTGES2;PTGES2;PTGES2	-5.489303
735035	CHCHD2	-5.477784
414209	GTF3C5;GTF3C5;GTF3C5;GTF3C5	-5.472700

hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 17.84 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]] 
write.table(res ,file="novakovic_gmeapr_nat_vs_fh.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
PPT2	68	-1.0729325	-1.0910510	0e+00	11.871777	0.0000000
RGL2	53	-1.2852678	-1.5508924	0e+00	10.749264	0.0000002
ZFYVE28	33	-1.4285748	-1.4046328	0e+00	9.862299	0.0000016
TRIM27	49	-1.6015934	-1.6817755	0e+00	9.617066	0.0000029
TAPBP	67	-1.1040507	-1.0105622	0e+00	9.323713	0.0000057
TBC1D14	37	-1.3758658	-1.3715893	0e+00	9.027650	0.0000113
TAP1	49	-1.2907637	-1.0712056	0e+00	8.924715	0.0000143
FBXO31	22	-1.8133422	-1.7678578	0e+00	8.918405	0.0000145
CSNK2B	35	-1.2633113	-1.2567261	0e+00	8.804052	0.0000188
PSMB9	46	-1.3377140	-1.2465304	0e+00	8.665506	0.0000259
STK19	50	-1.2692143	-1.4650770	0e+00	8.540304	0.0000346
BAT4	34	-1.2743951	-1.2810592	0e+00	8.531318	0.0000353
CLK1	15	-1.8188190	-1.7421604	0e+00	8.389792	0.0000489
CUTA	49	-1.3651519	-1.4842923	0e+00	8.349729	0.0000536
FBXO34	22	-1.7701334	-1.6716487	0e+00	8.330754	0.0000560
CENPT	35	-1.2425841	-1.1821302	0e+00	8.291259	0.0000614
DOM3Z	49	-1.2616431	-1.4458041	0e+00	8.213341	0.0000734
HCG4	38	-1.0772782	-0.8877846	0e+00	8.194727	0.0000766
ZNF509	15	-1.6065868	-1.5685087	0e+00	8.169737	0.0000811
ZFP36L2	28	-1.7872419	-1.7921027	0e+00	7.702155	0.0002381
NOTCH4	35	-1.5413044	-1.1685956	0e+00	7.653437	0.0002664
LOC100129726	27	-1.8312126	-1.8134168	0e+00	7.637814	0.0002761
C17orf90	14	-2.1352883	-2.1962643	0e+00	7.598156	0.0003025
PSMB8	47	-1.0070538	-0.8404355	0e+00	7.520729	0.0003615
POLR3C	18	-1.8064869	-1.8330882	0e+00	7.508604	0.0003717
RNF115	18	-1.8064869	-1.8330882	0e+00	7.508604	0.0003717
TRIM26	25	-1.6299851	-1.8569571	0e+00	7.480921	0.0003961
KIAA1949	60	-0.9894228	-0.8418996	0e+00	7.439314	0.0004359
SOCS2	34	-1.5860070	-1.6874261	0e+00	7.399174	0.0004780
ARIH2	25	-1.7107435	-1.6305116	0e+00	7.303878	0.0005953
ECSIT	22	-1.3519223	-1.1420932	1e-07	7.220801	0.0007207
TYMS	22	-1.6735187	-1.7450646	1e-07	7.219989	0.0007220
NBPF10	31	-1.3348423	-1.4271124	1e-07	7.164352	0.0008206
HLA-B	21	-1.4935737	-1.6147357	1e-07	7.143319	0.0008613
PHTF2	27	-1.5563733	-1.3315714	1e-07	6.921131	0.0014364
TMEM60	27	-1.5563733	-1.3315714	1e-07	6.921131	0.0014364
TMEM138	22	-1.8038857	-1.8450503	2e-07	6.821627	0.0018060
PPCS	19	-1.7931456	-1.8003560	2e-07	6.806645	0.0018692
CHD9	23	-1.4017263	-1.3902679	2e-07	6.798352	0.0019051
DHX16	36	-1.3260808	-1.4182011	2e-07	6.764911	0.0020574
SHBG	31	-1.0700955	-1.1569496	2e-07	6.739687	0.0021803
ACCS	14	-1.7148265	-1.6300210	2e-07	6.734286	0.0022074
GPSM3	39	-1.3511361	-1.0058110	2e-07	6.722312	0.0022689
HCG27	36	-1.0473087	-1.0534780	2e-07	6.710767	0.0023298
ZMAT5	15	-1.5529701	-1.4810247	2e-07	6.628578	0.0028150
DCP1A	15	-1.7276367	-1.6678233	3e-07	6.585759	0.0031064
LYAR	18	-1.4024637	-1.4479376	3e-07	6.570691	0.0032158
SLC38A9	16	-1.5593378	-1.6766791	3e-07	6.569087	0.0032275
NUMA1	22	-1.4362277	-1.5010721	3e-07	6.550032	0.0033719
TMEM11	16	-1.2238926	-1.1756100	3e-07	6.538897	0.0034592

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets,priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>%  kbl(caption = "Top enriched gene sets with GMEA-Mitch (promoter only)") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch (promoter only)

	set	setSize	pANOVA	s.dist	p.adjustANOVA
971	Signaling by FGFR2 IIIa TM	15	0.0005466	-0.5155081	0.0193551
287	Endosomal/Vacuolar pathway	10	0.0117112	-0.4603516	0.0924737
908	SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs	10	0.0118578	-0.4595518	0.0924737
933	Sema4D induced cell migration and growth-cone collapse	12	0.0061068	0.4571563	0.0706835
731	Processing of Intronless Pre-mRNAs	15	0.0030724	-0.4415069	0.0499881
309	FGFR2 mutant receptor activation	17	0.0016671	-0.4404556	0.0371710
374	Generation of second messenger molecules	15	0.0037127	0.4327388	0.0565839
729	Processing of Capped Intronless Pre-mRNA	23	0.0006349	-0.4115640	0.0218400
932	Sema4D in semaphorin signaling	15	0.0073551	0.3997500	0.0771156
308	FGFR2 alternative splicing	22	0.0016294	-0.3880865	0.0370157
1043	Synthesis of Leukotrienes (LT) and Eoxins (EX)	10	0.0352786	0.3844705	0.1652741
894	Role of phospholipids in phagocytosis	16	0.0079832	-0.3830958	0.0799924
51	Antigen Presentation: Folding, assembly and peptide loading of class I MHC	26	0.0009600	-0.3741970	0.0268810
1065	TNFR1-induced proapoptotic signaling	12	0.0256116	-0.3721565	0.1352472
664	Other semaphorin interactions	10	0.0430475	0.3695160	0.1877870
479	Interleukin-35 Signalling	11	0.0343815	-0.3684083	0.1623346
66	Assembly of the ORC complex at the origin of replication	10	0.0451391	0.3658835	0.1947936
1067	TNFs bind their physiological receptors	10	0.0470667	0.3626593	0.2002413
1180	alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	10	0.0487490	-0.3599350	0.2019338
1181	alpha-linolenic acid (ALA) metabolism	10	0.0487490	-0.3599350	0.2019338

#mitch_report(mres,outfile="gmeapr_mitch_nat_vs_fh.html",overwrite=FALSE)
rm(nat_vs_fh)

fh vs fz

dm <- fh_vs_fz$dma
head(dm,50) %>% kbl(caption = "Top significant genes with limma") %>% kable_paper("hover", full_width = F)

Top significant genes with limma

	Row.names	UCSC_RefGene_Name	Regulatory_Feature_Group	Islands_Name	Relation_to_Island	logFC	AveExpr	t	P.Value	adj.P.Val	B	unmeth	meth
84778	cg02660277	PTPRN2;PTPRN2;PTPRN2		chr7:157440024-157442721	N_Shore	-0.5768035	0.6357996	-5.081137	1.60e-06	0.5850073	1.8428713	T	C
741713	cg25789405				OpenSea	-0.4079722	3.4957897	-5.013896	2.10e-06	0.5850073	1.6855246	T	C
655472	cg22442197	RPS2;SNORA10		chr16:2014164-2015451	N_Shore	-0.3918995	1.6630997	-4.911083	3.20e-06	0.5850073	1.4468405	T	C
93377	cg02932204	PDZD7	Unclassified_Cell_type_specific		OpenSea	0.9767400	-0.7930996	4.848974	4.10e-06	0.5850073	1.3038088	T	C
225683	cg07224221	RTP3			OpenSea	-0.3810350	2.7413060	-4.839740	4.30e-06	0.5850073	1.2826195	T	C
594607	cg19983118		Promoter_Associated	chr8:103822614-103823263	Island	-0.3876992	-3.1419432	-4.832483	4.40e-06	0.5850073	1.2659808	T	C
450713	cg14745383	TRAPPC9;TRAPPC9	Gene_Associated		OpenSea	-0.3481772	3.6025232	-4.793163	5.20e-06	0.5898241	1.1760492	T	C
297858	cg09616692	GFOD2;GFOD2			OpenSea	-0.4280608	2.8285674	-4.741708	6.40e-06	0.6375191	1.0589225	T	C
199370	cg06385817	KCTD21-AS1;KCTD21-AS1			OpenSea	-0.3021376	1.6173215	-4.667788	8.70e-06	0.6788315	0.8918047	T	C
387340	cg12687426	KCNMB3;KCNMB3;KCNMB3;KCNMB3;KCNMB3		chr3:178978948-178979364	N_Shore	-1.0483941	2.5287214	-4.650590	9.30e-06	0.6788315	0.8531204	T	C
67059	cg02098463	NARR;RAB34;RAB34;RAB34;RAB34;RAB34;RAB34;RAB34;RAB34	Unclassified_Cell_type_specific	chr17:27044168-27045049	S_Shore	-0.4857457	-1.3036543	-4.644134	9.60e-06	0.6788315	0.8386187	T	C
220821	cg07070583	ANAPC10		chr4:146019163-146019826	N_Shelf	0.4023754	2.6870883	4.544814	1.42e-05	0.6788315	0.6168770	T	C
77048	cg02417408	PPM1M;PPM1M	Promoter_Associated	chr3:52279601-52280140	S_Shore	0.4825923	1.6328609	4.514574	1.61e-05	0.6788315	0.5498841	T	C
5560	cg00165981	COL4A3BP;COL4A3BP;COL4A3BP;POLK	Promoter_Associated	chr5:74806581-74807974	S_Shore	-0.4547210	-2.4140792	-4.465472	1.95e-05	0.6788315	0.4416317	T	C
612535	cg20704819	GABBR1;GABBR1;GABBR1			OpenSea	0.4492179	2.7782386	4.433776	2.21e-05	0.6788315	0.3721052	T	C
483409	cg15891419				OpenSea	-0.3351572	2.3630721	-4.416360	2.37e-05	0.6788315	0.3340225	T	C
353392	cg11514097	SKI	Unclassified		OpenSea	-0.4176008	-2.8383260	-4.381901	2.71e-05	0.6788315	0.2589255	T	C
745548	cg25950293	ADGRE5;ADGRE5;ADGRE5			OpenSea	-0.2798310	-1.1579085	-4.332335	3.29e-05	0.6788315	0.1514994	T	C
462440	cg15147113	SERPINE2;SERPINE2;SERPINE2;SERPINE2	Unclassified		OpenSea	-1.2977519	-3.0144816	-4.306317	3.63e-05	0.6788315	0.0953969	T	C
306086	cg09894786	CPNE5			OpenSea	-0.4529934	3.2544473	-4.279337	4.03e-05	0.6788315	0.0374288	T	C
670745	cg23042897				OpenSea	-0.4992080	1.0275294	-4.266142	4.24e-05	0.6788315	0.0091586	T	C
751487	cg26177273	PPP5C;PPP5C	Promoter_Associated	chr19:46850185-46850678	S_Shelf	-0.3800766	-3.7140066	-4.263663	4.28e-05	0.6788315	0.0038516	T	C
43487	cg01345338	FBLN1;FBLN1;FBLN1;FBLN1			OpenSea	-0.3108440	2.9862078	-4.260545	4.33e-05	0.6788315	-0.0028186	T	C
327870	cg10623043	CORO1B;CORO1B	Promoter_Associated		OpenSea	-0.4122624	-3.2209410	-4.255959	4.41e-05	0.6788315	-0.0126251	T	C
740098	cg25727569	CACNA1D;CACNA1D;CACNA1D			OpenSea	-0.3046565	2.2544287	-4.254408	4.44e-05	0.6788315	-0.0159407	T	C
156894	cg04985097	COL4A3BP;POLK;COL4A3BP;COL4A3BP;COL4A3BP;POLK	Promoter_Associated	chr5:74806581-74807974	Island	-0.5116783	-4.1255319	-4.253342	4.45e-05	0.6788315	-0.0182173	T	C
156263	cg04964098				OpenSea	-0.4101671	3.0553162	-4.243239	4.63e-05	0.6788315	-0.0397909	T	C
212343	cg06805893	KIAA2018;KIAA2018			OpenSea	0.4461742	2.4593802	4.234841	4.78e-05	0.6788315	-0.0576992	T	C
679495	cg23380672	CHST1	Unclassified_Cell_type_specific	chr11:45686160-45687495	N_Shelf	-0.3380035	-0.2572986	-4.230392	4.86e-05	0.6788315	-0.0671782	T	C
504028	cg16586970	TTC15		chr2:3391402-3392500	Island	-0.2882703	2.0322415	-4.203983	5.38e-05	0.6788315	-0.1233199	T	C
738328	cg25655333	SLC12A7		chr5:1053544-1053807	N_Shore	-0.4677466	2.4932902	-4.202248	5.41e-05	0.6788315	-0.1270001	T	C
290025	cg09355865	RHEB			OpenSea	-0.5662313	2.7891057	-4.183251	5.82e-05	0.6788315	-0.1672427	T	C
69615	cg02183001	NRP2;NRP2;NRP2;NRP2;NRP2;NRP2		chr2:206549599-206551316	S_Shore	-0.3577720	2.2967754	-4.161393	6.32e-05	0.6788315	-0.2134103	T	C
73795	cg02316792	CLNK			OpenSea	-0.3667169	-2.7693977	-4.154387	6.49e-05	0.6788315	-0.2281753	T	C
27175	cg00832811	MRPL22;MRPL22			OpenSea	0.4338761	2.7443631	4.154360	6.49e-05	0.6788315	-0.2282335	T	C
455574	cg14910288			chr18:10032458-10032907	S_Shore	0.3702678	0.1694659	4.153450	6.51e-05	0.6788315	-0.2301506	T	C
348665	cg11346248	SLFN12	Unclassified		OpenSea	0.5902811	-2.5338229	4.151250	6.57e-05	0.6788315	-0.2347827	T	C
28230	cg00865927			chr14:53417108-53418339	S_Shelf	0.4599890	1.9838292	4.150154	6.59e-05	0.6788315	-0.2370904	T	C
647826	cg22121946	SNX13			OpenSea	0.2824716	3.6181735	4.150095	6.60e-05	0.6788315	-0.2372138	T	C
105690	cg03328201	MIR130B		chr22:22006079-22007048	S_Shore	-0.3579761	2.8241256	-4.140589	6.84e-05	0.6788315	-0.2572114	T	C
575659	cg19251655				OpenSea	0.4527527	1.9209047	4.117547	7.45e-05	0.6788315	-0.3055702	T	C
210518	cg06748831	ZNF492	Promoter_Associated_Cell_type_specific	chr19:22817274-22817546	N_Shore	0.4174427	-2.6239112	4.107433	7.74e-05	0.6788315	-0.3267418	T	C
123200	cg03895317	CARD11			OpenSea	-0.2122747	2.6078414	-4.098606	8.00e-05	0.6788315	-0.3451940	T	C
373783	cg12210841	KALRN	Unclassified		OpenSea	-0.2642637	-3.4650489	-4.094358	8.13e-05	0.6788315	-0.3540653	T	C
127092	cg04021856	LYPD6	Unclassified_Cell_type_specific	chr2:150186463-150187492	Island	-0.4606105	-2.4637217	-4.094043	8.14e-05	0.6788315	-0.3547227	T	C
486874	cg16008993			chr19:39322264-39322574	S_Shelf	-0.2492613	1.9214052	-4.091151	8.23e-05	0.6788315	-0.3607581	T	C
275521	cg08871608	CNTD2		chr19:40729087-40729430	Island	0.7764512	-2.5700388	4.089167	8.29e-05	0.6788315	-0.3648974	T	C
160705	cg05104867	SH3RF1			OpenSea	0.3317847	2.3281628	4.086339	8.38e-05	0.6788315	-0.3707950	T	C
487689	cg16036409	LOC387647		chr10:29698362-29699044	Island	0.3876159	-2.6022922	4.081399	8.53e-05	0.6788315	-0.3810924	T	C
387383	cg12688597				OpenSea	-0.2295703	2.1645873	-4.067672	8.98e-05	0.6788315	-0.4096639	T	C

dm <- dm[,c("UCSC_RefGene_Name","t")]
hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 66.694 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res,file="novakovic_gmeawg_fh_vs_fz.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
SEPT9	259	-0.4477279	-0.4817682	0e+00	11.889599	0.0000000
PEX13	23	-1.7388799	-1.6303742	0e+00	10.927122	0.0000003
RAD51B	173	0.5601354	0.6935760	0e+00	10.155498	0.0000018
HOXC4	127	-0.5946637	-0.5552474	0e+00	9.269092	0.0000141
NR2F2	62	-0.9404317	-0.9341580	0e+00	9.207670	0.0000162
ARHGAP26	170	0.5430573	0.5974971	0e+00	9.102628	0.0000206
ANK3	142	0.6153503	0.6316516	0e+00	9.086325	0.0000214
LPP	219	0.4989713	0.5744406	0e+00	8.978309	0.0000275
SYNE1	130	0.6313045	0.7005238	0e+00	8.614721	0.0000635
NRN1	50	-0.8534446	-0.8166829	0e+00	8.062635	0.0002263
FRMD6	95	0.6313187	0.8248823	0e+00	7.683129	0.0005422
HDAC9	104	0.6195365	0.7954477	0e+00	7.316160	0.0012622
LOC150381	15	1.5151011	1.4584551	1e-07	7.289231	0.0013429
SYNE2	131	0.5440226	0.5681621	1e-07	7.214774	0.0015940
NEB	48	0.8063797	0.8932379	1e-07	7.183930	0.0017112
CDKAL1	128	0.6090262	0.8476601	1e-07	7.154128	0.0018327
ZNF407	96	0.6604618	0.7222256	1e-07	7.137303	0.0019050
RGL2	108	-0.5602145	-0.5877417	1e-07	7.068559	0.0022317
MYO16	113	0.5549779	0.7371818	1e-07	7.035816	0.0024063
EXOC4	123	0.6114540	0.6542444	1e-07	7.031933	0.0024279
APBB2	159	0.4756778	0.4743711	1e-07	7.009642	0.0025556
TP63	56	0.7151364	0.7158251	1e-07	7.005361	0.0025808
AKAP6	78	0.7262675	0.7186937	1e-07	6.992205	0.0026601
HOXC6	58	-0.7420280	-0.6578446	1e-07	6.926704	0.0030930
WDR64	23	1.1910585	1.3241054	1e-07	6.862025	0.0035896
BRD2	148	-0.4570100	-0.4235812	1e-07	6.842230	0.0037569
ZBTB20	144	0.4910900	0.6172656	1e-07	6.839905	0.0037769
LHX9	56	-0.7595122	-0.8407331	2e-07	6.821094	0.0039439
KLF10	30	-0.8726266	-1.0551347	2e-07	6.794568	0.0041922
POPDC2	14	1.3343081	1.3845157	2e-07	6.782473	0.0043104
HIST2H2BE	25	-1.0776050	-1.2192391	2e-07	6.729296	0.0048717
LOC284294	24	1.2536950	1.3096187	2e-07	6.672297	0.0055547
C10orf11	155	0.4746927	0.5867198	2e-07	6.634739	0.0060562
NCKAP5	135	0.5017301	0.6964668	3e-07	6.577605	0.0069075
SMYD3	214	0.4054749	0.4271409	3e-07	6.526894	0.0077627
LOC645323	80	-0.5692542	-0.6131951	3e-07	6.523182	0.0078290
SHOX2	39	-0.9376515	-1.0410453	3e-07	6.477248	0.0087021
PRRT1	66	-0.6327966	-0.5774272	3e-07	6.469976	0.0088487
FOSL2	32	-0.9420620	-1.0009545	3e-07	6.468673	0.0088750
C6orf27	59	-0.6431923	-0.6006390	4e-07	6.415966	0.0100198
OTX1	57	-0.7655136	-0.7322225	4e-07	6.413915	0.0100668
CTNNA1	74	0.7186917	0.8096095	4e-07	6.412128	0.0101079
HOXC5	79	-0.6148158	-0.5841435	4e-07	6.394041	0.0105374
C11orf21	37	-0.6649703	-0.5645214	4e-07	6.360632	0.0113795
CLIC5	50	0.8102313	1.0106889	4e-07	6.347561	0.0117268
TNFRSF10B	29	-1.1019188	-1.0773758	5e-07	6.290656	0.0133680
FER1L6	63	0.6012088	0.6420211	6e-07	6.214835	0.0159174
AUTS2	229	0.3870644	0.4092591	7e-07	6.164978	0.0178531
NPAT	44	-1.1247279	-1.1677714	7e-07	6.159683	0.0180714
LBX2	44	-0.6970455	-0.7396858	8e-07	6.115307	0.0200147

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets, priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>% kbl(caption = "Top enriched gene sets with GMEA-Mitch") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch

	set	setSize	pANOVA	s.dist	p.adjustANOVA
236	Constitutive Signaling by Overexpressed ERBB2	10	0.0007414	-0.6160367	0.0053446
1333	Synthesis of bile acids and bile salts via 27-hydroxycholesterol	15	0.0000406	0.6118615	0.0004341
227	Condensation of Prometaphase Chromosomes	11	0.0012417	-0.5621937	0.0082765
896	Peptide chain elongation	84	0.0000000	-0.5438128	0.0000000
1478	Viral mRNA Translation	84	0.0000000	-0.5317281	0.0000000
395	Eukaryotic Translation Elongation	88	0.0000000	-0.5288325	0.0000000
397	Eukaryotic Translation Termination	87	0.0000000	-0.5196264	0.0000000
1135	Response of EIF2AK4 (GCN2) to amino acid deficiency	95	0.0000000	-0.5124225	0.0000000
1193	Selenocysteine synthesis	87	0.0000000	-0.5105097	0.0000000
212	Class C/3 (Metabotropic glutamate/pheromone receptors)	39	0.0000000	0.5091370	0.0000009
1172	SRP-dependent cotranslational protein targeting to membrane	105	0.0000000	-0.5069120	0.0000000
13	APC/C:Cdc20 mediated degradation of Cyclin B	24	0.0000200	-0.5028324	0.0002383
822	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	89	0.0000000	-0.4988258	0.0000000
449	Formation of a pool of free 40S subunits	95	0.0000000	-0.4967367	0.0000000
567	Hormone ligand-binding receptors	13	0.0020913	0.4927968	0.0127311
903	Pexophagy	11	0.0048914	-0.4899506	0.0253357
1052	RUNX3 regulates p14-ARF	10	0.0078341	-0.4855624	0.0369459
1014	RIPK1-mediated regulated necrosis	27	0.0000133	-0.4840817	0.0001679
1116	Regulation of necroptotic cell death	27	0.0000133	-0.4840817	0.0001679
660	L13a-mediated translational silencing of Ceruloplasmin expression	104	0.0000000	-0.4811480	0.0000000

#mitch_report(mres,outfile="gmeawg_mitch_fh_vs_fz.html",overwrite=FALSE)
# Promoter
dm <- fh_vs_fz$dma
dm <- dm[grep("Promoter_Associated",dm$Regulatory_Feature_Group),]
dm <- dm[,c("UCSC_RefGene_Name","t")]
head(dm,50) %>% kbl(caption = "Top significant promoters with limma") %>% kable_paper("hover", full_width = F)

Top significant promoters with limma

	UCSC_RefGene_Name	t
594607		-4.832483
77048	PPM1M;PPM1M	4.514574
5560	COL4A3BP;COL4A3BP;COL4A3BP;POLK	-4.465472
751487	PPP5C;PPP5C	-4.263663
327870	CORO1B;CORO1B	-4.255959
156894	COL4A3BP;POLK;COL4A3BP;COL4A3BP;COL4A3BP;POLK	-4.253342
210518	ZNF492	4.107433
789766		4.044042
107956	KCTD5	-4.039400
215768	KIAA0391;KIAA0391;KIAA0391;KIAA0391;KIAA0391;PPP2R3C;PPP2R3C;PPP2R3C;PPP2R3C;KIAA0391;KIAA0391	-4.027846
721482	FAM179B;KLHL28	-4.017938
578267	YLPM1	-4.010320
361130	HIST1H4E	-3.997005
132042	ARL6IP4;ARL6IP4;ARL6IP4;ARL6IP4;ARL6IP4;ARL6IP4;ARL6IP4;ARL6IP4;OGFOD2;OGFOD2;OGFOD2;OGFOD2;OGFOD2;OGFOD2;OGFOD2	-3.988626
602636	CHD4	-3.914148
313002	TYW3;CRYZ;CRYZ;TYW3;TYW3;CRYZ;CRYZ	3.907690
533040	HYI	-3.898945
441421	MYOF;MYOF	-3.896213
711736	CHRNA5	-3.884927
263152	ZNF582	-3.854473
225374	PDCD4;PDCD4;PDCD4	-3.851200
82159	ATG4C;ATG4C	-3.840792
66502	SLC22A18AS;SLC22A18;SLC22A18	3.818757
636844	SSH1;SSH1	-3.814645
267301	KPNB1;KPNB1	3.803996
68656	BCAS3;BCAS3	-3.799855
427704	NUP50;NUP50	-3.786547
486196	DNAJC15;DNAJC15	3.778068
454417	C5orf13;C5orf13;C5orf13;C5orf13;C5orf13;C5orf13;C5orf13;C5orf13;C5orf13;C5orf13;C5orf13;C5orf13	-3.775190
285922	SPG21;SPG21;SPG21	-3.770245
749780	BAT3;BAT3;BAT3;BAT3	-3.763478
495486	YBX1	-3.748884
639708	C11orf63;C11orf63	-3.748757
93603		-3.728893
204404	CSNK1A1;CSNK1A1	-3.716857
60788	TNFAIP8L2	-3.716643
42269	TMEM127;TMEM127;CIAO1	3.713732
233801	ANKRD23	3.704541
197118	LPIN1;LPIN1;LPIN1;LPIN1	-3.698683
76154	NBPF3	3.696824
502810	CLCC1;CLCC1	-3.690988
790860	EXO1;EXO1;EXO1	-3.690791
259542	GPN3;GPN3;GPN3;FAM216A	-3.689834
588721	ACO1;ACO1	-3.674589
489170	ADK;ADK	-3.671283
406482	UBA2	-3.659952
666499	PHF14;PHF14;PHF14;PHF14	-3.659307
578749	BRI3BP	-3.646948
295390	OGDH;OGDH;OGDH	-3.619320
188612	KIF2A;KIF2A	-3.612075

hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 19.504 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res ,file="novakovic_gmeapr_fh_vs_fz.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
PEX13	21	-1.7568216	-1.6303742	0.0e+00	9.778840	0.0000020
PUS10	21	-1.7568216	-1.6303742	0.0e+00	9.778840	0.0000020
TSC22D1	29	-1.2704282	-1.2221258	0.0e+00	9.644508	0.0000027
EHMT2	35	-1.4109935	-1.5397958	0.0e+00	8.428670	0.0000448
LRRCC1	17	-1.2596894	-1.2687776	0.0e+00	8.007771	0.0001180
RGL2	53	-0.8132301	-0.7711957	0.0e+00	7.933780	0.0001399
ZNRD1	37	-0.9603581	-0.9288594	0.0e+00	7.494004	0.0003850
NCRNA00171	37	-0.9603581	-0.9288594	0.0e+00	7.494004	0.0003850
TTC31	21	-1.1762000	-1.1605374	1.0e-07	7.186252	0.0007818
C11orf57	14	-1.4564248	-1.4060926	1.0e-07	7.142109	0.0008654
PIH1D2	14	-1.4564248	-1.4060926	1.0e-07	7.142109	0.0008654
WIPF1	18	-1.4518793	-1.4964495	1.0e-07	7.112635	0.0009260
CFLAR	27	-1.1158669	-1.1766670	1.0e-07	6.961510	0.0013113
NEU1	37	-0.9212730	-0.8392188	1.0e-07	6.950104	0.0013461
C21orf59	18	-1.2086482	-1.3875697	2.0e-07	6.659392	0.0026288
ST8SIA4	16	-1.2370618	-1.1019930	2.0e-07	6.652948	0.0026678
RING1	26	-1.3407502	-1.4814460	3.0e-07	6.599785	0.0030150
ZNF224	15	-1.4905451	-1.3280032	3.0e-07	6.596669	0.0030365
BRD2	52	-0.8463690	-0.7278671	3.0e-07	6.484138	0.0039343
RUNX2	35	-0.8588211	-0.9833560	3.0e-07	6.467515	0.0040874
SPATA13	23	-1.1732224	-1.2203359	3.0e-07	6.461247	0.0041465
KLF10	23	-0.8710200	-1.0697673	4.0e-07	6.406987	0.0046979
LOC100302652	16	-1.2108385	-1.2940743	4.0e-07	6.403883	0.0047312
ACP2	19	-0.9373877	-0.8754269	4.0e-07	6.399872	0.0047747
SEPT9	35	-0.8756194	-0.8449604	4.0e-07	6.372510	0.0050848
TPX2	15	-1.4738588	-1.4954720	4.0e-07	6.352545	0.0053236
DUSP22	10	-0.9793184	-0.9863132	5.0e-07	6.340861	0.0054683
FBXO8	24	-1.0184286	-0.8790149	5.0e-07	6.318394	0.0057581
RPL23	12	-1.5105241	-1.4741091	5.0e-07	6.264282	0.0065216
SNORA21	12	-1.5105241	-1.4741091	5.0e-07	6.264282	0.0065216
MAP2K6	9	-0.8723899	-0.9198508	6.0e-07	6.190512	0.0077278
SFT2D2	13	-1.0527054	-1.1230508	9.0e-07	6.024799	0.0113170
NUDT5	18	-1.0216350	-1.1196114	1.0e-06	6.010713	0.0116891
RPP21	31	-0.8761845	-0.7780959	1.1e-06	5.975630	0.0126715
C6orf48	41	-0.9666925	-0.9644012	1.2e-06	5.904076	0.0149398
ZNF613	12	-1.6770864	-1.7755176	1.3e-06	5.883052	0.0156795
BCAP29	18	-1.5485121	-1.7043469	1.3e-06	5.877760	0.0158704
ASB3	28	-0.9779625	-1.0890423	1.5e-06	5.833439	0.0175741
ATM	22	-1.4584186	-1.2967383	1.5e-06	5.826516	0.0178550
NPAT	22	-1.4584186	-1.2967383	1.5e-06	5.826516	0.0178550
ATAD1	15	-1.6509129	-1.6986637	1.5e-06	5.814375	0.0183581
RAB1B	56	-0.8156194	-0.9107880	1.6e-06	5.807975	0.0186291
DLGAP1	13	-1.7675411	-1.8033308	1.6e-06	5.807773	0.0186362
TAPBP	67	-0.6217745	-0.6380393	1.6e-06	5.805094	0.0187500
NUP62	16	-1.1464507	-1.1653377	1.7e-06	5.766593	0.0204864
ATF5	16	-1.1464507	-1.1653377	1.7e-06	5.766593	0.0204864
MEPCE	23	-0.9068136	-1.1415234	1.7e-06	5.764325	0.0205902
ZCWPW1	23	-0.9068136	-1.1415234	1.7e-06	5.764325	0.0205902
CASP8	20	-1.3819733	-1.4230552	1.9e-06	5.729217	0.0223201
HIST2H2BE	22	-1.0930530	-1.2260823	1.9e-06	5.717943	0.0229052

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets,priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>%  kbl(caption = "Top enriched gene sets with GMEA-Mitch (promoter only)") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch (promoter only)

	set	setSize	pANOVA	s.dist	p.adjustANOVA
164	Condensation of Prometaphase Chromosomes	10	0.0022188	-0.5586687	0.0243528
405	HDR through MMEJ (alt-NHEJ)	11	0.0038011	-0.5039615	0.0357542
600	NOTCH2 Activation and Transmission of Signal to the Nucleus	12	0.0031193	-0.4927784	0.0319259
1195	p75NTR signals via NF-kB	11	0.0057583	-0.4808138	0.0456122
616	Negative regulation of FLT3	13	0.0037828	-0.4638590	0.0357542
1164	VLDLR internalisation and degradation	11	0.0077632	-0.4635743	0.0531072
764	RHO GTPases Activate ROCKs	13	0.0041215	-0.4595321	0.0370319
120	Caspase activation via Death Receptors in the presence of ligand	10	0.0123169	-0.4571024	0.0689746
784	RIPK1-mediated regulated necrosis	25	0.0000858	-0.4538505	0.0028692
870	Regulation of necroptotic cell death	25	0.0000858	-0.4538505	0.0028692
1172	Voltage gated Potassium channels	13	0.0058458	0.4415321	0.0460025
900	SARS-CoV-2 modulates autophagy	11	0.0114086	-0.4405478	0.0660382
533	Meiotic recombination	19	0.0013923	-0.4235978	0.0171057
911	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	27	0.0003382	-0.3985823	0.0074982
392	Glyoxylate metabolism and glycine degradation	19	0.0029203	-0.3944209	0.0305748
994	Signaling by NOTCH2	18	0.0048652	-0.3834098	0.0400010
394	Golgi Cisternae Pericentriolar Stack Reorganization	14	0.0130066	-0.3834010	0.0721656
601	NOTCH3 Activation and Transmission of Signal to the Nucleus	15	0.0110258	-0.3791076	0.0647563
368	Gap-filling DNA repair synthesis and ligation in GG-NER	23	0.0019598	-0.3730282	0.0221713
438	Impaired BRCA2 binding to RAD51	32	0.0003476	-0.3654667	0.0074982

#mitch_report(mres,outfile="gmeapr_mitch_fh_vs_fz.html",overwrite=FALSE)
rm(fh_vs_fz)

GIFT_vs_FX

dm <- GIFT_vs_FX$dma
head(dm,50) %>% kbl(caption = "Top significant genes with limma") %>% kable_paper("hover", full_width = F)

Top significant genes with limma

	Row.names	UCSC_RefGene_Name	Regulatory_Feature_Group	Islands_Name	Relation_to_Island	logFC	AveExpr	t	P.Value	adj.P.Val	B	unmeth	meth
649276	cg22179564		Unclassified_Cell_type_specific		OpenSea	-0.3700670	-0.6155396	-5.244603	5.00e-07	0.1736288	5.402427	T	C
599622	cg20185668	RBM6;RBM6			OpenSea	-0.3910661	2.7964488	-5.048881	1.30e-06	0.1736288	4.661865	T	C
253124	cg08129561	SLC4A8;SLC4A8;SLC4A8;SLC4A8;SLC4A8			OpenSea	-0.5378863	2.5459796	-4.941339	2.10e-06	0.1736288	4.262860	T	C
268646	cg08646202	ALG9;ALG9;ALG9;ALG9			OpenSea	-0.2921170	0.3275949	-4.909673	2.40e-06	0.1736288	4.146469	T	C
13056	cg00400743	PRMT10		chr4:148604954-148605625	N_Shore	-0.4235969	1.7094808	-4.898416	2.60e-06	0.1736288	4.105213	T	C
338870	cg11005961	LTN1	Promoter_Associated	chr21:30364965-30365342	S_Shore	-0.3266570	0.3943972	-4.890471	2.60e-06	0.1736288	4.076135	T	C
280404	cg09035199	RARB;RARB;RARB;RARB;RARB;RARB;RARB;RARB;RARB;RARB	NonGene_Associated		OpenSea	-0.5650709	1.4741939	-4.832438	3.40e-06	0.1736288	3.864715	T	C
430093	cg14099387	FAXDC2			OpenSea	-0.5121548	2.1105188	-4.802854	3.90e-06	0.1736288	3.757601	T	C
714964	cg24749153				OpenSea	-0.4056169	2.3084112	-4.785628	4.20e-06	0.1736288	3.695441	T	C
546139	cg18089482	SAMHD1		chr20:35579337-35580451	S_Shore	-0.5203406	2.5483414	-4.774383	4.40e-06	0.1736288	3.654946	T	C
179576	cg05723277				OpenSea	-0.4760910	1.8246200	-4.770164	4.50e-06	0.1736288	3.639771	T	C
269889	cg08688023	PHYHIPL;CCHE1;PHYHIPL		chr10:60935827-60937049	Island	-0.4504121	-3.8239932	-4.770103	4.50e-06	0.1736288	3.639553	T	C
81377	cg02556146				OpenSea	-0.4113147	2.1474439	-4.753382	4.80e-06	0.1736288	3.579494	T	C
683538	cg23538755	SGTA		chr19:2774196-2774550	Island	-0.4859806	3.1762626	-4.746868	4.90e-06	0.1736288	3.556140	T	C
45900	cg01421264	TRIM72;PYDC1		chr16:31225956-31228264	Island	-0.4264510	-3.1677364	-4.746192	4.90e-06	0.1736288	3.553718	T	C
751885	cg26192586				OpenSea	-0.3012470	2.8728638	-4.708075	5.80e-06	0.1736288	3.417509	T	C
399935	cg13139429				OpenSea	-0.4846444	1.8591595	-4.707571	5.80e-06	0.1736288	3.415712	T	C
126461	cg04002708	FAM193A;FAM193A;FAM193A;FAM193A;FAM193A;FAM193A			OpenSea	-0.4791275	0.8245716	-4.694780	6.10e-06	0.1736288	3.370179	T	C
33371	cg01025954				OpenSea	-0.3719150	1.5411520	-4.677823	6.60e-06	0.1736288	3.309948	T	C
158325	cg05029779	EIF5B			OpenSea	-0.2999053	3.4750917	-4.673193	6.70e-06	0.1736288	3.293531	T	C
227277	cg07276634	SEZ6L;SEZ6L;SEZ6L;SEZ6L;SEZ6L;SEZ6L			OpenSea	-0.3661253	1.8971943	-4.640503	7.70e-06	0.1736288	3.177933	T	C
375654	cg12278697	POR;SNORA14A			OpenSea	-0.4967767	1.8625097	-4.603496	9.00e-06	0.1736288	3.047763	T	C
736268	cg25577809			chr5:145758569-145758882	S_Shore	-0.3833417	2.3005650	-4.598571	9.20e-06	0.1736288	3.030495	T	C
673219	cg23138560			chr8:57905700-57906452	S_Shelf	-0.4170945	1.3423500	-4.597366	9.30e-06	0.1736288	3.026271	T	C
401188	cg13182602	BIN1;BIN1;BIN1;BIN1;BIN1;BIN1;BIN1;BIN1;BIN1;BIN1	Promoter_Associated_Cell_type_specific		OpenSea	-0.4954628	1.9209273	-4.589146	9.60e-06	0.1736288	2.997485	T	C
278926	cg08983181			chr12:105629690-105630099	S_Shelf	0.3357563	1.5670428	4.588086	9.60e-06	0.1736288	2.993778	T	C
345639	cg11242910				OpenSea	-0.5711026	-1.2360379	-4.574427	1.02e-05	0.1736288	2.946034	T	C
21449	cg00653017	ITCH;ITCH;ITCH			OpenSea	-0.4715464	2.1193627	-4.571612	1.03e-05	0.1736288	2.936208	T	C
711097	cg24605197				OpenSea	-0.3394933	2.7163069	-4.571365	1.03e-05	0.1736288	2.935343	T	C
31418	cg00967261	PLD1;PLD1			OpenSea	-0.3517468	0.8034182	-4.566036	1.05e-05	0.1736288	2.916754	T	C
344516	cg11206052	DENND5B-AS1;DENND5B;DENND5B		chr12:31742760-31744324	N_Shore	-0.3126815	0.3668386	-4.556314	1.10e-05	0.1736288	2.882877	T	C
214425	cg06869136	SCLT1			OpenSea	-0.4890077	1.7862067	-4.543812	1.16e-05	0.1736288	2.839391	T	C
679631	cg23387168	VARS2;VARS2;GTF2H4		chr6:30881533-30882296	N_Shore	-0.4593642	1.5086923	-4.535415	1.20e-05	0.1736288	2.810233	T	C
467795	cg15346619	DIP2C		chr10:678262-679515	N_Shelf	-0.4512849	0.5145263	-4.521425	1.27e-05	0.1736288	2.761737	T	C
370748	cg12105485				OpenSea	-0.3140478	1.8052195	-4.517964	1.29e-05	0.1736288	2.749754	T	C
85574	cg02687735	MUSK;MUSK;MUSK			OpenSea	-0.3809225	1.9546515	-4.514216	1.31e-05	0.1736288	2.736788	T	C
127497	cg04036996				OpenSea	-0.3292937	2.4798435	-4.508003	1.34e-05	0.1736288	2.715311	T	C
113661	cg03583494		Unclassified		OpenSea	-0.4196228	1.3188987	-4.494353	1.42e-05	0.1736288	2.668198	T	C
370882	cg12110244	KMT2E;KMT2E			OpenSea	-0.3394322	1.7799355	-4.493399	1.43e-05	0.1736288	2.664909	T	C
607561	cg20507224			chr22:25423973-25424230	N_Shelf	-0.3583432	1.9621538	-4.491020	1.44e-05	0.1736288	2.656711	T	C
498256	cg16397753				OpenSea	0.3324614	-0.9302204	4.488860	1.45e-05	0.1736288	2.649267	T	C
612264	cg20696198	MARCH8;MARCH8;MARCH8			OpenSea	-0.2860560	1.1623699	-4.465868	1.60e-05	0.1736288	2.570217	T	C
774593	cg27035201			chr14:61188116-61190772	S_Shelf	-0.3377076	2.2398649	-4.464431	1.61e-05	0.1736288	2.565284	T	C
728939	cg25295273	PLCB4;PLCB4;PLCB4			OpenSea	-0.3811339	2.1230375	-4.459174	1.64e-05	0.1736288	2.547254	T	C
729763	cg25325501			chr10:43393476-43394417	S_Shore	-0.3431952	1.4333607	-4.458626	1.64e-05	0.1736288	2.545378	T	C
247	cg00006926	DYM			OpenSea	-0.4237924	2.9661843	-4.456304	1.66e-05	0.1736288	2.537418	T	C
46366	cg01435860	ATP6AP1L			OpenSea	-0.3193909	0.3271874	-4.453969	1.68e-05	0.1736288	2.529419	T	C
691627	cg23855989	AQP5	Unclassified_Cell_type_specific	chr12:50354839-50356163	Island	-0.4947059	-2.4412902	-4.444127	1.74e-05	0.1736288	2.495737	T	C
412594	cg13556920	PIEZO2			OpenSea	-0.3921918	2.3835126	-4.441619	1.76e-05	0.1736288	2.487161	T	C
202267	cg06486467			chr15:102285686-102286416	N_Shelf	-0.4175454	1.9968653	-4.433836	1.82e-05	0.1736288	2.460575	T	C

dm <- dm[,c("UCSC_RefGene_Name","t")]
hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 74.141 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res,file="novakovic_gmeawg_GIFT_vs_FX.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
PTPRN2	1442	-0.5684360	-0.5568095	0	72.87803	0
MAD1L1	795	-0.5975530	-0.5722106	0	45.77968	0
DIP2C	589	-0.7340084	-0.7740951	0	42.92115	0
ATP11A	400	-0.8268551	-0.8784989	0	38.68885	0
PRDM16	653	-0.5693427	-0.5455675	0	36.02219	0
HDAC4	497	-0.6816289	-0.6932656	0	35.81561	0
SDK1	401	-0.7844672	-0.8135111	0	35.73795	0
TRAPPC9	411	-0.7507369	-0.7658974	0	35.35520	0
LPP	219	-1.1904991	-1.2636529	0	33.71493	0
INPP5A	414	-0.7527512	-0.6843884	0	32.92671	0
PDE4D	255	-0.9682933	-1.0699376	0	29.57555	0
DST	173	-1.1510320	-1.2795655	0	28.84993	0
TBCD	402	-0.6575496	-0.7702026	0	27.12309	0
MGMT	199	-0.9933347	-1.0009432	0	26.95757	0
AGAP1	410	-0.6820378	-0.6986403	0	26.87815	0
PARD3	183	-0.9823298	-0.8747063	0	26.77932	0
GMDS	177	-1.0781632	-1.1251105	0	26.64193	0
SMYD3	214	-1.0605642	-1.1771360	0	25.75724	0
RORA	226	-0.9574134	-1.0466047	0	25.68620	0
RAD51B	173	-1.0836045	-1.1900672	0	24.98789	0
AUTS2	229	-0.8908882	-0.8926102	0	24.92828	0
KCNMA1	225	-0.8949058	-0.8999417	0	24.81472	0
TNXB	513	-0.5265187	-0.5606071	0	24.11352	0
MYT1L	240	-0.8657741	-0.8769801	0	23.73505	0
SHROOM3	129	-1.1785168	-1.1737426	0	23.67486	0
ADARB2	463	-0.5885742	-0.5262194	0	23.27165	0
C6orf10	98	-1.2986451	-1.4217923	0	23.17614	0
SOX5	123	-1.2019694	-1.1654407	0	22.98940	0
PALLD	154	-1.0616026	-0.9491603	0	22.47346	0
CACNA1C	285	-0.7248364	-0.6632162	0	22.41229	0
FILIP1L	95	-1.3341261	-1.5179957	0	22.06267	0
EXT1	135	-1.1485060	-1.1668858	0	21.70833	0
EXOC4	123	-1.2444456	-1.2937239	0	21.70439	0
TRIO	227	-0.8751343	-0.9759931	0	21.67586	0
RPTOR	527	-0.5230419	-0.5400114	0	21.62577	0
NEDD4L	164	-1.0622257	-1.0661751	0	21.49679	0
ENOX1	105	-1.2656889	-1.2632686	0	21.37402	0
SYNE1	130	-1.1446056	-1.1479269	0	21.37176	0
C10orf11	155	-0.9818323	-0.9984783	0	21.24204	0
APBB2	159	-0.9900440	-1.0914609	0	21.18352	0
MCF2L	328	-0.6359351	-0.6372211	0	21.13642	0
C9orf3	166	-1.0242128	-1.1130193	0	21.11179	0
NPAS3	94	-1.2708702	-1.4835389	0	21.08580	0
LRBA	116	-1.1281591	-1.1194008	0	21.00718	0
TRIM26	185	-0.8971456	-0.8301153	0	20.96147	0
CUX1	314	-0.6242485	-0.5937226	0	20.94589	0
CDKAL1	128	-1.2782187	-1.4836399	0	20.78058	0
SYNE2	131	-1.1251312	-1.2540273	0	20.61442	0
ASAP1	143	-1.0869475	-1.2826123	0	20.58806	0
ERICH1	130	-1.1074804	-1.0929596	0	20.57828	0

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets, priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>% kbl(caption = "Top enriched gene sets with GMEA-Mitch") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch

	set	setSize	pANOVA	s.dist	p.adjustANOVA
259	DCC mediated attractive signaling	14	0.0000189	-0.6600638	0.0003527
48	Activation of RAC1	11	0.0006596	-0.5929524	0.0065878
1104	Regulation of commissural axon pathfinding by SLIT and ROBO	10	0.0033679	-0.5353787	0.0253506
612	Interaction between L1 and Ankyrins	28	0.0000036	-0.5055372	0.0000866
805	Nephrin family interactions	21	0.0000883	-0.4940925	0.0012049
1499	cGMP effects	15	0.0010256	-0.4895632	0.0098735
785	NRAGE signals death through JNK	53	0.0000000	-0.4864934	0.0000001
64	Adenylate cyclase activating pathway	10	0.0081052	-0.4834660	0.0483778
1159	SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion	13	0.0025477	-0.4832966	0.0201472
283	Defective EXT1 causes exostoses 1, TRPS2 and CHDS	12	0.0040545	-0.4790662	0.0291713
284	Defective EXT2 causes exostoses 2	12	0.0040545	-0.4790662	0.0291713
88	Apoptotic cleavage of cell adhesion proteins	11	0.0062595	-0.4759833	0.0396444
1333	Synthesis of bile acids and bile salts via 27-hydroxycholesterol	15	0.0015250	-0.4726408	0.0130909
362	EGR2 and SOX10-mediated initiation of Schwann cell myelination	27	0.0000426	-0.4549205	0.0006450
879	PKA activation in glucagon signalling	17	0.0011992	-0.4536725	0.0110455
212	Class C/3 (Metabotropic glutamate/pheromone receptors)	39	0.0000011	-0.4509063	0.0000340
853	Organic cation transport	10	0.0146000	-0.4459449	0.0753551
66	Adherens junctions interactions	26	0.0000978	-0.4413065	0.0012710
1251	Signaling by Hippo	19	0.0010274	-0.4349563	0.0098735
1146	Role of LAT2/NTAL/LAB on calcium mobilization	13	0.0069033	-0.4326699	0.0425335

#mitch_report(mres,outfile="gmeawg_mitch_GIFT_vs_FX.html",overwrite=FALSE)
# Promoter
dm <- GIFT_vs_FX$dma
dm <- dm[grep("Promoter_Associated",dm$Regulatory_Feature_Group),]
dm <- dm[,c("UCSC_RefGene_Name","t")]
head(dm,50) %>% kbl(caption = "Top significant promoters with limma") %>% kable_paper("hover", full_width = F)

Top significant promoters with limma

	UCSC_RefGene_Name	t
338870	LTN1	-4.890471
401188	BIN1;BIN1;BIN1;BIN1;BIN1;BIN1;BIN1;BIN1;BIN1;BIN1	-4.589146
616153	STK24	-4.371437
126867	SKIV2L2;DHX29	-4.274841
694550	GNG4;GNG4;GNG4	-4.220364
748886	TTC30A	-4.190293
521304	C1orf203;C1orf203;C1orf203;C1orf203;C1orf203	-4.171722
144139	ZNF254;ZNF254	-4.157274
783786	WDR70	-4.155738
569162	CHCHD3	-4.154586
239558	ZNF581	-4.151115
28971	CEP104;DFFB;DFFB;DFFB	4.150670
14503	PELI1	-4.088605
20655	WDR53;FBXO45	-4.084440
425679		-4.044694
282388		-4.011321
93882	PITX1	-3.983414
778913	PRKD2;PRKD2;PRKD2;PRKD2;PRKD2	-3.979843
581147	PRKAR2A	-3.954306
633060	GPATCH4;GPATCH4	-3.946888
324963	CHCHD6;CHCHD6	-3.938938
178917	DCAF6;BRP44;BRP44;BRP44;DCAF6;BRP44	-3.933307
535109	HCG4	-3.924940
124442	SLC7A1	-3.914966
433462	NBN;NBN	-3.914839
118116	GID4;ATPAF2	-3.890020
616631	YTHDC1;YTHDC1	-3.887668
454982	NDUFA3	-3.881479
146284	ATF7IP;ATF7IP	-3.878589
419255	NMRAL1;HMOX2	-3.857821
654285	LOC492303;ZNF326;ZNF326;ZNF326;ZNF326	-3.852197
245767	ZNF343	-3.850188
629157	STAU1;STAU1;STAU1;STAU1;STAU1	-3.837555
386933	CACNA2D4	-3.824762
381401	NAA20;NAA20;NAA20	-3.815665
123194	KLHL24	-3.814022
73472	MAP4K1;EIF3K;MAP4K1	-3.813908
524904	LOC388796;LOC388796	-3.790350
350193	FUZ;FUZ	-3.786874
626468	ETV1;ETV1;ETV1;ETV1	-3.786395
367544	EXOSC6;EXOSC6	-3.768287
437990		-3.765167
406237	PPP1R12B;PPP1R12B;PPP1R12B;PPP1R12B	-3.762318
167167	EXT1	-3.758753
73365	EZH2;EZH2	-3.754615
717083	ARHGEF3;ARHGEF3	-3.752732
781064	SDCBP;SDCBP;SDCBP;SDCBP;SDCBP	-3.750582
680682	CORO1C	-3.749360
500786	HIST1H1C;HIST1H1C	-3.748172
428596	ZNF746;ZNF746	-3.747854

hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 22.208 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res ,file="novakovic_gmeapr_GIFT_vs_FX.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
DUSP22	10	-2.3741338	-2.3628068	0.0000000	9.186128	0.0000078
CIDEB	17	-2.1313555	-2.3941727	0.0000000	8.012673	0.0001167
LTB4R	17	-2.1313555	-2.3941727	0.0000000	8.012673	0.0001167
LTB4R2	16	-2.1601697	-2.4691898	0.0000000	7.505544	0.0003750
HOXA4	14	-1.7988589	-1.7348443	0.0000000	7.377532	0.0005035
PPT2	68	-0.6363817	-0.7371197	0.0000001	6.831338	0.0017707
HCG27	36	-0.9614059	-0.8402380	0.0000006	6.220095	0.0072334
TRMT12	7	1.9879396	2.0838380	0.0000008	6.106332	0.0093987
HLA-F	36	-0.8194471	-1.0949642	0.0000029	5.533946	0.0351088
PRRT1	19	-1.0367345	-0.9954244	0.0000047	5.332271	0.0558541
ZEB2	10	0.9956977	0.9391972	0.0000085	5.068517	0.1025116
TRIM27	49	-0.6976474	-0.6619059	0.0000107	4.970235	0.1285341
ZDHHC24	23	-1.0237103	-1.0606286	0.0000117	4.930513	0.1408329
HCG4	38	-0.9621338	-0.8879615	0.0000119	4.925200	0.1425546
PCMT1	8	-1.3884745	-1.3917452	0.0000122	4.913639	0.1463883
DOM3Z	49	-0.6098174	-0.7869227	0.0000136	4.867438	0.1628062
MYCBP	14	-1.2378972	-1.3011781	0.0000194	4.711388	0.2331763
DPAGT1	16	0.8641267	0.9074759	0.0000214	4.668792	0.2571845
CAT	15	-1.2254877	-1.2652350	0.0000276	4.558887	0.3312172
FBXO34	22	-1.0264341	-0.8632887	0.0000278	4.556060	0.3333527
STK19	50	-0.5831302	-0.7719489	0.0000278	4.555743	0.3335681
HERC3	24	-1.0133372	-1.1117706	0.0000375	4.425762	0.4499137
BMF	19	-0.6905617	-0.8064702	0.0000488	4.311474	0.5853041
EIF3L	12	-0.9580501	-1.0822077	0.0000493	4.307317	0.5908843
SNORA21	12	1.0973862	1.0863649	0.0000575	4.240634	0.6888885
RPL23	12	1.0973862	1.0863649	0.0000575	4.240634	0.6888885
SPRED3	8	-1.6339252	-1.5125854	0.0000583	4.234255	0.6989652
ENO2	14	-1.0943843	-0.8564601	0.0000594	4.225943	0.7124126
BMP8B	12	-1.1818328	-1.2514762	0.0000669	4.174264	0.8023695
NUDT16	14	-1.1710311	-1.1027828	0.0000679	4.167997	0.8139629
ZNF681	14	-1.2459108	-1.3617887	0.0000767	4.115322	0.9188483
NANP	14	-0.7729482	-0.8450741	0.0000900	4.045747	1.0000000
ASH1L	17	0.9939871	1.2133682	0.0001022	3.990726	1.0000000
LRRC27	13	0.6571459	0.5514136	0.0001151	3.938943	1.0000000
RNF44	11	-1.0051924	-0.9749879	0.0001228	3.910713	1.0000000
PAICS	12	-0.8345597	-0.8874911	0.0001257	3.900608	1.0000000
PPAT	12	-0.8345597	-0.8874911	0.0001257	3.900608	1.0000000
SLC25A44	13	-0.8158709	-0.8346266	0.0001288	3.890049	1.0000000
SORD	13	-0.9290634	-0.8718388	0.0001315	3.880982	1.0000000
PEG10	56	-0.4608936	-0.4179385	0.0001387	3.857946	1.0000000
ADAMTS6	9	1.1165227	1.1216252	0.0001422	3.847012	1.0000000
FAM50B	29	-0.5539250	-0.6760743	0.0001474	3.831471	1.0000000
ING3	15	-0.9283981	-0.7177646	0.0001557	3.807705	1.0000000
C9orf9	13	-0.8781615	-0.7061844	0.0001591	3.798362	1.0000000
STXBP2	13	-0.9846099	-1.0314496	0.0001636	3.786344	1.0000000
MIR636	14	-1.0682156	-1.0903752	0.0001714	3.766078	1.0000000
LOC441046	12	-0.9701701	-1.0682308	0.0001729	3.762255	1.0000000
ZC3H12D	15	0.8461313	0.8804494	0.0001746	3.758024	1.0000000
DEPDC7	8	-0.8555801	-0.9205948	0.0001771	3.751834	1.0000000
PLD6	14	-1.2858113	-1.5380734	0.0001879	3.726168	1.0000000

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets,priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>%  kbl(caption = "Top enriched gene sets with GMEA-Mitch (promoter only)") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch (promoter only)

	set	setSize	pANOVA	s.dist	p.adjustANOVA
908	SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs	10	0.0042368	-0.5222861	0.5342063
729	Processing of Capped Intronless Pre-mRNA	23	0.0001167	-0.4641440	0.1405043
731	Processing of Intronless Pre-mRNAs	15	0.0026378	-0.4484636	0.5342063
715	Post-chaperonin tubulin folding pathway	13	0.0053243	-0.4464038	0.5342063
483	Interleukin-6 signaling	10	0.0148904	-0.4447055	0.5662402
1178	Zinc transporters	12	0.0080095	0.4421020	0.5662402
253	Downregulation of ERBB2:ERBB3 signaling	10	0.0201000	0.4245189	0.6200409
556	Metal ion SLC transporters	16	0.0052882	0.4027517	0.5342063
374	Generation of second messenger molecules	15	0.0095471	0.3865533	0.5662402
1195	p75NTR signals via NF-kB	11	0.0318157	0.3738316	0.7205169
484	Interleukin-7 signaling	14	0.0186116	-0.3632803	0.6200409
482	Interleukin-6 family signaling	13	0.0254773	-0.3578974	0.6673065
583	Mucopolysaccharidoses	10	0.0533088	-0.3529284	0.7920966
743	Purine catabolism	10	0.0594041	-0.3443056	0.7920966
763	RHO GTPases Activate NADPH Oxidases	14	0.0267688	0.3419273	0.6857365
840	Regulation of IFNG signaling	13	0.0340783	-0.3394872	0.7205169
380	Gluconeogenesis	24	0.0040577	-0.3389426	0.5342063
933	Sema4D induced cell migration and growth-cone collapse	12	0.0439317	0.3359303	0.7813479
440	Inactivation of CSF3 (G-CSF) signaling	19	0.0135598	-0.3272075	0.5662402
1046	Synthesis of PIPs at the Golgi membrane	12	0.0503119	0.3263547	0.7920966

#mitch_report(mres,outfile="gmeapr_mitch_GIFT_vs_FX.html",overwrite=TRUE)
rm(GIFT_vs_FX)

nat vs ART

dm <- nat_vs_ART$dma
head(dm,50) %>% kbl(caption = "Top significant genes with limma") %>% kable_paper("hover", full_width = F)

Top significant genes with limma

	Row.names	UCSC_RefGene_Name	Regulatory_Feature_Group	Islands_Name	Relation_to_Island	logFC	AveExpr	t	P.Value	adj.P.Val	B	unmeth	meth
656385	cg22481606	SUPT4H1	Promoter_Associated	chr17:56429455-56429906	Island	-0.3345892	-2.7425341	-6.850486	0	0.0000425	13.899446	T	C
153960	cg04891094	GGA1;GGA1;GGA1	Promoter_Associated	chr22:38004443-38005271	N_Shore	-0.2863306	-3.4858867	-6.733143	0	0.0000425	13.288747	T	C
11452	cg00352360	RPL23;SNORA21		chr17:37009471-37010118	N_Shore	-0.3490851	-2.6773154	-6.684668	0	0.0000425	13.038378	T	C
232993	cg07465122	DERL1;DERL1;DERL1;DERL1	Promoter_Associated	chr8:124054057-124054733	Island	-0.4425211	-4.5638047	-6.614369	0	0.0000425	12.677312	T	C
413802	cg13592399	NID2;NID2	Unclassified_Cell_type_specific	chr14:52534581-52536722	Island	-0.4426424	-3.6702528	-6.612680	0	0.0000425	12.668667	T	C
52374	cg01627351		Unclassified_Cell_type_specific		OpenSea	-0.3262812	-2.6059615	-6.602309	0	0.0000425	12.615615	T	C
195777	cg06262436	ISM1		chr20:13200670-13202616	Island	-0.3606290	-2.2356869	-6.556878	0	0.0000469	12.383826	T	C
45699	cg01414687	FABP3	Unclassified		OpenSea	-0.4012794	-1.2942828	-6.509397	0	0.0000483	12.142678	T	C
226991	cg07267166	ZNF323;ZNF323;ZKSCAN3	Promoter_Associated_Cell_type_specific		OpenSea	-0.4606248	-2.1185239	-6.506390	0	0.0000483	12.127443	T	C
564284	cg18789663	PLD5		chr1:242687922-242688682	Island	-0.2840534	-2.7742571	-6.462047	0	0.0000555	11.903317	T	C
12931	cg00397324	MX1;MX1	Promoter_Associated_Cell_type_specific	chr21:42798146-42798884	Island	-0.5399930	-4.3877013	-6.428624	0	0.0000607	11.735039	T	C
282452	cg09106556	ZNF302;ZNF302	Promoter_Associated	chr19:35168145-35168979	Island	-0.3969197	-2.5822744	-6.405823	0	0.0000616	11.620567	T	C
135434	cg04287982	NBPF3	Promoter_Associated	chr1:21766272-21767224	Island	-0.3366460	-2.5612903	-6.388291	0	0.0000616	11.532729	T	C
569574	cg19004138	C6orf170	Promoter_Associated	chr6:121655615-121656022	Island	-0.2774160	-3.0136260	-6.380400	0	0.0000616	11.493247	T	C
529461	cg17465697	TRIM11	Promoter_Associated	chr1:228593811-228594713	Island	-0.4611816	-2.4053329	-6.368027	0	0.0000616	11.431401	T	C
766156	cg26721193			chr8:93114056-93115979	Island	-0.4249064	-4.0401758	-6.346323	0	0.0000616	11.323104	T	C
538579	cg17802144	STC2	Unclassified	chr5:172754056-172757098	Island	-0.4124407	-2.3959002	-6.344065	0	0.0000616	11.311853	T	C
363209	cg11847929	TXNDC15	Promoter_Associated	chr5:134209887-134210504	Island	-0.4818679	-4.0694362	-6.335925	0	0.0000616	11.271307	T	C
583046	cg19545623	NSUN7;NSUN7	Unclassified	chr4:40751842-40752493	Island	-0.2136692	-3.0840198	-6.275196	0	0.0000775	10.969912	T	C
143693	cg04558112	NOB1	Promoter_Associated	chr16:69788469-69788984	Island	-0.3763683	-3.5888024	-6.272180	0	0.0000775	10.954994	T	C
621085	cg21046659	SUSD1;SUSD1;SUSD1;SUSD1;SUSD1;SUSD1;MIR3134	Promoter_Associated	chr9:114937020-114937824	Island	-0.3596132	-2.5528527	-6.255226	0	0.0000775	10.871225	T	C
660582	cg22649068	MCL1;MCL1	Unclassified	chr1:150551328-150552353	Island	-0.3732264	-2.9748394	-6.251056	0	0.0000775	10.850644	T	C
196265	cg06280512	PRKD2;PRKD2;PRKD2;PRKD2;PRKD2	Promoter_Associated	chr19:47217161-47217555	Island	-0.3682623	-3.3966598	-6.248502	0	0.0000775	10.838043	T	C
548517	cg18176703		Promoter_Associated	chr3:115502725-115503581	Island	-0.3818447	-4.2297030	-6.228654	0	0.0000811	10.740235	T	C
232844	cg07460665	CALCOCO2	Promoter_Associated	chr17:46908301-46908844	S_Shore	-0.3152375	-2.5189703	-6.220359	0	0.0000811	10.699419	T	C
229639	cg07352757	ATP11A;ATP11A		chr13:113495320-113495738	Island	0.4924649	3.2506144	6.216178	0	0.0000811	10.678863	T	C
740732	cg25749966	BAP1;PHF7;BAP1;PHF7		chr3:52443677-52445104	Island	-0.4242808	-2.7938925	-6.208058	0	0.0000811	10.638963	T	C
643083	cg21926875	EPCAM;EPCAM		chr2:47596629-47597256	N_Shore	-0.4150506	-1.3395065	-6.203579	0	0.0000811	10.616968	T	C
89122	cg02799478	ZNF416	Unclassified	chr19:58089801-58090524	Island	-0.1937357	-2.3027460	-6.186537	0	0.0000858	10.533379	T	C
250420	cg08041573	C21orf45	Promoter_Associated	chr21:33650908-33651513	S_Shore	-0.1944946	-2.2756627	-6.178079	0	0.0000868	10.491952	T	C
675978	cg23244910			chr6:106433984-106434459	Island	-0.4323995	-4.1862177	-6.170428	0	0.0000875	10.454510	T	C
524522	cg17295589	SCN4A		chr17:62019023-62019319	Island	0.4480269	2.7363579	6.147038	0	0.0000961	10.340243	T	C
562113	cg18709349	PNMAL2	Unclassified_Cell_type_specific	chr19:46999028-46999290	Island	-0.2660014	-2.6079105	-6.126876	0	0.0001038	10.241978	T	C
510348	cg16794867	AADACL2;MIR548H2			OpenSea	-0.2626045	-0.8815826	-6.113069	0	0.0001084	10.174814	T	C
497088	cg16359169	ZNF763	Promoter_Associated	chr19:12076029-12076366	Island	-0.3159514	-3.4937058	-6.100858	0	0.0001124	10.115498	T	C
188527	cg06016354	GPSM3;NOTCH4	Promoter_Associated	chr6:32163292-32164383	Island	-0.3675753	-2.4815954	-6.087173	0	0.0001175	10.049118	T	C
159885	cg05078106	CPNE1;CPNE1;CPNE1;RBM12;RBM12;CPNE1;CPNE1;RBM12;CPNE1;CPNE1;CPNE1;CPNE1;CPNE1;RBM12;CPNE1;CPNE1;CPNE1;CPNE1	Promoter_Associated	chr20:34252556-34252927	Island	-0.4407768	-4.2704061	-6.075850	0	0.0001214	9.994270	T	C
562398	cg18720285	CALCB	Unclassified_Cell_type_specific	chr11:15094957-15095872	S_Shore	-0.3319239	-2.2520336	-6.068005	0	0.0001233	9.956314	T	C
63985	cg02002231	FGF5;FGF5;FGF5;FGF5		chr4:81187494-81187913	Island	-0.3846747	-3.8141604	-6.058503	0	0.0001263	9.910381	T	C
200896	cg06438056	AK2;AK2;AK2;AK2	Promoter_Associated	chr1:33502201-33502719	Island	-0.4935853	-1.8637289	-6.044228	0	0.0001303	9.841469	T	C
493279	cg16234029	RAB31	Unclassified	chr18:9707752-9709311	Island	-0.3228399	-3.3209683	-6.039420	0	0.0001303	9.818288	T	C
787777	cg27527736	SOCS7	Promoter_Associated	chr17:36507657-36508939	Island	-0.4071532	-4.6635779	-6.036676	0	0.0001303	9.805062	T	C
740169	cg25729922	MUL1;MUL1	Promoter_Associated	chr1:20834416-20834883	Island	-0.5023031	-4.2328629	-6.034181	0	0.0001303	9.793037	T	C
773906	cg27009302	PPP6R2;PPP6R2;PPP6R2;PPP6R2			OpenSea	0.3388828	0.8751543	6.018164	0	0.0001365	9.715940	T	C
306368	cg09904891	TBX1;TBX1;TBX1	Unclassified	chr22:19742901-19744729	Island	-0.4495085	-2.7864657	-6.016787	0	0.0001365	9.709316	T	C
564906	cg18812579				OpenSea	0.4183297	2.5226990	5.993590	0	0.0001476	9.597924	T	C
545531	cg18066451	ZNF559	Promoter_Associated	chr19:9434784-9435144	N_Shore	-0.1684341	-2.5106507	-5.990378	0	0.0001476	9.582524	T	C
326646	cg10582639		Promoter_Associated		OpenSea	-0.2889988	-1.1935906	-5.981660	0	0.0001476	9.540753	T	C
422430	cg13864937	FAM111B;FAM111B;FAM111B;FAM111B;FAM111B;FAM111B	Unclassified	chr11:58873889-58874486	S_Shore	-0.3229995	-2.1528232	-5.976417	0	0.0001476	9.515650	T	C
603971	cg20362529	HGFAC		chr4:3449650-3449995	S_Shore	0.4266515	3.3291930	5.976185	0	0.0001476	9.514543	T	C

dm <- dm[,c("UCSC_RefGene_Name","t")]
hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 80.694 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res,file="novakovic_gmeawg_nat_vs_ART.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
HOXC4	127	-1.0667465	-0.9770705	0	19.623106	0.0000000
PCDHGA1	394	0.5766643	0.6931683	0	15.007174	0.0000000
PCDHGA2	382	0.5692678	0.6716988	0	14.287090	0.0000000
PAX6	120	-0.9684436	-0.9051345	0	14.230285	0.0000000
HOXC5	79	-1.1149033	-0.9770705	0	13.611124	0.0000000
BRD2	148	-0.8494887	-0.9445601	0	12.989363	0.0000000
IRX4	44	-1.5184228	-1.4846257	0	12.978858	0.0000000
SOCS2	55	-1.5296477	-1.3920225	0	12.038249	0.0000000
PCDHGA3	361	0.5340065	0.6380057	0	11.944607	0.0000000
KIAA1949	93	-1.0448891	-0.9116278	0	11.943768	0.0000000
FLJ45983	51	-1.4874763	-1.6373890	0	11.490935	0.0000001
ZFP36L2	43	-1.7973697	-1.5553069	0	11.449953	0.0000001
PRDM8	56	-1.4064038	-1.1853856	0	11.413189	0.0000001
CSNK2B	74	-1.0753342	-1.2403019	0	11.323590	0.0000001
LHX9	56	-1.1929850	-1.2757049	0	11.116000	0.0000002
ALX4	77	-1.0171222	-1.1974640	0	10.885601	0.0000003
EMX2OS	79	-1.0399258	-1.0462276	0	10.705850	0.0000005
PAX2	59	-1.2700197	-1.1264172	0	10.641628	0.0000006
GNL1	106	-0.8864780	-0.6572826	0	10.639134	0.0000006
NFIX	104	-1.0573300	-1.0151138	0	10.627700	0.0000006
EMX2	43	-1.4678604	-1.5624062	0	10.533473	0.0000008
CUTA	60	-1.4234042	-1.3387574	0	10.528448	0.0000008
PAX7	100	-0.9219771	-0.9548813	0	10.462462	0.0000009
LOC100129726	33	-2.0089425	-1.9044585	0	10.435630	0.0000010
OTX1	57	-1.0651060	-0.9942043	0	10.333791	0.0000012
TBX5	79	-0.9072154	-1.0124541	0	10.004698	0.0000026
WT1	81	-0.9394533	-0.9953315	0	9.945535	0.0000030
PRR3	67	-1.1276795	-0.8157770	0	9.800860	0.0000041
PCDHGB1	343	0.4897681	0.6040116	0	9.728633	0.0000049
ASCL2	45	-1.2407188	-1.1977158	0	9.650769	0.0000058
PITX1	35	-1.3557347	-1.3764869	0	9.628954	0.0000061
CCND2	73	-1.2816497	-1.4348694	0	9.588407	0.0000067
RAB1B	62	-1.1803814	-1.2935643	0	9.478030	0.0000087
TAPBP	140	-0.7333065	-0.6919535	0	9.416488	0.0000100
GFI1	71	-1.3163969	-1.1114954	0	9.197598	0.0000166
BAT4	62	-1.1457254	-1.3491556	0	9.109197	0.0000203
HIC1	61	-1.1342847	-1.0183232	0	9.037631	0.0000239
ECE2	56	-0.9813588	-0.9984091	0	9.029134	0.0000244
HOXC6	58	-0.9744790	-0.8363048	0	9.019526	0.0000250
BRUNOL4	91	-0.8150206	-0.8553564	0	8.960349	0.0000286
PAX9	54	-1.1004084	-1.1108396	0	8.676744	0.0000550
EVX1	46	-1.3810117	-1.3078273	0	8.629512	0.0000613
DLX4	33	-1.4524684	-1.4773784	0	8.535548	0.0000761
GATA3	67	-1.0037114	-1.0919961	0	8.494481	0.0000836
EN1	41	-1.1923646	-1.0630140	0	8.478414	0.0000868
ZEB1	62	-1.0400276	-0.8997191	0	8.444933	0.0000937
RNF39	80	-0.9502754	-1.1428861	0	8.420843	0.0000991
KILLIN	53	-1.0000505	-1.0506950	0	8.414030	0.0001006
PRDM6	71	-0.8891103	-0.8630102	0	8.400431	0.0001038
NKX6-2	34	-1.6150048	-1.6522116	0	8.379580	0.0001089

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets, priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>% kbl(caption = "Top enriched gene sets with GMEA-Mitch") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch

	set	setSize	pANOVA	s.dist	p.adjustANOVA
318	Digestion of dietary carbohydrate	10	0.0001561	0.6903826	0.0006721
781	NOTCH4 Activation and Transmission of Signal to the Nucleus	11	0.0002739	-0.6335118	0.0011433
1183	SUMOylation of immune response proteins	10	0.0008470	-0.6093114	0.0030451
1364	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	14	0.0000941	-0.6026881	0.0004345
441	Folding of actin by CCT/TriC	10	0.0012902	-0.5876205	0.0043907
884	POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation	10	0.0021316	-0.5608034	0.0068860
426	FOXO-mediated transcription of cell cycle genes	16	0.0001193	-0.5554594	0.0005345
773	NGF-stimulated transcription	39	0.0000000	-0.5360006	0.0000001
375	ERKs are inactivated	13	0.0008185	-0.5359540	0.0029919
299	Defensins	40	0.0000000	0.5353054	0.0000001
117	Beta defensins	32	0.0000002	0.5339469	0.0000015
1033	RNA Polymerase III Chain Elongation	18	0.0001130	-0.5254987	0.0005172
596	Inhibition of DNA recombination at telomere	20	0.0000487	-0.5244834	0.0002434
413	FGFR2 alternative splicing	26	0.0000068	-0.5097052	0.0000402
243	Crosslinking of collagen fibrils	10	0.0053759	-0.5082862	0.0152968
786	NRIF signals cell death from the nucleus	16	0.0004808	-0.5040225	0.0018716
1069	Regulated proteolysis of p75NTR	11	0.0039039	-0.5024363	0.0116630
746	Mitochondrial translation termination	87	0.0000000	-0.4985749	0.0000000
955	Processing of Intronless Pre-mRNAs	19	0.0001724	-0.4976767	0.0007377
395	Eukaryotic Translation Elongation	88	0.0000000	-0.4974693	0.0000000

#mitch_report(mres,outfile="gmeawg_mitch_nat_vs_ART.html",overwrite=FALSE)
# Promoter
dm <- nat_vs_ART$dma
dm <- dm[grep("Promoter_Associated",dm$Regulatory_Feature_Group),]
dm <- dm[,c("UCSC_RefGene_Name","t")]
head(dm,50) %>% kbl(caption = "Top significant promoters with limma") %>% kable_paper("hover", full_width = F)

Top significant promoters with limma

	UCSC_RefGene_Name	t
656385	SUPT4H1	-6.850486
153960	GGA1;GGA1;GGA1	-6.733143
232993	DERL1;DERL1;DERL1;DERL1	-6.614369
226991	ZNF323;ZNF323;ZKSCAN3	-6.506390
12931	MX1;MX1	-6.428624
282452	ZNF302;ZNF302	-6.405823
135434	NBPF3	-6.388291
569574	C6orf170	-6.380400
529461	TRIM11	-6.368027
363209	TXNDC15	-6.335925
143693	NOB1	-6.272180
621085	SUSD1;SUSD1;SUSD1;SUSD1;SUSD1;SUSD1;MIR3134	-6.255226
196265	PRKD2;PRKD2;PRKD2;PRKD2;PRKD2	-6.248502
548517		-6.228654
232844	CALCOCO2	-6.220359
250420	C21orf45	-6.178079
497088	ZNF763	-6.100858
188527	GPSM3;NOTCH4	-6.087173
159885	CPNE1;CPNE1;CPNE1;RBM12;RBM12;CPNE1;CPNE1;RBM12;CPNE1;CPNE1;CPNE1;CPNE1;CPNE1;RBM12;CPNE1;CPNE1;CPNE1;CPNE1	-6.075850
200896	AK2;AK2;AK2;AK2	-6.044228
787777	SOCS7	-6.036676
740169	MUL1;MUL1	-6.034181
545531	ZNF559	-5.990378
326646		-5.981660
192165	MCM2	-5.975632
730955	TOP3B;TOP3B	-5.970753
1190	RHOG	-5.966710
729101	DCTPP1	-5.911897
402778	SEC1P;DBP	-5.908924
543495	WRNIP1;WRNIP1	-5.899305
85093	STK11	-5.898733
56458	CD44;CD44;CD44;CD44;CD44	-5.891039
682134	NICN1	-5.876907
140489	OXNAD1;DPH3;DPH3;DPH3;DPH3	-5.876647
148611	MIS12;DERL2	-5.869767
256304	IFITM1	-5.869597
194646	SNX8	-5.863972
396240	HSPA9	-5.856412
618976	MINK1;MINK1;MINK1;MINK1;MINK1;MINK1;MINK1;MINK1	-5.833895
421067	SCARNA2	-5.822453
117276	RHOT2	-5.810874
34987	CCT3;C1orf182;CCT3;CCT3	-5.799623
594102	ZFP91;LPXN;LPXN;ZFP91-CNTF	-5.799428
701239	RORA;RORA;RORA;RORA	-5.775858
415994	FAM32A	-5.775432
550083	DFFB;KIAA0562	-5.773348
46943	SELK	-5.771475
608982	KIAA0513	-5.766831
457675	TAF1A;TAF1A	-5.763679
612822	CETN3	-5.763520

hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 22.107 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res ,file="novakovic_gmeapr_nat_vs_ART.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
RGL2	53	-1.682826	-1.730574	0	15.358992	0.0000000
CSNK2B	35	-1.709149	-1.893934	0	14.366299	0.0000000
TAPBP	67	-1.412703	-1.419678	0	14.350895	0.0000000
BAT4	34	-1.711029	-1.913100	0	13.801392	0.0000000
RAB1B	56	-1.366706	-1.489808	0	12.266772	0.0000000
PSMB8	47	-1.299367	-1.333948	0	11.845580	0.0000000
PPT2	68	-1.102195	-1.227875	0	11.229525	0.0000001
TRIM27	49	-1.793371	-1.845707	0	10.837203	0.0000002
KIAA1949	60	-1.348092	-1.377748	0	10.804066	0.0000002
NBPF10	31	-1.725947	-1.835080	0	10.125222	0.0000009
ZNF509	15	-1.914183	-1.980563	0	10.079267	0.0000010
TBC1D14	37	-1.603081	-1.746384	0	10.026621	0.0000011
ZFYVE28	33	-1.505015	-1.442628	0	9.995816	0.0000012
TAP1	49	-1.476957	-1.364212	0	9.825837	0.0000018
CENPT	35	-1.425508	-1.475804	0	9.519184	0.0000036
STK19	50	-1.316276	-1.509938	0	9.517937	0.0000036
SOCS2	34	-1.805556	-1.488708	0	9.272233	0.0000064
DOM3Z	49	-1.308147	-1.502152	0	9.158799	0.0000083
KLC2	35	-1.508465	-1.818306	0	9.120729	0.0000091
CUTA	49	-1.538610	-1.713535	0	8.970935	0.0000128
PSMB9	46	-1.472688	-1.373166	0	8.816179	0.0000183
OGFOD2	31	-1.520769	-1.516188	0	8.811906	0.0000185
TYMS	22	-2.013430	-2.082017	0	8.640742	0.0000274
KILLIN	47	-1.043791	-1.050695	0	8.640713	0.0000274
MIR548N	39	-1.683209	-1.437621	0	8.537123	0.0000348
CLK1	15	-1.918787	-1.856382	0	8.485431	0.0000392
PPP2R5B	15	-1.876334	-1.887370	0	8.388026	0.0000491
ZFP36L2	28	-1.976038	-1.915181	0	8.380155	0.0000499
ZEB1	22	-1.540087	-1.631192	0	8.349835	0.0000536
LOC100129726	27	-2.024328	-1.925903	0	8.324435	0.0000568
ARIH2	25	-1.897886	-1.888130	0	8.302650	0.0000597
C6orf48	41	-1.079098	-1.147913	0	8.263899	0.0000653
PTEN	46	-1.020865	-1.042020	0	8.256162	0.0000664
NAP1L4	35	-1.401881	-1.561928	0	8.098782	0.0000954
DHX16	36	-1.354653	-1.305167	0	8.033836	0.0001108
POLR3C	18	-2.079396	-1.957201	0	7.978459	0.0001259
RNF115	18	-2.079396	-1.957201	0	7.978459	0.0001259
ZNF585A	15	-2.150275	-1.934257	0	7.949796	0.0001344
PSMG2	23	-1.776392	-1.895169	0	7.928968	0.0001410
MSH5	37	-1.636158	-1.212596	0	7.900756	0.0001505
NOTCH4	35	-1.681060	-1.487546	0	7.875065	0.0001596
NBPF20	38	-1.469969	-1.665761	0	7.795673	0.0001916
BLCAP	44	-1.370815	-1.455412	0	7.782389	0.0001976
LOC100130987	37	-1.370285	-1.548100	0	7.744057	0.0002158
NQO2	19	-1.692380	-1.852223	0	7.710398	0.0002332
DDAH2	36	-1.210811	-1.042357	0	7.701891	0.0002378
SACM1L	28	-1.655077	-1.666592	0	7.637626	0.0002757
ACACA	24	-1.837557	-1.949349	0	7.622095	0.0002857
FBXO34	22	-1.819070	-1.775201	0	7.574305	0.0003189
C18orf56	19	-2.040280	-2.149136	0	7.569646	0.0003223

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets,priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>%  kbl(caption = "Top enriched gene sets with GMEA-Mitch (promoter only)") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch (promoter only)

	set	setSize	pANOVA	s.dist	p.adjustANOVA
971	Signaling by FGFR2 IIIa TM	15	0.0001821	-0.5581152	0.0039142
1067	TNFs bind their physiological receptors	10	0.0136503	0.4504207	0.0617855
309	FGFR2 mutant receptor activation	17	0.0020240	-0.4324432	0.0179187
66	Assembly of the ORC complex at the origin of replication	10	0.0227522	0.4159543	0.0875198
24	Abortive elongation of HIV-1 transcript in the absence of Tat	22	0.0007826	-0.4137308	0.0099187
908	SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs	10	0.0268030	-0.4044156	0.1021227
1043	Synthesis of Leukotrienes (LT) and Eoxins (EX)	10	0.0274046	0.4028326	0.1037582
448	Inhibition of DNA recombination at telomere	18	0.0036852	-0.3954009	0.0255002
664	Other semaphorin interactions	10	0.0336253	0.3880113	0.1183767
1034	Striated Muscle Contraction	10	0.0373579	-0.3802133	0.1270590
287	Endosomal/Vacuolar pathway	10	0.0387769	-0.3774223	0.1304116
1183	mRNA Capping	26	0.0010153	-0.3724163	0.0117510
744	Purine ribonucleoside monophosphate biosynthesis	10	0.0457147	-0.3649088	0.1467746
1065	TNFR1-induced proapoptotic signaling	12	0.0304590	-0.3608241	0.1115936
308	FGFR2 alternative splicing	22	0.0036454	-0.3581322	0.0254333
51	Antigen Presentation: Folding, assembly and peptide loading of class I MHC	26	0.0017777	-0.3541561	0.0162144
1073	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	12	0.0363596	-0.3489570	0.1247205
21	Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	16	0.0163879	-0.3466231	0.0704681
214	Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	16	0.0163879	-0.3466231	0.0704681
562	Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	12	0.0376851	-0.3465197	0.1278110

#mitch_report(mres,outfile="gmeapr_mitch_nat_vs_ART.html",overwrite=FALSE)
rm(nat_vs_ART)

nat vs FX

dm <- nat_vs_FX$dma
head(dm,50) %>% kbl(caption = "Top significant genes with limma") %>% kable_paper("hover", full_width = F)

Top significant genes with limma

	Row.names	UCSC_RefGene_Name	Regulatory_Feature_Group	Islands_Name	Relation_to_Island	logFC	AveExpr	t	P.Value	adj.P.Val	B	unmeth	meth
510348	cg16794867	AADACL2;MIR548H2			OpenSea	-0.3152285	-0.8947336	-7.187824	0	0.0000164	15.031224	T	C
656385	cg22481606	SUPT4H1	Promoter_Associated	chr17:56429455-56429906	Island	-0.3535777	-2.7303776	-6.805777	0	0.0000523	13.119808	T	C
564284	cg18789663	PLD5		chr1:242687922-242688682	Island	-0.3210138	-2.7770272	-6.778618	0	0.0000523	12.986004	T	C
12931	cg00397324	MX1;MX1	Promoter_Associated_Cell_type_specific	chr21:42798146-42798884	Island	-0.5902617	-4.3814171	-6.675642	0	0.0000628	12.481283	T	C
256518	cg08242354				OpenSea	-0.2753750	0.8243791	-6.628659	0	0.0000628	12.252403	T	C
11452	cg00352360	RPL23;SNORA21		chr17:37009471-37010118	N_Shore	-0.3700254	-2.6662365	-6.616299	0	0.0000628	12.192340	T	C
529461	cg17465697	TRIM11	Promoter_Associated	chr1:228593811-228594713	Island	-0.4817736	-2.3852059	-6.382789	0	0.0001551	11.069463	T	C
363209	cg11847929	TXNDC15	Promoter_Associated	chr5:134209887-134210504	Island	-0.4971998	-4.0433518	-6.356680	0	0.0001551	10.945347	T	C
200896	cg06438056	AK2;AK2;AK2;AK2	Promoter_Associated	chr1:33502201-33502719	Island	-0.5309732	-1.8524502	-6.316619	0	0.0001551	10.755487	T	C
533323	cg17602885	CLSTN1;CLSTN1			OpenSea	0.3194582	5.0730278	6.308969	0	0.0001551	10.719311	T	C
774705	cg27039610			chr17:19015446-19015696	S_Shore	-0.3704710	-3.3623237	-6.298035	0	0.0001551	10.667650	T	C
63985	cg02002231	FGF5;FGF5;FGF5;FGF5		chr4:81187494-81187913	Island	-0.4116486	-3.8048055	-6.295295	0	0.0001551	10.654712	T	C
226991	cg07267166	ZNF323;ZNF323;ZKSCAN3	Promoter_Associated_Cell_type_specific		OpenSea	-0.4674857	-2.0904600	-6.282901	0	0.0001551	10.596230	T	C
13401	cg00411784				OpenSea	-0.1978393	0.4559388	-6.269857	0	0.0001551	10.534756	T	C
766156	cg26721193			chr8:93114056-93115979	Island	-0.4561883	-4.0321057	-6.257861	0	0.0001551	10.478289	T	C
599354	cg20173334	THAP1;THAP1	Promoter_Associated	chr8:42698430-42698723	Island	-0.2718246	-1.9987841	-6.244534	0	0.0001551	10.415627	T	C
153960	cg04891094	GGA1;GGA1;GGA1	Promoter_Associated	chr22:38004443-38005271	N_Shore	-0.2820657	-3.4642698	-6.244273	0	0.0001551	10.414400	T	C
583046	cg19545623	NSUN7;NSUN7	Unclassified	chr4:40751842-40752493	Island	-0.2270453	-3.0780469	-6.236560	0	0.0001551	10.378177	T	C
213076	cg06826756	NUP153;NUP153;NUP153		chr6:17706292-17707339	S_Shore	-0.2226600	-2.0462226	-6.203714	0	0.0001742	10.224199	T	C
85093	cg02671671	STK11	Promoter_Associated	chr19:1205368-1207422	Island	-0.3279153	-3.5589058	-6.182866	0	0.0001843	10.126720	T	C
338484	cg10992198	WDR62;WDR62	Gene_Associated		OpenSea	-0.2007770	1.1871350	-6.152533	0	0.0002051	9.985243	T	C
621085	cg21046659	SUSD1;SUSD1;SUSD1;SUSD1;SUSD1;SUSD1;MIR3134	Promoter_Associated	chr9:114937020-114937824	Island	-0.3741130	-2.5346019	-6.139869	0	0.0002051	9.926303	T	C
143693	cg04558112	NOB1	Promoter_Associated	chr16:69788469-69788984	Island	-0.3920005	-3.5737773	-6.134942	0	0.0002051	9.903391	T	C
89122	cg02799478	ZNF416	Unclassified	chr19:58089801-58090524	Island	-0.2086531	-2.2981805	-6.098571	0	0.0002221	9.734599	T	C
413802	cg13592399	NID2;NID2	Unclassified_Cell_type_specific	chr14:52534581-52536722	Island	-0.4322839	-3.6338875	-6.097275	0	0.0002221	9.728598	T	C
457675	cg14985987	TAF1A;TAF1A	Promoter_Associated	chr1:222763021-222763270	S_Shore	-0.2731548	-3.0495016	-6.090401	0	0.0002221	9.696768	T	C
524522	cg17295589	SCN4A		chr17:62019023-62019319	Island	0.4670356	2.7160996	6.083305	0	0.0002221	9.663937	T	C
562113	cg18709349	PNMAL2	Unclassified_Cell_type_specific	chr19:46999028-46999290	Island	-0.2820844	-2.6001903	-6.078354	0	0.0002221	9.641041	T	C
181735	cg05796321	GFI1;GFI1;GFI1	Promoter_Associated	chr1:92945907-92952609	Island	-0.2087773	-2.0764892	-6.072467	0	0.0002221	9.613836	T	C
34987	cg01076200	CCT3;C1orf182;CCT3;CCT3	Promoter_Associated	chr1:156308173-156308442	Island	-0.4149812	-3.5306130	-6.066419	0	0.0002221	9.585899	T	C
250420	cg08041573	C21orf45	Promoter_Associated	chr21:33650908-33651513	S_Shore	-0.2064355	-2.2687188	-6.055870	0	0.0002221	9.537215	T	C
282452	cg09106556	ZNF302;ZNF302	Promoter_Associated	chr19:35168145-35168979	Island	-0.4055010	-2.5590123	-6.049813	0	0.0002221	9.509286	T	C
701239	cg24219929	RORA;RORA;RORA;RORA	Promoter_Associated	chr15:60883298-60885350	Island	-0.3235457	-2.8755062	-6.048801	0	0.0002221	9.504621	T	C
188527	cg06016354	GPSM3;NOTCH4	Promoter_Associated	chr6:32163292-32164383	Island	-0.3900996	-2.4691684	-6.036941	0	0.0002290	9.449990	T	C
52374	cg01627351		Unclassified_Cell_type_specific		OpenSea	-0.3296654	-2.5863228	-6.025580	0	0.0002331	9.397717	T	C
196265	cg06280512	PRKD2;PRKD2;PRKD2;PRKD2;PRKD2	Promoter_Associated	chr19:47217161-47217555	Island	-0.3736255	-3.3745043	-6.018295	0	0.0002331	9.364227	T	C
584060	cg19585816	ANK1	Unclassified_Cell_type_specific	chr8:41753340-41755250	Island	-0.3427528	-2.2220996	-6.016802	0	0.0002331	9.357370	T	C
232993	cg07465122	DERL1;DERL1;DERL1;DERL1	Promoter_Associated	chr8:124054057-124054733	Island	-0.4398388	-4.5332141	-6.008614	0	0.0002366	9.319767	T	C
650316	cg22225892	NOP2;NOP2	Promoter_Associated	chr12:6676999-6677755	Island	-0.3197268	-4.7440473	-5.993310	0	0.0002491	9.249574	T	C
462248	cg15140743	TXNDC12;TXNDC12;TXNDC12;BTF3L4;BTF3L4;BTF3L4;BTF3L4;BTF3L4;BTF3L4	Promoter_Associated	chr1:52521780-52522296	Island	-0.2522620	-1.6095225	-5.966633	0	0.0002779	9.127479	T	C
135434	cg04287982	NBPF3	Promoter_Associated	chr1:21766272-21767224	Island	-0.3367112	-2.5383669	-5.939184	0	0.0003045	9.002202	T	C
195777	cg06262436	ISM1		chr20:13200670-13202616	Island	-0.3608168	-2.2106737	-5.938841	0	0.0003045	9.000638	T	C
564906	cg18812579				OpenSea	0.4355588	2.5038534	5.931838	0	0.0003081	8.968737	T	C
207281	cg06647562	GFI1;GFI1;GFI1	Promoter_Associated	chr1:92945907-92952609	Island	-0.2508142	-3.5312611	-5.925168	0	0.0003091	8.938377	T	C
793182	ch.4.27623090R				OpenSea	-0.2032081	-2.9766582	-5.918188	0	0.0003091	8.906622	T	C
511513	cg16839093		Unclassified	chr1:8002408-8002699	Island	-0.3874275	-2.1978126	-5.917771	0	0.0003091	8.904728	T	C
434607	cg14238081	RAB15	Unclassified	chr14:65438412-65439363	Island	-0.4115437	-4.0139476	-5.906933	0	0.0003195	8.855477	T	C
441302	cg14446129	HAT1;HAT1	Unclassified	chr2:172778733-172779299	Island	-0.2611469	-3.0016631	-5.894806	0	0.0003284	8.800435	T	C
642103	cg21888603	TFR2			OpenSea	-0.3251811	0.6317923	-5.893133	0	0.0003284	8.792843	T	C
643083	cg21926875	EPCAM;EPCAM		chr2:47596629-47597256	N_Shore	-0.4182516	-1.3117119	-5.854489	0	0.0003827	8.617952	T	C

dm <- dm[,c("UCSC_RefGene_Name","t")]
hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 66.336 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res,file="novakovic_gmeawg_nat_vs_FX.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
HOXC4	127	-1.1486313	-1.2697455	0	21.74569	0.0e+00
DAB1	173	-0.7061150	-0.6959995	0	15.87329	0.0e+00
PAX6	120	-1.0412454	-1.0340735	0	15.61948	0.0e+00
HOXC5	79	-1.2207997	-1.2870948	0	14.94105	0.0e+00
PDE4D	255	-0.6250354	-0.6367808	0	14.07772	0.0e+00
IRX4	44	-1.6009980	-1.5797117	0	14.05724	0.0e+00
CSNK2B	74	-1.1417019	-1.1409799	0	13.90015	0.0e+00
KIAA1949	93	-1.0291424	-0.9862753	0	13.82061	0.0e+00
BRD2	148	-0.9044531	-0.9427308	0	13.77329	0.0e+00
EMX2OS	79	-1.0946048	-1.1188815	0	13.46734	0.0e+00
PRDM8	56	-1.5567538	-1.7402419	0	12.95941	0.0e+00
GNL1	106	-1.0034405	-0.9330124	0	12.85763	0.0e+00
ALX4	77	-1.0912844	-1.1444132	0	12.73095	0.0e+00
SOCS2	55	-1.6283810	-1.6751530	0	12.48009	0.0e+00
CUTA	60	-1.5439235	-1.5946977	0	12.44951	0.0e+00
PPT2	96	-0.9856930	-1.0314315	0	12.25236	0.0e+00
TP73	131	-0.8921918	-1.0087429	0	12.01090	0.0e+00
ZFP36L2	43	-1.7684321	-1.5945707	0	12.00396	0.0e+00
BRUNOL4	91	-0.8536990	-0.8348102	0	11.46992	1.0e-07
PAX7	100	-0.9446125	-1.0483043	0	11.45177	1.0e-07
NFIX	104	-1.0576348	-1.0758846	0	11.31932	1.0e-07
EMX2	43	-1.4845418	-1.6234302	0	11.29313	1.0e-07
PAX2	59	-1.3126853	-1.2580499	0	11.26280	1.0e-07
MIR548N	124	-0.8491261	-0.6910729	0	11.20566	2.0e-07
OTX1	57	-1.0828696	-0.9926050	0	11.16489	2.0e-07
FLJ45983	51	-1.4547025	-1.6013950	0	10.99569	3.0e-07
BAT4	62	-1.1847825	-1.1591665	0	10.94129	3.0e-07
TBX5	79	-0.9827362	-1.0974311	0	10.90483	3.0e-07
ASCL2	45	-1.3060068	-1.3653913	0	10.89649	3.0e-07
PCDHGA1	394	0.4730166	0.5662274	0	10.86669	4.0e-07
GALNT9	273	-0.4574307	-0.4625249	0	10.85187	4.0e-07
BNC1	37	-1.5870600	-1.6692375	0	10.82539	4.0e-07
NBEA	75	-0.9921915	-0.9033926	0	10.77062	4.0e-07
RNF39	80	-1.0683998	-1.3343467	0	10.67652	6.0e-07
ZEB1	62	-1.1257013	-1.0299504	0	10.67043	6.0e-07
PRR3	67	-1.1760014	-1.0482389	0	10.41026	1.0e-06
GFI1	71	-1.3946690	-1.1855281	0	10.30606	1.3e-06
WT1	81	-0.9605802	-0.9408214	0	10.29205	1.3e-06
LOXL3	51	-1.1361706	-1.1621940	0	10.25927	1.4e-06
HOXC6	58	-1.0866335	-1.2450872	0	10.21252	1.6e-06
PKNOX2	143	-0.7256666	-0.7726842	0	10.19844	1.7e-06
PCDHGA2	382	0.4630430	0.5522445	0	10.14133	1.9e-06
LOC100129726	33	-1.9361917	-1.7722959	0	10.13061	1.9e-06
NOTCH4	182	-0.6179221	-0.5741528	0	10.11029	2.0e-06
EYA4	85	-0.8734142	-0.8654568	0	10.10635	2.0e-06
TAPBP	140	-0.7568086	-0.8142898	0	10.08022	2.2e-06
PITX1	35	-1.6090183	-1.5334430	0	10.07143	2.2e-06
TPM1	54	-0.9530824	-0.7613746	0	10.06242	2.3e-06
PRDM6	71	-1.0050461	-0.9594589	0	10.01542	2.5e-06
CCND2	73	-1.2544063	-1.4208491	0	10.00050	2.6e-06

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets, priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>% kbl(caption = "Top enriched gene sets with GMEA-Mitch") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch

	set	setSize	pANOVA	s.dist	p.adjustANOVA
781	NOTCH4 Activation and Transmission of Signal to the Nucleus	11	0.0001082	-0.6739738	0.0004252
426	FOXO-mediated transcription of cell cycle genes	16	0.0000125	-0.6306631	0.0000625
884	POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation	10	0.0005928	-0.6271844	0.0018449
441	Folding of actin by CCT/TriC	10	0.0008784	-0.6074598	0.0026062
117	Beta defensins	32	0.0000000	0.5991701	0.0000001
243	Crosslinking of collagen fibrils	10	0.0011351	-0.5942923	0.0032481
1052	RUNX3 regulates p14-ARF	10	0.0011878	-0.5919357	0.0033799
1364	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	14	0.0001294	-0.5906959	0.0004969
299	Defensins	40	0.0000000	0.5859833	0.0000000
955	Processing of Intronless Pre-mRNAs	19	0.0000197	-0.5654647	0.0000935
984	RAF-independent MAPK1/3 activation	22	0.0000074	-0.5516444	0.0000404
119	Beta-catenin phosphorylation cascade	16	0.0001520	-0.5468164	0.0005609
339	Disorders of Developmental Biology	11	0.0018150	-0.5430165	0.0047651
340	Disorders of Nervous System Development	11	0.0018150	-0.5430165	0.0047651
676	Loss of function of MECP2 in Rett syndrome	11	0.0018150	-0.5430165	0.0047651
902	Pervasive developmental disorders	11	0.0018150	-0.5430165	0.0047651
953	Processing of Capped Intronless Pre-mRNA	28	0.0000009	-0.5352768	0.0000068
1124	Repression of WNT target genes	13	0.0008992	-0.5317631	0.0026576
1069	Regulated proteolysis of p75NTR	11	0.0024847	-0.5266982	0.0062648
54	Activation of the TFAP2 (AP-2) family of transcription factors	11	0.0024896	-0.5265938	0.0062648

#mitch_report(mres,outfile="gmeawg_mitch_nat_vs_FX.html",overwrite=FALSE)
# Promoter
dm <- nat_vs_FX$dma
dm <- dm[grep("Promoter_Associated",dm$Regulatory_Feature_Group),]
dm <- dm[,c("UCSC_RefGene_Name","t")]
head(dm,50) %>% kbl(caption = "Top significant promoters with limma") %>% kable_paper("hover", full_width = F)

Top significant promoters with limma

	UCSC_RefGene_Name	t
656385	SUPT4H1	-6.805777
12931	MX1;MX1	-6.675642
529461	TRIM11	-6.382789
363209	TXNDC15	-6.356680
200896	AK2;AK2;AK2;AK2	-6.316619
226991	ZNF323;ZNF323;ZKSCAN3	-6.282901
599354	THAP1;THAP1	-6.244534
153960	GGA1;GGA1;GGA1	-6.244273
85093	STK11	-6.182866
621085	SUSD1;SUSD1;SUSD1;SUSD1;SUSD1;SUSD1;MIR3134	-6.139869
143693	NOB1	-6.134942
457675	TAF1A;TAF1A	-6.090401
181735	GFI1;GFI1;GFI1	-6.072467
34987	CCT3;C1orf182;CCT3;CCT3	-6.066419
250420	C21orf45	-6.055870
282452	ZNF302;ZNF302	-6.049813
701239	RORA;RORA;RORA;RORA	-6.048801
188527	GPSM3;NOTCH4	-6.036941
196265	PRKD2;PRKD2;PRKD2;PRKD2;PRKD2	-6.018295
232993	DERL1;DERL1;DERL1;DERL1	-6.008614
650316	NOP2;NOP2	-5.993310
462248	TXNDC12;TXNDC12;TXNDC12;BTF3L4;BTF3L4;BTF3L4;BTF3L4;BTF3L4;BTF3L4	-5.966633
135434	NBPF3	-5.939184
207281	GFI1;GFI1;GFI1	-5.925168
468667		-5.827509
663043	SLCO4A1	-5.769214
743573	SELM	-5.769162
761329	AMPD2;AMPD2;AMPD2	-5.767422
278763	IRF1	-5.766804
548517		-5.760811
219269	MAP3K11	-5.756010
46943	SELK	-5.753993
266616	ACAD10;BRAP;ACAD10	-5.747739
704198	POLR2E	-5.744475
740169	MUL1;MUL1	-5.739092
396240	HSPA9	-5.732673
138167	SETD1A;SETD1A	-5.709954
303761	GTPBP5	-5.704790
240346	ZNF91	-5.703741
787777	SOCS7	-5.701856
402778	SEC1P;DBP	-5.700898
533320	SESN2	-5.699106
682134	NICN1	-5.696730
618976	MINK1;MINK1;MINK1;MINK1;MINK1;MINK1;MINK1;MINK1	-5.693669
622271	B9D1;B9D1	-5.688810
547792	C5orf39	-5.682909
748708	HLA-E	-5.677408
1190	RHOG	-5.669865
140489	OXNAD1;DPH3;DPH3;DPH3;DPH3	-5.665737
326646		-5.650195

hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 20.51 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res ,file="novakovic_gmeapr_nat_vs_FX.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
RGL2	53	-1.6598715	-1.6196721	0	15.292755	0.0000000
PPT2	68	-1.2371746	-1.3085334	0	14.004610	0.0000000
TAPBP	67	-1.3925703	-1.3478906	0	13.097931	0.0000000
CSNK2B	35	-1.6349392	-1.6249811	0	12.576755	0.0000000
BAT4	34	-1.6471265	-1.6382744	0	12.186135	0.0000000
TRIM27	49	-1.8970818	-2.1116120	0	11.905574	0.0000000
RAB1B	56	-1.3023456	-1.3416057	0	11.561452	0.0000000
PSMB8	47	-1.2650637	-1.2039563	0	11.301017	0.0000001
TAP1	49	-1.5580561	-1.3400091	0	11.276720	0.0000001
KIAA1949	60	-1.2233174	-1.0851519	0	10.412625	0.0000005
PSMB9	46	-1.5716386	-1.4195433	0	10.408912	0.0000005
TBC1D14	37	-1.5635310	-1.5036408	0	10.399161	0.0000005
ZFYVE28	33	-1.6162155	-1.4483076	0	10.308538	0.0000006
STK19	50	-1.4784270	-1.4902772	0	10.228110	0.0000007
CLK1	15	-1.9669520	-1.9472343	0	10.208559	0.0000007
NBPF10	31	-1.6273895	-1.5466270	0	10.189350	0.0000008
CUTA	49	-1.6077410	-1.6562161	0	9.982461	0.0000012
DOM3Z	49	-1.4801356	-1.5125474	0	9.922210	0.0000014
CENPT	35	-1.4222295	-1.4119198	0	9.881774	0.0000016
C6orf48	41	-1.2530350	-1.2890288	0	9.581128	0.0000031
FBXO34	22	-1.9526373	-1.7813011	0	8.982586	0.0000125
KLC2	35	-1.4245534	-1.4886468	0	8.970608	0.0000128
SOCS2	34	-1.8112163	-1.7322954	0	8.909567	0.0000148
ZNF509	15	-1.9463541	-1.9239452	0	8.760662	0.0000208
HCG27	36	-1.3285851	-1.4703459	0	8.745497	0.0000215
FBXO31	22	-1.9943904	-1.8819314	0	8.741402	0.0000217
TYMS	22	-2.0416589	-2.2697098	0	8.734073	0.0000221
KILLIN	47	-1.0784690	-1.0882659	0	8.694968	0.0000242
DHX16	36	-1.5129876	-1.5819241	0	8.626966	0.0000283
NOTCH4	35	-1.7367396	-1.4367892	0	8.595567	0.0000304
POLR3C	18	-2.0373399	-1.8999520	0	8.594272	0.0000305
RNF115	18	-2.0373399	-1.8999520	0	8.594272	0.0000305
PTEN	46	-1.0373989	-1.0316013	0	8.434924	0.0000440
NBPF20	38	-1.4325226	-1.4882440	0	8.429692	0.0000445
NAP1L4	35	-1.3770783	-1.4163181	0	8.367882	0.0000513
GPSM3	39	-1.5832695	-1.3774310	0	8.290001	0.0000614
FLOT1	65	-0.8454444	-0.6245437	0	8.286407	0.0000619
CHD9	23	-1.7681992	-1.6972188	0	8.258658	0.0000660
BLCAP	44	-1.3555963	-1.7030744	0	8.192084	0.0000769
ZFP36L2	28	-1.9486889	-1.8705647	0	8.185068	0.0000782
ZNF585A	15	-2.1317349	-2.2245270	0	8.150555	0.0000847
MIR548N	39	-1.6607001	-1.7650916	0	8.131658	0.0000884
ARIH2	25	-1.9805620	-1.8584254	0	8.127227	0.0000893
LOC100129726	27	-1.9929892	-2.0041124	0	8.087524	0.0000979
SMAP1	19	-1.3621264	-1.4026796	0	8.043663	0.0001082
MSH5	37	-1.7174934	-1.5076655	0	8.009688	0.0001170
PRKCSH	27	-1.3993530	-1.1936877	0	7.938844	0.0001378
CCDC151	27	-1.3993530	-1.1936877	0	7.938844	0.0001378
TRIM26	25	-1.8570221	-1.9283690	0	7.906518	0.0001484
LOC100130987	37	-1.3146454	-1.3319091	0	7.820751	0.0001808

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets,priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>%  kbl(caption = "Top enriched gene sets with GMEA-Mitch (promoter only)") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch (promoter only)

	set	setSize	pANOVA	s.dist	p.adjustANOVA
971	Signaling by FGFR2 IIIa TM	15	0.0001345	-0.5693393	0.0038487
309	FGFR2 mutant receptor activation	17	0.0011056	-0.4570200	0.0144354
1067	TNFs bind their physiological receptors	10	0.0134499	0.4513872	0.0637545
448	Inhibition of DNA recombination at telomere	18	0.0020551	-0.4196610	0.0198535
908	SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs	10	0.0217358	-0.4191286	0.0896229
287	Endosomal/Vacuolar pathway	10	0.0227876	-0.4158460	0.0926903
1043	Synthesis of Leukotrienes (LT) and Eoxins (EX)	10	0.0233439	0.4141631	0.0943155
1180	alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	10	0.0253785	-0.4082896	0.1003315
1181	alpha-linolenic acid (ALA) metabolism	10	0.0253785	-0.4082896	0.1003315
1034	Striated Muscle Contraction	10	0.0280080	-0.4012747	0.1067141
374	Generation of second messenger molecules	15	0.0074101	0.3993777	0.0450594
731	Processing of Intronless Pre-mRNAs	15	0.0075380	-0.3985220	0.0451102
66	Assembly of the ORC complex at the origin of replication	10	0.0299462	0.3964592	0.1126724
24	Abortive elongation of HIV-1 transcript in the absence of Tat	22	0.0013136	-0.3957703	0.0152074
744	Purine ribonucleoside monophosphate biosynthesis	10	0.0307453	-0.3945514	0.1142511
308	FGFR2 alternative splicing	22	0.0015887	-0.3889963	0.0175484
664	Other semaphorin interactions	10	0.0337398	0.3877614	0.1212617
51	Antigen Presentation: Folding, assembly and peptide loading of class I MHC	26	0.0006900	-0.3845673	0.0105154
562	Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	12	0.0218844	-0.3822112	0.0897632
479	Interleukin-35 Signalling	11	0.0315120	-0.3744982	0.1160259

#mitch_report(mres,outfile="gmeapr_mitch_nat_vs_FX.html",overwrite=FALSE)
rm(nat_vs_FX)

nat vs fz

dm <- nat_vs_fz$dma
head(dm,50) %>% kbl(caption = "Top significant genes with limma") %>% kable_paper("hover", full_width = F)

Top significant genes with limma

	Row.names	UCSC_RefGene_Name	Regulatory_Feature_Group	Islands_Name	Relation_to_Island	logFC	AveExpr	t	P.Value	adj.P.Val	B	unmeth	meth
256518	cg08242354				OpenSea	-0.3152483	0.8943181	-6.506412	0.0e+00	0.0031011	9.380666	T	C
752334	cg26210521	SLC2A9;SLC2A9			OpenSea	-0.3006819	1.7161926	-5.895749	1.0e-07	0.0239683	7.133158	T	C
338484	cg10992198	WDR62;WDR62	Gene_Associated		OpenSea	-0.2236919	1.2387011	-5.801023	1.0e-07	0.0242064	6.791288	T	C
462440	cg15147113	SERPINE2;SERPINE2;SERPINE2;SERPINE2	Unclassified		OpenSea	-1.8030982	-2.7736616	-5.697909	1.0e-07	0.0284421	6.421547	T	C
510348	cg16794867	AADACL2;MIR548H2			OpenSea	-0.2993101	-0.7937804	-5.622730	2.0e-07	0.0314964	6.153628	T	C
216261	cg06924355	PAQR3	Promoter_Associated	chr4:79860213-79860745	S_Shore	-0.4292641	-3.5008896	-5.499973	3.0e-07	0.0444505	5.719318	T	C
682894	cg23516310				OpenSea	-0.3800761	-3.3826145	-5.400713	5.0e-07	0.0581116	5.371151	T	C
588078	cg19738653	EGR3;EGR3;EGR3		chr8:22547486-22553427	Island	-0.4332157	-3.8424535	-5.264446	9.0e-07	0.0902447	4.897814	T	C
675978	cg23244910			chr6:106433984-106434459	Island	-0.5356667	-4.0629840	-5.157211	1.4e-06	0.0913558	4.529301	T	C
477211	cg15681038	ZNF529;ZNF529;ZNF529;ZNF529	Unclassified	chr19:37063892-37064749	Island	-0.4274625	-2.9125259	-5.114545	1.7e-06	0.0913558	4.383696	T	C
562113	cg18709349	PNMAL2	Unclassified_Cell_type_specific	chr19:46999028-46999290	Island	-0.3004195	-2.5214645	-5.105183	1.8e-06	0.0913558	4.351825	T	C
745548	cg25950293	ADGRE5;ADGRE5;ADGRE5			OpenSea	-0.3605505	-1.1142821	-5.096878	1.8e-06	0.0913558	4.323578	T	C
193752	cg06193286	C2orf27B	Unclassified_Cell_type_specific	chr2:132558959-132559614	Island	-0.3410338	-1.7213069	-5.079993	2.0e-06	0.0913558	4.266216	T	C
648944	cg22166325	EDC3;EDC3;EDC3	Promoter_Associated	chr15:74988166-74988669	Island	-0.2641791	-3.7598410	-5.077844	2.0e-06	0.0913558	4.258921	T	C
219269	cg07019283	MAP3K11	Promoter_Associated	chr11:65382824-65383857	N_Shore	-0.4456602	-2.9140297	-5.076773	2.0e-06	0.0913558	4.255288	T	C
138589	cg04391789	ZNF423;ZNF423			OpenSea	-0.2891846	1.8764809	-5.074975	2.0e-06	0.0913558	4.249188	T	C
571354	cg19075839	ZFP41	Promoter_Associated	chr8:144328103-144329545	Island	-0.3338502	-4.3106330	-5.069197	2.0e-06	0.0913558	4.229587	T	C
599354	cg20173334	THAP1;THAP1	Promoter_Associated	chr8:42698430-42698723	Island	-0.3094981	-1.9303116	-5.030632	2.4e-06	0.0913558	4.099071	T	C
87148	cg02737619	SKI	Promoter_Associated_Cell_type_specific	chr1:2222198-2222569	Island	-0.3079778	-3.7221095	-5.017204	2.5e-06	0.0913558	4.053744	T	C
410616	cg13495442				OpenSea	-0.2747198	0.1563120	-5.013056	2.6e-06	0.0913558	4.039753	T	C
744	cg00021576		Promoter_Associated	chr1:244211034-244212088	Island	-0.3529272	-1.9490529	-5.008835	2.6e-06	0.0913558	4.025525	T	C
551926	cg18310707	SNRNP27	Promoter_Associated		OpenSea	-0.3263827	-1.7584646	-5.004169	2.7e-06	0.0913558	4.009801	T	C
774705	cg27039610			chr17:19015446-19015696	S_Shore	-0.4034834	-3.2636540	-5.003888	2.7e-06	0.0913558	4.008856	T	C
55129	cg01720455	EVX2	Unclassified_Cell_type_specific	chr2:176944087-176948446	Island	-0.3786807	-2.7838600	-4.995601	2.8e-06	0.0913558	3.980951	T	C
587964	cg19734655	C6orf64	Promoter_Associated	chr6:39082427-39083054	S_Shore	-0.4587254	-2.1205466	-4.978353	3.0e-06	0.0940864	3.922945	T	C
232247	cg07440414	TCF7;TCF7;TCF7;TCF7;TCF7;TCF7;TCF7		chr5:133449320-133451260	Island	-0.2948422	-3.2189218	-4.962221	3.2e-06	0.0952171	3.868788	T	C
286016	cg09225922		Promoter_Associated	chr20:42285961-42286535	Island	-0.3430989	-4.4054469	-4.941517	3.4e-06	0.0952171	3.799413	T	C
549297	cg18206914	SCO2;SCO2;SCO2;SCO2	Promoter_Associated	chr22:50963608-50970768	Island	-0.2848839	-3.4656419	-4.920330	3.7e-06	0.0952171	3.728577	T	C
297182	cg09594696	FASTK;FASTK;FASTK;FASTK	Promoter_Associated	chr7:150777607-150780879	Island	-0.3392796	-3.1836271	-4.918194	3.8e-06	0.0952171	3.721443	T	C
266616	cg08577424	ACAD10;BRAP;ACAD10	Promoter_Associated	chr12:112123246-112124059	Island	-0.4000659	-2.6743240	-4.915314	3.8e-06	0.0952171	3.711830	T	C
287581	cg09275667	PYGO1	Unclassified_Cell_type_specific	chr15:55879792-55881228	Island	-0.2351864	-3.0703485	-4.915226	3.8e-06	0.0952171	3.711535	T	C
34987	cg01076200	CCT3;C1orf182;CCT3;CCT3	Promoter_Associated	chr1:156308173-156308442	Island	-0.4259090	-3.4111305	-4.914563	3.8e-06	0.0952171	3.709323	T	C
689521	cg23768702	TCEB3CL;TCEB3C;KATNAL2		chr18:44554879-44556671	S_Shore	0.3817691	-0.1394471	4.900194	4.1e-06	0.0978513	3.661401	T	C
120216	cg03795663	VWA8			OpenSea	-0.3413279	3.5753351	-4.874909	4.5e-06	0.1024983	3.577252	T	C
747390	cg26022526	HTRA3		chr4:8271214-8272091	Island	-0.3358447	-2.5930522	-4.861398	4.8e-06	0.1024983	3.532382	T	C
628670	cg21344124	RHOBTB2;RHOBTB2;RHOBTB2;RHOBTB2	Promoter_Associated	chr8:22856800-22857728	Island	-0.3568038	-4.7035555	-4.859125	4.8e-06	0.1024983	3.524839	T	C
725717	cg25162889		Unclassified_Cell_type_specific		OpenSea	-0.3119025	-3.2519279	-4.853185	4.9e-06	0.1024983	3.505138	T	C
136181	cg04312358	NUMBL	Promoter_Associated	chr19:41196279-41197107	S_Shore	-0.4950689	-3.3068769	-4.838147	5.2e-06	0.1024983	3.455319	T	C
775331	cg27062184	GNB4	Promoter_Associated_Cell_type_specific	chr3:179168735-179169593	Island	-0.2980898	-4.3889302	-4.835273	5.3e-06	0.1024983	3.445810	T	C
447970	cg14650344	CHMP2B	Promoter_Associated	chr3:87275872-87276842	Island	-0.2748903	-3.7454951	-4.835160	5.3e-06	0.1024983	3.445436	T	C
282452	cg09106556	ZNF302;ZNF302	Promoter_Associated	chr19:35168145-35168979	Island	-0.4359337	-2.4486503	-4.829328	5.4e-06	0.1024983	3.426143	T	C
306086	cg09894786	CPNE5			OpenSea	-0.4792227	3.2350611	-4.828701	5.4e-06	0.1024983	3.424068	T	C
475516	cg15623480	HOXA11AS;HOXA11		chr7:27224267-27224596	Island	-0.3820331	-3.4338129	-4.802522	6.0e-06	0.1053504	3.337629	T	C
153960	cg04891094	GGA1;GGA1;GGA1	Promoter_Associated	chr22:38004443-38005271	N_Shore	-0.3060028	-3.3879715	-4.792579	6.3e-06	0.1053504	3.304867	T	C
649835	cg22204640	GDPD5	Promoter_Associated	chr11:75236189-75237781	Island	-0.3548485	-3.9796570	-4.769257	6.9e-06	0.1053504	3.228161	T	C
136882	cg04336164	PPP3R1	Promoter_Associated	chr2:68479061-68480040	N_Shore	-0.2392601	-2.9688400	-4.756079	7.2e-06	0.1053504	3.184909	T	C
140025	cg04438997	SOX9		chr17:70116274-70119998	N_Shore	-0.2900127	-2.6934440	-4.755313	7.3e-06	0.1053504	3.182397	T	C
55025	cg01717636	IPP;IPP;IPP;IPP	Promoter_Associated	chr1:46216233-46216514	Island	-0.3814961	-3.8181178	-4.752418	7.4e-06	0.1053504	3.172906	T	C
12931	cg00397324	MX1;MX1	Promoter_Associated_Cell_type_specific	chr21:42798146-42798884	Island	-0.5670991	-4.1962993	-4.750186	7.4e-06	0.1053504	3.165592	T	C
35744	cg01099580	MINPP1	Promoter_Associated	chr10:89264370-89265371	Island	-0.2967800	-3.0538276	-4.743492	7.6e-06	0.1053504	3.143659	T	C

dm <- dm[,c("UCSC_RefGene_Name","t")]
hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 72.005 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res,file="novakovic_gmeawg_nat_vs_fz.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
HOXC4	127	-1.1875790	-1.1031823	0	26.398661	0.0e+00
HOXC5	79	-1.2599605	-1.2178436	0	18.263701	0.0e+00
PAX6	120	-0.9887631	-0.9234234	0	18.258093	0.0e+00
SEPT9	259	-0.6306013	-0.5840370	0	17.518752	0.0e+00
BRD2	148	-0.8900896	-0.9315461	0	15.966871	0.0e+00
OTX1	57	-1.2646270	-1.1532097	0	15.632118	0.0e+00
NR2F2	62	-1.1616635	-1.2036614	0	15.526316	0.0e+00
LHX9	56	-1.3196230	-1.3495833	0	14.673719	0.0e+00
FLJ45983	51	-1.4208726	-1.4821152	0	14.072120	0.0e+00
GNL1	106	-0.9179817	-0.9590553	0	13.959262	0.0e+00
PRRT1	66	-1.2247348	-1.3485454	0	13.723521	0.0e+00
HOXC6	58	-1.2534913	-1.1156817	0	13.385683	0.0e+00
EMX2OS	79	-1.1593909	-1.3153080	0	13.076130	0.0e+00
ZIC1	49	-1.1538329	-1.2646770	0	12.947796	0.0e+00
GFI1	71	-1.1964906	-0.9843714	0	12.755287	0.0e+00
RGL2	108	-0.9483925	-0.9375402	0	12.704642	0.0e+00
RAB1B	62	-1.2337204	-1.2390034	0	12.504795	0.0e+00
ALX4	77	-1.0567182	-1.1547808	0	12.357399	0.0e+00
MSX1	49	-1.4071589	-1.3507229	0	11.867708	0.0e+00
HAND2	40	-1.2035657	-1.1332475	0	11.781798	0.0e+00
ZFP36L2	43	-1.4490928	-1.4122584	0	11.771992	0.0e+00
PAX9	54	-1.0647395	-1.1085178	0	11.753182	0.0e+00
NR4A2	37	-1.2562839	-1.2526399	0	11.692391	1.0e-07
NFIX	104	-1.0228244	-1.1149845	0	11.648708	1.0e-07
PRDM13	37	-1.3919151	-1.3551365	0	11.413694	1.0e-07
PRR3	67	-0.9978243	-1.0211254	0	11.360449	1.0e-07
LOC220930	24	-1.6542425	-1.6117606	0	11.324879	1.0e-07
HES1	31	-1.6094254	-1.4427283	0	11.216439	2.0e-07
CUTA	60	-1.2774783	-1.3892101	0	11.204249	2.0e-07
BDNF	81	-0.9069598	-0.8961371	0	11.061756	2.0e-07
HCG9	46	-1.2183795	-1.2784924	0	10.987714	3.0e-07
ONECUT1	36	-1.1006687	-1.0047163	0	10.945678	3.0e-07
PFDN6	48	-1.0658623	-1.0789011	0	10.736228	5.0e-07
ADM	28	-1.5218408	-1.3356577	0	10.696472	5.0e-07
BAT4	62	-1.1799959	-1.3398200	0	10.695631	5.0e-07
DLX5	43	-1.1741726	-1.2662590	0	10.673363	6.0e-07
NR2E1	57	-1.2364899	-1.4485577	0	10.670258	6.0e-07
EMX2	43	-1.3599442	-1.5612246	0	10.622258	6.0e-07
TP73	131	-0.7382128	-0.7499546	0	10.590483	7.0e-07
RARA	85	-0.9749696	-0.8681765	0	10.478441	9.0e-07
IGF2	116	-0.7658289	-0.7124495	0	10.425156	1.0e-06
PEG10	103	-0.7917712	-0.7934416	0	10.336691	1.2e-06
DUSP6	39	-1.2686186	-1.1501495	0	10.330440	1.2e-06
TBX5	79	-0.8794719	-0.8660849	0	10.238840	1.5e-06
INS-IGF2	145	-0.6662797	-0.5851670	0	10.188160	1.7e-06
NBEA	75	-0.9733918	-0.9210092	0	10.166815	1.8e-06
EN1	41	-1.3216851	-1.3208538	0	10.159720	1.8e-06
PITX2	69	-0.8694151	-0.8745734	0	10.156058	1.8e-06
CCND2	73	-1.0428287	-1.2240644	0	10.118818	2.0e-06
RNF39	80	-0.9130992	-1.0806485	0	9.960513	2.9e-06

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets, priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>% kbl(caption = "Top enriched gene sets with GMEA-Mitch") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch

	set	setSize	pANOVA	s.dist	p.adjustANOVA
1052	RUNX3 regulates p14-ARF	10	0.0003064	-0.6591201	0.0012289
318	Digestion of dietary carbohydrate	10	0.0007084	0.6183168	0.0025570
1364	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	14	0.0000898	-0.6044263	0.0004073
1183	SUMOylation of immune response proteins	10	0.0011559	-0.5933512	0.0038990
884	POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation	10	0.0012806	-0.5880107	0.0042818
54	Activation of the TFAP2 (AP-2) family of transcription factors	11	0.0007668	-0.5857600	0.0027376
117	Beta defensins	32	0.0000000	0.5806221	0.0000001
227	Condensation of Prometaphase Chromosomes	11	0.0010728	-0.5694347	0.0036507
395	Eukaryotic Translation Elongation	88	0.0000000	-0.5670264	0.0000000
236	Constitutive Signaling by Overexpressed ERBB2	10	0.0019680	-0.5651415	0.0062259
896	Peptide chain elongation	84	0.0000000	-0.5617635	0.0000000
1478	Viral mRNA Translation	84	0.0000000	-0.5612356	0.0000000
299	Defensins	40	0.0000000	0.5572166	0.0000000
1340	Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	12	0.0009499	-0.5509093	0.0032838
397	Eukaryotic Translation Termination	87	0.0000000	-0.5501863	0.0000000
1172	SRP-dependent cotranslational protein targeting to membrane	105	0.0000000	-0.5495408	0.0000000
903	Pexophagy	11	0.0018450	-0.5421749	0.0058855
399	Expression and translocation of olfactory receptors	366	0.0000000	0.5362630	0.0000000
375	ERKs are inactivated	13	0.0008148	-0.5361542	0.0028886
1135	Response of EIF2AK4 (GCN2) to amino acid deficiency	95	0.0000000	-0.5341482	0.0000000

#mitch_report(mres,outfile="gmeawg_mitch_nat_vs_fz.html",overwrite=FALSE)
# Promoter
dm <- nat_vs_fz$dma
dm <- dm[grep("Promoter_Associated",dm$Regulatory_Feature_Group),]
dm <- dm[,c("UCSC_RefGene_Name","t")]
head(dm,50) %>% kbl(caption = "Top significant promoters with limma") %>% kable_paper("hover", full_width = F)

Top significant promoters with limma

	UCSC_RefGene_Name	t
216261	PAQR3	-5.499973
648944	EDC3;EDC3;EDC3	-5.077844
219269	MAP3K11	-5.076773
571354	ZFP41	-5.069197
599354	THAP1;THAP1	-5.030632
87148	SKI	-5.017204
744		-5.008835
551926	SNRNP27	-5.004169
587964	C6orf64	-4.978353
286016		-4.941517
549297	SCO2;SCO2;SCO2;SCO2	-4.920330
297182	FASTK;FASTK;FASTK;FASTK	-4.918194
266616	ACAD10;BRAP;ACAD10	-4.915314
34987	CCT3;C1orf182;CCT3;CCT3	-4.914563
628670	RHOBTB2;RHOBTB2;RHOBTB2;RHOBTB2	-4.859125
136181	NUMBL	-4.838147
775331	GNB4	-4.835273
447970	CHMP2B	-4.835160
282452	ZNF302;ZNF302	-4.829328
153960	GGA1;GGA1;GGA1	-4.792579
649835	GDPD5	-4.769257
136882	PPP3R1	-4.756079
55025	IPP;IPP;IPP;IPP	-4.752418
12931	MX1;MX1	-4.750186
35744	MINPP1	-4.743492
751787	SLC2A1	-4.741462
328682	IMPAD1	-4.740465
354079	LRRC58	-4.738148
225202	P4HB	-4.702361
675106	NFXL1	-4.682983
590696	SNAP23;SNAP23	-4.682214
315695	ATP8B2	-4.680612
552585	SLC25A15	-4.662925
631700	KRTCAP2;TRIM46	-4.642804
609304	NIPA2;NIPA2;NIPA2;NIPA2;NIPA2;NIPA2;NIPA2;NIPA2	-4.635160
656385	SUPT4H1	-4.631300
701239	RORA;RORA;RORA;RORA	-4.608019
303761	GTPBP5	-4.596190
649365	CCNDBP1;CCNDBP1;CCNDBP1;CCNDBP1;CCNDBP1	-4.592103
557365	BMPR2;BMPR2	-4.591928
769263	ZNF547;TRAPPC2P1	-4.571574
695950		-4.569957
555237	XPR1;XPR1	-4.554746
263521	IFT57	-4.554146
461858	MRPL42;MRPL42;MRPL42	-4.547421
462529	FUT10	-4.513932
702185	ERLIN2;ERLIN2;ERLIN2	-4.506830
225401	RIMS3	-4.505720
780272	TYSND1;TYSND1	-4.491847
48951	ARMC8;ARMC8;ARMC8;ARMC8;ARMC8;ARMC8	-4.486465

hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 20.529 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res ,file="novakovic_gmeapr_nat_vs_fz.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
RGL2	53	-1.668678	-1.745921	0	20.295908	0.00e+00
RAB1B	56	-1.407783	-1.332594	0	16.445206	0.00e+00
TAPBP	67	-1.333347	-1.508036	0	16.240355	0.00e+00
PSMB8	47	-1.198424	-1.208636	0	13.636452	0.00e+00
NBPF20	38	-1.393867	-1.379166	0	13.590074	0.00e+00
TRIM27	49	-1.635903	-1.691690	0	13.560229	0.00e+00
NBPF10	31	-1.454797	-1.450934	0	12.788520	0.00e+00
CSNK2B	35	-1.656482	-1.556937	0	12.559701	0.00e+00
BAT4	34	-1.670384	-1.581707	0	12.191591	0.00e+00
GNL1	52	-1.180772	-1.232981	0	11.789357	0.00e+00
PPT2	68	-1.031465	-1.205072	0	11.718648	0.00e+00
TAP1	49	-1.360332	-1.516572	0	11.117147	1.00e-07
EHMT2	35	-1.503181	-1.540378	0	11.022234	1.00e-07
PRKCSH	27	-1.331706	-1.259443	0	10.806976	2.00e-07
CCDC151	27	-1.331706	-1.259443	0	10.806976	2.00e-07
KIAA1949	60	-1.147239	-1.214195	0	10.508776	4.00e-07
KLC2	35	-1.212721	-1.255402	0	10.382140	5.00e-07
C6orf48	41	-1.463784	-1.604540	0	10.332303	6.00e-07
MCCC1	14	-2.105888	-2.195692	0	10.320975	6.00e-07
BRD2	52	-1.174716	-1.277524	0	10.113260	9.00e-07
PPP2R3C	23	-1.662453	-1.548881	0	10.009762	1.20e-06
KIAA0391	23	-1.662453	-1.548881	0	10.009762	1.20e-06
RUNX2	35	-1.347981	-1.436262	0	9.995669	1.20e-06
TYMS	22	-1.812415	-1.920205	0	9.874918	1.60e-06
AFF1	28	-1.548084	-1.458477	0	9.820296	1.80e-06
DDAH2	36	-1.293499	-1.468395	0	9.648161	2.70e-06
CUTA	49	-1.381656	-1.607257	0	9.629784	2.80e-06
NUDT6	24	-1.388815	-1.471791	0	9.559831	3.30e-06
SPATA5	24	-1.388815	-1.471791	0	9.559831	3.30e-06
MSH5	37	-1.467168	-1.337687	0	9.442382	4.30e-06
STK19	50	-1.195793	-1.314655	0	9.400054	4.80e-06
DOM3Z	49	-1.214716	-1.314685	0	9.376979	5.00e-06
C11orf48	29	-1.270433	-1.131915	0	9.361459	5.20e-06
DCAKD	21	-1.547671	-1.687209	0	9.289528	6.20e-06
TADA2A	17	-1.630561	-1.668822	0	9.259398	6.60e-06
LOC100130987	37	-1.426187	-1.471837	0	9.222588	7.20e-06
ZEB1	22	-1.466264	-1.397497	0	9.216940	7.30e-06
MIR548N	39	-1.311694	-1.410090	0	9.193767	7.70e-06
ZNF48	28	-1.193093	-1.239248	0	9.135430	8.80e-06
KILLIN	47	-1.132898	-1.200718	0	9.060930	1.04e-05
PFKFB3	30	-1.448081	-1.722266	0	9.035160	1.10e-05
PSMB9	46	-1.284879	-1.467776	0	9.027330	1.12e-05
ADK	30	-1.548570	-1.480849	0	8.997062	1.21e-05
OGFOD2	31	-1.433871	-1.516103	0	8.996589	1.21e-05
BLCAP	44	-1.285417	-1.260008	0	8.996447	1.21e-05
ZNF688	22	-1.615701	-1.647813	0	8.963930	1.30e-05
PTEN	46	-1.081565	-1.187633	0	8.960826	1.31e-05
TSC22D1	29	-1.346105	-1.289153	0	8.946756	1.35e-05
ACACA	24	-1.567362	-1.611116	0	8.923441	1.43e-05
ELOVL1	15	-1.786986	-1.882727	0	8.910770	1.47e-05

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets,priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>%  kbl(caption = "Top enriched gene sets with GMEA-Mitch (promoter only)") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch (promoter only)

	set	setSize	pANOVA	s.dist	p.adjustANOVA
1067	TNFs bind their physiological receptors	10	0.0023971	0.5544281	0.0151103
120	Caspase activation via Death Receptors in the presence of ligand	10	0.0046411	-0.5169874	0.0226228
174	Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	19	0.0007205	-0.4481583	0.0065182
217	Defects in vitamin and cofactor metabolism	16	0.0025809	-0.4351973	0.0161005
971	Signaling by FGFR2 IIIa TM	15	0.0037110	-0.4327610	0.0194261
448	Inhibition of DNA recombination at telomere	18	0.0017044	-0.4271826	0.0122880
533	Meiotic recombination	19	0.0014958	-0.4208508	0.0111168
784	RIPK1-mediated regulated necrosis	25	0.0002886	-0.4189356	0.0033739
870	Regulation of necroptotic cell death	25	0.0002886	-0.4189356	0.0033739
164	Condensation of Prometaphase Chromosomes	10	0.0224654	-0.4168375	0.0743086
874	Removal of the Flap Intermediate	12	0.0140788	-0.4093617	0.0504442
66	Assembly of the ORC complex at the origin of replication	10	0.0260380	0.4064734	0.0816398
725	Prefoldin mediated transfer of substrate to CCT/TriC	17	0.0044884	-0.3981229	0.0222388
388	Glycogen synthesis	11	0.0227385	-0.3966536	0.0747082
430	IKK complex recruitment mediated by RIP1	17	0.0055541	-0.3885119	0.0256213
332	Formation of tubulin folding intermediates by CCT/TriC	14	0.0125736	-0.3852583	0.0464375
745	Purine salvage	11	0.0298003	-0.3783612	0.0892528
734	Processive synthesis on the lagging strand	13	0.0197078	-0.3735577	0.0665956
1038	Synaptic adhesion-like molecules	10	0.0437100	0.3683496	0.1189787
900	SARS-CoV-2 modulates autophagy	11	0.0345373	-0.3680902	0.0990070

#mitch_report(mres,outfile="gmeapr_mitch_nat_vs_fz.html",overwrite=FALSE)
rm(nat_vs_fz)

nat vs GIFT

dm <- nat_vs_GIFT$dma
head(dm,50) %>% kbl(caption = "Top significant genes with limma") %>% kable_paper("hover", full_width = F)

Top significant genes with limma

	Row.names	UCSC_RefGene_Name	Regulatory_Feature_Group	Islands_Name	Relation_to_Island	logFC	AveExpr	t	P.Value	adj.P.Val	B	unmeth	meth
733585	cg25472804		Unclassified		OpenSea	0.4339596	1.7628532	5.310944	7.00e-07	0.185394	5.177627	T	C
272999	cg08792630	FOXO3;FOXO3	Unclassified_Cell_type_specific	chr6:108878830-108883404	S_Shore	0.4888729	-0.2260408	5.208040	1.10e-06	0.185394	4.815200	T	C
534372	cg17643276	LRRC8A;LRRC8A;LRRC8A;CCBL1;CCBL1;CCBL1;CCBL1;CCBL1	Promoter_Associated	chr9:131643911-131644749	Island	-0.3643889	-2.5283135	-5.107473	1.60e-06	0.185394	4.464444	T	C
633406	cg21538355			chr12:38557328-38557693	N_Shore	0.5023508	1.2922696	5.102670	1.70e-06	0.185394	4.447781	T	C
398954	cg13101990				OpenSea	0.3601978	2.3071676	5.056988	2.00e-06	0.185394	4.289691	T	C
24396	cg00744351	CHRNE;C17orf107	Promoter_Associated_Cell_type_specific	chr17:4802265-4805402	Island	-1.0525500	-2.5517544	-5.035687	2.20e-06	0.185394	4.216230	T	C
415481	cg13644640	NSMCE2			OpenSea	0.3647545	2.5925378	5.009672	2.40e-06	0.185394	4.126731	T	C
452798	cg14817867	PRPSAP2			OpenSea	0.3817479	1.3463816	5.007999	2.50e-06	0.185394	4.120984	T	C
421788	cg13844500				OpenSea	0.5367183	1.7494402	4.955242	3.00e-06	0.185394	3.940281	T	C
286154	cg09230221	SIK3			OpenSea	0.3265281	3.1259106	4.937664	3.30e-06	0.185394	3.880301	T	C
325866	cg10553748	CHRNE;C17orf107	Promoter_Associated_Cell_type_specific	chr17:4802265-4805402	Island	-0.4327479	-0.0675902	-4.929315	3.40e-06	0.185394	3.851850	T	C
433519	cg14206684	PDZD2			OpenSea	0.2977342	2.4300270	4.916973	3.60e-06	0.185394	3.809845	T	C
715435	cg24768135	CHRNE;C17orf107		chr17:4802265-4805402	Island	-0.6914787	0.0391235	-4.878236	4.20e-06	0.185394	3.678377	T	C
10857	cg00334550	LAMA2;LAMA2		chr6:129251113-129251319	N_Shore	0.4820291	1.4817752	4.869575	4.30e-06	0.185394	3.649062	T	C
144359	cg04578717				OpenSea	0.4209535	1.3232274	4.863002	4.40e-06	0.185394	3.626832	T	C
392029	cg12856878	NOS1AP;NOS1AP		chr1:162039450-162040052	N_Shore	0.4253668	2.4559606	4.843408	4.80e-06	0.185394	3.560667	T	C
174078	cg05540918	FBXO25;FBXO25;FBXO25			OpenSea	0.4487235	1.6882291	4.825778	5.20e-06	0.185394	3.501257	T	C
288891	cg09317790	SPECC1;SPECC1;SPECC1;SPECC1;SPECC1;SPECC1			OpenSea	0.5465339	1.3149955	4.818929	5.30e-06	0.185394	3.478213	T	C
504491	cg16602117				OpenSea	0.3598326	1.8647276	4.817606	5.30e-06	0.185394	3.473763	T	C
15447	cg00473624	ASRGL1;ASRGL1		chr11:62138621-62138873	S_Shore	0.3640062	3.1289066	4.816529	5.40e-06	0.185394	3.470140	T	C
377000	cg12327691	COX15;CUTC;COX15		chr10:101491680-101492232	S_Shore	0.2912606	2.6797302	4.795695	5.80e-06	0.185394	3.400170	T	C
235783	cg07555059				OpenSea	0.4210625	0.4014365	4.783938	6.10e-06	0.185394	3.360757	T	C
571864	cg19095317			chr2:118616575-118618163	Island	0.6362713	-2.0724217	4.776540	6.30e-06	0.185394	3.335988	T	C
712618	cg24665647	WTAP;WTAP;WTAP			OpenSea	0.3539185	3.2574765	4.757519	6.80e-06	0.185394	3.272398	T	C
300985	cg09725610	COG4		chr16:70557089-70557486	N_Shelf	0.3707756	2.2432211	4.746237	7.10e-06	0.185394	3.234749	T	C
70809	cg02223784	IRF5;IRF5;IRF5;IRF5;IRF5;IRF5;IRF5			OpenSea	0.3800526	1.7107691	4.745183	7.10e-06	0.185394	3.231232	T	C
562113	cg18709349	PNMAL2	Unclassified_Cell_type_specific	chr19:46999028-46999290	Island	-0.2648554	-2.5187685	-4.734974	7.40e-06	0.185394	3.197212	T	C
14923	cg00458927	CCT4		chr2:62115445-62115990	S_Shore	0.3956384	1.4831721	4.733421	7.50e-06	0.185394	3.192041	T	C
427759	cg14027403	SEMA4G		chr10:102729299-102729710	S_Shelf	0.3640980	2.9125687	4.725826	7.70e-06	0.185394	3.166765	T	C
13522	cg00415389	TRIM24;TRIM24			OpenSea	0.6624782	1.5215808	4.719321	7.90e-06	0.185394	3.145134	T	C
697650	cg24080291	NARS2;NARS2		chr11:78285405-78285995	N_Shelf	0.3308265	1.6507318	4.708108	8.30e-06	0.185394	3.107887	T	C
601498	cg20264106	CREG2	Unclassified_Cell_type_specific	chr2:102003277-102004187	N_Shore	-0.4270361	-3.7844737	-4.705414	8.40e-06	0.185394	3.098945	T	C
122634	cg03876823	AHCY			OpenSea	-0.3320293	-0.7170525	-4.705229	8.40e-06	0.185394	3.098331	T	C
173254	cg05512099	PLEKHF1		chr19:30156038-30156795	N_Shore	0.3527481	-0.1987732	4.699393	8.60e-06	0.185394	3.078974	T	C
679631	cg23387168	VARS2;VARS2;GTF2H4		chr6:30881533-30882296	N_Shore	0.5071057	1.5654515	4.698290	8.60e-06	0.185394	3.075317	T	C
653760	cg22368624	WDR27			OpenSea	0.4053101	1.5871537	4.682498	9.20e-06	0.185394	3.023010	T	C
430885	cg14125010				OpenSea	0.3238096	2.1850723	4.681407	9.20e-06	0.185394	3.019400	T	C
610897	cg20644425	MIR372;MIR371;MIR373			OpenSea	0.3637532	3.2558750	4.677083	9.40e-06	0.185394	3.005098	T	C
55286	cg01726265	CHRNE;C17orf107	Promoter_Associated_Cell_type_specific	chr17:4802265-4805402	Island	-0.8492769	-3.2027467	-4.664728	9.80e-06	0.185394	2.964273	T	C
100452	cg03157686	GMNN;GMNN;GMNN		chr6:24775046-24775729	N_Shore	0.3836299	2.9100899	4.663539	9.90e-06	0.185394	2.960349	T	C
36397	cg01119104	PRHOXNB			OpenSea	0.3800401	2.8046954	4.659673	1.00e-05	0.185394	2.947588	T	C
464990	cg15240369	VPS53;VPS53			OpenSea	0.3668031	3.2297067	4.651252	1.04e-05	0.185394	2.919818	T	C
701713	cg24240804	CRYBB3			OpenSea	0.3630726	1.4522992	4.649301	1.05e-05	0.185394	2.913389	T	C
182848	cg05835455	KCNMA1-AS3;KCNMA1;KCNMA1;KCNMA1;KCNMA1;KCNMA1;KCNMA1			OpenSea	0.6196026	2.1858282	4.648894	1.05e-05	0.185394	2.912047	T	C
449206	cg14691808				OpenSea	0.3802057	2.3522736	4.643488	1.07e-05	0.185394	2.894241	T	C
402429	cg13227105	C17orf82	Promoter_Associated	chr17:59488115-59490485	Island	-0.3030152	-2.9374417	-4.626767	1.14e-05	0.185394	2.839238	T	C
512934	cg16892934	BMPR2			OpenSea	0.4039554	0.9491985	4.621837	1.17e-05	0.185394	2.823044	T	C
317481	cg10273420	ZNF487		chr10:43950884-43951437	S_Shelf	0.2956451	2.1550741	4.616413	1.19e-05	0.185394	2.805237	T	C
317874	cg10286609	PPL			OpenSea	0.4157892	2.2281421	4.613281	1.21e-05	0.185394	2.794961	T	C
739622	cg25709335	CARKD		chr13:111277412-111277651	S_Shelf	0.3328697	2.4998085	4.611766	1.21e-05	0.185394	2.789993	T	C

dm <- dm[,c("UCSC_RefGene_Name","t")]
hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 73.864 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res,file="novakovic_gmeawg_nat_vs_GIFT.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
PTPRN2	1442	0.4663840	0.4794398	0	44.72671	0
ATP11A	400	0.7943149	0.9000771	0	33.31933	0
DIP2C	589	0.6171640	0.6885163	0	29.65552	0
MAD1L1	795	0.4797836	0.4492380	0	28.86424	0
INPP5A	414	0.6818937	0.7450028	0	27.39602	0
PCDHGA1	394	0.7389625	0.7176045	0	25.30379	0
LPP	219	0.9525394	1.1190506	0	25.14056	0
PCDHGA2	382	0.7413319	0.7133749	0	24.63797	0
RAD51B	173	0.9736852	1.0188852	0	22.89112	0
C6orf10	98	1.2852506	1.3211957	0	22.44212	0
PCDHGA3	361	0.7284166	0.7010847	0	22.32873	0
SDK1	401	0.6161993	0.6569363	0	21.84598	0
SMYD3	214	0.9329098	1.0744266	0	21.42175	0
TRAPPC9	411	0.5897733	0.5823076	0	21.36180	0
HDAC4	497	0.5359310	0.5377130	0	21.28586	0
MYT1L	240	0.8270247	0.8302018	0	21.26245	0
PRDM16	653	0.4573145	0.4887787	0	21.02944	0
RPTOR	527	0.5057114	0.5687027	0	20.05317	0
SHROOM3	129	1.0648480	1.0894468	0	20.03097	0
MGMT	199	0.8534771	0.8066423	0	19.85322	0
GMDS	177	0.9007339	1.0905293	0	19.17881	0
PCDHGB1	343	0.6821469	0.6731219	0	19.01243	0
WWOX	209	0.8895298	0.9278567	0	18.24849	0
TRIO	227	0.7497827	0.8451137	0	17.97521	0
ARHGAP26	170	0.8844363	0.9780844	0	17.68191	0
C10orf11	155	0.8728811	1.0378155	0	17.43356	0
MTHFD1L	104	1.0969062	1.2055766	0	17.33855	0
PCDHGA4	327	0.6640735	0.6220370	0	17.25962	0
ZBTB20	144	1.0157345	1.1144652	0	17.22659	0
EYS	73	1.4035772	1.3701934	0	17.02737	0
CUX1	314	0.6010691	0.6399903	0	16.94643	0
PRKCA	185	0.8306477	0.9977410	0	16.81771	0
TBCD	402	0.5533275	0.6165696	0	16.72859	0
EXT1	135	0.9304088	0.9921439	0	16.36695	0
ELMO1	178	0.9066839	0.9956089	0	16.23729	0
CDKAL1	128	1.0853353	1.2697597	0	16.01735	0
PRKCE	171	0.7891450	0.8450728	0	15.83519	0
PCCA	142	0.8722329	0.9899629	0	15.83408	0
BCAS3	140	0.9581513	1.1597238	0	15.77016	0
ANK3	142	0.9381659	1.0265660	0	15.75040	0
RNU6-71P	70	1.3434269	1.4618730	0	15.67769	0
NEDD4L	164	0.8251206	1.0177460	0	15.63398	0
HDAC9	104	1.0474234	1.0873397	0	15.57463	0
NEB	48	1.4278950	1.5561344	0	15.19859	0
NAALADL2	71	1.2620011	1.3860801	0	15.12351	0
LTBP1	111	0.9229144	0.8764041	0	15.07103	0
FOXP1	268	0.6130826	0.7220939	0	14.72706	0
WWC2	87	1.0715329	1.2782788	0	14.69865	0
PTK2	124	1.0465926	1.2477696	0	14.69630	0
ARID1B	186	0.7485287	0.9271757	0	14.62425	0

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets, priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>% kbl(caption = "Top enriched gene sets with GMEA-Mitch") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch

	set	setSize	pANOVA	s.dist	p.adjustANOVA
318	Digestion of dietary carbohydrate	10	0.0003630	0.6510559	0.0023601
395	Eukaryotic Translation Elongation	88	0.0000000	-0.6062955	0.0000000
1364	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	14	0.0000970	-0.6015567	0.0007449
896	Peptide chain elongation	84	0.0000000	-0.5999715	0.0000000
1478	Viral mRNA Translation	84	0.0000000	-0.5998171	0.0000000
611	Interaction With Cumulus Cells And The Zona Pellucida	11	0.0006768	0.5917281	0.0040878
1183	SUMOylation of immune response proteins	10	0.0012855	-0.5878118	0.0072239
397	Eukaryotic Translation Termination	87	0.0000000	-0.5813963	0.0000000
1333	Synthesis of bile acids and bile salts via 27-hydroxycholesterol	15	0.0000985	0.5806084	0.0007528
1193	Selenocysteine synthesis	87	0.0000000	-0.5641401	0.0000000
1172	SRP-dependent cotranslational protein targeting to membrane	105	0.0000000	-0.5623077	0.0000000
1135	Response of EIF2AK4 (GCN2) to amino acid deficiency	95	0.0000000	-0.5604286	0.0000000
449	Formation of a pool of free 40S subunits	95	0.0000000	-0.5469640	0.0000000
212	Class C/3 (Metabotropic glutamate/pheromone receptors)	39	0.0000000	0.5452157	0.0000001
259	DCC mediated attractive signaling	14	0.0004201	0.5443395	0.0026527
822	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	89	0.0000000	-0.5416596	0.0000000
493	GTP hydrolysis and joining of the 60S ribosomal subunit	105	0.0000000	-0.5268438	0.0000000
1154	SARS-CoV-2 modulates host translation machinery	46	0.0000000	-0.5242983	0.0000000
1065	Recycling of bile acids and salts	18	0.0001190	0.5237852	0.0008871
660	L13a-mediated translational silencing of Ceruloplasmin expression	104	0.0000000	-0.5159333	0.0000000

#mitch_report(mres,outfile="gmeawg_mitch_nat_vs_GIFT.html",overwrite=FALSE)
# Promoter
dm <- nat_vs_GIFT$dma
dm <- dm[grep("Promoter_Associated",dm$Regulatory_Feature_Group),]
dm <- dm[,c("UCSC_RefGene_Name","t")]
head(dm,50) %>% kbl(caption = "Top significant promoters with limma") %>% kable_paper("hover", full_width = F)

Top significant promoters with limma

	UCSC_RefGene_Name	t
534372	LRRC8A;LRRC8A;LRRC8A;CCBL1;CCBL1;CCBL1;CCBL1;CCBL1	-5.107473
24396	CHRNE;C17orf107	-5.035687
325866	CHRNE;C17orf107	-4.929315
55286	CHRNE;C17orf107	-4.664728
402429	C17orf82	-4.626767
584406	GTF2H4	-4.500323
79794	YPEL3;YPEL3;TBX6	-4.445117
574238	MLC1;MLC1;MLC1	-4.440480
619550	ZNF708;ZNF708;ZNF708	-4.405688
470654	ZNF578	-4.369236
157245	API5;API5;API5;API5	-4.347243
577851	C19orf60;C19orf60	-4.330642
196265	PRKD2;PRKD2;PRKD2;PRKD2;PRKD2	-4.319973
412687	DDX55	-4.307390
171586	C10orf125;C10orf125	-4.298547
583240	ZNF691	-4.288028
649173	TP53;WRAP53;WRAP53;TP53;TP53;TP53	-4.213133
310320	ZNF691	-4.190355
525256	OGG1;OGG1;OGG1;OGG1;OGG1;OGG1;OGG1;OGG1	-4.175333
420249	TMEM57	4.174631
345725	CNN2;CNN2;CNN2;CNN2;CNN2;CNN2;CNN2;CNN2	-4.151842
727379	QTRT1	-4.132475
569665	NHP2;NHP2	-4.105495
579402	PSMA5	-4.092823
312430	LOC100996583	-4.079075
432677	NCDN;KIAA0319L;NCDN;NCDN	-4.072545
569574	C6orf170	-4.070511
747523	ZC3H4	4.068181
497088	ZNF763	-4.063823
731132	COPS7B	-4.055432
51258	C11orf63;C11orf63	-4.040119
130473	ZDHHC20;ZDHHC20;ZDHHC20;ZDHHC20	-4.015493
497625	SPATA2L	-4.013219
124442	SLC7A1	4.006751
232993	DERL1;DERL1;DERL1;DERL1	-4.003182
282452	ZNF302;ZNF302	-3.996673
662868	PCYOX1	-3.989958
368947	DHDH	-3.980300
684064	PANX1	-3.975914
159885	CPNE1;CPNE1;CPNE1;RBM12;RBM12;CPNE1;CPNE1;RBM12;CPNE1;CPNE1;CPNE1;CPNE1;CPNE1;RBM12;CPNE1;CPNE1;CPNE1;CPNE1	-3.957171
38443	C7orf30	-3.948926
215119	MPV17L2	-3.937609
265705	RPS27L	-3.928377
264974	SDF2L1	-3.927373
228400	C10orf125;C10orf125	-3.923867
240803	ARRDC2;ARRDC2;ARRDC2	-3.909364
750412	ATP6V0A2;ATP6V0A2	-3.895212
214706	API5;API5;API5;API5;API5	3.890159
452026	SFRS4	-3.883231
767520	DHX34	3.879202

hist(dm$t,breaks=seq(from=-10,to=10,by=1))

tic() ; gmea <- calc_sc(dm) ; time2 <- toc()

## 30.594 sec elapsed

df <- gmea[[1]]
res <- gmea[[2]]
write.table(res ,file="novakovic_gmeapr_nat_vs_GIFT.tsv")
head(res,50) %>% kbl(caption = "Top significant genes with GMEA") %>% kable_paper("hover", full_width = F)

Top significant genes with GMEA

	nprobes	mean	median	p-value(sc)	sig	fdr(sc)
TAPBP	67	-0.9916050	-1.0625486	0e+00	14.764158	0.0000000
RGL2	53	-1.0297273	-1.0809160	0e+00	11.344310	0.0000001
KIAA1949	60	-1.1092916	-1.1390458	0e+00	10.644501	0.0000003
DUSP22	10	1.9795618	1.9484030	0e+00	9.430868	0.0000045
HSPA1A	27	-1.1626803	-1.1975088	0e+00	8.643113	0.0000273
HSPA1L	27	-1.1626803	-1.1975088	0e+00	8.643113	0.0000273
NBPF10	31	-1.2273592	-1.3742586	0e+00	8.509935	0.0000371
EFTUD2	16	-1.2839371	-1.2626824	0e+00	8.421731	0.0000455
CCDC103	16	-1.2839371	-1.2626824	0e+00	8.421731	0.0000455
NCRNA00171	37	-0.8870023	-0.8168871	0e+00	8.225103	0.0000715
ZNRD1	37	-0.8870023	-0.8168871	0e+00	8.225103	0.0000715
SLC39A1	34	-1.1425107	-0.9850966	0e+00	8.128099	0.0000894
OGFOD2	31	-1.2344837	-1.2776511	0e+00	7.958173	0.0001321
TBC1D14	37	-1.0827651	-1.2187242	0e+00	7.761820	0.0002077
GNL1	52	-0.7643285	-0.6501824	0e+00	7.675797	0.0002531
CSNK2B	35	-1.1323326	-1.1099430	0e+00	7.633921	0.0002787
PSMB8	47	-0.9268830	-0.9570959	0e+00	7.378642	0.0005017
EHMT2	35	-1.0328043	-1.0263474	0e+00	7.352680	0.0005325
BAT4	34	-1.1343602	-1.2122303	0e+00	7.314758	0.0005811
FEN1	21	-1.1262341	-1.3168120	1e-07	7.180579	0.0007914
MGAT1	37	-1.0021351	-0.9367824	1e-07	7.159424	0.0008308
RUNX2	35	-1.2920362	-1.4243967	1e-07	6.997250	0.0012068
IGF1R	24	-1.2017411	-1.1787561	1e-07	6.964086	0.0013025
SPRY1	21	-1.3157042	-1.2040993	1e-07	6.901578	0.0015040
RPL15	21	-1.0440881	-0.9743367	2e-07	6.766907	0.0020506
NKIRAS1	21	-1.0440881	-0.9743367	2e-07	6.766907	0.0020506
ZNF768	10	-1.2954176	-1.2666069	2e-07	6.766040	0.0020543
NUP205	14	-1.0413346	-1.0051882	2e-07	6.761215	0.0020771
ACACA	24	-1.2300415	-1.3269524	2e-07	6.748208	0.0021401
LRRC27	13	-1.1709804	-1.1535376	2e-07	6.720825	0.0022792
NAA15	19	-1.1910623	-1.0006488	2e-07	6.680594	0.0025002
RNFT1	14	-1.4687761	-1.6121243	2e-07	6.674015	0.0025381
C11orf10	20	-1.1129002	-1.3019408	2e-07	6.643685	0.0027215
MICB	24	-1.2726539	-1.1476967	2e-07	6.638514	0.0027539
ST8SIA4	16	-1.4481880	-1.4157426	2e-07	6.638180	0.0027558
DDAH2	36	-0.9760790	-0.8200298	2e-07	6.626377	0.0028314
IER2	21	-1.0433803	-0.9672311	3e-07	6.549923	0.0033762
RAB1B	56	-0.7948277	-0.8077187	3e-07	6.542725	0.0034323
GNRHR2	20	-1.0670919	-1.1966960	3e-07	6.537742	0.0034716
PEX11B	20	-1.0670919	-1.1966960	3e-07	6.537742	0.0034716
GPBP1	13	-1.4007330	-1.3916565	3e-07	6.532987	0.0035093
ATXN2	14	-1.2294427	-1.1704552	3e-07	6.497756	0.0038055
TMBIM6	24	-1.1454074	-1.1528247	3e-07	6.479691	0.0039668
SOCS2	34	-0.9031480	-0.7628694	3e-07	6.459880	0.0041516
C2orf63	17	-1.2565189	-1.3817968	3e-07	6.459472	0.0041551
HLA-E	31	-0.9432118	-1.0219455	4e-07	6.454707	0.0042006
QPCTL	19	-1.1283242	-1.0577030	4e-07	6.442957	0.0043155
SNRPD2	19	-1.1283242	-1.0577030	4e-07	6.442957	0.0043155
TMUB2	19	-1.4434861	-1.3544479	4e-07	6.424586	0.0045012
AFF1	28	-1.0865925	-1.0275984	4e-07	6.364460	0.0051691

gmea_volc(res)

gmea_barplot(res)

gmea_probe_bias(res)

dmscore <- data.frame( res$median * res$sig)
rownames(dmscore) <- rownames(res)
colnames(dmscore) <- "metric"
mres <- mitch_calc(x=dmscore, genesets=genesets,priority="effect")

## Note: Enrichments with large effect sizes may not be
##             statistically significant.

head(mres$enrichment_result,20) %>%  kbl(caption = "Top enriched gene sets with GMEA-Mitch (promoter only)") %>% kable_paper("hover", full_width = F)

Top enriched gene sets with GMEA-Mitch (promoter only)

	set	setSize	pANOVA	s.dist	p.adjustANOVA
607	NRIF signals cell death from the nucleus	14	0.0000910	-0.6040206	0.0024896
1195	p75NTR signals via NF-kB	11	0.0016298	-0.5485752	0.0152111
900	SARS-CoV-2 modulates autophagy	11	0.0026863	-0.5226402	0.0215623
600	NOTCH2 Activation and Transmission of Signal to the Nucleus	12	0.0077447	-0.4439908	0.0421928
1131	Translesion Synthesis by POLH	17	0.0018909	-0.4352676	0.0168846
601	NOTCH3 Activation and Transmission of Signal to the Nucleus	15	0.0036933	-0.4329833	0.0258051
994	Signaling by NOTCH2	18	0.0023366	-0.4144319	0.0194353
164	Condensation of Prometaphase Chromosomes	10	0.0258793	-0.4069066	0.0930111
120	Caspase activation via Death Receptors in the presence of ligand	10	0.0305904	-0.3949179	0.1049311
814	RORA activates gene expression	11	0.0264408	-0.3865341	0.0941854
162	Competing endogenous RNAs (ceRNAs) regulate PTEN translation	10	0.0355735	0.3838540	0.1189735
84	Bile acid and bile salt metabolism	15	0.0128452	0.3710785	0.0585820
971	Signaling by FGFR2 IIIa TM	15	0.0130526	-0.3702284	0.0593032
234	Diseases associated with N-glycosylation of proteins	18	0.0081654	-0.3601779	0.0438890
1059	TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)	13	0.0248934	-0.3593333	0.0897356
1080	TRAF6-mediated induction of TAK1 complex within TLR4 complex	10	0.0509293	-0.3565192	0.1532283
121	Caspase activation via extrinsic apoptotic signalling pathway	15	0.0198597	-0.3473634	0.0766380
505	Lagging Strand Synthesis	17	0.0132256	-0.3471402	0.0596393
368	Gap-filling DNA repair synthesis and ligation in GG-NER	23	0.0040580	-0.3462160	0.0271432
1133	Translesion synthesis by POLK	15	0.0208313	-0.3446852	0.0791196

#mitch_report(mres,outfile="gmeapr_mitch_nat_vs_GIFT.html",overwrite=FALSE)
rm(nat_vs_GIFT)

Session Information

For reproducibility.

sessionInfo()

## R version 4.2.1 (2022-06-23)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 22.04.1 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       
## 
## attached base packages:
##  [1] grid      stats4    parallel  stats     graphics  grDevices utils    
##  [8] datasets  methods   base     
## 
## other attached packages:
##  [1] ENmix_1.32.0                                       
##  [2] doParallel_1.0.17                                  
##  [3] qqman_0.1.8                                        
##  [4] RCircos_1.2.2                                      
##  [5] beeswarm_0.4.0                                     
##  [6] forestplot_3.1.0                                   
##  [7] abind_1.4-5                                        
##  [8] checkmate_2.1.0                                    
##  [9] reshape2_1.4.4                                     
## [10] gplots_3.1.3                                       
## [11] GEOquery_2.64.2                                    
## [12] RColorBrewer_1.1-3                                 
## [13] IlluminaHumanMethylation450kmanifest_0.4.0         
## [14] topconfects_1.12.0                                 
## [15] DMRcatedata_2.14.0                                 
## [16] ExperimentHub_2.4.0                                
## [17] AnnotationHub_3.4.0                                
## [18] BiocFileCache_2.4.0                                
## [19] dbplyr_2.2.1                                       
## [20] DMRcate_2.10.0                                     
## [21] limma_3.52.1                                       
## [22] missMethyl_1.30.0                                  
## [23] IlluminaHumanMethylationEPICanno.ilm10b4.hg19_0.6.0
## [24] IlluminaHumanMethylation450kanno.ilmn12.hg19_0.6.1 
## [25] minfi_1.42.0                                       
## [26] bumphunter_1.38.0                                  
## [27] locfit_1.5-9.6                                     
## [28] iterators_1.0.14                                   
## [29] foreach_1.5.2                                      
## [30] Biostrings_2.64.0                                  
## [31] XVector_0.36.0                                     
## [32] SummarizedExperiment_1.26.1                        
## [33] Biobase_2.56.0                                     
## [34] MatrixGenerics_1.8.0                               
## [35] matrixStats_0.62.0                                 
## [36] GenomicRanges_1.48.0                               
## [37] GenomeInfoDb_1.32.2                                
## [38] IRanges_2.30.0                                     
## [39] S4Vectors_0.34.0                                   
## [40] BiocGenerics_0.42.0                                
## [41] R.utils_2.12.0                                     
## [42] R.oo_1.25.0                                        
## [43] R.methodsS3_1.8.2                                  
## [44] plyr_1.8.7                                         
## [45] tictoc_1.1                                         
## [46] mitch_1.8.0                                        
## [47] eulerr_6.1.1                                       
## [48] kableExtra_1.3.4                                   
## [49] dplyr_1.0.10                                       
## 
## loaded via a namespace (and not attached):
##   [1] rappdirs_0.3.3                rtracklayer_1.56.0           
##   [3] GGally_2.1.2                  tidyr_1.2.1                  
##   [5] ggplot2_3.3.6                 bit64_4.0.5                  
##   [7] knitr_1.40                    DelayedArray_0.22.0          
##   [9] data.table_1.14.2             rpart_4.1.16                 
##  [11] KEGGREST_1.36.0               RCurl_1.98-1.9               
##  [13] AnnotationFilter_1.20.0       generics_0.1.3               
##  [15] GenomicFeatures_1.48.1        preprocessCore_1.58.0        
##  [17] RSQLite_2.2.18                bit_4.0.4                    
##  [19] tzdb_0.3.0                    webshot_0.5.4                
##  [21] xml2_1.3.3                    httpuv_1.6.6                 
##  [23] assertthat_0.2.1              xfun_0.33                    
##  [25] hms_1.1.2                     jquerylib_0.1.4              
##  [27] evaluate_0.17                 promises_1.2.0.1             
##  [29] fansi_1.0.3                   restfulr_0.0.15              
##  [31] scrime_1.3.5                  progress_1.2.2               
##  [33] caTools_1.18.2                readxl_1.4.1                 
##  [35] DBI_1.1.3                     geneplotter_1.74.0           
##  [37] htmlwidgets_1.5.4             reshape_0.8.9                
##  [39] purrr_0.3.5                   ellipsis_0.3.2               
##  [41] backports_1.4.1               permute_0.9-7                
##  [43] calibrate_1.7.7               annotate_1.74.0              
##  [45] biomaRt_2.52.0                deldir_1.0-6                 
##  [47] sparseMatrixStats_1.8.0       vctrs_0.4.2                  
##  [49] ensembldb_2.20.1              cachem_1.0.6                 
##  [51] Gviz_1.40.1                   BSgenome_1.64.0              
##  [53] GenomicAlignments_1.32.0      prettyunits_1.1.1            
##  [55] mclust_5.4.10                 svglite_2.1.0                
##  [57] cluster_2.1.4                 RPMM_1.25                    
##  [59] lazyeval_0.2.2                crayon_1.5.2                 
##  [61] genefilter_1.78.0             edgeR_3.38.1                 
##  [63] pkgconfig_2.0.3               nlme_3.1-160                 
##  [65] ProtGenerics_1.28.0           nnet_7.3-18                  
##  [67] rlang_1.0.6                   lifecycle_1.0.3              
##  [69] filelock_1.0.2                dichromat_2.0-0.1            
##  [71] cellranger_1.1.0              rngtools_1.5.2               
##  [73] base64_2.0.1                  Matrix_1.5-1                 
##  [75] Rhdf5lib_1.18.2               base64enc_0.1-3              
##  [77] png_0.1-7                     viridisLite_0.4.1            
##  [79] rjson_0.2.21                  bitops_1.0-7                 
##  [81] KernSmooth_2.23-20            rhdf5filters_1.8.0           
##  [83] blob_1.2.3                    DelayedMatrixStats_1.18.0    
##  [85] doRNG_1.8.2                   stringr_1.4.1                
##  [87] nor1mix_1.3-0                 readr_2.1.3                  
##  [89] jpeg_0.1-9                    scales_1.2.1                 
##  [91] memoise_2.0.1                 magrittr_2.0.3               
##  [93] zlibbioc_1.42.0               compiler_4.2.1               
##  [95] BiocIO_1.6.0                  illuminaio_0.38.0            
##  [97] Rsamtools_2.12.0              cli_3.4.1                    
##  [99] DSS_2.44.0                    htmlTable_2.4.1              
## [101] Formula_1.2-4                 MASS_7.3-58.1                
## [103] tidyselect_1.2.0              stringi_1.7.8                
## [105] highr_0.9                     yaml_2.3.5                   
## [107] askpass_1.1                   latticeExtra_0.6-30          
## [109] sass_0.4.2                    VariantAnnotation_1.42.1     
## [111] tools_4.2.1                   rstudioapi_0.14              
## [113] foreign_0.8-83                bsseq_1.32.0                 
## [115] gridExtra_2.3                 digest_0.6.29                
## [117] BiocManager_1.30.18           shiny_1.7.2                  
## [119] quadprog_1.5-8                Rcpp_1.0.9                   
## [121] siggenes_1.70.0               BiocVersion_3.15.2           
## [123] later_1.3.0                   org.Hs.eg.db_3.15.0          
## [125] httr_1.4.4                    AnnotationDbi_1.58.0         
## [127] biovizBase_1.44.0             colorspace_2.0-3             
## [129] rvest_1.0.3                   XML_3.99-0.11                
## [131] splines_4.2.1                 statmod_1.4.37               
## [133] multtest_2.52.0               systemfonts_1.0.4            
## [135] xtable_1.8-4                  jsonlite_1.8.2               
## [137] dynamicTreeCut_1.63-1         R6_2.5.1                     
## [139] echarts4r_0.4.4               Hmisc_4.7-1                  
## [141] pillar_1.8.1                  htmltools_0.5.3              
## [143] mime_0.12                     glue_1.6.2                   
## [145] fastmap_1.1.0                 BiocParallel_1.30.2          
## [147] interactiveDisplayBase_1.34.0 beanplot_1.3.1               
## [149] codetools_0.2-18              utf8_1.2.2                   
## [151] lattice_0.20-45               bslib_0.4.0                  
## [153] tibble_3.1.8                  curl_4.3.3                   
## [155] gtools_3.9.3                  openssl_2.0.3                
## [157] interp_1.1-3                  survival_3.4-0               
## [159] rmarkdown_2.17                munsell_0.5.0                
## [161] rhdf5_2.40.0                  GenomeInfoDbData_1.2.8       
## [163] impute_1.70.0                 HDF5Array_1.24.0             
## [165] gtable_0.3.1