RnBeads: BLUEPRINT WGBS - bpRel201609_rnb

Option	Value
analyze.sites	no
region.types	cpgislands, genes, promoters, tiling1kb, gencode22promoters, ensembleRegBuildBPall
differential.permutations	0
differential.comparison.columns	cmp_ct_mono_vs_neut, cmp_ct_mono_vs_neut_VB, cmp_ct_mono_vs_mf, cmp_ct_mono_vs_mf_VB, cmp_ct_TCD4_TN_vs_CM, cmp_ct_TCD4_TN_vs_EM, cmp_ct_TCD4_CM_vs_EM, cmp_ct_TCD8_TN_vs_CM, cmp_ct_TCD8_TN_vs_EM, cmp_ct_TCD8_CM_vs_EM, cmp_ct_neut_myel_vs_meta, cmp_ct_neut_meta_vs_band, cmp_ct_neut_band_vs_segm, cmp_ct_neut_early_vs_mature
differential.comparison.columns.all.pairwise	default
columns.pairing	default
differential.site.test.method	limma
covariate.adjustment.columns	tissueTypeShort, DONOR_SEX
differential.adjustment.sva	yes
differential.adjustment.celltype	yes
differential.enrichment.go	yes
differential.enrichment.lola	yes
differential.enrichment.lola.dbs	${LOLACore}, ${LOLAExt}

	comparison	adjustment	covariateTable
1	mono vs. neut (based on cmp_ct_mono_vs_neut)	tissueTypeShort,DONOR_SEX	csv
2	mono vs. neut (based on cmp_ct_mono_vs_neut_VB)	DONOR_SEX	csv
3	Mf vs. mono (based on cmp_ct_mono_vs_mf)	tissueTypeShort,DONOR_SEX	csv
4	Mf vs. mono (based on cmp_ct_mono_vs_mf_VB)	DONOR_SEX	csv
5	EM vs. TN (based on cmp_ct_TCD4_TN_vs_CM)	DONOR_SEX	csv
6	EM vs. TN (based on cmp_ct_TCD4_TN_vs_EM)	DONOR_SEX	csv
7	CM vs. EM (based on cmp_ct_TCD4_CM_vs_EM)	DONOR_SEX	csv
8	EM vs. TN (based on cmp_ct_TCD8_TN_vs_CM)	tissueTypeShort,DONOR_SEX	csv
9	EM vs. TN (based on cmp_ct_TCD8_TN_vs_EM)	tissueTypeShort,DONOR_SEX	csv
10	CM vs. EM (based on cmp_ct_TCD8_CM_vs_EM)	DONOR_SEX	csv
11	meta vs. myel (based on cmp_ct_neut_myel_vs_meta)	DONOR_SEX	csv
12	band vs. meta (based on cmp_ct_neut_meta_vs_band)	DONOR_SEX	csv
13	band vs. segm (based on cmp_ct_neut_band_vs_segm)	DONOR_SEX	csv
14	early vs. mature (based on cmp_ct_neut_early_vs_mature)	tissueTypeShort,DONOR_SEX	csv

Differential methylation on the region level was computed based on a variety of metrics. Of particular interest for the following plots and analyses are the following quantities for each region: the mean methylation difference in a region of the two groups being and of quotient of mean methylation levelsas well as a p-value obtained from statistical testing (limma or t-test; depending on parameter settings). Additionally each region was assigned a rank based on each of these three criteria. A combined rank is computed as the maximum (i.e. worst) value among the three ranks. The smaller the combined rank for a region, the more evidence for differential methylation it exhibits. Regions were defined based on the region types specified in the analysis. This section includes scatterplots of the region group means as well as volcano plots of each pairwise comparison colored according to the combined rank of a given region.

The following rank cutfoffs have been automatically selected for the analysis of differentially methylated regions:

	cpgislands	genes	promoters	tiling1kb	gencode22promoters	ensembleRegBuildBPall
mono vs. neut (based on cmp_ct_mono_vs_neut)	0	0	0	0	0	0
mono vs. neut (based on cmp_ct_mono_vs_neut_VB)	0	0	0	0	0	0
Mf vs. mono (based on cmp_ct_mono_vs_mf)	0	0	0	0	0	0
Mf vs. mono (based on cmp_ct_mono_vs_mf_VB)	0	0	0	0	0	0
EM vs. TN (based on cmp_ct_TCD4_TN_vs_CM)	0	0	0	0	0	0
EM vs. TN (based on cmp_ct_TCD4_TN_vs_EM)	0	0	0	0	0	0
CM vs. EM (based on cmp_ct_TCD4_CM_vs_EM)	0	0	0	0	0	0
EM vs. TN (based on cmp_ct_TCD8_TN_vs_CM)	0	0	0	0	0	0
EM vs. TN (based on cmp_ct_TCD8_TN_vs_EM)	0	0	0	0	0	0
CM vs. EM (based on cmp_ct_TCD8_CM_vs_EM)	0	0	0	0	0	0
meta vs. myel (based on cmp_ct_neut_myel_vs_meta)	0	0	0	0	0	0
band vs. meta (based on cmp_ct_neut_meta_vs_band)	0	0	0	0	0	0
band vs. segm (based on cmp_ct_neut_band_vs_segm)	0	0	0	0	0	0
early vs. mature (based on cmp_ct_neut_early_vs_mature)	0	0	0	0	0	0

comparison
regions
differential methylation measure

Figure 1

Scatterplot for differential methylation (regions). If the selected criterion is not rankGradient: The transparency corresponds to point density. The 1% of the points in the sparsest populated plot regions are drawn explicitly. Additionally, the colored points represent differentially methylated regions (according to the selected criterion). If the selected criterion is rankGradient: median combined ranks accross hexagonal bins are shown as a gradient according to the color legend.

comparison
regions
difference metric
significance metric

Figure 2

Volcano plot for differential methylation quantified by various metrics. Color scale according to combined ranking.

Differential Methylation Tables

A tabular overview of measures for differential methylation on the region level for the individual comparisons are provided in this section.

id: region id
Chromosome: chromosome of the region
Start: start coordinate of the region
End: end coordinate of the region
mean.g1,mean.g2: (where g1 and g2 is replaced by the respective group names in the table) mean methylation in each of the two groups
mean.diff: difference in methylation means between the two groups: mean.g1-mean.g2. In case of paired analysis, it is the mean of the pairwise differences.
mean.quot.log2: log2 of the quotient in methylation: log2((mean.g1+epsilon)/(mean.g2+epsilon)), where epsilon:=0.01. In case of paired analysis, it is the mean of the pairwise quotients.
diffmeth.p.val: p-value obtained from linear models employed in the limma package (or alternatively from a two-sided Welch t-test; which type of p-value is computed is specified in the differential.site.test.method option).
max.g1,max.g2: maximum methylation level in group 1 and 2 respectively
min.g1,min.g2: minimum methylation level in group 1 and 2 respectively
sd.g1,sd.g2: standard deviation of methylation levels
min.diff: Minimum of 0 and the smallest pairwise difference between samples of the two groups
diffmeth.p.adj.fdr: FDR adjusted p-value of all sites
combinedRank: mean.diff, mean.quot.log2 and diffmeth.p.val are ranked for all regions. This aggregates them using the maximum, i.e. worst rank of a site among the three measures
num.na.g1,num.na.g2: number of NA methylation values for groups 1 and 2 respectively
mean.covg.g1,mean.covg.g2: mean coverage of groups 1 and 2 respectively (In case of Infinium array methylation data, coverage is defined as combined beadcount.)
min.covg.g1,min.covg.g2: minimum coverage of groups 1 and 2 respectively
max.covg.g1,max.covg.g2: maximum coverage of groups 1 and 2 respectively
covg.thresh.nsamples.g1,covg.thresh.nsamples.g2: number of samples in group 1 and 2 respectively exceeding the coverage threshold (5) for this region.
Strand: strand of the site
var.g1, var.g2: (g1 and g2 are replaced by the corrspondinhg group used in the differentiality analysis) the variances found in the groups
var.diff: difference in variance values between the two groups g1 and g2 (=var.g1-var.g2). In case of paired analysis, it is the variance of the pairwise differences.
var.log.ratio: Log2 of the ratio between the variances of the two groups g1 and g2 (=log2(var.g1+eps/var.g2+eps), default eps=0.01). In case of paired analysis, it is the variance of the pairwise quotients.
diffVar.p.val: p-value resulting from applying the selected differentially variability method (diffVar or iEVORA)
diffVar.p.adj.fdr: FDR-adjusted p-value for differential variability
log10P: negative decadic logarithm of the p-value
log10FDR: negative decadic logarithmn of the FDR-adjusted p-value
combinedRank.var: var.diff, var.log.ratio and comb.p.val.var are ranked for all sites and the higher (=worst) rank is selected.

The tables for the individual comparisons can be found here:

	cpgislands	genes	promoters	tiling1kb	gencode22promoters	ensembleRegBuildBPall
mono vs. neut (based on cmp_ct_mono_vs_neut)	csv	csv	csv	csv	csv	csv
mono vs. neut (based on cmp_ct_mono_vs_neut_VB)	csv	csv	csv	csv	csv	csv
Mf vs. mono (based on cmp_ct_mono_vs_mf)	csv	csv	csv	csv	csv	csv
Mf vs. mono (based on cmp_ct_mono_vs_mf_VB)	csv	csv	csv	csv	csv	csv
EM vs. TN (based on cmp_ct_TCD4_TN_vs_CM)	csv	csv	csv	csv	csv	csv
EM vs. TN (based on cmp_ct_TCD4_TN_vs_EM)	csv	csv	csv	csv	csv	csv
CM vs. EM (based on cmp_ct_TCD4_CM_vs_EM)	csv	csv	csv	csv	csv	csv
EM vs. TN (based on cmp_ct_TCD8_TN_vs_CM)	csv	csv	csv	csv	csv	csv
EM vs. TN (based on cmp_ct_TCD8_TN_vs_EM)	csv	csv	csv	csv	csv	csv
CM vs. EM (based on cmp_ct_TCD8_CM_vs_EM)	csv	csv	csv	csv	csv	csv
meta vs. myel (based on cmp_ct_neut_myel_vs_meta)	csv	csv	csv	csv	csv	csv
band vs. meta (based on cmp_ct_neut_meta_vs_band)	csv	csv	csv	csv	csv	csv
band vs. segm (based on cmp_ct_neut_band_vs_segm)	csv	csv	csv	csv	csv	csv
early vs. mature (based on cmp_ct_neut_early_vs_mature)	csv	csv	csv	csv	csv	csv

Differential Variability

Differential variability on the region level was computed similar to differential methylation, but the mean of variances, the log-ratio of the quotient of variances as well as the p-values from the differentiality test were employed. Ranking was performed in line with the ranking of differential methylation.

The following rank cutoffs have been automatically selected for the analysis of differentially variable regions:

	cpgislands	genes	promoters	tiling1kb	gencode22promoters	ensembleRegBuildBPall
mono vs. neut (based on cmp_ct_mono_vs_neut)	0	0	0	0	0	0
mono vs. neut (based on cmp_ct_mono_vs_neut_VB)	0	0	0	0	0	0
Mf vs. mono (based on cmp_ct_mono_vs_mf)	0	0	0	0	0	0
Mf vs. mono (based on cmp_ct_mono_vs_mf_VB)	0	0	0	0	0	0
EM vs. TN (based on cmp_ct_TCD4_TN_vs_CM)	0	0	0	0	0	0
EM vs. TN (based on cmp_ct_TCD4_TN_vs_EM)	0	0	0	0	0	0
CM vs. EM (based on cmp_ct_TCD4_CM_vs_EM)	0	0	0	0	0	0
EM vs. TN (based on cmp_ct_TCD8_TN_vs_CM)	0	0	0	0	0	0
EM vs. TN (based on cmp_ct_TCD8_TN_vs_EM)	0	0	0	0	0	0
CM vs. EM (based on cmp_ct_TCD8_CM_vs_EM)	0	0	0	0	0	0
meta vs. myel (based on cmp_ct_neut_myel_vs_meta)	0	0	0	0	0	0
band vs. meta (based on cmp_ct_neut_meta_vs_band)	0	0	0	0	0	0
band vs. segm (based on cmp_ct_neut_band_vs_segm)	0	0	0	0	0	0
early vs. mature (based on cmp_ct_neut_early_vs_mature)	0	0	0	0	0	0

comparison
regions
differential variability measure

Figure 3

Scatterplot for differential variable regions. The transparency corresponds to point density. The 1% of the points in the sparsest populated plot regions are drawn explicitly. Additionally, the colored points represent differentially methylated regions (according to the selected criterion).

comparison
regions
difference metric
significance metric

Figure 4

Volcano plot for differential variability quantified by various metrics. Color scale according to combined ranking.

comparison
regions
rankCutoff

Figure 5

Scatterplot comparing differentially methylated (DMRs) and variable regions (DVRs), as well as regions that are both differentially methylated and variable.

GO Enrichment Analysis

GO Enrichment Analysis was conducted. The wordclouds and tables below contains significant GO terms as determined by a hypergeometric test.

comparison
Hypermethylation/hypomethylation
ontology
regions
differential methylation measure

Figure 6

Wordclouds for GO enrichment terms.

comparison
Hypermethylation/hypomethylation
ontology
regions
differential methylation measure

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0070942	0	648.24	0.0089	3	8	neutrophil mediated cytotoxicity
GO:0051873	0	360.0444	0.0133	3	12	killing by host of symbiont cells
GO:0031640	0	88.7857	0.0621	4	56	killing of cells of other organism
GO:0043312	0	21.7899	0.518	7	467	neutrophil degranulation
GO:0045055	0	17.7004	0.7864	8	709	regulated exocytosis
GO:0042119	0	21.2662	0.5302	7	478	neutrophil activation
GO:0002275	0	19.5123	0.5756	7	519	myeloid cell activation involved in immune response
GO:0002444	0	19.3561	0.5801	7	523	myeloid leukocyte mediated immunity
GO:0051818	0	215.9467	0.02	3	18	disruption of cells of other organism involved in symbiotic interaction
GO:0044663	0	Inf	0.0022	2	2	establishment or maintenance of cell type involved in phenotypic switching
GO:0002263	0	15.1375	0.7331	7	661	cell activation involved in immune response
GO:0060414	0	675.3333	0.0055	2	5	aorta smooth muscle tissue morphogenesis
GO:0035821	0	33.771	0.1553	4	140	modification of morphology or physiology of other organism
GO:0045123	0	68.783	0.0555	3	50	cellular extravasation
GO:1900239	0	337.6042	0.0089	2	8	regulation of phenotypic switching
GO:0016192	0	8.1639	1.972	9	1778	vesicle-mediated transport
GO:0051851	0	52.9508	0.071	3	64	modification by host of symbiont morphology or physiology
GO:0032940	1e-04	8.694	1.5239	8	1374	secretion by cell
GO:0050829	1e-04	50.8582	0.0744	3	71	defense response to Gram-negative bacterium
GO:0038166	1e-04	225.0278	0.0122	2	11	angiotensin-activated signaling pathway
GO:0044130	1e-04	168.7396	0.0155	2	14	negative regulation of growth of symbiont in host
GO:0098542	1e-04	13.3187	0.5102	5	460	defense response to other organism
GO:0045321	1e-04	8.5992	1.2467	7	1124	leukocyte activation
GO:0044144	1e-04	144.6161	0.0177	2	16	modulation of growth of symbiont involved in interaction with host
GO:0043207	2e-04	9.5316	0.9028	6	814	response to external biotic stimulus
GO:0042089	2e-04	32.222	0.1142	3	103	cytokine biosynthetic process
GO:0044110	2e-04	119.0735	0.0211	2	19	growth involved in symbiotic interaction
GO:0009617	2e-04	11.6058	0.5823	5	525	response to bacterium
GO:0040012	2e-04	9.1265	0.9405	6	848	regulation of locomotion
GO:1990776	3e-04	101.1937	0.0244	2	22	response to angiotensin
GO:0019730	3e-04	88.5824	0.0278	2	30	antimicrobial humoral response
GO:0019731	5e-04	71.8933	0.0335	2	32	antibacterial humoral response
GO:0070944	0.001	Inf	0.001	1	1	neutrophil mediated killing of bacterium
GO:0009620	0.001	48.9758	0.0482	2	46	response to fungus
GO:0033002	0.0011	17.3254	0.2085	3	188	muscle cell proliferation
GO:0002777	0.0011	Inf	0.0011	1	1	antimicrobial peptide biosynthetic process
GO:0002812	0.0011	Inf	0.0011	1	1	biosynthetic process of antibacterial peptides active against Gram-negative bacteria
GO:0032644	0.0011	Inf	0.0011	1	1	regulation of fractalkine production
GO:0033367	0.0011	Inf	0.0011	1	1	protein localization to mast cell secretory granule
GO:0033371	0.0011	Inf	0.0011	1	1	T cell secretory granule organization
GO:0033373	0.0011	Inf	0.0011	1	1	maintenance of protease location in mast cell secretory granule
GO:0033375	0.0011	Inf	0.0011	1	1	protease localization to T cell secretory granule
GO:0033377	0.0011	Inf	0.0011	1	1	maintenance of protein location in T cell secretory granule
GO:0033382	0.0011	Inf	0.0011	1	1	maintenance of granzyme B location in T cell secretory granule
GO:0050754	0.0011	Inf	0.0011	1	1	positive regulation of fractalkine biosynthetic process
GO:0050756	0.0011	Inf	0.0011	1	1	fractalkine metabolic process
GO:0070946	0.0011	Inf	0.0011	1	1	neutrophil mediated killing of gram-positive bacterium
GO:1904676	0.0011	Inf	0.0011	1	1	negative regulation of somatic stem cell division
GO:1905175	0.0011	Inf	0.0011	1	1	negative regulation of vascular smooth muscle cell dedifferentiation
GO:0048662	0.0011	47	0.0499	2	45	negative regulation of smooth muscle cell proliferation
GO:2000147	0.0013	10.1933	0.4947	4	446	positive regulation of cell motility
GO:0061844	0.0014	41.2296	0.0566	2	51	antimicrobial humoral immune response mediated by antimicrobial peptide
GO:0035904	0.0015	40.4025	0.0577	2	52	aorta development
GO:0051270	0.002	6.9335	0.9505	5	857	regulation of cellular component movement
GO:0006940	0.0022	33.0943	0.0699	2	63	regulation of smooth muscle contraction
GO:0050725	0.0022	953.5294	0.0022	1	2	positive regulation of interleukin-1 beta biosynthetic process
GO:0070947	0.0022	953.5294	0.0022	1	2	neutrophil mediated killing of fungus
GO:0048844	0.0023	32.0397	0.0721	2	65	artery morphogenesis
GO:0010631	0.0024	13.0877	0.274	3	247	epithelial cell migration
GO:0050764	0.0025	30.5777	0.0754	2	68	regulation of phagocytosis
GO:0090130	0.0027	12.615	0.2839	3	256	tissue migration
GO:0032602	0.0032	27.2584	0.0843	2	76	chemokine production
GO:0045079	0.0033	476.7353	0.0033	1	3	negative regulation of chemokine biosynthetic process
GO:0045360	0.0033	476.7353	0.0033	1	3	regulation of interleukin-1 biosynthetic process
GO:0090678	0.0033	476.7353	0.0033	1	3	cell dedifferentiation involved in phenotypic switching
GO:1903238	0.0033	476.7353	0.0033	1	3	positive regulation of leukocyte tethering or rolling
GO:1905111	0.0033	476.7353	0.0033	1	3	positive regulation of pulmonary blood vessel remodeling
GO:0048644	0.0037	24.892	0.0921	2	83	muscle organ morphogenesis
GO:0019732	0.0044	317.8039	0.0044	1	4	antifungal humoral response
GO:0045415	0.0044	317.8039	0.0044	1	4	negative regulation of interleukin-8 biosynthetic process
GO:0060474	0.0044	317.8039	0.0044	1	4	positive regulation of flagellated sperm motility involved in capacitation
GO:0090191	0.0044	317.8039	0.0044	1	4	negative regulation of branching involved in ureteric bud morphogenesis
GO:0097029	0.0044	317.8039	0.0044	1	4	mature conventional dendritic cell differentiation
GO:2000724	0.0044	317.8039	0.0044	1	4	positive regulation of cardiac vascular smooth muscle cell differentiation
GO:2001274	0.0044	317.8039	0.0044	1	4	negative regulation of glucose import in response to insulin stimulus
GO:0022617	0.0045	22.6433	0.1009	2	91	extracellular matrix disassembly
GO:0032496	0.0046	10.3266	0.3449	3	311	response to lipopolysaccharide
GO:0008626	0.0055	238.3382	0.0055	1	5	granzyme-mediated apoptotic signaling pathway
GO:0036446	0.0055	238.3382	0.0055	1	5	myofibroblast differentiation
GO:0070945	0.0055	238.3382	0.0055	1	5	neutrophil mediated killing of gram-negative bacterium
GO:1900028	0.0055	238.3382	0.0055	1	5	negative regulation of ruffle assembly
GO:1904673	0.0055	238.3382	0.0055	1	5	negative regulation of somatic stem cell population maintenance
GO:0098657	0.0057	6.617	0.7487	4	675	import into cell
GO:0051234	0.0062	3.6541	5.4192	11	4886	establishment of localization
GO:0001878	0.0066	190.6588	0.0067	1	6	response to yeast
GO:0002778	0.0066	190.6588	0.0067	1	6	antibacterial peptide production
GO:0045416	0.0066	190.6588	0.0067	1	6	positive regulation of interleukin-8 biosynthetic process
GO:0006508	0.0073	4.3799	1.8489	6	1667	proteolysis
GO:0030334	0.0075	6.0853	0.8108	4	731	regulation of cell migration
GO:0010668	0.0077	158.8725	0.0078	1	7	ectodermal cell differentiation
GO:0032963	0.0078	16.9034	0.1342	2	121	collagen metabolic process
GO:0048870	0.0087	6.1229	0.8613	4	971	cell motility
GO:0042117	0.0088	136.1681	0.0089	1	8	monocyte activation
GO:0043696	0.0088	136.1681	0.0089	1	8	dedifferentiation
GO:0045348	0.0088	136.1681	0.0089	1	8	positive regulation of MHC class II biosynthetic process
GO:2000035	0.0088	136.1681	0.0089	1	8	regulation of stem cell division
GO:0006909	0.0097	15.2333	0.1505	2	152	phagocytosis

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0061337	2e-04	15.2093	0.3017	4	136	cardiac conduction
GO:0090153	4e-04	79.3186	0.0311	2	14	regulation of sphingolipid biosynthetic process
GO:0140115	6e-04	67.979	0.0355	2	16	export across plasma membrane
GO:0002684	8e-04	4.716	2.0696	8	933	positive regulation of immune system process
GO:0030219	0.001	16.8297	0.1996	3	90	megakaryocyte differentiation
GO:0022898	0.0012	9.5598	0.4725	4	213	regulation of transmembrane transporter activity
GO:1902036	0.0014	15.2434	0.2196	3	99	regulation of hematopoietic stem cell differentiation
GO:0051239	0.0014	3.1341	6.0935	14	2747	regulation of multicellular organismal process
GO:0086011	0.0015	39.6299	0.0577	2	26	membrane repolarization during action potential
GO:0065007	0.0015	4.8275	25.0374	33	11287	biological regulation
GO:0000173	0.0022	Inf	0.0022	1	1	inactivation of MAPK activity involved in osmosensory signaling pathway
GO:0002642	0.0022	Inf	0.0022	1	1	positive regulation of immunoglobulin biosynthetic process
GO:0010734	0.0022	Inf	0.0022	1	1	negative regulation of protein glutathionylation
GO:0030221	0.0022	Inf	0.0022	1	1	basophil differentiation
GO:0060217	0.0022	Inf	0.0022	1	1	hemangioblast cell differentiation
GO:0048534	0.0023	4.4007	1.8833	7	849	hematopoietic or lymphoid organ development
GO:0060047	0.0024	7.8755	0.5701	4	257	heart contraction
GO:1904062	0.0029	7.456	0.6011	4	271	regulation of cation transmembrane transport
GO:1903522	0.003	7.3996	0.6056	4	273	regulation of blood circulation
GO:0051172	0.0043	2.8792	5.3415	12	2408	negative regulation of nitrogen compound metabolic process
GO:0001808	0.0044	462.6286	0.0044	1	2	negative regulation of type IV hypersensitivity
GO:0060032	0.0044	462.6286	0.0044	1	2	notochord regression
GO:0060375	0.0044	462.6286	0.0044	1	2	regulation of mast cell differentiation
GO:2000649	0.0045	22.093	0.0998	2	45	regulation of sodium ion transmembrane transporter activity
GO:0003013	0.0046	5.1364	1.1047	5	498	circulatory system process
GO:0030111	0.0049	6.4468	0.6921	4	312	regulation of Wnt signaling pathway
GO:0010948	0.0051	6.3626	0.701	4	316	negative regulation of cell cycle process
GO:0050852	0.0056	9.1097	0.3616	3	163	T cell receptor signaling pathway
GO:0090090	0.0057	9.0525	0.3638	3	164	negative regulation of canonical Wnt signaling pathway
GO:0070265	0.0057	19.3806	0.1131	2	51	necrotic cell death
GO:0019222	0.0059	2.4651	14.0327	22	6326	regulation of metabolic process
GO:0002637	0.0061	18.6182	0.1176	2	53	regulation of immunoglobulin production
GO:0019083	0.0064	8.6715	0.3793	3	171	viral transcription
GO:1902806	0.0065	8.6197	0.3815	3	172	regulation of cell cycle G1/S phase transition
GO:0010959	0.0066	5.8813	0.7564	4	341	regulation of metal ion transport
GO:0045163	0.0066	231.3	0.0067	1	3	clustering of voltage-gated potassium channels
GO:0045799	0.0066	231.3	0.0067	1	3	positive regulation of chromatin assembly or disassembly
GO:0090156	0.0066	231.3	0.0067	1	3	cellular sphingolipid homeostasis
GO:1900138	0.0066	231.3	0.0067	1	3	negative regulation of phospholipase A2 activity
GO:1902445	0.0066	231.3	0.0067	1	3	regulation of mitochondrial membrane permeability involved in programmed necrotic cell death
GO:2000297	0.0066	231.3	0.0067	1	3	negative regulation of synapse maturation
GO:0010803	0.0071	17.2599	0.1264	2	57	regulation of tumor necrosis factor-mediated signaling pathway
GO:0031324	0.0072	2.6763	5.6809	12	2561	negative regulation of cellular metabolic process
GO:0030888	0.0073	16.9506	0.1287	2	58	regulation of B cell proliferation
GO:0002244	0.0078	8.0422	0.4082	3	184	hematopoietic progenitor cell differentiation
GO:0010604	0.008	2.5617	6.5217	13	2940	positive regulation of macromolecule metabolic process
GO:0010605	0.008	2.6309	5.763	12	2598	negative regulation of macromolecule metabolic process
GO:0051348	0.0082	5.529	0.803	4	362	negative regulation of transferase activity
GO:0042531	0.0083	15.8167	0.1375	2	62	positive regulation of tyrosine phosphorylation of STAT protein
GO:0032760	0.0086	15.5564	0.1397	2	63	positive regulation of tumor necrosis factor production
GO:0007418	0.0088	154.1905	0.0089	1	4	ventral midline development
GO:0021938	0.0088	154.1905	0.0089	1	4	smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation
GO:0048295	0.0088	154.1905	0.0089	1	4	positive regulation of isotype switching to IgE isotypes
GO:0060018	0.0088	154.1905	0.0089	1	4	astrocyte fate commitment
GO:1900060	0.0088	154.1905	0.0089	1	4	negative regulation of ceramide biosynthetic process
GO:1903273	0.0088	154.1905	0.0089	1	4	regulation of sodium ion export
GO:1903278	0.0088	154.1905	0.0089	1	4	positive regulation of sodium ion export across plasma membrane
GO:1904637	0.0088	154.1905	0.0089	1	4	cellular response to ionomycin
GO:2001274	0.0088	154.1905	0.0089	1	4	negative regulation of glucose import in response to insulin stimulus
GO:0048519	0.0097	2.3216	10.8539	18	4893	negative regulation of biological process
GO:0032944	0.0098	7.3816	0.4437	3	200	regulation of mononuclear cell proliferation

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0140115	3e-04	96.3631	0.0256	2	16	export across plasma membrane
GO:0022898	3e-04	13.9139	0.3412	4	213	regulation of transmembrane transporter activity
GO:0002684	5e-04	6.0782	1.4947	7	933	positive regulation of immune system process
GO:0060047	7e-04	11.4625	0.4117	4	257	heart contraction
GO:0086011	8e-04	56.1771	0.0417	2	26	membrane repolarization during action potential
GO:1904062	9e-04	10.8519	0.4342	4	271	regulation of cation transmembrane transport
GO:1903522	9e-04	10.7699	0.4374	4	273	regulation of blood circulation
GO:0002642	0.0016	Inf	0.0016	1	1	positive regulation of immunoglobulin biosynthetic process
GO:0010734	0.0016	Inf	0.0016	1	1	negative regulation of protein glutathionylation
GO:0030221	0.0016	Inf	0.0016	1	1	basophil differentiation
GO:0060217	0.0016	Inf	0.0016	1	1	hemangioblast cell differentiation
GO:2000649	0.0023	31.3178	0.0721	2	45	regulation of sodium ion transmembrane transporter activity
GO:0001808	0.0032	648.08	0.0032	1	2	negative regulation of type IV hypersensitivity
GO:0043376	0.0032	648.08	0.0032	1	2	regulation of CD8-positive, alpha-beta T cell differentiation
GO:0060032	0.0032	648.08	0.0032	1	2	notochord regression
GO:0060375	0.0032	648.08	0.0032	1	2	regulation of mast cell differentiation
GO:0030178	0.0036	10.9347	0.3108	3	194	negative regulation of Wnt signaling pathway
GO:0048568	0.0039	7.0565	0.6585	4	411	embryonic organ development
GO:0061337	0.0042	23.1905	0.0965	2	65	cardiac conduction
GO:0032760	0.0045	22.0519	0.1009	2	63	positive regulation of tumor necrosis factor production
GO:0046324	0.0045	22.0519	0.1009	2	63	regulation of glucose import
GO:0045163	0.0048	324.02	0.0048	1	3	clustering of voltage-gated potassium channels
GO:0045799	0.0048	324.02	0.0048	1	3	positive regulation of chromatin assembly or disassembly
GO:1900138	0.0048	324.02	0.0048	1	3	negative regulation of phospholipase A2 activity
GO:1902445	0.0048	324.02	0.0048	1	3	regulation of mitochondrial membrane permeability involved in programmed necrotic cell death
GO:2000297	0.0048	324.02	0.0048	1	3	negative regulation of synapse maturation
GO:1900076	0.005	21.0143	0.1057	2	66	regulation of cellular response to insulin stimulus
GO:1903779	0.0057	19.4855	0.1137	2	71	regulation of cardiac conduction
GO:0007418	0.0064	216	0.0064	1	4	ventral midline development
GO:0019732	0.0064	216	0.0064	1	4	antifungal humoral response
GO:0021938	0.0064	216	0.0064	1	4	smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation
GO:0060018	0.0064	216	0.0064	1	4	astrocyte fate commitment
GO:1903273	0.0064	216	0.0064	1	4	regulation of sodium ion export
GO:1903278	0.0064	216	0.0064	1	4	positive regulation of sodium ion export across plasma membrane
GO:1904637	0.0064	216	0.0064	1	4	cellular response to ionomycin
GO:2001274	0.0064	216	0.0064	1	4	negative regulation of glucose import in response to insulin stimulus
GO:0002028	0.0072	17.2276	0.1282	2	80	regulation of sodium ion transport
GO:0021700	0.0072	8.426	0.4005	3	250	developmental maturation
GO:0051239	0.0073	3.075	4.4009	10	2747	regulation of multicellular organismal process
GO:0003013	0.0077	5.7817	0.7978	4	498	circulatory system process
GO:0061760	0.008	161.99	0.008	1	5	antifungal innate immune response
GO:0030097	0.0083	4.5662	1.2945	5	808	hemopoiesis
GO:0030219	0.0091	15.2604	0.1442	2	90	megakaryocyte differentiation
GO:0002865	0.0096	129.584	0.0096	1	6	negative regulation of acute inflammatory response to antigenic stimulus
GO:0018344	0.0096	129.584	0.0096	1	6	protein geranylgeranylation

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0042220	8e-04	58.7855	0.0417	2	52	response to cocaine
GO:0031327	9e-04	7.7868	1.2929	6	1614	negative regulation of cellular biosynthetic process
GO:0021852	0.0016	1351.25	0.0016	1	2	pyramidal neuron migration
GO:0014063	0.0024	675.5833	0.0024	1	3	negative regulation of serotonin secretion
GO:0023021	0.0024	675.5833	0.0024	1	3	termination of signal transduction
GO:0140076	0.0024	675.5833	0.0024	1	3	negative regulation of lipoprotein transport
GO:0045934	0.003	6.8327	1.0926	5	1364	negative regulation of nucleobase-containing compound metabolic process
GO:0009892	0.0032	5.5255	2.2701	7	2834	negative regulation of metabolic process
GO:0007198	0.0032	450.3611	0.0032	1	4	adenylate cyclase-inhibiting serotonin receptor signaling pathway
GO:0015870	0.004	337.75	0.004	1	5	acetylcholine transport
GO:0016199	0.004	337.75	0.004	1	5	axon midline choice point recognition
GO:0071502	0.004	337.75	0.004	1	5	cellular response to temperature stimulus
GO:0006685	0.0048	270.1833	0.0048	1	6	sphingomyelin catabolic process
GO:0032229	0.0048	270.1833	0.0048	1	6	negative regulation of synaptic transmission, GABAergic
GO:0010558	0.005	6.0122	1.2272	5	1532	negative regulation of macromolecule biosynthetic process
GO:0033504	0.0056	225.1389	0.0056	1	7	floor plate development
GO:0033601	0.0056	225.1389	0.0056	1	7	positive regulation of mammary gland epithelial cell proliferation
GO:0021859	0.0064	192.9643	0.0064	1	8	pyramidal neuron differentiation
GO:0042756	0.0064	192.9643	0.0064	1	8	drinking behavior
GO:0048664	0.0072	168.8333	0.0072	1	9	neuron fate determination
GO:0090370	0.008	150.0648	0.008	1	10	negative regulation of cholesterol efflux
GO:2001256	0.008	150.0648	0.008	1	10	regulation of store-operated calcium entry
GO:0010985	0.0088	135.05	0.0088	1	11	negative regulation of lipoprotein particle clearance
GO:0043374	0.0088	135.05	0.0088	1	11	CD8-positive, alpha-beta T cell differentiation
GO:0045892	0.0093	6.1075	0.8843	4	1104	negative regulation of transcription, DNA-templated
GO:0003376	0.0096	122.7652	0.0096	1	12	sphingosine-1-phosphate signaling pathway

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0007198	0	953.4118	0.0047	2	4	adenylate cyclase-inhibiting serotonin receptor signaling pathway
GO:0002568	0	635.5686	0.0059	2	5	somatic diversification of T cell receptor genes
GO:0033153	0	635.5686	0.0059	2	5	T cell receptor V(D)J recombination
GO:0051172	0	7.9236	2.8192	11	2408	negative regulation of nitrogen compound metabolic process
GO:0042127	0	8.4639	1.8346	9	1567	regulation of cell proliferation
GO:0031324	0	7.3657	2.9983	11	2561	negative regulation of cellular metabolic process
GO:0009890	0	8.0834	1.9118	9	1633	negative regulation of biosynthetic process
GO:2000774	1e-04	211.7778	0.0129	2	11	positive regulation of cellular senescence
GO:0006837	1e-04	158.8039	0.0164	2	14	serotonin transport
GO:2000113	1e-04	7.3254	1.7233	8	1472	negative regulation of cellular macromolecule biosynthetic process
GO:0000122	2e-04	9.4873	0.8874	6	758	negative regulation of transcription from RNA polymerase II promoter
GO:1903507	2e-04	7.7773	1.3323	7	1138	negative regulation of nucleic acid-templated transcription
GO:0007210	3e-04	100.2539	0.0246	2	21	serotonin receptor signaling pathway
GO:0051253	3e-04	7.2638	1.4189	7	1212	negative regulation of RNA metabolic process
GO:0046631	3e-04	27.4432	0.1323	3	113	alpha-beta T cell activation
GO:0071901	4e-04	24.1275	0.1499	3	128	negative regulation of protein serine/threonine kinase activity
GO:0071353	6e-04	67.9916	0.0351	2	30	cellular response to interleukin-4
GO:0010629	6e-04	5.7788	2.1308	8	1820	negative regulation of gene expression
GO:0090342	0.001	48.7813	0.048	2	41	regulation of cell aging
GO:0048568	0.0012	10.3541	0.4812	4	411	embryonic organ development
GO:0061153	0.0012	Inf	0.0012	1	1	trachea gland development
GO:1903769	0.0012	Inf	0.0012	1	1	negative regulation of cell proliferation in bone marrow
GO:1904837	0.0012	45.2885	0.0515	2	44	beta-catenin-TCF complex assembly
GO:0021879	0.0015	40.4581	0.0574	2	49	forebrain neuron differentiation
GO:0042220	0.0017	38.0235	0.0609	2	52	response to cocaine
GO:0007405	0.0018	36.5566	0.0632	2	54	neuroblast proliferation
GO:0002562	0.0019	35.8646	0.0644	2	55	somatic diversification of immune receptors via germline recombination within a single locus
GO:0019222	0.0023	4.3907	7.4061	14	6326	regulation of metabolic process
GO:0021852	0.0023	900.5	0.0023	1	2	pyramidal neuron migration
GO:0072272	0.0023	900.5	0.0023	1	2	proximal/distal pattern formation involved in metanephric nephron development
GO:0110023	0.0023	900.5	0.0023	1	2	negative regulation of cardiac muscle myoblast proliferation
GO:0043367	0.0024	31.1456	0.0738	2	63	CD4-positive, alpha-beta T cell differentiation
GO:0050795	0.0027	29.6801	0.0773	2	66	regulation of behavior
GO:0042310	0.0032	26.7423	0.0855	2	73	vasoconstriction
GO:0014062	0.0033	476.6471	0.0033	1	3	regulation of serotonin secretion
GO:0031326	0.0035	3.8645	4.9932	11	4265	regulation of cellular biosynthetic process
GO:0014063	0.0035	450.2222	0.0035	1	3	negative regulation of serotonin secretion
GO:0021943	0.0035	450.2222	0.0035	1	3	formation of radial glial scaffolds
GO:0023021	0.0035	450.2222	0.0035	1	3	termination of signal transduction
GO:0030538	0.0035	450.2222	0.0035	1	3	embryonic genitalia morphogenesis
GO:0035986	0.0035	450.2222	0.0035	1	3	senescence-associated heterochromatin focus assembly
GO:0044336	0.0035	450.2222	0.0035	1	3	canonical Wnt signaling pathway involved in negative regulation of apoptotic process
GO:0048619	0.0035	450.2222	0.0035	1	3	embryonic hindgut morphogenesis
GO:0071895	0.0035	450.2222	0.0035	1	3	odontoblast differentiation
GO:0071899	0.0035	450.2222	0.0035	1	3	negative regulation of estrogen receptor binding
GO:2000111	0.0035	450.2222	0.0035	1	3	positive regulation of macrophage apoptotic process
GO:0033673	0.0035	11.3253	0.3126	3	267	negative regulation of kinase activity
GO:0000079	0.0039	24.3318	0.0937	2	80	regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0045936	0.004	7.2904	0.6743	4	576	negative regulation of phosphate metabolic process
GO:0009887	0.0042	5.686	1.1274	5	963	animal organ morphogenesis
GO:0007568	0.0043	10.5145	0.336	3	287	aging
GO:0071866	0.0047	300.1296	0.0047	1	4	negative regulation of apoptotic process in bone marrow
GO:0072086	0.0047	300.1296	0.0047	1	4	specification of loop of Henle identity
GO:0035282	0.0051	21.0719	0.1077	2	92	segmentation
GO:0042472	0.0053	20.6113	0.11	2	94	inner ear morphogenesis
GO:0030098	0.0056	9.523	0.37	3	316	lymphocyte differentiation
GO:0015870	0.0058	225.0833	0.0059	1	5	acetylcholine transport
GO:0016199	0.0058	225.0833	0.0059	1	5	axon midline choice point recognition
GO:0032713	0.0058	225.0833	0.0059	1	5	negative regulation of interleukin-4 production
GO:0071502	0.0058	225.0833	0.0059	1	5	cellular response to temperature stimulus
GO:1902262	0.0058	225.0833	0.0059	1	5	apoptotic process involved in blood vessel morphogenesis
GO:0035239	0.0067	8.9124	0.3945	3	337	tube morphogenesis
GO:0006685	0.007	180.0556	0.007	1	6	sphingomyelin catabolic process
GO:0021861	0.007	180.0556	0.007	1	6	forebrain radial glial cell differentiation
GO:0032229	0.007	180.0556	0.007	1	6	negative regulation of synaptic transmission, GABAergic
GO:0032696	0.007	180.0556	0.007	1	6	negative regulation of interleukin-13 production
GO:0032714	0.007	180.0556	0.007	1	6	negative regulation of interleukin-5 production
GO:1902807	0.0077	16.9097	0.1335	2	114	negative regulation of cell cycle G1/S phase transition
GO:0030223	0.0082	150.037	0.0082	1	7	neutrophil differentiation
GO:0033504	0.0082	150.037	0.0082	1	7	floor plate development
GO:0048341	0.0082	150.037	0.0082	1	7	paraxial mesoderm formation
GO:0060710	0.0082	150.037	0.0082	1	7	chorio-allantoic fusion
GO:0071864	0.0082	150.037	0.0082	1	7	positive regulation of cell proliferation in bone marrow
GO:0019219	0.0084	3.3737	4.7134	10	4026	regulation of nucleobase-containing compound metabolic process
GO:0034641	0.0085	3.4277	7.3651	13	6291	cellular nitrogen compound metabolic process
GO:0010556	0.009	3.3273	4.7626	10	4068	regulation of macromolecule biosynthetic process
GO:0034654	0.0093	3.3131	4.7778	10	4081	nucleobase-containing compound biosynthetic process
GO:0021859	0.0093	128.5952	0.0094	1	8	pyramidal neuron differentiation
GO:0021873	0.0093	128.5952	0.0094	1	8	forebrain neuroblast division
GO:0030854	0.0093	128.5952	0.0094	1	8	positive regulation of granulocyte differentiation
GO:0042756	0.0093	128.5952	0.0094	1	8	drinking behavior
GO:0048069	0.0093	128.5952	0.0094	1	8	eye pigmentation
GO:0061525	0.0093	128.5952	0.0094	1	8	hindgut development
GO:0065007	0.0094	7.8923	13.2142	18	11287	biological regulation
GO:0097746	0.0094	15.2619	0.1475	2	126	regulation of blood vessel diameter
GO:0006355	0.01	3.3422	4.0367	9	3448	regulation of transcription, DNA-templated

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0038115	0.0012	Inf	0.0012	1	1	chemokine (C-C motif) ligand 19 signaling pathway
GO:0038116	0.0012	Inf	0.0012	1	1	chemokine (C-C motif) ligand 21 signaling pathway
GO:0097022	0.0012	Inf	0.0012	1	1	lymphocyte migration into lymph node
GO:2000522	0.0012	Inf	0.0012	1	1	positive regulation of immunological synapse formation
GO:2000526	0.0012	Inf	0.0012	1	1	positive regulation of glycoprotein biosynthetic process involved in immunological synapse formation
GO:0051896	0.0019	13.984	0.2526	3	205	regulation of protein kinase B signaling
GO:0071228	0.0025	853.0526	0.0025	1	2	cellular response to tumor cell
GO:1901003	0.0025	853.0526	0.0025	1	2	negative regulation of fermentation
GO:2000525	0.0025	853.0526	0.0025	1	2	positive regulation of T cell costimulation
GO:0010660	0.0031	27.1768	0.0838	2	68	regulation of muscle cell apoptotic process
GO:0023052	0.0032	3.9088	7.4841	14	6073	signaling
GO:0007154	0.0033	3.8862	7.5112	14	6095	cell communication
GO:0035986	0.0037	426.5	0.0037	1	3	senescence-associated heterochromatin focus assembly
GO:0140076	0.0037	426.5	0.0037	1	3	negative regulation of lipoprotein transport
GO:2000111	0.0037	426.5	0.0037	1	3	positive regulation of macrophage apoptotic process
GO:2000547	0.0037	426.5	0.0037	1	3	regulation of dendritic cell dendrite assembly
GO:2000106	0.0042	23.2785	0.0974	2	79	regulation of leukocyte apoptotic process
GO:0002408	0.0049	284.3158	0.0049	1	4	myeloid dendritic cell chemotaxis
GO:0007198	0.0049	284.3158	0.0049	1	4	adenylate cyclase-inhibiting serotonin receptor signaling pathway
GO:0097029	0.0049	284.3158	0.0049	1	4	mature conventional dendritic cell differentiation
GO:0002885	0.0061	213.2237	0.0062	1	5	positive regulation of hypersensitivity
GO:0015870	0.0061	213.2237	0.0062	1	5	acetylcholine transport
GO:0001952	0.0065	18.4559	0.122	2	99	regulation of cell-matrix adhesion
GO:0014062	0.0074	170.5684	0.0074	1	6	regulation of serotonin secretion
GO:0002606	0.0086	142.1316	0.0086	1	7	positive regulation of dendritic cell antigen processing and presentation
GO:2000271	0.0086	142.1316	0.0086	1	7	positive regulation of fibroblast apoptotic process
GO:0072610	0.0098	121.8195	0.0099	1	8	interleukin-12 secretion

Differential Methylation

Parameter Overview

Introduction: Differential Methylation of Sample Groups

Comparisons

P-values

Region Level

Differential Methylation Tables

Differential Variability

GO Enrichment Analysis

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0050911	4e-04	32.3111	0.16	3	371	detection of chemical stimulus involved in sensory perception of smell
GO:0009593	7e-04	26.4681	0.1941	3	450	detection of chemical stimulus
GO:0050906	7e-04	25.7565	0.1993	3	462	detection of stimulus involved in sensory perception
GO:0007606	8e-04	25.4145	0.2019	3	468	sensory perception of chemical stimulus
GO:0021891	0.0026	540.5667	0.0026	1	6	olfactory bulb interneuron development
GO:0021930	0.0043	300.2407	0.0043	1	10	cerebellar granule cell precursor proliferation
GO:0021534	0.0047	270.2	0.0047	1	11	cell proliferation in hindbrain
GO:0015671	0.0065	192.9524	0.0065	1	15	oxygen transport

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0006614	4e-04	96.0655	0.0318	2	86	SRP-dependent cotranslational protein targeting to membrane
GO:0072599	5e-04	83.1237	0.0366	2	99	establishment of protein localization to endoplasmic reticulum
GO:0000184	7e-04	72.5766	0.0418	2	113	nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
GO:0006612	0.0013	52.8651	0.0569	2	154	protein targeting to membrane
GO:0019083	0.0016	47.497	0.0632	2	171	viral transcription
GO:0006413	0.0017	46.3873	0.0647	2	175	translational initiation
GO:0043043	0.0021	19.3041	0.2965	3	802	peptide biosynthetic process
GO:0031424	0.0028	35.7121	0.0836	2	226	keratinization
GO:0006364	0.0033	32.8807	0.0906	2	245	rRNA processing
GO:0043603	0.0053	13.7885	0.4067	3	1100	cellular amide metabolic process
GO:0006402	0.0058	24.4585	0.1209	2	327	mRNA catabolic process
GO:0009913	0.0065	22.8761	0.129	2	349	epidermal cell differentiation
GO:0043588	0.0088	19.4791	0.1508	2	408	skin development