RnBeads: TCGA_integration

Option	Value
analyze.sites	yes
region.types	tiling, genes, promoters, cpgislands
differential.permutations	0
differential.comparison.columns	Type, Study, Gender
differential.comparison.columns.all.pairwise	default
columns.pairing	default
differential.site.test.method	limma
covariate.adjustment.columns	default
differential.adjustment.sva	yes
differential.adjustment.celltype	yes
differential.enrichment	yes

	Rank Cutoff
Control Analyte vs. non.Control Analyte (based on Type)	111928
Metastatic vs. non.Metastatic (based on Type)	9048
Primary Blood Derived Cancer - Peripheral Blood vs. non.Primary Blood Derived Cancer - Peripheral Blood (based on Type)	104493
Primary solid Tumor vs. non.Primary solid Tumor (based on Type)	130459
Recurrent Solid Tumor vs. non.Recurrent Solid Tumor (based on Type)	27438
Solid Tissue Normal vs. non.Solid Tissue Normal (based on Type)	106831
Acute Myeloid Leukemia vs. non.Acute Myeloid Leukemia (based on Study)	104493
Breast invasive carcinoma vs. non.Breast invasive carcinoma (based on Study)	95716
Colon adenocarcinoma vs. non.Colon adenocarcinoma (based on Study)	106549
Glioblastoma multiforme vs. non.Glioblastoma multiforme (based on Study)	119784
Head and Neck squamous cell carcinoma vs. non.Head and Neck squamous cell carcinoma (based on Study)	113705
Kidney renal clear cell carcinoma vs. non.Kidney renal clear cell carcinoma (based on Study)	60341
Lung adenocarcinoma vs. non.Lung adenocarcinoma (based on Study)	86511
Lung squamous cell carcinoma vs. non.Lung squamous cell carcinoma (based on Study)	112672
Rectum adenocarcinoma vs. non.Rectum adenocarcinoma (based on Study)	109642
Thyroid carcinoma vs. non.Thyroid carcinoma (based on Study)	147645
Uterine Corpus Endometrioid Carcinoma vs. non.Uterine Corpus Endometrioid Carcinoma (based on Study)	104213
FEMALE vs. MALE (based on Gender)	87947

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 difference in means across all sites in a region of the two groups being compared and the mean of quotients in mean methylation as well as a combined p-value calculated from all site p-values in the region [1]. 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:

	tiling	genes	promoters	cpgislands
Control Analyte vs. non.Control Analyte (based on Type)	4520	857	1442	1307
Metastatic vs. non.Metastatic (based on Type)	5062	975	1610	2136
Primary Blood Derived Cancer - Peripheral Blood vs. non.Primary Blood Derived Cancer - Peripheral Blood (based on Type)	5262	0	2034	1587
Primary solid Tumor vs. non.Primary solid Tumor (based on Type)	6922	2757	3819	3715
Recurrent Solid Tumor vs. non.Recurrent Solid Tumor (based on Type)	5809	1543	2235	1900
Solid Tissue Normal vs. non.Solid Tissue Normal (based on Type)	10720	1826	3791	3125
Acute Myeloid Leukemia vs. non.Acute Myeloid Leukemia (based on Study)	5262	0	2034	1587
Breast invasive carcinoma vs. non.Breast invasive carcinoma (based on Study)	6895	958	2040	2017
Colon adenocarcinoma vs. non.Colon adenocarcinoma (based on Study)	3815	546	2842	3941
Glioblastoma multiforme vs. non.Glioblastoma multiforme (based on Study)	6376	726	1283	3008
Head and Neck squamous cell carcinoma vs. non.Head and Neck squamous cell carcinoma (based on Study)	10567	1694	2485	2327
Kidney renal clear cell carcinoma vs. non.Kidney renal clear cell carcinoma (based on Study)	3156	747	2432	2767
Lung adenocarcinoma vs. non.Lung adenocarcinoma (based on Study)	6116	1260	2687	3517
Lung squamous cell carcinoma vs. non.Lung squamous cell carcinoma (based on Study)	9573	1504	3452	2496
Rectum adenocarcinoma vs. non.Rectum adenocarcinoma (based on Study)	3452	996	3033	4201
Thyroid carcinoma vs. non.Thyroid carcinoma (based on Study)	1017	371	2360	964
Uterine Corpus Endometrioid Carcinoma vs. non.Uterine Corpus Endometrioid Carcinoma (based on Study)	6527	454	1997	2963
FEMALE vs. MALE (based on Gender)	5308	1308	883	2179

comparison
regions
differential methylation measure

Figure 3

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 4

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
[symbol]: associated gene symbol to the given region [only valid for gene associated regions]
[entrezID]: Entrez ID of the gene associated with the region [only valid for gene associated regions]
mean.mean.g1,mean.mean.g2: (where g1 and g2 is replaced by the respective group names in the table) mean of mean methylation levels for group 1 and 2 across all sites in a region
mean.mean.diff: Mean difference in means across all sites in a region
mean.mean.quot.log2: log2 of the mean quotient in means across all sites in a region
comb.p.val: Combined p-value aggregating p-values of all sites in the region using a generalization of Fisher's method [1]
comb.p.adj.fdr: FDR adjusted combined p-value
combinedRank: mean.mean.diff, mean.mean.quot.log2 and comb.p.val are ranked for all regions. This column aggregates them using the maximum, i.e. worst rank of a site among the three measures
num.sites: number of sites associated with the region
mean.num.na.g1,mean.num.na.g2: Mean number of NA methylation values accross all sites in group 1 and group 2 respectively
mean.mean.covg.g1,mean.mean.covg.g2: Mean value of mean coverage values (across all samples in a group) across all sites in a region
mean.nsamples.covg.thresh.g1,mean.nsamples.covg.thresh.g2: mean number of samples (accross all considered sites) that have a coverage larger than 5 for the site in group 1 and group 2 respectively

The tables for the individual comparisons can be found here:

	tiling	genes	promoters	cpgislands
Control Analyte vs. non.Control Analyte (based on Type)	csv	csv	csv	csv
Metastatic vs. non.Metastatic (based on Type)	csv	csv	csv	csv
Primary Blood Derived Cancer - Peripheral Blood vs. non.Primary Blood Derived Cancer - Peripheral Blood (based on Type)	csv	csv	csv	csv
Primary solid Tumor vs. non.Primary solid Tumor (based on Type)	csv	csv	csv	csv
Recurrent Solid Tumor vs. non.Recurrent Solid Tumor (based on Type)	csv	csv	csv	csv
Solid Tissue Normal vs. non.Solid Tissue Normal (based on Type)	csv	csv	csv	csv
Acute Myeloid Leukemia vs. non.Acute Myeloid Leukemia (based on Study)	csv	csv	csv	csv
Breast invasive carcinoma vs. non.Breast invasive carcinoma (based on Study)	csv	csv	csv	csv
Colon adenocarcinoma vs. non.Colon adenocarcinoma (based on Study)	csv	csv	csv	csv
Glioblastoma multiforme vs. non.Glioblastoma multiforme (based on Study)	csv	csv	csv	csv
Head and Neck squamous cell carcinoma vs. non.Head and Neck squamous cell carcinoma (based on Study)	csv	csv	csv	csv
Kidney renal clear cell carcinoma vs. non.Kidney renal clear cell carcinoma (based on Study)	csv	csv	csv	csv
Lung adenocarcinoma vs. non.Lung adenocarcinoma (based on Study)	csv	csv	csv	csv
Lung squamous cell carcinoma vs. non.Lung squamous cell carcinoma (based on Study)	csv	csv	csv	csv
Rectum adenocarcinoma vs. non.Rectum adenocarcinoma (based on Study)	csv	csv	csv	csv
Thyroid carcinoma vs. non.Thyroid carcinoma (based on Study)	csv	csv	csv	csv
Uterine Corpus Endometrioid Carcinoma vs. non.Uterine Corpus Endometrioid Carcinoma (based on Study)	csv	csv	csv	csv
FEMALE vs. MALE (based on Gender)	csv	csv	csv	csv

Enrichment Analysis

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 5

Wordclouds for GO enrichment terms.

comparison
Hypermethylation/hypomethylation
ontology
regions
differential methylation measure

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0007264	1e-04	14.1206	0.5178	5	486	small GTPase mediated signal transduction
GO:0006184	9e-04	11.4756	0.4645	4	436	GTP catabolic process
GO:0060764	0.0011	Inf	0.0011	1	1	cell-cell signaling involved in mammary gland development
GO:1901068	0.0011	10.9768	0.4847	4	455	guanosine-containing compound metabolic process
GO:0009150	0.0012	8.1077	0.8757	5	822	purine ribonucleotide metabolic process
GO:0019693	0.0013	7.9323	0.8938	5	839	ribose phosphate metabolic process
GO:0035483	0.0021	1004.5714	0.0021	1	2	gastric emptying
GO:0007266	0.0025	31.2062	0.0756	2	71	Rho protein signal transduction
GO:0009203	0.0026	8.6567	0.6083	4	571	ribonucleoside triphosphate catabolic process
GO:0009146	0.0026	8.6093	0.6115	4	574	purine nucleoside triphosphate catabolic process
GO:0046130	0.0027	8.5004	0.619	4	581	purine ribonucleoside catabolic process
GO:0006979	0.0028	12.6774	0.293	3	275	response to oxidative stress
GO:0046578	0.003	12.3984	0.2994	3	281	regulation of Ras protein signal transduction
GO:0009261	0.003	8.2467	0.6371	4	598	ribonucleotide catabolic process
GO:0009164	0.0031	8.1891	0.6413	4	602	nucleoside catabolic process
GO:0009117	0.0031	6.4836	1.0781	5	1012	nucleotide metabolic process
GO:0060435	0.0032	502.25	0.0032	1	3	bronchiole development
GO:0060574	0.0032	502.25	0.0032	1	3	intestinal epithelial cell maturation
GO:0009205	0.0034	7.9392	0.6605	4	620	purine ribonucleoside triphosphate metabolic process
GO:0006195	0.0038	7.6908	0.6808	4	639	purine nucleotide catabolic process
GO:0055086	0.0038	6.147	1.1325	5	1063	nucleobase-containing small molecule metabolic process
GO:0009141	0.0039	7.6403	0.685	4	643	nucleoside triphosphate metabolic process
GO:0051461	0.0043	334.8095	0.0043	1	4	positive regulation of corticotropin secretion
GO:0060455	0.0043	334.8095	0.0043	1	4	negative regulation of gastric acid secretion
GO:0060482	0.0043	334.8095	0.0043	1	4	lobar bronchus development
GO:0060535	0.0043	334.8095	0.0043	1	4	trachea cartilage morphogenesis
GO:2000987	0.0043	334.8095	0.0043	1	4	positive regulation of behavioral fear response
GO:1901292	0.0044	7.4092	0.7053	4	662	nucleoside phosphate catabolic process
GO:0042278	0.0051	7.0811	0.7362	4	691	purine nucleoside metabolic process
GO:0060480	0.0053	251.0893	0.0053	1	5	lung goblet cell differentiation
GO:0009119	0.0056	6.8808	0.7564	4	710	ribonucleoside metabolic process
GO:0031175	0.0062	6.6618	0.7798	4	732	neuron projection development
GO:0060452	0.0064	200.8571	0.0064	1	6	positive regulation of cardiac muscle contraction
GO:0060547	0.0064	200.8571	0.0064	1	6	negative regulation of necrotic cell death
GO:0006927	0.0074	167.369	0.0075	1	7	transformed cell apoptotic process
GO:0042756	0.0074	167.369	0.0075	1	7	drinking behavior
GO:2000252	0.0074	167.369	0.0075	1	7	negative regulation of feeding behavior
GO:1901215	0.0076	17.4384	0.1332	2	125	negative regulation of neuron death
GO:1901657	0.0077	6.2614	0.8267	4	776	glycosyl compound metabolic process
GO:0043117	0.0085	143.449	0.0085	1	8	positive regulation of vascular permeability
GO:0045647	0.0085	143.449	0.0085	1	8	negative regulation of erythrocyte differentiation
GO:1901564	0.0093	4.3664	1.9911	6	1869	organonitrogen compound metabolic process
GO:0032099	0.0096	125.5089	0.0096	1	9	negative regulation of appetite
GO:0060638	0.0096	125.5089	0.0096	1	9	mesenchymal-epithelial cell signaling

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0018191	9e-04	Inf	9e-04	1	1	peptidyl-serine octanoylation
GO:0048685	9e-04	Inf	9e-04	1	1	negative regulation of collateral sprouting of intact axon in response to injury
GO:2000373	9e-04	Inf	9e-04	1	1	positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity
GO:0010911	0.0017	1278.8182	0.0017	1	2	regulation of isomerase activity
GO:0006659	0.0034	426.2121	0.0034	1	4	phosphatidylserine biosynthetic process
GO:0060368	0.0034	426.2121	0.0034	1	4	regulation of Fc receptor mediated stimulatory signaling pathway
GO:0070571	0.0034	426.2121	0.0034	1	4	negative regulation of neuron projection regeneration
GO:0022617	0.0042	24.4807	0.0989	2	116	extracellular matrix disassembly
GO:0016098	0.0051	255.6909	0.0051	1	6	monoterpenoid metabolic process
GO:0017121	0.006	213.0606	0.006	1	7	phospholipid scrambling
GO:0097267	0.0076	159.7727	0.0077	1	9	omega-hydroxylase P450 pathway
GO:0006954	0.0085	8.7899	0.4406	3	517	inflammatory response
GO:0042738	0.0085	142.0101	0.0085	1	10	exogenous drug catabolic process
GO:0048679	0.0085	142.0101	0.0085	1	10	regulation of axon regeneration
GO:0019373	0.0093	127.8	0.0094	1	11	epoxygenase P450 pathway
GO:0045741	0.0093	127.8	0.0094	1	11	positive regulation of epidermal growth factor-activated receptor activity
GO:0070989	0.0093	127.8	0.0094	1	11	oxidative demethylation

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0033137	0.001	51.3736	0.0466	2	16	negative regulation of peptidyl-serine phosphorylation
GO:0019751	0.0027	11.8387	0.2795	3	96	polyol metabolic process
GO:0002041	0.0029	Inf	0.0029	1	1	intussusceptive angiogenesis
GO:0019428	0.0029	Inf	0.0029	1	1	allantoin biosynthetic process
GO:0019628	0.0029	Inf	0.0029	1	1	urate catabolic process
GO:0070997	0.0034	7.1192	0.6232	4	214	neuron death
GO:0032312	0.0036	24.7745	0.0903	2	31	regulation of ARF GTPase activity
GO:0072593	0.0053	9.2349	0.3553	3	122	reactive oxygen species metabolic process
GO:0046168	0.0058	350.95	0.0058	1	2	glycerol-3-phosphate catabolic process
GO:0006116	0.0087	175.4625	0.0087	1	3	NADH oxidation
GO:2000304	0.0087	175.4625	0.0087	1	3	positive regulation of ceramide biosynthetic process

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0007422	0	51.4791	0.245	9	75	peripheral nervous system development
GO:0022008	0	11.7408	2.066	15	761	neurogenesis
GO:0045944	0	9.4957	2.2917	15	717	positive regulation of transcription from RNA polymerase II promoter
GO:0007389	0	11.6402	1.3885	12	425	pattern specification process
GO:0009891	0	6.946	4.2798	19	1310	positive regulation of biosynthetic process
GO:1902680	0	7.3166	3.4565	17	1058	positive regulation of RNA biosynthetic process
GO:0048935	0	228.065	0.032	4	10	peripheral nervous system neuron development
GO:0010628	0	6.9269	3.633	17	1112	positive regulation of gene expression
GO:0048880	0	190.8435	0.0359	4	11	sensory system development
GO:0048665	0	65.7036	0.1013	5	31	neuron fate specification
GO:0048731	0	6.8646	7.2036	22	2881	system development
GO:0045935	0	6.2581	3.9825	17	1219	positive regulation of nucleobase-containing compound metabolic process
GO:0044707	0	8.0043	11.2742	26	4769	single-multicellular organism process
GO:0034654	0	4.8035	11.3072	28	3461	nucleobase-containing compound biosynthetic process
GO:0048522	0	4.8743	10.6418	27	3329	positive regulation of cellular process
GO:0031326	0	4.6871	10.7551	27	3292	regulation of cellular biosynthetic process
GO:2000026	0	5.783	3.9237	16	1201	regulation of multicellular organismal development
GO:0048937	0	244.7093	0.0229	3	7	lateral line nerve glial cell development
GO:0050935	0	244.7093	0.0229	3	7	iridophore differentiation
GO:0048485	0	58.0166	0.0882	4	27	sympathetic nervous system development
GO:0048892	0	195.7535	0.0261	3	8	lateral line nerve development
GO:0010556	0	4.1627	10.2781	25	3146	regulation of macromolecule biosynthetic process
GO:0030182	0	7.7247	2.0045	11	816	neuron differentiation
GO:1901576	0	4.1414	16.4104	32	5023	organic substance biosynthetic process
GO:0021522	0	44.4571	0.1111	4	34	spinal cord motor neuron differentiation
GO:0009887	0	6.0631	2.5614	12	784	organ morphogenesis
GO:0051252	0	3.878	9.4744	23	2900	regulation of RNA metabolic process
GO:0048588	0	19.3265	0.3038	5	93	developmental cell growth
GO:0032990	0	5.9243	2.3457	11	718	cell part morphogenesis
GO:0090304	0	3.5738	13.996	28	4284	nucleic acid metabolic process
GO:0031018	0	29.6063	0.1601	4	49	endocrine pancreas development
GO:0051094	0	5.5902	2.4764	11	758	positive regulation of developmental process
GO:0045165	0	16.2203	0.3643	5	134	cell fate commitment
GO:0048484	0	61.125	0.0621	3	19	enteric nervous system development
GO:0021912	0	637.8636	0.0098	2	3	regulation of transcription from RNA polymerase II promoter involved in spinal cord motor neuron fate specification
GO:0080090	0	3.3857	14.5253	28	4446	regulation of primary metabolic process
GO:0021510	0	23.6559	0.1972	4	63	spinal cord development
GO:0014033	1e-04	22.5585	0.2058	4	63	neural crest cell differentiation
GO:0045686	1e-04	48.886	0.0751	3	23	negative regulation of glial cell differentiation
GO:0014013	1e-04	21.8158	0.2124	4	65	regulation of gliogenesis
GO:0021913	1e-04	318.9091	0.0131	2	4	regulation of transcription from RNA polymerase II promoter involved in ventral spinal cord interneuron specification
GO:0048846	1e-04	44.4355	0.0817	3	25	axon extension involved in axon guidance
GO:0060560	1e-04	13.0432	0.4411	5	135	developmental growth involved in morphogenesis
GO:0021675	1e-04	20.1558	0.2287	4	70	nerve development
GO:0045687	1e-04	42.5005	0.0849	3	26	positive regulation of glial cell differentiation
GO:0051171	1e-04	3.2376	11.6339	24	3561	regulation of nitrogen compound metabolic process
GO:0051090	1e-04	7.6433	1.0749	7	329	regulation of sequence-specific DNA binding transcription factor activity
GO:0048468	1e-04	4.3389	4.0549	13	1450	cell development
GO:0009890	1e-04	4.4143	3.4337	12	1051	negative regulation of biosynthetic process
GO:0034641	1e-04	3.1895	18.1288	31	5549	cellular nitrogen compound metabolic process
GO:0061564	1e-04	6.2124	1.529	8	468	axon development
GO:0044767	1e-04	6.1452	4.1565	12	2656	single-organism developmental process
GO:0048667	1e-04	6.1433	1.5453	8	473	cell morphogenesis involved in neuron differentiation
GO:0048663	1e-04	35.5951	0.0992	3	34	neuron fate commitment
GO:0002065	1e-04	17.2628	0.2646	4	81	columnar/cuboidal epithelial cell differentiation
GO:0030318	2e-04	33.6929	0.1045	3	32	melanocyte differentiation
GO:0046483	2e-04	3.0777	17.4558	30	5343	heterocycle metabolic process
GO:0006725	2e-04	3.0693	17.4852	30	5352	cellular aromatic compound metabolic process
GO:0040007	2e-04	4.6819	2.6006	10	796	growth
GO:0001755	2e-04	30.3009	0.1151	3	36	neural crest cell migration
GO:0045934	2e-04	4.2564	3.1886	11	976	negative regulation of nucleobase-containing compound metabolic process
GO:0000902	3e-04	4.1772	3.2442	11	993	cell morphogenesis
GO:0000122	3e-04	5.4279	1.7381	8	532	negative regulation of transcription from RNA polymerase II promoter
GO:0030030	3e-04	4.1008	3.2997	11	1010	cell projection organization
GO:0014031	3e-04	13.6838	0.33	4	101	mesenchymal cell development
GO:1902679	3e-04	4.3576	2.7803	10	851	negative regulation of RNA biosynthetic process
GO:1901360	3e-04	2.8928	18.1288	30	5549	organic cyclic compound metabolic process
GO:0002118	4e-04	91.0844	0.0294	2	9	aggressive behavior
GO:0051957	4e-04	91.0844	0.0294	2	9	positive regulation of amino acid transport
GO:0021953	5e-04	12.4939	0.3618	4	121	central nervous system neuron differentiation
GO:0060573	5e-04	79.6932	0.0327	2	10	cell fate specification involved in pattern specification
GO:0048066	5e-04	21.6884	0.1568	3	48	developmental pigmentation
GO:0060579	6e-04	70.8333	0.0359	2	11	ventral spinal cord interneuron fate commitment
GO:0006355	6e-04	3.2169	6.9599	16	2454	regulation of transcription, DNA-templated
GO:0045595	6e-04	4.8812	1.9666	8	669	regulation of cell differentiation
GO:0035113	6e-04	11.3284	0.3953	4	121	embryonic appendage morphogenesis
GO:0009888	7e-04	3.7491	3.6536	11	1213	tissue development
GO:0050885	7e-04	19.1286	0.1764	3	54	neuromuscular process controlling balance
GO:0050767	7e-04	7.8831	0.7208	5	238	regulation of neurogenesis
GO:0051952	8e-04	18.7594	0.1797	3	55	regulation of amine transport
GO:0010629	8e-04	3.905	3.0776	10	942	negative regulation of gene expression
GO:2000113	8e-04	3.905	3.0776	10	942	negative regulation of cellular macromolecule biosynthetic process
GO:0030902	8e-04	10.7712	0.4149	4	127	hindbrain development
GO:0031960	8e-04	10.6836	0.4182	4	128	response to corticosteroid
GO:0014048	8e-04	57.9463	0.0425	2	13	regulation of glutamate secretion
GO:0001658	0.001	17.1077	0.196	3	60	branching involved in ureteric bud morphogenesis
GO:0060485	0.001	10.0303	0.4443	4	136	mesenchyme development
GO:0009790	0.001	5.0832	1.6181	7	554	embryo development
GO:0001967	0.0011	49.0245	0.049	2	15	suckling behavior
GO:0044260	0.0011	2.6799	21.2097	32	6492	cellular macromolecule metabolic process
GO:0010001	0.0011	16.19	0.207	3	69	glial cell differentiation
GO:0001756	0.0012	15.9813	0.2091	3	64	somitogenesis
GO:0048709	0.0012	15.9813	0.2091	3	64	oligodendrocyte differentiation
GO:0050789	0.0013	2.9559	26.793	37	8201	regulation of biological process
GO:0021854	0.0014	42.4818	0.0555	2	17	hypothalamus development
GO:0048568	0.0015	5.4044	1.2578	6	385	embryonic organ development
GO:0051412	0.0015	39.8239	0.0588	2	18	response to corticosterone
GO:0051674	0.0016	4.1344	2.2477	8	688	localization of cell
GO:0060173	0.0016	8.8152	0.5031	4	154	limb development
GO:0007631	0.0016	14.3765	0.2315	3	74	feeding behavior
GO:0043586	0.0017	37.4786	0.0621	2	19	tongue development
GO:0045666	0.0019	13.5291	0.245	3	75	positive regulation of neuron differentiation
GO:0021511	0.0019	35.3939	0.0653	2	20	spinal cord patterning
GO:0044062	0.0021	33.5287	0.0686	2	21	regulation of excretion
GO:0045907	0.0021	33.5287	0.0686	2	21	positive regulation of vasoconstriction
GO:0048863	0.0023	5.9687	0.9344	5	286	stem cell differentiation
GO:0051216	0.0025	7.7669	0.5685	4	174	cartilage development
GO:0014706	0.0026	5.7796	0.9638	5	295	striated muscle tissue development
GO:0016477	0.0027	3.4754	3.0286	9	927	cell migration
GO:0021536	0.0029	11.5834	0.2847	3	91	diencephalon development
GO:0040011	0.0029	3.0501	4.319	11	1322	locomotion
GO:0048704	0.003	11.3153	0.2908	3	89	embryonic skeletal system morphogenesis
GO:0045923	0.0032	26.5341	0.0849	2	26	positive regulation of fatty acid metabolic process
GO:0006351	0.0032	7.559	0.6301	4	310	transcription, DNA-templated
GO:0001657	0.0032	11.0566	0.2973	3	91	ureteric bud development
GO:0021764	0.0033	Inf	0.0033	1	1	amygdala development
GO:0051296	0.0033	Inf	0.0033	1	1	establishment of meiotic spindle orientation
GO:0051355	0.0033	Inf	0.0033	1	1	proprioception involved in equilibrioception
GO:1902103	0.0033	Inf	0.0033	1	1	negative regulation of metaphase/anaphase transition of meiotic cell cycle
GO:2000763	0.0033	Inf	0.0033	1	1	positive regulation of transcription from RNA polymerase II promoter involved in norepinephrine biosynthetic process
GO:2000764	0.0033	Inf	0.0033	1	1	positive regulation of semaphorin-plexin signaling pathway involved in outflow tract morphogenesis
GO:2001260	0.0033	Inf	0.0033	1	1	regulation of semaphorin-plexin signaling pathway
GO:0009953	0.0033	10.9315	0.3006	3	92	dorsal/ventral pattern formation
GO:0044708	0.0034	7.1008	0.6227	4	202	single-organism behavior
GO:0061061	0.0034	4.5489	1.4832	6	454	muscle structure development
GO:0050768	0.0037	10.5728	0.3104	3	95	negative regulation of neurogenesis
GO:0048812	0.0037	6.9354	0.6394	4	214	neuron projection morphogenesis
GO:0043009	0.0038	4.4624	1.5216	6	496	chordate embryonic development
GO:0045596	0.0042	4.3577	1.5453	6	473	negative regulation of cell differentiation
GO:0045471	0.0046	9.7214	0.3365	3	103	response to ethanol
GO:0035115	0.0052	20.5323	0.1078	2	33	embryonic forelimb morphogenesis
GO:0046903	0.0052	3.3621	2.728	8	835	secretion
GO:0035176	0.0055	19.8892	0.1111	2	34	social behavior
GO:0045777	0.0055	19.8892	0.1111	2	34	positive regulation of blood pressure
GO:0051963	0.0055	19.8892	0.1111	2	34	regulation of synapse assembly
GO:0001501	0.0059	6.0564	0.7274	4	241	skeletal system development
GO:0097485	0.006	4.7402	1.1663	5	357	neuron projection guidance
GO:0003223	0.0065	311.8444	0.0065	1	2	ventricular compact myocardium morphogenesis
GO:0007198	0.0065	311.8444	0.0065	1	2	adenylate cyclase-inhibiting serotonin receptor signaling pathway
GO:0021986	0.0065	311.8444	0.0065	1	2	habenula development
GO:0035574	0.0065	311.8444	0.0065	1	2	histone H4-K20 demethylation
GO:0042412	0.0065	311.8444	0.0065	1	2	taurine biosynthetic process
GO:0042706	0.0065	311.8444	0.0065	1	2	eye photoreceptor cell fate commitment
GO:0043134	0.0065	311.8444	0.0065	1	2	regulation of hindgut contraction
GO:0046671	0.0065	311.8444	0.0065	1	2	negative regulation of retinal cell programmed cell death
GO:0061032	0.0065	311.8444	0.0065	1	2	visceral serous pericardium development
GO:0071502	0.0065	311.8444	0.0065	1	2	cellular response to temperature stimulus
GO:0072560	0.0065	311.8444	0.0065	1	2	type B pancreatic cell maturation
GO:1990009	0.0065	311.8444	0.0065	1	2	retinal cell apoptotic process
GO:0060538	0.0067	8.4443	0.3855	3	118	skeletal muscle organ development
GO:0032890	0.0068	17.6742	0.1241	2	38	regulation of organic acid transport
GO:0050880	0.0069	8.3709	0.3888	3	119	regulation of blood vessel size
GO:0035137	0.0072	17.1953	0.1274	2	39	hindlimb morphogenesis
GO:0048675	0.0076	16.6222	0.1316	2	43	axon extension
GO:0002009	0.0077	4.442	1.2415	5	380	morphogenesis of an epithelium
GO:0010623	0.0079	16.3112	0.1339	2	41	developmental programmed cell death
GO:0001708	0.0079	16.2751	0.1342	2	46	cell fate specification
GO:0009755	0.0083	15.9023	0.1372	2	42	hormone-mediated signaling pathway
GO:0048523	0.0083	2.4487	7.2783	14	2539	negative regulation of cellular process
GO:0030534	0.0089	7.5796	0.428	3	131	adult behavior
GO:0050769	0.0095	7.4044	0.4378	3	134	positive regulation of neurogenesis
GO:0050877	0.0098	3.2476	2.4241	7	742	neurological system process
GO:0001692	0.0098	155.9111	0.0098	1	3	histamine metabolic process
GO:0001992	0.0098	155.9111	0.0098	1	3	regulation of systemic arterial blood pressure by vasopressin
GO:0003253	0.0098	155.9111	0.0098	1	3	cardiac neural crest cell migration involved in outflow tract morphogenesis
GO:0010841	0.0098	155.9111	0.0098	1	3	positive regulation of circadian sleep/wake cycle, wakefulness
GO:0014063	0.0098	155.9111	0.0098	1	3	negative regulation of serotonin secretion
GO:0019448	0.0098	155.9111	0.0098	1	3	L-cysteine catabolic process
GO:0021530	0.0098	155.9111	0.0098	1	3	spinal cord oligodendrocyte cell fate specification
GO:0032100	0.0098	155.9111	0.0098	1	3	positive regulation of appetite
GO:0032849	0.0098	155.9111	0.0098	1	3	positive regulation of cellular pH reduction
GO:0035814	0.0098	155.9111	0.0098	1	3	negative regulation of renal sodium excretion
GO:0042631	0.0098	155.9111	0.0098	1	3	cellular response to water deprivation
GO:0046005	0.0098	155.9111	0.0098	1	3	positive regulation of circadian sleep/wake cycle, REM sleep
GO:0048936	0.0098	155.9111	0.0098	1	3	peripheral nervous system neuron axonogenesis
GO:0055014	0.0098	155.9111	0.0098	1	3	atrial cardiac muscle cell development
GO:1901993	0.0098	155.9111	0.0098	1	3	regulation of meiotic cell cycle phase transition
GO:2000078	0.0098	155.9111	0.0098	1	3	positive regulation of type B pancreatic cell development
GO:0007420	0.0099	4.1864	1.3244	5	440	brain development

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0072331	2e-04	15.1336	0.311	4	151	signal transduction by p53 class mediator
GO:0071706	5e-04	21.7937	0.1586	3	77	tumor necrosis factor superfamily cytokine production
GO:0097202	7e-04	19.418	0.1771	3	86	activation of cysteine-type endopeptidase activity
GO:0010821	8e-04	18.9584	0.1812	3	88	regulation of mitochondrion organization
GO:0051239	8e-04	3.9563	3.8948	11	1891	regulation of multicellular organismal process
GO:0070201	0.001	7.5978	0.7827	5	380	regulation of establishment of protein localization
GO:0001736	0.0011	47.2357	0.0494	2	24	establishment of planar polarity
GO:0090200	0.0011	47.2357	0.0494	2	24	positive regulation of release of cytochrome c from mitochondria
GO:0008637	0.0013	15.6251	0.2183	3	106	apoptotic mitochondrial changes
GO:0060071	0.0014	41.5585	0.0556	2	27	Wnt signaling pathway, planar cell polarity pathway
GO:0097193	0.0014	9.3259	0.4964	4	241	intrinsic apoptotic signaling pathway
GO:0043433	0.0015	14.7586	0.2307	3	112	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0010950	0.0017	14.1063	0.241	3	117	positive regulation of endopeptidase activity
GO:0002588	0.0021	Inf	0.0021	1	1	positive regulation of antigen processing and presentation of peptide antigen via MHC class II
GO:0032788	0.0021	Inf	0.0021	1	1	saturated monocarboxylic acid metabolic process
GO:0032789	0.0021	Inf	0.0021	1	1	unsaturated monocarboxylic acid metabolic process
GO:1902044	0.0021	Inf	0.0021	1	1	regulation of Fas signaling pathway
GO:0032608	0.0021	33.5006	0.068	2	33	interferon-beta production
GO:0032760	0.0021	33.5006	0.068	2	33	positive regulation of tumor necrosis factor production
GO:0052547	0.0025	7.9269	0.5808	4	282	regulation of peptidase activity
GO:0010633	0.0026	29.6635	0.0762	2	37	negative regulation of epithelial cell migration
GO:1902041	0.0028	28.8374	0.0783	2	38	regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:0042771	0.003	27.3158	0.0824	2	40	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:2000027	0.0034	11.0658	0.3048	3	148	regulation of organ morphogenesis
GO:0071347	0.0035	25.3117	0.0886	2	43	cellular response to interleukin-1
GO:0032501	0.0035	2.9699	11.3302	19	5501	multicellular organismal process
GO:2001233	0.0036	7.163	0.6406	4	311	regulation of apoptotic signaling pathway
GO:0012501	0.0037	3.5292	3.2913	9	1598	programmed cell death
GO:0032092	0.0038	24.1309	0.0927	2	45	positive regulation of protein binding
GO:0002277	0.0041	501.7857	0.0041	1	2	myeloid dendritic cell activation involved in immune response
GO:0002580	0.0041	501.7857	0.0041	1	2	regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II
GO:0002583	0.0041	501.7857	0.0041	1	2	regulation of antigen processing and presentation of peptide antigen
GO:0033278	0.0041	501.7857	0.0041	1	2	cell proliferation in midbrain
GO:0035574	0.0041	501.7857	0.0041	1	2	histone H4-K20 demethylation
GO:0043331	0.0044	22.5523	0.0989	2	48	response to dsRNA
GO:1902110	0.0044	22.5523	0.0989	2	48	positive regulation of mitochondrial membrane permeability involved in apoptotic process
GO:0060341	0.0044	4.4933	1.6004	6	777	regulation of cellular localization
GO:0035794	0.0045	22.0709	0.1009	2	49	positive regulation of mitochondrial membrane permeability
GO:0034097	0.0046	5.2429	1.1163	5	542	response to cytokine
GO:0002218	0.0048	9.7704	0.344	3	167	activation of innate immune response
GO:0046822	0.0052	9.4779	0.3543	3	172	regulation of nucleocytoplasmic transport
GO:2001238	0.0055	19.9416	0.1112	2	54	positive regulation of extrinsic apoptotic signaling pathway
GO:0051169	0.0061	6.1374	0.7435	4	361	nuclear transport
GO:0043932	0.0062	250.875	0.0062	1	3	ossification involved in bone remodeling
GO:2000659	0.0062	250.875	0.0062	1	3	regulation of interleukin-1-mediated signaling pathway
GO:2001181	0.0062	250.875	0.0062	1	3	positive regulation of interleukin-10 secretion
GO:2000116	0.0063	8.7927	0.381	3	185	regulation of cysteine-type endopeptidase activity
GO:0051707	0.0066	4.787	1.2173	5	591	response to other organism
GO:0051607	0.0066	8.6482	0.3872	3	188	defense response to virus
GO:0051098	0.007	8.4628	0.3955	3	192	regulation of binding
GO:0000723	0.0074	16.9885	0.1298	2	63	telomere maintenance
GO:0051222	0.0074	8.285	0.4037	3	196	positive regulation of protein transport
GO:0016265	0.0076	3.1162	3.6703	9	1782	death
GO:0010626	0.0082	167.2381	0.0082	1	4	negative regulation of Schwann cell proliferation
GO:0010917	0.0082	167.2381	0.0082	1	4	negative regulation of mitochondrial membrane potential
GO:0060708	0.0082	167.2381	0.0082	1	4	spongiotrophoblast differentiation
GO:0090191	0.0082	167.2381	0.0082	1	4	negative regulation of branching involved in ureteric bud morphogenesis
GO:1901029	0.0082	167.2381	0.0082	1	4	negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
GO:0009607	0.0084	4.4979	1.2914	5	627	response to biotic stimulus
GO:0001843	0.0086	15.6958	0.1401	2	68	neural tube closure
GO:0045807	0.0096	14.7947	0.1483	2	72	positive regulation of endocytosis

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0042742	0	34.8335	0.2401	6	147	defense response to bacterium
GO:0006952	0	10.6871	2.1464	12	1314	defense response
GO:0051707	0	10.0932	0.9654	7	591	response to other organism
GO:0009607	0	9.4818	1.0242	7	627	response to biotic stimulus
GO:0048007	1e-04	267.6571	0.0114	2	7	antigen processing and presentation, exogenous lipid antigen via MHC class Ib
GO:0002475	1e-04	167.25	0.0163	2	10	antigen processing and presentation via MHC class Ib
GO:0002544	5e-04	74.2804	0.0327	2	20	chronic inflammatory response
GO:0006955	5e-04	5.632	1.9994	8	1224	immune response
GO:0050911	0.001	49.4885	0.0474	2	29	detection of chemical stimulus involved in sensory perception of smell
GO:0002017	0.0033	638.9091	0.0033	1	2	regulation of blood volume by renal aldosterone
GO:0070488	0.0033	638.9091	0.0033	1	2	neutrophil aggregation
GO:0071621	0.0054	20.189	0.1111	2	68	granulocyte chemotaxis
GO:0010838	0.0081	159.6932	0.0082	1	5	positive regulation of keratinocyte proliferation
GO:0060763	0.0081	159.6932	0.0082	1	5	mammary duct terminal end bud growth
GO:0009593	0.0096	14.947	0.1487	2	91	detection of chemical stimulus
GO:0035865	0.0098	127.7455	0.0098	1	6	cellular response to potassium ion

Differential Methylation

Parameter Overview

Introduction: Differential Methylation of Sample Groups

Comparisons

P-values

Site Level

Differential Methylation Tables

Region Level

Differential Methylation Tables

Enrichment Analysis

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0009609	0.0031	669.381	0.0031	1	2	response to symbiotic bacterium
GO:0048871	0.0034	11.3431	0.3062	3	196	multicellular organismal homeostasis
GO:2000189	0.0047	334.6667	0.0047	1	3	positive regulation of cholesterol homeostasis
GO:0022600	0.0057	19.7	0.1141	2	73	digestive system process
GO:0007621	0.0062	223.0952	0.0062	1	4	negative regulation of female receptivity
GO:0006954	0.0078	5.8674	0.8078	4	517	inflammatory response
GO:0006591	0.0078	167.3095	0.0078	1	5	ornithine metabolic process
GO:0060398	0.0078	167.3095	0.0078	1	5	regulation of growth hormone receptor signaling pathway

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0021852	0.001	Inf	0.001	1	1	pyramidal neuron migration
GO:0071218	0.004	360.5897	0.004	1	4	cellular response to misfolded protein
GO:0061351	0.0046	23.0446	0.1024	2	103	neural precursor cell proliferation
GO:0007135	0.005	270.4231	0.005	1	5	meiosis II
GO:0016199	0.005	270.4231	0.005	1	5	axon midline choice point recognition
GO:0034755	0.005	270.4231	0.005	1	5	iron ion transmembrane transport
GO:0051177	0.005	270.4231	0.005	1	5	meiotic sister chromatid cohesion
GO:0000084	0.006	216.3231	0.006	1	6	mitotic S phase
GO:0021859	0.006	216.3231	0.006	1	6	pyramidal neuron differentiation
GO:0048172	0.006	216.3231	0.006	1	6	regulation of short-term neuronal synaptic plasticity
GO:0006515	0.0079	154.4945	0.008	1	8	misfolded or incompletely synthesized protein catabolic process
GO:0035520	0.0079	154.4945	0.008	1	8	monoubiquitinated protein deubiquitination
GO:0048664	0.0079	154.4945	0.008	1	8	neuron fate determination
GO:0060080	0.0079	154.4945	0.008	1	8	regulation of inhibitory postsynaptic membrane potential
GO:0051967	0.0099	120.1453	0.0099	1	10	negative regulation of synaptic transmission, glutamatergic

GOMFID	Pvalue	OddsRatio	ExpCount	Count	Size	Term
GO:0009952	0	21.8905	0.3619	6	196	anterior/posterior pattern specification
GO:0007389	0	12.0186	0.7848	7	425	pattern specification process
GO:0006579	0	1171.0833	0.0055	2	3	amino-acid betaine catabolic process
GO:0035115	0	60.9739	0.0609	3	33	embryonic forelimb morphogenesis
GO:0009086	2e-04	117.0333	0.0222	2	12	methionine biosynthetic process
GO:0060039	4e-04	77.9944	0.0314	2	17	pericardium development
GO:0032502	7e-04	3.8521	8.57	17	4641	developmental process
GO:0048706	0.0014	15.5373	0.2216	3	120	embryonic skeletal system development
GO:0035113	0.0014	15.4046	0.2234	3	121	embryonic appendage morphogenesis
GO:0009954	0.0016	38.9556	0.0591	2	32	proximal/distal pattern formation
GO:0032501	0.0018	3.5172	10.1581	18	5501	multicellular organismal process
GO:0033693	0.0018	Inf	0.0018	1	1	neurofilament bundle assembly
GO:0060980	0.0018	Inf	0.0018	1	1	cell migration involved in coronary vasculogenesis
GO:0072051	0.0018	Inf	0.0018	1	1	juxtaglomerular apparatus development
GO:0072227	0.0018	Inf	0.0018	1	1	metanephric macula densa development
GO:0009066	0.0019	35.4066	0.0646	2	35	aspartate family amino acid metabolic process
GO:0007417	0.0019	5.4441	1.3665	6	740	central nervous system development
GO:0014706	0.002	8.5992	0.5447	4	295	striated muscle tissue development
GO:0035108	0.0022	13.0576	0.2622	3	142	limb morphogenesis
GO:0000096	0.0027	29.1958	0.0776	2	42	sulfur amino acid metabolic process
GO:0007517	0.0028	7.8034	0.5983	4	324	muscle organ development
GO:0048736	0.0028	12.0095	0.2844	3	154	appendage development
GO:0048513	0.0028	3.9708	3.2754	9	2048	organ development
GO:0022029	0.0028	28.4817	0.0794	2	43	telencephalon cell migration
GO:0009792	0.0033	5.7479	1.0415	5	564	embryo development ending in birth or egg hatching
GO:0007626	0.0035	10.9794	0.3102	3	168	locomotory behavior
GO:0003218	0.0037	562.12	0.0037	1	2	cardiac left ventricle formation
GO:0050666	0.0037	562.12	0.0037	1	2	regulation of homocysteine metabolic process
GO:0072233	0.0037	562.12	0.0037	1	2	metanephric thick ascending limb development
GO:0044106	0.0045	10.0536	0.3379	3	183	cellular amine metabolic process
GO:0006351	0.005	3.077	5.6764	12	3074	transcription, DNA-templated
GO:0048705	0.0054	9.4171	0.3601	3	195	skeletal system morphogenesis
GO:0001692	0.0055	281.04	0.0055	1	3	histamine metabolic process
GO:0014707	0.0055	281.04	0.0055	1	3	branchiomeric skeletal muscle development
GO:0021570	0.0055	281.04	0.0055	1	3	rhombomere 4 development
GO:0031133	0.0055	281.04	0.0055	1	3	regulation of axon diameter
GO:0034653	0.0055	281.04	0.0055	1	3	retinoic acid catabolic process
GO:0055014	0.0055	281.04	0.0055	1	3	atrial cardiac muscle cell development
GO:0061056	0.0055	281.04	0.0055	1	3	sclerotome development