Question: Hello everyone,

I've tried to work with the TCGA DNA methylation data, but I'm having problems to understand better these data.

The TCGA's website isn't working anymore to get the biological data. In its place this GDC website (https://gdc-portal.nci.nih.gov/) is working. I was able to get clinical, mRNA and miRNA data in that site, however, I didn't find the DNA methylation data. Isn't there dna methylation data in that portal?

Fortunately, I found another site: cancer genomics browser (https://genome-cancer.ucsc.edu/proj/site/hgHeatmap/) where I was able to get the DNA methylation data for breast cancer (HumanMethylation450).

There are multiple files in the dna methylation file. levels of methylation are in the "genomicmatrix.txt" file, which each sample methylation has beta-value and a probe. On the other hand, the probe.txt file contains correspondence between the probe with the genes. Here is a little example about the genomicMatrixand probe file.

genomicMatrix:

sample	TCGA-OL-A66H-01	TCGA-3C-AALK-01	TCGA-AC-A5EH-01
cg13332474	-0.4808	-0.2968	-0.1997
cg00651829	-0.4821	-0.2110	-0.4108
cg17027195	-0.4633	-0.4250	-0.4667
cg09868354	-0.4345	-0.3630	-0.4230
cg03050183	-0.4252	-0.3749	0.1269

cg01989731	NA	NA	NA
cg06819656	0.4028	0.3047	0.3755
cg04244851	0.4398	0.3894	0.2533

cg19669385	-0.1353	0.3650	0.0664

cg04244855	0.4292	0.4008	0.2468

cg17689707	-0.4842	0.0109	-0.2484
cg04244857	-0.0918	0.2731	-0.0084
cg02434381	-0.4443	-0.4273	-0.4175
cg05777492	-0.4595	-0.4780	-0.4786
cg23340034	0.0933	0.3611	0.4120

cg26361545	0.4339	0.4389	0.4348

cg10609310	0.2913	0.0337	-0.1307

When looking at the file genomicmatrix.txt see several negative and NA values. I thought of disregarding them. Have positive values, I do not find any value above 0.8, ie no hypermethylation values. Why?

Probe:

id	gene	chrom	chromStart	chromEnd	strand

cg00035864	TTTY18	chrY	8613009	8613010	.

cg13275322	WAS	chrX	48426764	48426765	.

cg13798679	chr1	36390157	36390158	.

cg13799227	chr1	226719204	226719205	.

cg13799302	CYP2J2	chr1	60164980	60164981	.

cg13799671	CD58	chr1	116881090	116881091	.

cg13805052	MORN1,LOC100129534	chr1	2272923	2272924	.

Here I consider only genes that are not on chromosome X and Y. I noticed that there are some probes that associate with more than one gene, in this case thought to obtain the median of methylation values ​​to result in final gene methylation level.

I was thinking of converting these files into a single file with the following header:

gene | beta value | sample
CD58| 0.4 | TCGA-OL-A66H-01

Please can someone help me these questions?

Thank you for attention.

Answer: It turned out one can filter the legacy archive from GDC and get back the DNAme data, e.g.,

https://gdc-portal.nci.nih.gov/legacy-archive/search/f?filters=%7B%22op%22:%22and%22,%22content%22:%5B%7B%22op%22:%22in%22,%22content%22:%7B%22field%22:%22files.data_category%22,%22value%22:%5B%22DNA%20methylation%22%5D%7D%7D,%7B%22op%22:%22in%22,%22content%22:%7B%22field%22:%22files.data_type%22,%22value%22:%5B%22Methylation%20beta%20value%22%5D%7D%7D%5D%7D

Beta values should be from 0 to 1. My guess is that the genomicMatrix file you are looking at is zero-centered. So the data is from -0.5 to 0.5 with the methylated and unmethylated peaks at around 0.4 and -0.4.