Question: How To Call Loss / Gain On Cgh Data When Tumor And Normal Are Not Analysed Together?
1
gravatar for Michi
8.3 years ago by
Michi950
Barcelona
Michi950 wrote:

Hello Biostars

I wanted to tackle the TCGA CGH (comparative genomic hybridization) data from their Glioblastoma Project. I was surprised by the fact, that they would compare their tumour and normal samples separately to a reference genome! Nevertheless, for a few cases they actually put the tumour and the normal sample on the same chip, what allows a direct comparison of gains and losses between normal and tumor.

So I can get something like this:

barcode chromosome      start   stop    num.mark        seg.mean (log2)
tumour:TCGA-06-0238-01A-02D-0311-04    3       85466920        85652956        24      -0.7886
normal:TCGA-06-0238-10A-01D-0311-04    3       85458029        85652956        25      -0.7479

Given their high similarity i can assume that their is no loss in the tumour compared to the normal CGH

But I am no quite sure how i should treat the cases where segments are very different in size, the difference between the values are bigger, there is a loss/gain in the normal, but not in the tumour, etc.

I am tempted to just map the segments to genes, and make a substraction, but since they are two different experiments, I doubt this is correct.. any suggestions / thoughts?

tcga comparative cancer • 3.5k views
ADD COMMENTlink modified 8.3 years ago • written 8.3 years ago by Michi950

could you specify which paper explains the reason? I'm also interested to know.

"Actually, reading more carefully supplementary material, I found this paper, which explains why they did not match the normal and tumour samples, and how they analysed it accounting for noise (as Jan Oosting said)"

ADD REPLYlink written 6.5 years ago by edtuer0

How do you get calculate gains or losses from these TCGA data? I do not know much about SNP array data analysis, your help will be appreciated.

ADD REPLYlink written 6.2 years ago by lilingjoyo0
3
gravatar for Jan Oosting
8.3 years ago by
Jan Oosting870
Leiden, NL
Jan Oosting870 wrote:

The reason to use a panel of normal samples for reference is noise.

The effect of noise is additive also when subtracting the normal signal from the tumor signal. Taking an average of all normal samples will reduce the noise level in your reference.

Quantitively the noise will be reduced approximately to the inverse of the square root of the number of samples in your reference pool. If you have paired samples you can distinguish tumor specific from germline effects or cnv in the way you show.

ADD COMMENTlink written 8.3 years ago by Jan Oosting870

just a late request of clarification: by "the way I show" you mean substraction? Thanks

ADD REPLYlink written 7.4 years ago by Michi950
0
gravatar for Chris Miller
8.3 years ago by
Chris Miller20k
Washington University in St. Louis, MO
Chris Miller20k wrote:

Just take the ratio of tumor to normal at each locus. That won't help you identify regions that are altered in both, but presumably, what you're looking for are tumor-specific events.

ADD COMMENTlink written 8.3 years ago by Chris Miller20k
0
gravatar for Michi
8.3 years ago by
Michi950
Barcelona
Michi950 wrote:

Thanks for your answers!

Actually, reading more carefully supplementary material, I found this paper, which explains why they did not match the normal and tumour samples, and how they analysed it accounting for noise (as Jan Oosting said)

ADD COMMENTlink written 8.3 years ago by Michi950
1

which paper? can you update the link for the paper please? i need to read on this also. thanks.

ADD REPLYlink written 6.4 years ago by bounlu170
1

sorry, i dont remember right now. somehow the link got lost. i guess during the migration of the platform.

ADD REPLYlink written 6.4 years ago by Michi950
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