collapse multiple CpG site for a gene
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7.1 years ago
Ezhil La ▴ 10

Hi,

I am working on 450K BeadChip methylation arrays. There are multiple CpG sites for a gene and I would like to know better ways of collapsing multiple probes into a single one representing a gene. Could you please suggest some methods and also the software for doing this step?

In gene expression arrays, I normally select a probe with high variance (or average some times) to represent a gene.

Thanks in advance.

Kind regards,

Ezhil

genome • 2.2k views
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A gene-level expression estimate makes some sense, a gene-level methylation metric less so. A better question to ask yourself is whether you really do want to summarize over whole genes (hint: you probably don't).

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Probably not but I am not sure that it is a correct way. I thought of averaging all probes within 200KB of transcription start site (TSS) to represent a gene-level methylation. Obviously 200KB is arbitrary and also the assumption of something close to TSS is very important than other gene-regions made me to look for alternate ways.

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Why not to:

for each gene select probe with highest variance

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Here's what I do, in a nutshell: for each methylation site, link it to it's nearest neighbouring gene and to it's 2 nearest methylation sites in a cytoscape network; import the site-specific methylation p-values, run jActiveModules. However, I disagree that a gene-level summary of the methylation data is of no biological varlue (and I certainly wouldn't cherry pick the highest variance probe, no reason to introduce a bias for no reason)

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