How to determine if a somatic mutation alters transcription factor binding site?
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5 weeks ago

Hi,

I have a list of (non-coding) loci that are recurrently mutated in a certain type of cancer. A couple of these loci are associated with changes in the expression of their target genes.

My question is: I want to know if somatic mutations at these sites disrupt or create transcription factor binding sites (TFBS) and thus providing a rationale of why they change gene expression.

For example: I have 4 recurrently mutated loci that are associated with gene expression changes. How do I know if the somatic mutations in any of these 4 loci create or disrupt TFBS? Maybe only two of the 4 loci disrupt/create TFBS? or maybe none of them? How can I investigate this?

What tools are available?

Thank you :)

cancer motif TFBS somatic-mutation • 192 views
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Computationally, you would check if the mutation intersects the core transcription factor motif in a given region, and then calculate a perturbation score. I recently saw on Twitter https://github.com/colossal-compsci/tfboot which builds on existing tools. But actually, to be credible this should be done by experiment, for example by something like gel shift assays, ChIP-seq in cell lines that have or do not have the condition, luciferase assays of such a region with or without mutation etc.

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