discovering novel regulators
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8.2 years ago
jiwpark00 ▴ 230

Hi,

So maybe this is too far-fetched question but I have a question. I was thinking about whether or not this is possible...Let's say you are studying disease X, where people have discovered multiple regulators from loss-of-function screening in animals or cells. This is a common occurrence, where after the screening, people identify "novel" genes for that are regulators. And sometimes, it turns out that those "novel" genes were studied in other areas but no one suspected them to play a role in this context.

I guess my question is, statistically or computationally speaking, is this sort of "screening" feasible given just the available information (literature, data sets, etc)? That is, if you take a core list of known regulators for disease X, can you discover "novel" regulators? I know this has been done but I feel like those hits are never surprising - they are very biased towards more studied genes so the hits that are not as well-known (which turn out to be the ones that people actually discover) do not show up.

Just a thought.

genetics computational biology screening • 1.7k views
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8.2 years ago
natasha.sernova ★ 4.0k

I've used two key words: disease and regulators

I've got the following papers:

There are some papers:Transcriptional Regulatory Elements in the Human Genome

http://bejerano.stanford.edu/readings/public/10_Intro_TxRegReview.pdf

Identifying regulatory elements in eukaryotic genomes

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764519/

A novel motif-discovery algorithm to identify co-regulatory motifs in large transcription factor and microRNA co-regulatory networks in human

http://bioinformatics.oxfordjournals.org/content/31/14/2348.full

iRegulon: From a Gene List to a Gene Regulatory Network Using Large Motif and Track Collections

http://journals.plos.org/ploscompbiol/article?id=10.1371%2Fjournal.pcbi.1003731

Use of Forward Genetics to Discover Novel Regulators of NF-κB

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869522/

Tool:IPA Training:Maximizing the Biological Interpretation of Gene, Transcript & Protein Expression Data with IPA

https://chhe.research.ncsu.edu/wordpress/wp-content/uploads/2015/10/IPA-Data-Analysis-training-slides-2016_04.pdf

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Thanks for the links of the papers although first two were not as useful to my question. I get what you mean by looking at the motif and pathway analysis based on experimental data (IPA, MetaCore, etc.) but is it still possible to do this:

Say I have two genes A and B that both regulate (not necessarily transcriptionally - it could be a number of different ways) gene C, and upstream of gene A in one tissue is a gene D. Now, based on the known experimental condition and prediction, could we make an association between gene A and B (through their both involvement with gene C) and somehow identify gene D as a "potential" regulator of gene B as well? Obviously, this will depend on tissues, but I'm just wondering whether this is possible because known computational search will not pick up gene D as a regulator of gene B because this could be conditional based on gene A. Hope that makes sense...

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