Question: Identifying genes that are regulated under negative feedback
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3.2 years ago by
A3.9k
A3.9k wrote:

Hi,

As I understood, by computing individual adjusted p-values between each gene (RNA-seq) and polymorphisms in its vicinity (genotyping), then selecting the highest association, we can discover eQTL allelic imbalance. Moreover, by DESeq2 or SKAT we can calculate Cis and Trans actions between gene and variant. Now, from these genes, how can we identify genes under negative feedback regulation???

Thank you

ADD COMMENTlink modified 3.1 years ago by Biostar ♦♦ 20 • written 3.2 years ago by A3.9k

As I understood, by computing individual adjusted p-values between each gene (RNA-seq) and polymorphisms in its vicinity (genotyping), then selecting the highest association, we can discover eQTL allelic imbalance.

This makes sense to me.

Moreover, by DESeq2 or SKAT we can calculate Cis and Trans actions between gene and variant.

But here you lose me. What's the relation between DESeq2 and SKAT?
DESeq2 is used for differential expression analysis, SKAT is for rare variant association analysis.

Do you have a reference in which this approach is used? Sounds interesting.

ADD REPLYlink written 3.2 years ago by WouterDeCoster45k

Thank you, right now I am reading a paper in which SKAT has been used to identify trans-eQTL and few minutes ago I came across a paper cited DESeq2 for discovering cis-eQTL. but the question is, from these genes which ones are being regulated by negative feedback???

https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-15-471

https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-015-0094-0

ADD REPLYlink written 3.2 years ago by A3.9k

If we assume the expression of gene A in three individuals, if the genotypes are TT, TC and CC but still the expression of this gene in these people are the same, we can say that gene A is under negative feedback regulation. for this, eQTL allelic imbalance due to the negative feedback effect can't change the expression of this gene. But what would be the statistical approach for testing either the variance of gene A (with three genotypes) ratios in different sample is low compare to gene B without negative feedback effect?

ADD REPLYlink modified 3.2 years ago • written 3.2 years ago by A3.9k

If p is the expression of a gene in an individual, and α is the expression of a specific allele of this gene, under negative feedback effect, a two-fold change of α is less than a twofold change in p

ADD REPLYlink written 3.1 years ago by A3.9k
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