Question: GO analysis- analyze upregulated and downregulated genes separately?
1
gravatar for ssukumaran
4.5 years ago by
ssukumaran10
United States
ssukumaran10 wrote:

Hi forum,

 I have  a list of differentially expressed genes from an RNA Seq analysis that I wish to do Gene ontology analysis of.Is it better to analyze up regulated and down regulated genes separately? As I understand it, Go analysis does not consider the direction of change -only the gene names are considered... Thanks for your input!

 

rna-seq • 5.5k views
ADD COMMENTlink modified 4.5 years ago by andrew480 • written 4.5 years ago by ssukumaran10

Yes, I have seen some papers where upregulated and downregulated genes are categorized separately on GO term;

Once you get significant level of GO term in the subset of genes, you can go for pathway or network analysis to see the enrichment of your detected genes in certain pathway or process

ADD REPLYlink written 4.5 years ago by Manvendra Singh2.1k

C: Hypergeometric test in GSEA

ADD REPLYlink written 4.5 years ago by EagleEye6.6k
2
gravatar for andrew
4.5 years ago by
andrew480
United States
andrew480 wrote:

I don't think it makes sense to do this.  Just because a gene is upregulated or downregulated does not mean that the process, function or component that the gene is annotated to is also respectively directionally regulated.  There is no directionality associated to how a gene impacts a GO term (aside from some GO terms having directionality  like "negative regulation of cell proliferation"). This is one of the limitations to GO analysis.  It is specifically for this reason that one should consider all DEGs when performing a GO analysis.  Then use advanced pruning algorithms like Elim or Weight as proposed by Alexa et al (2006) to identify truly enriched GO terms.

 

You can read more about this here:  http://eepurl.com/bubBe9

ADD COMMENTlink written 4.5 years ago by andrew480
1

Your link takes me to the following place:

http://us6.campaign-archive1.com/?u=c55d2c432a0f7a17ba0a260bc&id=65d0584514

Which just looks like an advertisement. Either way, I'm not sure how the 'elim' algorithm does anything to address the subject of up/down enrichment.

You should read the article linked by tiago.

ADD REPLYlink written 4.5 years ago by pld4.8k
1
gravatar for tiago211287
4.5 years ago by
tiago2112871.1k
USA
tiago2112871.1k wrote:

Check this: "Separate enrichment analysis of pathways for up- and downregulated genes"

ADD COMMENTlink written 4.5 years ago by tiago2112871.1k
0
gravatar for pld
4.5 years ago by
pld4.8k
United States
pld4.8k wrote:

Yes, when the enrichment software you're using doesn't consider the fold change, you should run up and down genes separately. I think this is because GO enrichment usually looks for significant enrichment with respect to the whole set of GO annotations for that species.

You should take care to check for similar/same terms between groups. Otherwise, look for GO/pathway software that considers fold change.

ADD COMMENTlink written 4.5 years ago by pld4.8k

Thanks! This makes sense.

ADD REPLYlink written 4.5 years ago by ssukumaran10
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