What's Pathway Enrichment Analysis?

Question

[Chaimaa]

Dear all,

I have a list of significant disease genes related to some disease, could anyone helps me to understand how to do these 2 points:

1. Giving a set of genes/proteins, how to do a Pathway Enrichment Analysis
2. For a set of genes/proteins, how to mark the genes in a Pathway.

Thanks

Answer 1

[andrew.j.skelton73]

I'm assuming that you're working in R here, but the statistical principles are the same. To look for enrichment of genes, you should apply a hypergeometric test, which is implemented in the phyper function. Additionally, you'll need your universe set, or all the genes that you analysed.

If you want to apply your results to a pathway for visualisation, then there's the gage package in bioconductor which will also provide functions for enrichment tests. The specific package for mapping to pathways and doing visualisations is pathview.

If this is a bit too much code, then there are web implementations for this task which you might consider, namely Reactome, or a more recent way is OpenTarget's batch search (note that the batch search is limited to 200 genes per search at the moment, but I believe they're working on expanding that limit!)

[Chaimaa]

I'm working In MATLAB. what about Q2? Thanks for your nice explanation

[andrew.j.skelton73]

If you're working in Matlab, then there is the hypergeom function

[WouterDeCoster]

If this answer was helpful you should upvote it, if the answer resolved your question you should mark it as accepted. It's not because Andrew answered your first question he should also answer the second one.

[Chaimaa]

Sorry, I didn't observe that definitely i will upvote .done!

[andrew.j.skelton73]

Q2 is answered by Pathview.

[Ben]

I remember that enrichment analysis was analyzed with Fisher`s exact test

Answer 2

[EagleEye]

Hi,

If you are working on LINUX or Windows 10, try GeneSCF command line tool. To know what is pathway analysis and what for it is used look into GeneSCF article.

Answer 3

[Benn]

1. Pathway enrichment can be done with many tools. Such as KEGG or Reactome pathways in R goseq (see manual), or with R clusterProfiler (see manual).

2. Visualization of your expression data in pathways can be done with pathview, a package in R.

[Chaimaa]

I don't have any idea about R; my experimentations are all in MATLAB

[WouterDeCoster]

If the language was a requirement then you should have mentioned that in your initial post. I also don't think Matlab is the best choice for this type of analysis. Most of this is commonly done in R.

[Benn]

Sorry I don't work with MATLAB, so I cannot help you with that.

[Chaimaa]

it's ok, anyway thanks for your reply.

[LLTommy]

Well, there still should a way to export your data from matlab into R. And I am sure you could also call web services from matlab. I like matlab. But in bioinformatics, R is dominant, so you might want to think about switching in the future!

Answer 4

[bigmawen]

As Andrew said, Pathway analysis + data visualization can be done in R/Bioconductor using gage and pathview package. The full workflow is described in their package vignettes:
for RNA-Seq data
http://bioconductor.org/packages/release/bioc/vignettes/gage/inst/doc/RNA-seqWorkflow.pdf
for microarray data and generic omics analysis
http://bioconductor.org/packages/release/bioc/vignettes/gage/inst/doc/gage.pdf

For people not familiar with R, Pathview Web server provides a user friendly access to Pathview and the full GAGE/Pathview pathway analysis workflow. It can be used for multiple types of omics data and their integrated analysis too.
Pathview Web server:
https://pathview.uncc.edu/
The paper:
https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkx372

Answer 5

[theobroma22]

Pathway Enrichment Analysis is similar to KEGG Orthology or KO Pathway Analysis. The pathways are constructed using many genomes, as such, the orthology part of KO. There exists organism specific pathways such as those only observed in plants. Also, even if your organism of study is not human you could still end up with human pathways like disease related pathways. You can do KO Pathway using Blast2GO.