Question: DESeq2 w. pathway/network info as a prior knowledge
2
gravatar for guidobarzaghi
5 months ago by
University of Copenhagen
guidobarzaghi20 wrote:

Good evening everyone,

I was wondering if anyone has ever tried to perform a differential expression analysis using pathway/network information as prior knowledge. To be more specific, I am wondering if it is possible to feed DESeq2 the prior knowledge of pathways so that the algorithm is more prone to consider statistically significant genes part of an up-/down-regulated pathway even without a big LFC (and vice-versa).

ANY help here will be highly appreciated!

deseq2 pathway ihw • 413 views
ADD COMMENTlink modified 4 months ago by Michael Love24k • written 5 months ago by guidobarzaghi20

Perhaps GSVA is what you’re looking for? It’s a Bioconductor package that shifts the differential expression analysis from genes to gene sets (e.g.: pathways).

ADD REPLYlink modified 5 months ago • written 5 months ago by enricoferrero570
Answer: DESeq2 w. pathway/network info as a prior knowledge
3
gravatar for Michael Love
4 months ago by
Michael Love24k
United States
Michael Love24k wrote:

To answer your exact question, you could use IHW to estimate weights for partitions of the genes. It would give a better chance to those genes in a partition that has more power under an alternative hypothesis. As long as the partition is independent of the p-values under the null, which it should be.

One important note: users should not run gene set testing on a dataset, find the significant sets and then rerun with IHW using a particular partition based on the first run results. This would obviously violate the independence of the p-values and the partition under the null, but just to be very clear about that. The partition has to be decided prior to looking at the results.

However, I think a more straightforward approach is simply gene set testing. I like to use goseq following DESeq2, but other options are roast and camera from the limma package (these cannot be used directly with DESeq2).

ADD COMMENTlink modified 4 months ago • written 4 months ago by Michael Love24k

As far as IHW is concerned, in my case the covariate used to compute the weights would be categorical (ideally a single number indicating with pathway is that gene involved in), wouldn't that be a problem? Otherwise, how else would you think of feeding that information to the model?

ADD REPLYlink written 4 months ago by guidobarzaghi20

It’s not a problem, take a look at the paper and vignette for IHW.

I think this approach is basically just what you asked for.

We don’t have any easy built in way to give prior info to change DESeq2 test statistics.

ADD REPLYlink written 4 months ago by Michael Love24k

Perfect! Thanks a lot for your help (again)

ADD REPLYlink written 4 months ago by guidobarzaghi20

Perfect! Thanks a lot for your help (again)

ADD REPLYlink written 4 months ago by guidobarzaghi20
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