TSEM aggregated Cauchy association omnibus meta-analysis and Miami plot

[Giuseppe Fanelli]

Hi all,

could someone share with me the script to implement a Cauchy association test on TSEM results? I tried to use the ACAT R package but I'm not sure on how to adapt the code to TSEM output.

I think it would be a good idea to implement it directly in TSEM code.

Also, what package do you suggest to build the MIAMI plot related to TSEM/Cauchy association omnibus meta-analysis results? Do you have scripts to share?

Many thanks in advance,

best, Giuseppe

[Michel Nivard]

I don’t know ACAT, why is it used for? Combining p-values across traits or across genes/snps? 

Best,

Michel

Op vr 3 mei 2024 om 10:15 schreef Giuseppe Fanelli <drgiusep...@gmail.com>

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[Giuseppe Fanelli]

Hi Michel,

ACAT is used to perform an Aggregated Cauchy Association Test (ACAT) (https://github.com/yaowuliu/ACAT; https://doi.org/10.1016/j.ajhg.2019.01.002) and meta-analyze results across tissues.
I found a reference to its use in previous papers using TSEM: eg https://doi.org/10.1101/2023.11.28.23299133 (preprint) and https://doi.org/10.1001/jamapsychiatry.2023.1808.

best, Giuseppe

[Michel Nivard]

So the way a cat appears to work is it computes a total p-Val’s based on the tissue p-Vals

I’d do something like this:

1. Run the twases

2. Merge on gene name

3. extract the p-vals into on matrix that is N genes rows and N tissues columns keep the gene names as row names for merging back to things.

Then:

apply(ACAT,1, p.matrix)

Runs acat across the rows I think.

Best,

Michel

Op vr 3 mei 2024 om 12:26 schreef Giuseppe Fanelli <drgiusep...@gmail.com>

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[Giuseppe Fanelli]

Many thanks Michel for your useful suggestion!

Best, Giuseppe