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broadinstitute / cmQTL

High-dimensional phenotyping to define the genetic basis of cellular morphology
BSD 3-Clause "New" or "Revised" License
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Sep 1, 2020 Discussions (TADs instead of genes) #54

Closed gwaybio closed 2 years ago

gwaybio commented 4 years ago

Slides are here 2020-08-31-group-jatin.

Lots of cool progress and other things that were discussed on this call.

I am just quickly noting here one quick thought that I had regarding combining signal across different genes (e.g. SKAT test):

It might be worth considering collapsing signal at the topologically associating domain level rather than assigning per gene rare variant burden. This makes the unit of comparison TADs instead of genes (reduces number of tests) and would change how we tell association stories. This wouldn't make sense to do if the rare variants in the database are all coding. It might make sense to do since TADs are consistent across cell types and it would sidestep the issue of improper gene assignment based on proximity.

jatinarora-upmc commented 4 years ago

@gwaygenomics thanks much for initiating this thread, Greg. Looking at TADs is a very interesting thought in itself, particularly in a functional perspective and with non-coding variants. Since, cmQTL is a sort of new kind of area/study, so I feel our major focus would be to find true positive associations with high stringency (for both genes and TADs), even though with false negatives. Considering TADs are consistent across cell type, this might help in alleviating the concern about associations arising from tissue used for iPSC regeneration. Let me think more in this !