Open danielnachun opened 9 months ago
 mr.ash priors
Not sure if mr.ash package itself accepts these other models. We might have to implement if we want. I would suggest we stick to the originaly published.
 vignette for CTWAS - currently challenging to run CTWAS
As of now the main
branch for cTWAS is broken. I've talked to people in Xin's group -- it should be possible to involve them in the xQTL project focused on delivering this part. I'll talk to Xin more formally in the following couple of weeks.
Updates on the original post
omp
on the loops to parallel, just like what we do for other Rcpp applications under src
I recently reread the SuSiE-inf paper (https://pubmed.ncbi.nlm.nih.gov/38036779/) and now understand that this model is really just extending SuSiE to do variance components estimation to handle stratification instead of residualizing ancestry PCs. I have some ideas on how to do this in a way that is more suitable for QTLs and could be treated as a 'pre-processing' step rather than having to modify how SuSiE itself runs. This approach could also be make to work with mr.ash
or other penalized regression methods. Importantly, nothing in pecotmr
would need to be modified for any of this to work, including the original implementation of SuSiE-inf. Consequently I've cleaned up and corrected various mistakes in my original post to incorporate this knowledge along with some other topics as well.
As our work on this package progress, this issue can help us enumerate possible future features of the package depending on the time and interests of contributors. Some features will be needed for the manuscript submission, and others will make more sense to consider for future releases.
TWAS
Individual
mr.ash
glmnet
glmnet
qbayes
ncvreg
L0Learn
SSLASSO
BGLR
Summary
mr.ash
qbayes
lassosum
for LASSO and elastic net (manuscript, GitHub)Longer term
ncvreg
,L0Learn
,SSLASSO
andBGLR
for summary data - might be a lot of work for little gain ifmr.ash
generalizes all of thesemr.ash
to work with otherebnm
priors -deconvolveR
is most interesting because it is a smooth approximation of NPMLE instead of a scale mixture of normalsMendelian randomization
"Omnigenic model" that incorporates all variants as instruments (this will be a separate manuscript, possibly in combination with the trans-QTL extension) - inspired by [OMR] (https://academic.oup.com/bib/article/22/6/bbab322/6347949), and could exploit the fact that SuSiE gives us posterior effect sizes and standard errors, unlike most other fine mapping methods.How will this method handle weak instrument bias without removing variants - consider debiasing estimators like dIVW and pIVW - does OMR have this issue too?Should show that SuSiE does a comparable job in terms of adjusting for LD as LD scores (used by OMR and MRAID, and the variant selection methods used by MR.LDP, MR-Corr2 and MR-CUE.Are the heterogeneity tests and Egger regression still valid for testing for horizontal pleiotropy in the presence of so many weak instruments?Colocalization
Polygenic molecular risk scores (PMRS)
mr.ash
and other penalized regression methods can be used for prediction for genome-wide TWAS but not MR, because penalized regression doesn't produce valid standard errorsInterfaces with other packages
mvsusier
/mvsusiF
colocBoost
is the current solution, hopefully we can figure something out here latersusiF
Other