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Primo

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primo's Introduction

Primo: Package in R for Integrative Multi-Omics association analysis

The goal of Primo is to provide computationally efficient tools to integrate data across phenotypes, cell/tissue types, populations or sources when performing joint analysis of multi-omics data.

Setup

Please note that this package uses functions from the limma package, which is downloadable from Bioconductor, and the lcmix package, which is downloadable from R-Forge. If installation of Primo fails and you have not yet installed the limma or lcmix packages, please try running the following commands:

if (!requireNamespace("BiocManager", quietly = TRUE))
 install.packages("BiocManager")
BiocManager::install("limma")

install.packages("MASS")
install.packages("matrixStats")
install.packages("nnls")
install.packages("R.methodsS3")
install.packages("lcmix",repos="http://r-forge.r-project.org")

Once you have installed limma and lcmix, you can install and load functions from Primo:

devtools::install_github("kjgleason/Primo")
library("Primo")

Citation

To cite Primo in publications, please use:

Kevin J. Gleason, Fan Yang, Brandon L. Pierce, Xin He, and Lin S. Chen. Primo: integration of multiple GWAS and omics QTL summary statistics for elucidation of molecular mechanisms of trait-associated SNPs and detection of pleiotropy in complex traits. Genome Biol (2020); 21(1):236. doi:10.1186/s13059-020-02125-w.

Licenses

The code is released under GNU General Public License (GPL).

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primo's Issues

Conditional Analysis - Error in data.frame PP_Grouped

As part of a research internship I would like to use primo to investigate the genetic pleiotropy of human aggressive behavior, subcortical brain volumes and a set of NMR metabolomics summary statistics including amino acids and lipoprotein particle concentrations.
Using the vignette on the primo github page I've attempted to apply primo to my dataset. However, when attempting to run conditional analyses I've come across an error when it creates the PP_grouped dataset, which suggests that one of the necessary input variables has 0 rows. So far I've been unable to determine what causes this error and how I might remedy this.
Could you advise me in how to proceed?

Location for manual please?

Is there a manual for this package?

Also, is this package submitted to bioconductor or CRAN? I can't in any repository, sorry.

Check for missing/NA

estimate_config() will terminate with an error when there are any missing values in betas, sds, mafs or dfs:

Error in while (diff > tol) { : missing value where TRUE/FALSE needed

Consider checking for NA at beginning of function and producing a more interpretable error message.

Manual for conditional analysis

Hi,

First time using your package.
I'm wondering if you have a manual for running conditional analysis. Thanks

Primo with multiple related outcomes in overlapping samples

Hello,

I was wondering do you recommend using this software with metabolite QTL summary statistics. In my scenario I have 3 related outcomes (coming from diabetic retinopathy). I don't have GWAS data. I will just have QTL summary statistics, genotypes and phenotypes for 3 related outcomes. I am using the same cohort to analyze those 3 outcomes (so they are overlapping samples). Can your software help me determine which QTLs would be specific or shared across those 3 outcomes? In your paper I read that your software doesn't have problem with overlapping samples, please confirm. Also is there is issue with related phenotypes (outcomes) like in my case?

I downloaded codes used in your paper and in order to run this code can I just replace each of the bellow QTL summary statistics with summary statistics calculated for every of my outcomes? Or should I proceed differently?

##=== determine SNPs present in all studies ===##
esnp <- unique(cis.eQTL.res$SNP)
msnp <- unique(cis.meQTL.res$SNP)
psnp <- unique(cis.pQTL.res$SNP)

Also I am planning to put Primo in my grant proposal. Can you please tell me with this paragraph is applicable for analysis I plan to do (above):

"Due to pleiotropic effects of SNPs and linkage disequilibrium (LD) among SNPs in a region, it is commonly observed that SNPs are associated with multiple molecular and/or complex traits ref, ref. In order to probabilistically assess if the same mQTL within a locus is likely to be causally contributing to multiple outcomes we can use the multi-omics colocalization method Primo ref. Primo will help to account for linkage disequilibrium LD by enabling conditional association analyses in gene regions harboring known trait-associated SNPs."

Thank you so much for looking into this,
Ana

Inclusion of SNP

Hello kjgleason,

I download 5 summary statistics of GWAS and QTL data, but some of QTL data sets are incomplete and have only the results of significant SNPs. for GWAS-reported SNPs that could not be mapped to a variant of incomplete QTL data, could we add a tstatistic of 0 for the missing data?

Thank you so much and best regards.

Fix parallel processing

Parallel processing no longer working since EM-steps were recoded in Rcpp.