Users Manual¶

Installation¶

Before installation, we highly recommend creating a new environment using conda so that it will not affect the software versions of other projects. For example, run:
```
conda create -n env-mrpeg python=3.8
```
We currently only support Python 3.8+.
If you are using a Mac with an Apple M1 or newer chip, you should install the cbgen package (or other required packages) from conda-forge first to ensure compatibility (see this link for a previous issue). One easy workaround is to initialize conda using miniforge. On most HPC systems, this is usually not necessary.
```
conda install -c conda-forge cbgen
```

Finally, download the latest repository and install via pip:

git clone https://github.com/gusevlab/mrpeg.git
cd mrpeg
pip install .

Data Preparation¶

mrpeg requires users to input GWAS summary data, eQTL summary data, and gene-to-gene effects matrix to perform inference.

Users can check testing data in Testing Data section to see the format requirement.

Testing Data¶

We provide example data in ./data/ folder to test out mrpeg.

We simulated GWAS summary and eQTL summary data using real cis-eQTLs identified in eQTLGen whose genotypes are from 1000G project.

Using ./data/make_example.py, we simulated GWAS, eQTL summary data. Users can run the script in ./data/run_example.sh.

Usage¶

mrpeg software is very easy to use.

Performing inference¶

cd ./data/
mrpeg peg --gwas example_gwas.tsv.gz \
  --eqtl example_eqtl.tsv.gz \
  --perturb example_perturbation.tsv.gz \
  --gwas-cols chrom snp a1 a0 beta se \
  --eqtl-cols chrom snp a1 a0 z gene \
  --ref-geno plink/geno_chr\* \
  --trait "mediating_gene" \
  --top-signal 1 \
  -o tmp_results_mediating_gene

Gene annotation¶

We also implement two functions for gene annotation.

Find the GWAS closest genes:

cd ./data/
mrpeg closest --gwas example_gwas.tsv.gz \
  --gwas-cols chrom snp pos beta se \
  --ref ref_gene_info.tsv.gz \
  --ref-cols CHR TSS TES ID2 \
  --trait example \
  -o tmp_results_closest

Compute the GWAS signals given gene annotations:

cd ./data/
mrpeg signal --gwas example_gwas.tsv.gz \
  --gwas-cols chrom snp pos beta se \
  --ref ref_gene_info.tsv.gz \
  --ref-cols CHR P_MID_FLANK0 P_MID_FLANK1 ID2 \
  --window 0 \
  --trait example \
  --chr 1 \
  -o tmp_results_signal