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Polygenic Risk Score (PRS) Continuous Shrinkage (CS) Pipeline Using Snakemake

Overview

This Snakemake pipeline is designed for calculating polygenic risk scores (PRS) using PRS-CS Auto. It automates preprocessing of summary statistics, genotype data preparation, filtering with HapMap3 SNPs, scoring PRS, and removing the APOE region for Alzheimer's Disease research.

Workflow Steps

  1. Munge Summary Statistics

    • Converts raw summary statistics into a format compatible with PRS-CS Auto.
    • Container: codewithrakshya/mungesumstats_docker

  2. Process BIM/PVAR Files into PLINK Format

    • Generates BED/BIM/FAM files from BIM/PVAR files.
    • Uses plink.yaml conda environment

  3. Prepare HapMap3 SNP List (Optional)

    • Prepares a list of HapMap3 SNPs for filtering purposes.

  4. Filter Genotype Data

    • Filters genotype data to include only HapMap3 SNPs.
    • Uses PLINK for SNP extraction.

  5. Run PRS-CS Auto

    • Executes PRS-CS Auto for each chromosome.
    • Produces PRS weights for subsequent analysis.

  6. Concatenate Chromosome-Specific PRS Weights

    • Concatenates PRS weights from all chromosomes into a single file.

  7. Remove APOE Region

    • Removes SNPs located in the APOE region (chr19:44,408,822-45,408,822).

  8. Calculate PRS with PLINK

    • Scores individuals based on concatenated PRS weights using PLINK.

Prerequisites

  • Snakemake v8.0+
  • Singularity or Docker installed for containerized execution
  • Conda environment set up for PLINK and PRS-CS (envs/plink.yaml, envs/prscs.yaml)

Configuration

Edit parameters in config/config.yaml:

  • Cohort information
  • Paths to summary statistics files
  • Paths for reference genomes and other necessary input files

Execution

Run the pipeline using the command:

snakemake --use-conda --use-singularity --cores <num_cores>

Directory Structure

├── config
│   └── config.yaml
├── envs
│   ├── plink.yaml
│   └── prscs.yaml
├── scripts
│   └── munge_sumstats.R
├── resources
│   └── (input files)
├── results
│   └── prscs_results
└── Snakefile

Configuration (config.yaml)

Adjust paths, filenames, and parameters such as ref_dir, sample sizes, and chromosome lists directly within config.yaml.

Troubleshooting

  • Ensure containers and conda environments are correctly set up.
  • Verify paths in config.yaml and availability of summary statistics and genotype files.

For issues, review Snakemake logs in .snakemake/log/.

For questions or support, please contact Rakshya Sharma.