/imputation-tools

# imputation-tools

Primary LanguagePython

imputation-tools

A set of tools to impute high throughput genotyping data. Data in plink binary format is expected as input. imputation-tools will:

  1. Split the data by chromosomes
  2. Align the data according to reference strand using bcftools fixref
  3. Phase the data with Eagle2 and impute the data using Minimac3 using 1000 genomes reference panel
  4. Perform standard association test with plink2 --glm
  5. Visualize the GWAS results using qqman

Prerequisites

imputation-tools was tested on Ubuntu 18.04.4 LTS. It requires a number of packages that can be installed using conda (Miniconda 3 should be sufficient).

Installation

Clone repoitory, unpack files, install environment and required packages, activate environment:

git clone https://github.com/oborisov/imputation-tools.git  
cd imputation-tools
gunzip data/*gz app/*gz
conda env create --file environment.yml  
conda activate imputation-tools

Running

snakemake --config chromosome=22 bfile=data/sim1_GSA BCFTOOLS_PLUGINS=$(which bcftools | sed 's/bin\/bcftools/libexec\/bcftools/')

The running time for chromosome 22 of the included test data is approximately 90 minutes (2.50GHz CPU, 1 thread).

Available options

The following options can be passed to the imputation-tools via --config command:

  1. chromosome
  2. path to binary plink file prefix
  3. path to BCFTOOLS_PLUGINS, should be determined automatically based on the bcftools installation via conda

While running, imputation-tools downloads required files for QC and imputation:

  1. fasta file for the analyzed chromosome to align the data according to reference strand
  2. reference vcf file to phase and impute the analyzed chromosome

Output

imputation-tools outputs Manhattan plot for the analyzed chromosome: chr22_example

used software

snakemake: https://snakemake.readthedocs.io/en/stable/
plink2: https://www.cog-genomics.org/plink/2.0/
bcftools: http://samtools.github.io/bcftools/bcftools.html
samtools: http://samtools.github.io/
tabix: http://www.htslib.org/doc/tabix.html
Eagle2: https://data.broadinstitute.org/alkesgroup/Eagle/
Minimac3: https://genome.sph.umich.edu/wiki/Minimac3

Docker (under development)

pull latest version of container: docker pull olegborisov/imputation-tools:latest
run application: docker run olegborisov/imputation-tools conda run -n snakemake snakemake