Molgenis-impute

Molgenis-impute performs genotype imputation and automates preprocessing, phasing, chunking, and imputation steps to support GWAS, meta-analysis, and fine-mapping of large-scale genotype datasets.

Key Features:

• Automated pipeline setup: Automates setup and execution of imputation pipeline steps including liftover, phasing, quality control, chunking/merging, and imputation.
• Genome build liftover and quality control: Performs genome build liftover and genotype quality control prior to phasing and imputation.
• Genotype phasing (SHAPEIT2): Uses SHAPEIT2 for genotype phasing.
• Imputation (IMPUTE2): Performs genotype imputation using IMPUTE2.
• Sample and chromosomal chunking/merging: Supports chunking and merging by sample and chromosome to enable parallel processing.
• Integration with MOLGENIS-compute: Submits and monitors computational tasks via MOLGENIS-compute for execution on HPC environments.
• Flexibility and customization: Enables adaptation and integration with other workflows through the MOLGENIS-compute framework to add or modify computational steps.
• Scalability and tested performance: Tested on PBS/SGE clusters, cloud VMs, and grid HPC systems, and applied to impute over 30,000 samples using the 1,000 Genomes Project and Genome of the Netherlands reference datasets.

Scientific Applications:

• GWAS, meta-analysis, and fine-mapping: Provides imputed genotype data required for genome-wide association studies, meta-analyses, and fine-mapping of association signals.
• Large-scale genotype cohort processing: Enables imputation of large genotype cohorts through parallelized chunking and HPC execution.
• Reference-panel-based imputation: Supports use of reference panels such as the 1,000 Genomes Project and the Genome of the Netherlands for genotype imputation.

Methodology:

Performs genome build liftover, genotype quality control, phasing with SHAPEIT2, sample and chromosomal chunking/merging, and imputation with IMPUTE2, with task submission and monitoring via MOLGENIS-compute on HPC systems.