nf-core pipeline ·

nf-core/variantcatalogue

Generates population variant catalogues and allele frequencies from whole genome sequence data.

Run it with the research agent Documentation Source code

What nf-core/variantcatalogue is

nf-core/variantcatalogue is a bioinformatics analysis pipeline designed to build population-scale variant catalogues from whole genome sequencing data. It determines the presence and frequency of genomic variants across cohorts, translating raw sequencing data into structured, frequency-annotated catalogues.

Originally developed by S. Correard with contributions from W. Wasserman, M. Elsiddieg, and B. Hewitson, the pipeline addresses the operational complexity of running multi-stage cohort genomics. It standardises quality control, short-read alignment, nuclear and mitochondrial variant discovery, cohort-level joint calling, and functional annotation into a single reproducible workflow.

The software matters to geneticists and computational biologists needing standardized population baselines or allele frequency databases. By handling distinct processing paths for both the nuclear genome and circular mitochondrial genome alongside rigorous quality control metrics, it ensures high-confidence variant discovery across cohorts.

What the pipeline does

The pipeline operates via three primary subworkflows executed using Nextflow DSL2. First, the mapping stage indexes the reference using BWA, trims reads with Trimmomatic, and aligns reads via BWA MEM. It evaluates quality and coverage using FastQC, Mosdepth, and Picard metrics (Collect WGS Metrics, Alignment Summary Metrics, Quality Score Distribution) before aggregating outputs into MultiQC.

Second, the nuclear small variant subworkflow calls variants per sample using DeepVariant and performs joint calling across the cohort using GLnexus. Multi-allelic sites are split using Bedtools norm, and identifiers are assigned via Bedtools Annotate. Hail then carries out sample-level QC, sex inference, variant QC, and population frequency calculations, followed by functional variant annotation using VEP. Third, the mitochondrial subworkflow aligns reads against both standard and shifted mitochondrial reference genomes using BWA, marks duplicates, computes Picard HS metrics, calls variants with GATK Mutect2, lifts over shifted coordinates, merges the call sets, and calculates final frequencies in Hail.

Key facts

Pipeline engine: Nextflow (DSL2)
Minimum Nextflow version: >=22.10.1
Primary input format: Sample sheet (.csv) with whole genome sequencing reads
Supported container platforms: Docker, Singularity, Podman, Shifter, Charliecloud, Conda
Core aligner: BWA MEM
Nuclear variant callers: DeepVariant, GLnexus
Mitochondrial variant caller: GATK Mutect2
Cohort analysis and QC engine: Hail
Annotation tool: VEP

What you can use it for

Population frequency database generation: Constructing reference catalogues detailing SNV and indel allele frequencies across a defined population cohort from raw whole genome sequences.
Dual-reference mitochondrial variant discovery: Calling mitochondrial variants and assessing homoplasmy or heteroplasmy frequencies by resolving circular chromosome boundary artifacts with shifted and unshifted reference alignments.
Standardised cohort QC and sex validation: Evaluating sequencing quality across a multi-sample cohort, establishing alignment and coverage metrics, and conducting Hail-based sample QC alongside chromosomal sex inference.

Run it here

The research agent runs nf-core/variantcatalogue with Nextflow on its own machine — up to 32 cores, 256 GiB of memory and 24 hours per run, which covers the test profile and real single-sample runs. It builds the samplesheet, checks it against the pipeline's schema and reads the results back. When a run is too big for one machine, it gives you the exact command for your own cluster instead.

Ask the research agent

Strengths and limits

Good at

Processes nuclear and mitochondrial genomes within distinct, tailored subworkflows in a single execution.
Uses a dual-reference strategy (standard and shifted reference genomes) with GATK Mutect2 to resolve variant calling issues over circular mitochondrial origins.
Integrates DeepVariant and GLnexus for joint calling, paired with Hail for sample QC, sex inference, and cohort-level frequency calculations.
Employs isolated Nextflow DSL2 process containers to ensure maintainability and computational reproducibility.

Watch out for

Structural variant identification is not currently available in the pipeline.
Restricted to whole genome sequencing analysis rather than targeted or exome capture formats.
Requires high-capacity compute environments capable of executing Hail and joint variant calling across full cohorts.

Questions

Can I run nf-core/variantcatalogue without my own cluster?

What licence is nf-core/variantcatalogue under?

MIT, like every nf-core pipeline.

What variant types does the pipeline call?

It calls single-nucleotide variants (SNVs) and indels in both nuclear and mitochondrial DNA. Structural variant analysis is not currently implemented.

How does the pipeline address variant calling over the circular mitochondrial boundary?

It aligns extracted mitochondrial reads to both the standard mitochondrial reference and an alternate shifted reference genome using BWA, calls variants using GATK Mutect2, and performs liftover before merging the resulting calls.

Which software tools handle cohort-level frequency calculations and sample QC?

Hail performs sample QC, sex inference, variant QC, and the final variant frequency calculations for both nuclear and mitochondrial subworkflows.

How to cite it

Correard et al., 2022. doi: 10.1101/2022.10.03.508010

Written from nf-core/variantcatalogue's own README. Statements citing a figure that does not appear there are removed before publication. Licence and running details come from our registry.