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nf-core pipeline · chromosome-conformation-capture, hi-c

nf-core/hic

A Nextflow pipeline for processing, normalising, and analysing chromosome conformation capture (Hi-C) sequencing data.

What nf-core/hic is

nf-core/hic is a bioinformatics analysis pipeline designed for Chromosome Conformation Capture (Hi-C) sequencing datasets. Originally developed by Nicolas Servant, the workflow automates the end-to-end processing of paired-end sequencing reads into high-resolution contact maps and downstream genomic architecture features.

The pipeline addresses key computational challenges in Hi-C analysis, including handling chimeric reads spanning ligation junctions, removing PCR duplicates, and filtering out non-informative ligation products. By standardising data transformation into multiple contact matrix formats and applying established matrix-balancing techniques, it enables researchers to study three-dimensional genome organisation systematically.

Built within the Nextflow framework using DSL2, nf-core/hic encapsulates individual steps within software containers, ensuring consistency across diverse compute environments while handling quality control, contact normalisation, compartment calling, and domain identification.

What the pipeline does

The workflow begins by running FastQC to assess raw read quality. Paired-end sequencing reads are then mapped to a reference genome using Bowtie 2 within the HiC-Pro framework. HiC-Pro implements a two-step mapping strategy to rescue reads spanning ligation junctions, identifies valid interaction products, removes duplicate reads, and constructs raw and normalised contact maps using iced.

Following initial interaction processing, the pipeline employs cooler to generate genome-wide contact maps across multiple resolutions and balances matrices using normalisation algorithms. Contact maps can be exported to several downstream formats. Finally, the workflow executes biological domain calling by determining genomic compartments via cooltools, and calling topologically associating domains (TADs) using both cooltools and HiCExplorer, before consolidating metrics into a MultiQC quality control report.

Key facts

Pipeline engine
Nextflow DSL2
Latest release
2.1.0
Release date
2023-06-01
Original author
Nicolas Servant
Primary input format
Paired-end FASTQ (specified in CSV samplesheet)
Key tools
FastQC, HiC-Pro, Bowtie 2, iced, cooler, cooltools, HiCExplorer, MultiQC

What you can use it for

Hi-C contact matrix construction
Processing raw paired-end Hi-C FASTQ files into normalised, multi-resolution contact maps across standard matrix formats.
Genomic compartment identification
Detecting A/B genomic compartments across chromosomes from balanced contact maps using cooltools.
Topologically associating domain (TAD) calling
Identifying structural chromatin domains and boundary regions across the genome with HiCExplorer and cooltools.
Hi-C library quality assessment
Evaluating sequencing quality, valid interaction rates, and duplicate levels across samples in a unified MultiQC summary.

Run it here

The research agent runs nf-core/hic 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.

Strengths and limits

Good at

  • Uses a two-step Bowtie 2 mapping strategy via HiC-Pro to rescue reads spanning ligation junctions.
  • Produces multi-resolution contact maps normalised through balancing algorithms with cooler and iced.
  • Combines both HiCExplorer and cooltools for robust domain and compartment characterisation.
  • Implements Nextflow DSL2 with single-container process definitions to ensure reproducibility and modularity.

Watch out for

  • Requires paired-end sequencing data configured in a strict CSV samplesheet format.
  • Pipeline execution parameters cannot be passed via the -c Nextflow configuration option and must be provided through CLI or params files.

Questions

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

The research agent runs nf-core/hic 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.

What licence is nf-core/hic under?

MIT, like every nf-core pipeline.

What input data does nf-core/hic require?

It requires a CSV samplesheet specifying sample names and paths to paired-end FASTQ files (fastq_1 and fastq_2), alongside a designated reference genome.

Which tools are used for matrix normalisation?

Raw contact maps are normalised using the iced balancing algorithm within HiC-Pro and matrix balancing algorithms in cooler.

How are topologically associating domains (TADs) identified?

TAD calling is executed using tools from both HiCExplorer and cooltools.

Can custom pipeline parameters be defined in a custom Nextflow -c config file?

No. Configuration files supplied via the Nextflow -c option must not contain pipeline parameters; parameters must be supplied using the command line interface or the Nextflow -params-file option.

How to cite it

doi: 10.5281/zenodo.2669512

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