MACS: Model-based Analysis for ChIP-Seq

September 22, 2026 ยท View on GitHub

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Introduction

With the improvement of sequencing techniques, chromatin immunoprecipitation followed by high throughput sequencing (ChIP-Seq) is getting popular to study genome-wide protein-DNA interactions. To address the lack of powerful ChIP-Seq analysis method, we presented the Model-based Analysis of ChIP-Seq (MACS), for identifying transcript factor binding sites. MACS captures the influence of genome complexity to evaluate the significance of enriched ChIP regions and MACS improves the spatial resolution of binding sites through combining the information of both sequencing tag position and orientation. MACS can be easily used for ChIP-Seq data alone, or with a control sample with the increase of specificity. Moreover, as a general peak-caller, MACS can also be applied to any "DNA enrichment assays" if the question to be asked is simply: where we can find significant reads coverage than the random background.

Please find MACS3 documentations through MACS3 website.

What's new in MACS 3.0.5

  • Added PETrackII.return_anndata for efficient creation of sparse barcode-by-peak AnnData matrices from single-cell fragment data.
  • Switched peak calling, pileup output, and peak-model construction to faster NumPy-backed PileupV2 routines, and optimized fragment exclusion and score caches.
  • Added hmmratac --jump to control fragment-length EM updates.
  • Fixed decimal-score truncation in bdgdiff (#715), incorrect summit scores for maxima in below-cutoff gaps (#741), and an IndexError during hmmratac peak refinement (#735).
  • Made successful hmmratac --cutoff-analysis-only runs exit with status 0 (#704).
  • MACS3 now requires Python 3.12 or later. The cykhash dependency was removed, while pandas and anndata were added for AnnData export.

See the ChangeLog for the complete release notes.

Contribute

Please read our CODE OF CONDUCT and How to contribute documents. If you have any questions, suggestion/ideas, or just want to have conversions with developers and other users in the community, we recommend using the MACS Discussions instead of posting to our Issues page.

Support MACS3

I maintain MACS3 in my spare time. If you find the project useful and would like to support its continued development, you can Buy Me a Coffee. Your contribution will help cover my ever-growing consumption of coffee and tokens.

Ackowledgement

MACS3 project is sponsored by CZI's Essential Open Source Software for Science through EOSS2 (2020-2022) and EOSS4 (2021-2025). And we particularly want to thank the user community for their supports, feedbacks and contributions over the years.

Citation

For MACS version 2 and 3, please cite our 2026 paper MACS3: A Peak-calling Platform for Bulk and Single-cell Regulatory Genomics

If you are using MACS version 1, please cite our 2008 paper Model-based Analysis of ChIP-Seq (MACS)

Note

Now the default branch of MACS3 has been renamed to 'main'. If you are still using old 'master' branch in your cloned Git repository for MACS3, please use the following command to rename it:

git branch -m master main
git fetch origin
git branch -u origin/main main
git remote set-head origin -a