Statistically rigorous and computationally efficient chromatin stripe detection with Quagga

  1. Jie Liu1,6
  1. 1Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48103, USA;
  2. 2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
  3. 3Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA;
  4. 4Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts 02139, USA;
  5. 5Department of Biochemistry and Molecular Biology, University of Texas Health Science Center Houston, Houston, Texas 77030, USA;
  6. 6Department of Computer Science and Engineering, University of Michigan, Ann Arbor, Michigan 48103, USA
  1. 7 These authors contributed equally to this work.

  • Corresponding authors: Xiaotian.Zhang{at}uth.tmc.edu, drjieliu{at}umich.edu
  • Abstract

    Chromatin stripes are architectural chromatin features in which a singular loop anchor interacts with a contiguous region of DNA so, at the bulk sequencing level, it appears as a long stripe on chromatin contact matrices. Stripes are thought to play an important role in gene regulation and have been implicated in regulating a cell's lineage determination. Therefore, integrated analysis of stripes with genomic and epigenomic features at a genome-wide scale shows vast potential in understanding the cooperation between regulatory elements in 3D nucleome. To this end, we present Quagga, a computational tool for detection and statistical verification of genomic architectural stripes from Hi-C or Micro-C chromatin contact maps, that relies on robust image processing techniques and rigorous statistical tests for enrichment. Quagga outperforms other stripe detection methods in accuracy and is highly versatile, working with Hi-C, Micro-C, and other chromatin conformation capture data. By reporting on all tools’ performance in classifying CTCF-cohesin anchored stripes, enhancer–promoter interacting stripes, and indeterminate stripes, we also demonstrate a thorough, integrated analysis to determine the output stripes’ quality. Our work provides a flexible and convenient tool to help scientists explore the relationships between chromatin architectural stripes and important biological questions.

    Footnotes

    • [Supplemental material is available for this article.]

    • Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.280132.124.

    • Freely available online through the Genome Research Open Access option.

    • Received October 18, 2024.
    • Accepted October 28, 2025.

    This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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