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Updated: Mar 25, 2026

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MADRe: Strain-level metagenomic classification through assembly-driven database reduction.

Josipa Lipovac1, Mile Šikić1,2, Riccardo Vicedomini3

  • 1Laboratory for Bioinformatics and Computational Biology, Faculty of Electrical Engineering and Computing, University of Zagreb, 3 Unska Street, 10000, Zagreb, Croatia.

Gigascience
|March 23, 2026
PubMed
Summary
This summary is machine-generated.

MADRe, a novel pipeline, enhances strain-level metagenomic classification by reducing large reference databases. This method improves precision in identifying microbial strains, even with unknown sample compositions.

Keywords:
database reductionmetagenomic classificationmetagenomicsstrain-level

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Area of Science:

  • Microbiology
  • Bioinformatics
  • Genomics

Background:

  • Strain-level metagenomic classification is crucial for microbial ecology.
  • Challenges include unknown sample composition and redundant reference databases.
  • Existing methods struggle with accuracy and scalability.

Purpose of the Study:

  • To present MADRe, a modular and scalable pipeline for long-read strain-level metagenomic classification.
  • To introduce Metagenome Assembly-Driven Database Reduction for improved accuracy.
  • To leverage statistical strategies for enhanced database reduction and read reassignment.

Main Methods:

  • MADRe combines long-read metagenome assembly with contig-to-reference reassignment.
  • An expectation-maximization framework is used for reference database reduction.
  • Probabilistic read mapping reassignment is performed on the reduced database.

Main Results:

  • MADRe was evaluated on simulated, mock, and real metagenomic datasets.
  • The pipeline consistently improved precision by reducing false-positive strain detections.
  • Individual steps of MADRe can be used separately, with the classification step performing comparably to other tools.

Conclusions:

  • MADRe offers a sensitive and precise approach to strain-level metagenomic classification.
  • The Metagenome Assembly-Driven Database Reduction strategy effectively addresses database redundancy.
  • MADRe is an open-source tool available for broader research applications.