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Metax enables accurate cross-domain taxonomic profiling of metagenomes.

Sep 2026 · Cell · 0 citations · 92 references
Medicine

TL;DR

This broad evaluation demonstrated that Metax resolved bacterial and viral signatures of peri-implantitis in oral microbiomes and revealed signals suggestive of reagent-borne contaminants and reference misassemblies in plasma-cell-free DNA.

Abstract

Taxonomic profiling is fundamental to microbiome research, yet achieving high species-level accuracy remains challenging for complex communities that span bacteria, viruses, eukaryotes, and archaea, and these limitations are exacerbated in low-biomass, host-dominated samples. We introduce Metax, a cross-domain taxonomic profiler that integrates coverage-based probabilistic modeling with an expectation-maximization framework to distinguish true microbial signals from artifacts. Across >600 samples from host-associated, environmental, wastewater, and low-biomass clinical settings, including benchmarks with limited reference representation, Metax improved profiling accuracy, achieving on average 55% higher F1 scores and 45% lower Bray-Curtis dissimilarity than other methods. Moreover, this broad evaluation demonstrated that Metax resolved bacterial and viral signatures of peri-implantitis in oral microbiomes and revealed signals suggestive of reagent-borne contaminants and reference misassemblies in plasma-cell-free DNA. By leveraging genome-wide coverage evidence, Metax enables robust cross-domain profiling across diverse sample types and sequencing depths, including settings where reference databases are highly incomplete.

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