Annotation of glycoside hydrolases in unassembled metagenomes using CAZyO_GH.

Authors

Nicholas G Griffin, Alison E Hughes, Daniel S Erdody, Eliott Berlemont, Shannon Sweeney, Tara Fareghbal, Klaus B Hagedorn, Renaud Berlemont

Published in

Bioinformatics advances. Volume 6. Issue 1. Pages vbag137. Epub Jul 09, 2026.

Abstract

Functional characterization of microbiomes often relies on the sequencing of metagenomic DNA extracted from environmental samples, with current approaches using metagenome-assembled genomes (MAGs). Although glycoside hydrolases (GHs) are central to carbon cycling, accurate annotation of GHs in metagenomic datasets remains challenging due to the multidomain architecture of carbohydrate-active enzymes and the prevalence of unassembled short reads due to limitations in the MAG-generation process.
Here, we present CAZyO_GH (CAZymes Open-source GH annotation), a curated reference database for the domain-specific identification of 135 protein domains spanning 99 GH families with well-defined catalytic domain signatures. CAZyO_GH focuses on individual GH domains, enabling robust annotation of both assembled and unassembled metagenomic data. We validated CAZyO_GH by reanalyzing genomes listed in CAZy db, where predicted GH profiles closely matched reported values. Next, we used CAZyO_GH to analyze 12 human gut metagenomes and 12 newly sequenced soil microbiomes to reveal environment-specific GH repertoires. By accurately detecting catalytic domains independent of the genomic context, CAZyO_GH improves sensitivity and specificity in short-read metagenomic annotation. This framework provides a scalable and reproducible approach to investigate carbohydrate-active enzymes across ecosystems, advancing our capacity to characterize microbial functional potential in global carbon cycling.
CAZyO_GH data is available on figshare (https://figshare.com/projects/CAZyO_GH/267770).

PMID:
42437291
Bibliographic data and abstract were imported from PubMed on 12 Jul 2026.

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