MetaGEAR Explorer: Rapid interactive searches and cross-cohort analyses of microbiome gene associations in disease

ABSTRACT The human gut microbiome has been linked to inflammatory bowel disease (IBD) and colorectal cancer (CRC), yet identifying disease-associated microbial genes across diverse human cohort studies remains challenging due to inconsistent data processing and the high dimensionality of gene-level abundance profiles. Here we present MetaGEAR Explorer, a web platform comprising a user interface and web services for interactive and programmatic gene-centric exploration of >33 million microbial gene families across 9,053 metagenomic samples from 24 IBD, CRC, and healthy cohorts. MetaGEAR Explorer facilitates gene searches against a catalog of non-redundant gene families via nucleotide or amino acid sequence queries (BLAST) and Pfam domain-based searches. For matched gene families, the platform computes disease-stratified prevalence, cross-cohort disease associations, species-level taxonomic stratification, and functional domain annotations. Importantly, users can also explore the genomic context of individual gene families via contig-based co-localization networks derived from metagenomic species pangenome (MSP) assignments and pivot from sequence to domain searches to identify functional homologs. Additionally, the platform features a dedicated catalog to interactively browse 13,795 MSPs and export results programmatically via API endpoints. We demonstrate MetaGEAR Explorer’s utility using the narG-encoding nitrate reductase gene and a case study of colibactin self-protection genes (clbS and DUF1706 homologs), where the platform revealed a consistent shift from commensals to Gammaproteobacteria carriers in disease. In summary, MetaGEAR Explorer enables rapid cross-cohort functional meta-analyses and is freely available at https://metagear-explorer.schirmerlab.de. Competing Interest Statement The authors have declared no competing interest. Footnotes ↵† Co-first Authorship