WasteFams: a database of protein families from global wastewater microbiomes

Wastewater surveillance has emerged as a critical tool for global epidemiology, yet the functional diversity of wastewater microbiomes remains poorly characterized at the protein level. Here, we present WasteFams, the first comprehensive database dedicated to the systematic exploration of protein families in wastewater metagenomic and metatranscriptomic studies worldwide. Integrating data from 580 metagenomes, 132 metatranscriptomes, and 1709 reference genomes (504 metagenomes, 129 metatranscriptomes, and 1151 reference genomes after filtering), WasteFams catalogs 3887 non-redundant protein families (containing ⪰100 members) derived from over 105 million predicted proteins. Each protein family is enriched with multi-layered annotations, including AlphaFold3 structural predictions, taxonomic classifications, and biome-specific metadata. To further expand their functional annotation, we integrated deep genomic context analysis to link protein families to mobile genetic elements, biosynthetic gene clusters, antibiotic resistance genes, and CRISPR elements. Accessible through the EnvoFams portal, WasteFams provides a user-friendly interface featuring advanced search capabilities, sequence and structural similarity tools, and interactive visualization modules. As global initiatives increasingly leverage wastewater for public health and environmental insights, WasteFams can serve as a critical resource for discovering novel microbial functions, monitoring resistance mechanisms, and exploring the biotechnological potential of secondary metabolites within wastewater-engineered ecosystems.