MetagenomicKG: a knowledge graph for metagenomic applications.

Motivation: The sheer volume and variety of genomic content within microbial communities makes metagenomics a field rich in biomedical knowledge. To traverse these complex communities and their vast unknowns, metagenomic studies often depend on distinct reference databases, such as the Genome Taxonomy Database (GTDB), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the Bacterial and Viral Bioinformatics Resource Center (BV-BRC), for various analytical purposes. These databases are crucial for genetic and functional annotation of microbial communities. Nevertheless, the inconsistent nomenclature or identifiers of these databases present challenges for effective integration, representation, and utilization. Knowledge graphs (KGs) offer an appropriate solution by organizing biological entities and their interrelations into a cohesive network. The graph structure not only facilitates the unveiling of hidden patterns but also enriches our biological understanding with deeper insights. Despite KGs having shown potential in various biomedical fields, their application in metagenomics remains underexplored. Results: We present MetagenomicKG, a novel knowledge graph specifically tailored for metagenomic analysis. MetagenomicKG integrates taxonomic, functional, and pathogenesis-related information from widely used databases, and further links these with established biomedical knowledge graphs to expand biological connections. Through several use cases, we demonstrate its utility in enabling hypothesis generation regarding the relationships between microbes and diseases, generating sample-specific graph embeddings, and providing robust pathogen prediction. Availability and Implementation: The source code and technical details for constructing the MetagenomicKG and reproducing all analyses are available at Github: https://github.com/KoslickiLab/MetagenomicKG. We also host a Neo4j instance: http://mkg.cse.psu.edu:7474 for accessing and querying this graph.