2025/07/18 by Josh L. Espinoza, Allan Phillips, Christopher L. Dupont · 1 voice
Biochemistry, Genetics and Molecular Biology · #Bioinformatics and Genomic Networks #Genomics and Phylogenetic Studies #Gut microbiota and health
paper · doi:10.1101/2025.07.14.664802
openalex publication_date 2025/07/18 · openalex created_date 2025/11/02 · openalex updated_date 2026/08/04
Functional profiling of meta-omics is essential for understanding microbial communities, yet support for custom genome-resolved reference databases is limited. We introduce Leviathan for integrated taxonomic and functional profiling at both genome and pangenome resolution. Leviathan combines Sylph for ultrafast alignment-free taxonomic profiling with Salmon for pseudo-alignment-based read quantification in DNA-space against (pan)genome-resolved gene catalogs, producing dual metrics per (pan)genome: pathway abundance and graph-based pathway coverage. Benchmarking alignment backends on synthetic metagenomes, we show that DNA-space pseudo-alignments retain competitive (pan)genome-level classification performance compared to traditional alignment, reducing computational runtime and memory requirements, while translated searches in protein-space lose classification resolution from ambiguous mapping events. Leviathan's utility is demonstrated through two case studies: a marine plastisphere metagenomics dataset analyzing metabolic shifts between early and mature biofilm communities and a dental caries metatranscriptomics dataset where co-expression network analysis identified organism-specific transcriptional patterns diagnostic of health and disease states. Leviathan is available at https://github.com/jolespin/leviathan.