Metabuli: sensitive and specific metagenomic classification via joint analysis of amino-acid and DNA

Current metagenomic classifiers analyze either DNA or amino-acid (AA) sequences. DNA-based methods have better specificity in distinguishing well-studied clades, but they have limited sensitivity in detecting under-studied clades. AA-based methods suffer the opposite problem. To tackle this trade-off, we developed Metabuli for a joint analysis of DNA and AA using a novel k-mer, metamer . In benchmarks, Metabuli was simultaneously as specific as DNA-based methods and as sensitive as AA-based methods. In the CAMI2 plant-associated dataset, Metabuli covers 99% and 98% of classifications of state-of-the-art DNA-based and AA-based classifiers, respectively. Metabuli is available as free and open-source software for Linux and macOS at metabuli.steineggerlab.com .