Abstract
Profiling metagenomes against databases allows for the detection and quantification of microorganisms, even at low abundances where assembly is not possible. We introduce sylph, a species-level metagenome profiler that estimates genome-to-metagenome containment average nucleotide identity (ANI) through zero-inflated Poisson k-mer statistics, enabling ANI-based taxa detection. On the Critical Assessment of Metagenome Interpretation II (CAMI2) Marine dataset, sylph was the most accurate profiling method of seven tested. For multisample profiling, sylph took >10-fold less central processing unit time compared to Kraken2 and used 30-fold less memory. Sylph's ANI estimates provided an orthogonal signal to abundance, allowing for an ANI-based metagenome-wide association study for Parkinson disease (PD) against 289,232 genomes while confirming known butyrate-PD associations at the strain level. Sylph took <1 min and 16 GB of random-access memory to profile metagenomes against 85,205 prokaryotic and 2,917,516 viral genomes, detecting 30-fold more viral sequences in the human gut compared to RefSeq. Sylph offers precise, efficient profiling with accurate containment ANI estimation even for low-coverage genomes.
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