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In the context of metagenomics, we introduce a new approach to protein database search called PAUDA, which runs ~10,000 times faster than BLASTX, while achieving about one-third of the assignment rate of reads to KEGG orthology groups, and producing gene and taxon abundance profiles that are highly correlated to those obtained with BLASTX. PAUDA requires &lt;80 CPU hours to analyze a dataset of 246 million Illumina DNA reads from permafrost soil for which a previous BLASTX analysis (on a subset of 176 million reads) reportedly required 800,000 CPU hours, leading to the same clustering of samples by functional profiles.

A poor man’s BLASTX—high-throughput metagenomic protein database search using PAUDA