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USEARCH searches a database for the top global hit, or top few hits. This is distinctly different from traditional search algorithms such as BLAST, which use local alignments and report all hits at a given E-value threshold.

The advantages of the USEARCH algorithm include its ultra-high speed, which can be orders of magnitude faster than BLAST, and reduced data output since in most applications only the top hit or the top few hits are relevant. Also, in some applications, e,g, taxonomy assignment, global alignments give better biological predictions as local alignments may give short hits with misleadingly high identity.

The USEARCH algorithm is implemented in the usearch_global command. A local alignment variant is also provided (usearch_local), though this is rarely used in practice. USEARCH is not effective on very large databases, say much greater than 1M sequences or 1Gb as a FASTA file. For huge databases, UBLAST is recommended even if global hits are required.

For both USEARCH and UBLAST commands, accept parameters give a rich set of options for filtering hits.

UBLAST UBLAST searches a database for all local hits meeting the given accept criteria including an E-value threshold and other options. Hits that are global or approximately global alignments can be selected if needed.

UBLAST achieves much higher speed than BLAST on large databases with comparable sensitivity in most cases. UBLAST consistently achieves better sensitivity and speed compared to MEGABLAST. On protein and translated  searches, UBLAST can achieve speeds hundreds of times faster than BLASTP or BLASTX with comparable sensitivity to identities of 50% or less.