USEARCH is a unique high-throughput sequence analysis tool. It is a distributed as single binary program that implements a suite of algorithms comparable to BLASTN, BLASTP, BLASTX, BLASTCLUST, CD-HIT, CD-HIT-EST, CD-HIT-2D, CD-HIT-EST-2D, CD-HIT-OTU, CD-HIT-454, ChimeraSlayer, Perseus, RAPsearch and more. It supports a rich set of sequence matching options, including E-values, identity, coverage (fraction of query or target sequence covered by the alignment) and maximum gap length, and a range of output file formats including FASTA, BLAST-like, user-defined tabbed text and a native format designed for clustering applications. Supported alignment styles include local (gapped and ungapped), like BLAST, and global, which is most often used in clustering applications. User-settable parameters allow tuning of substitution scores, gap penalties and Karlin-Altschul statistics.
In bioinformatics, sequence clustering algorithms attempt to group sequences that are somehow related. The sequences can be either of genomic, "transcriptomic" (ESTs) or protein origin. For proteins, homologous sequences are typically grouped into families. For EST data, clustering is important to group sequences originating from the same gene before the ESTs are assembled to reconstruct the original mRNA.
Some clustering algorithms use single-linkage clustering, constructing a transitive closure of sequences with a similarity over a particular threshold. UCLUST and CD-HIT use a greedy algorithm that identifies a representative sequence for each cluster and assigns a new sequence to that cluster if it is sufficiently similar to the representative; if a sequence is not matched then it becomes the representative sequence for a new cluster. The similarity score is often based on sequence alignment. Sequence clustering is often used to make a non-redundant set of representative sequences.
Sequence clusters are often synonymous with (but not identical to) protein families. Determining a representative tertiary structure for each sequence cluster is the aim of many structural genomics initiatives.