INTRODUCTIONThe BLAST algorithm was developed as a way to perform DNA and protein sequence similarity searches by an algorithm that is faster than FASTA but considered to be equally as sensitive. Both of these methods follow a heuristic (tried-and-true) method that almost always works to find related sequences in a database search, but does not have the underlying guarantee of an optimal solution like the dynamic programming algorithm. FASTA finds short common patterns in query and database sequences and joins these into an alignment. BLAST is similar to FASTA, but gains a further increase in speed by searching only for rarer, more significant patterns in nucleic acid and protein sequences. BLAST is very popular due to its availability on the World Wide Web through a large server at the National Center for Biotechnology Information (NCBI) and at many other sites. The BLAST algorithm has evolved to provide molecular biologists with a set of very powerful search tools that are freely available to run on many computer platforms. This article is intended to be a "user's guide" to the principles underlying BLAST.