Which BLAST program should I use?

Depending on the nature of the sequence it is possible to use different BLAST programs for the database search. There are five versions of the BLAST program, blastn, blastp, blastx, tblastn, tblastx:

Option Query Type DB Type Comparison Note
blastn Nucleotide Nucleotide Nucleotide-Nucleotide  
blastp Protein Protein Protein-Protein  
tblastn Protein Nucleotide Protein-Protein The database is translated into protein
blastx Nucleotide Protein Protein-Protein The queries are translated into protein
tblastx Nucleotide Nucleotide Protein-Protein The queries and database are translated into protein

The most commonly used method is to BLAST a nucleotide sequence against a nucleotide database (blastn) or a protein sequence against a protein database (blastp). But often another BLAST program will produce more interesting hits. E.g. if a nucleotide sequence is translated before the search, it is more likely to find better and more accurate hits than just a blastn search. One of the reasons for this is that protein sequences are evolutionarily more conserved than nucleotide sequences. Another good reason for translating the query sequence before the search is that you get protein hits which are likely to be annotated. Thus you can directly see the protein function of the sequenced gene.