Comparison of the Programs

• Concept:
  SW and BLAST produce local alignments, while FASTA is global alignment tool. BLAST can report more than one HSP per database entry, while FASTA reports only one segment (match).
• Speed:
  BLAST > FASTA $\gg$ SW
  BLAST (package) is a highly efficient search tool.
• Sensitivity:
  SW > FASTA > BLAST (old version!)
  FASTA is more sensitive, missing less homologue (but the opposite can also happen - if there are no identical residues conserved, but this is infrequent). It also gives better separation between true homologues and random hits.
• Statistics:
  BLAST calculates probabilities, and it sometimes fails entirely if some of the assumptions used are invalid. FastA calculates significance 'on the fly' from the given dataset which is more relevant but can be problematic if the dataset is small .