FASTA Search Programs


The FASTA programs search protein and deoxyribonucleic acid (DNA) databases for sequences with statistically significant similarity. The programs compare proteins, DNA and short peptides and oligonucleotides, and run on most popular computers. FASTA and BLAST both seek to identify homologous proteins or DNA sequences. BLAST is faster, but FASTA is more flexible, providing both rigorous (SSEARCH, LALIGN, GGSEARCH and GLSEARCH) and heuristic (FASTA, FASTX/Y, TFASTX/Y and FASTS/M/F) algorithms, a wider range of scoring matrices and different approaches for estimating statistical significance. In addition, the FASTA programs offer options to search a small, representative database, but then the report results from a larger sequence set linked to the initial significant hits. The FASTA programs can also annotate the alignments to include the conservation state of aligned functional residues, such as active sites, and subalignment scores associated with domain boundaries. The FASTA programs provide flexible and rigorous alternatives to BLAST for protein, translated‐DNA and DNA alignment.

Key Concepts:

  • The FASTA program uses a heuristic (approximate) strategy for finding similar sequences, but the FASTA package includes SSEARCH and GGSEARCH, which provide rigorous algorithms.

  • Homologs can be identified because they share excess (statistically significant) sequence similarity.

  • E()‐values (expect‐values) report the significance (expectation) of a sequence similarity score.

  • Sequence alignments are more accurate when the scoring matrix matches the evolutionary distance of the aligned sequences.

  • The FASTA programs can align against sequences not included in the initial search using library expansion.

  • The FASTA programs can use external annotations to modify aligned sequences and to partition similarity scores.

Keywords: sequence similarity; homology; statistical significance; protein sequence comparison; DNA sequence comparison

Figure 1.

FASTA alignment showing annotated functional sites and domains. Alignment of Uniprot proteins AKT2_HUMAN and KS6A5_HUMAN, using an annotation script to highlight functional residues and domain. ‘qSite’ and ‘Site’ locations specify residues annotated in the query and library sequence, respectively. Symbols (#‐binding, *‐modified residue) indicate the type of functional residue. The numbers, letters, and symbol after a ‘Site’ annotation, e.g. 181 K=81 K, indicate the query residue coordinate, query residue, conservation state, library residue coordinate and library residue. In cases where the residue has changed, the state of the replacement residue is indicated with a ‘<’, for nonconservative changes (the functional symbol is highlighted in red, e.g. #), and ‘>’ for conservative changes (highlighted in green, e.g. *). ‘Region’ annotations indicate the boundaries and scores associated with annotated domains. After the query start‐end and library start‐end for a region aligment, the raw similarity score, bit score, fraction identical and Q‐value (−10 log p) for the score is shown. Regions with Q‐values >30 have probabilities<0.001.



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Further Reading

Pearson WR (2013) An introduction to similarity (“homology”) searching. Current Protocols in Bioinformatics 42: 3.1.1–3.1.8. doi:10.1002/0471250953.bi0301s42.

Pearson WR (2014) BLAST and FASTA similarity searching for multiple sequence alignment. Methods in Molecular Biolology 1079: 75–101.

Pearson WR and Sierk ML (2005) The limits of protein sequence comparison? Current Opinion in Structural Biology 15: 254–260.


EMBL‐EBI European Bioinformatics Institute. FASTA similarity searching.

FASTA Programs at the University of Virginia. FASTA server.

Site for downloading current versions of the FASTA programs.

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Pearson, William R(Apr 2014) FASTA Search Programs. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005255.pub2]