Heuristic homology search methods

1. Heuristic homology search methods EMBnet www.embnet.org

2. Heuristic methods Heuristic methods make 'reasonable assumptions' about the nature of the sequence alignments. This allows them to cut corners by trying out only the most likely alignments The benefit is that they run MUCH faster than an exhaustive search. The drawback is that they can miss some alignments EMBnet www.embnet.org

3. FASTA FASTA identifies all the exact matches of length ktup between the two sequences High scoring diagonals (diagonals with many matches) are identified. Matches are extended along the diagonal to join shorter diagonals together. A Smith-Waterman alignment is performed on just the area containing the diagonal ktup is typically 4-6 for DNA or 1-2 for protein. EMBnet www.embnet.org

4. FASTA Output FASTA output gives three scores and a histogram: Initial score: The alignment score using exact matching ktuples Final score The alignment score using Smith-Waterman Probability: The probabilily of the sequence alignment occuring by chance. Histogram: The predicted and observed number of matches with a specific alignment score. FASTA only reports one alignment per sequence EMBnet www.embnet.org

5. BLAST Basic Local Alignment of Sequences Tool BLAST finds the high scoring exact matches between two sequences It then tries to extend the score for an ungapped alignment to the maximum. Some versions of BLAST will provide a gapped alignment. ktup is typically 3 for proteins and 9-11 for nucleic acids EMBnet www.embnet.org

6. Caveats Neither FASTA nor BLAST are good at detecting large areas of lower homology. They can miss some matches. Neither FASTA nor BLAST are good with short sequences. EMBnet www.embnet.org