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BLOSUM 62
Global alignments that do not include gaps : a matrix of 200
PAMS for sequences that are thought to be related.
“Unknown sequences” : a 120 PAM matrix was the best
compromise.
Local alignment method PAM40, PAM120 and PAM250. The
lower PAM matrices (40-120) find short alignments of highly
similar sequences, while higher PAM matrices (120-250)
find longer, weaker local alignments.
Standard Blast: Overall the BLOSUM 62 matrix is the most
effective.
All other substitution matrices perform better than BLOSUM
62 for a proportion of the families.
Algorithms
Step 1 Preprocessing
•finds regions of similarity by making an index showing all of the
amino acid positions for each sequence i.e. a C at position 1, S at
position 2, etc.
•Step 2 Heuristic searching
•these indexes are used to find if a row of the same characters are
found in the same order in the two sequences being compared.
•If these rows are long enough, the sequences are similar.
•Initn = init1 = opt indicates 100% homology over the matched stretch.
• Initn > init1 indicates that there is more than one matching region in the database
sequence, with poorly matching separating regions(s).
•Opt > initn shows that the matching regions are greatly improved by the addition
of gaps in one or both of the sequences. Such differences in score are indicative of
non-homologous sequences.
•Opt < initn FASTA only optimizes within a narrow band along the same diagonal
as the INIT1 region (best single region of match). If any of the (n-1) regions lie
outside the band, then they are excluded from the optimized score. i.e.: There is too
large a separation between the good scoring regions for FASTA to join them.
Finding a local alignment: BLAST algorithm
.
Sequence Pre-Filters
Reducing matches due to biased amino acid composition
Many amino acid sequences are highly repetitive in nature,
especially naive translations of genomic DNA. Matches
between such segments are more likely to be due to these
local amino acid composition biases than to common
descent. Filters have been developed to mask out regions
showing highly-biased local composition.
SEG (Wooton & Federhen, Computers & Chemistry 17:149.
1993)
XNU(Claverie & States, Computers & Chemistry, 17:191.
1993)
The end
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