Sequence Alignment I Dot Matrices

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# Sequence Alignment I Dot Matrices - PowerPoint PPT Presentation

Sequence Alignment I Dot Matrices. Reading. Mount, Chapters 1, 2, and 3 (up to page 94). Why compare sequences? . To find whether two (or more) genes or proteins are evolutionarily related to each other To find structurally or functionally similar regions within proteins.

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### Sequence Alignment IDot Matrices

• Mount, Chapters 1, 2, and 3 (up to page 94)
Why compare sequences?
• To find whether two (or more) genes or proteins are evolutionarily related to each other
• To find structurally or functionally similar regions within proteins
Similar genes arise by gene duplication
• Copy of a gene inserted next to the original
• Two copies mutate independently
• Each can take on separate functions
• All or part can be transferred from one part of genome to another
Sequence Comparison Methods
• Dot matrix analysis
• Dynamic Programming
• Word or k-tuple methods (FASTA and BLAST)
Dot matrices

c

g

g

a

c

a

c

a

c

g

Interpretation
• Regions of similarity appear as diagonal runs of dots
• Reverse diagonals (perpendicular to diagonal) indicate inversions
• Reverse diagonals crossing diagonals (Xs) indicate palindromes
Interpretation
• Can link separate diagonals to form alignment with gaps
• Each a.a. or base can only be used once
• Can't double back
• A gap is introduced by each vertical or horizontal skip
Filtering
• Dot matrices for long sequences can be noisy due to insignificant matches
• Solution: use a window and a threshold
• compare character by character within a window (have to choose window size)
• require certain fraction of matches within window in order to display it with a dot
Dot plot comparison using windows

Window size = 11

Stringency = 7

(Put a dot only if 7 out of next 11 positions are identical.)

Uses for dot matrices
• Aligning two proteins or two nucleic acid sequences
• Finding amino acid repeats within a protein by comparing a protein sequence to itself
• Repeats appear as a set of diagonal runs stacked vertically and/or horizontally
Repeats

Human LDL receptor protein sequence (Genbank P01130)

W = 1

S = 1

(Mount, Fig. 3.6)

Repeats

W = 23

S = 7

(Mount, Fig. 3.6)

Using substitution matrices
• Dots can have weights
• Some matches are rewarded more than others, depending on likelihood
• Use PAM or BLOSUM matrix (more on these later)
• Put a dot only if a minimum total or average weight is achieved
• See Mount, Fig. 3.5