Podcast
Questions and Answers
What is the main purpose of using the BLOSUM matrices?
What is the main purpose of using the BLOSUM matrices?
How are the BLOSUM matrices numbered in relation to the PAM matrices?
How are the BLOSUM matrices numbered in relation to the PAM matrices?
What does the BLOSUM50 matrix represent?
What does the BLOSUM50 matrix represent?
How are probability ratios expressed in the context of substitution matrices?
How are probability ratios expressed in the context of substitution matrices?
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Why are substitution matrices considered symmetrical?
Why are substitution matrices considered symmetrical?
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In the context of substitution matrices, what does symmetrical mean?
In the context of substitution matrices, what does symmetrical mean?
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How do BLOSUM matrices differ from PAM matrices?
How do BLOSUM matrices differ from PAM matrices?
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Why was the BLOSUM62 matrix created?
Why was the BLOSUM62 matrix created?
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What is a characteristic of log odd ratios in substitution matrices?
What is a characteristic of log odd ratios in substitution matrices?
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Why are BLOSUM and PAM matrices crucial for sequence alignment?
Why are BLOSUM and PAM matrices crucial for sequence alignment?
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Study Notes
Sequence Alignment
- Global alignment of DNA sequences using dynamic programming and a scoring scheme is possible.
- Scoring scheme:
- Match: +3
- Mismatch: -2
- Gap: -3
Practice Questions
- Align DNA sequences using dynamic programming and the provided scoring scheme.
- Examples:
- Seq 1: GCTTAGC
- Seq 2: GCATTGC
Gap Penalty
- Gap penalty score: g(g) = -d - (g -1) e
- Linear gap penalty score: d = gap opening penalty, e = gap extension penalty, g = gap length
- Affine gap penalty score: g(g) = -d - (g -1) e
Scoring Insertions or Deletions
- Using GAP penalty, score insertions or deletions.
- Example:
- Total Score: 4
- Total Score: 8 + (-3.2) = 4.8
Substitution Matrices
- Used to score substitution events in alignments.
- Particularly important in protein sequence alignments.
- Each scoring matrix represents a particular theory of evolution.
- Examples of substitution matrices:
- Identity scoring matrix
- Genetic code scoring scheme
- Chemical Similarity Scoring
- PAM substitution matrices
Identity Scoring Matrix
- Simplest scoring scheme.
- Score 1 for identical pairs.
- Score 0 for non-identical pairs.
- Unable to detect similarity.
Genetic Code Scoring Scheme
- Introduced by Fitch in 1966.
- Scores based on the number of nucleotide base changes required to interconvert the codons for the two amino acids.
- Used in the construction of phylogenetic trees and in the determination of homology between protein sequences.
Chemical Similarity Scoring
- Introduced by MacLachlan in 1972.
- Gives greater weight to the alignment of amino acids with similar physico-chemical properties.
- Amino acids are classified based on polar or non-polar character, size, shape, and charge.
PAM Substitution Matrices
- Constructed by Dayhoff, Schwarz, and Orcutt in 1978.
- Based on 71 protein families with 85% identical sequences.
- Obtained frequencies for residue X being substituted by residue Y over time period Z.
- Ignores evolutionary direction.
- Based on 1572 residue changes.
- Defined a substitution matrix as 1 PAM (point accepted mutation) if the expected number of substitutions was 1% of the sequence length.
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Description
Explore the practice questions on globally aligning DNA sequences using dynamic programming and a specific scoring scheme. Test your knowledge on sequence alignment with provided sequences, GCTTAGC and GCATTGC, along with scoring criteria for matches, mismatches, and gaps.