Sequence alignment

Question 1

Explain global alignment

Answer 1

Global alignment aims to maximize the alignment quality over the whole sequences. Gaps are typically penalized.

Question 2

Explain local alignment

Answer 2

Local alignment tries to match sub-regions of the sequences. Gaps typically not penalized.

Question 3

List the four possible components of a scoring function

Answer 3

• Match
• Mismatch
• Gap
• Gap extension

Question 4

What can you do with a substitution matrix?

Answer 4

Substitution matrix can be used to score sequence alignments. It holds all the possible values for a scoring function: points given for each possible match, mismatch, gap and gap extension.

Question 5

Describe the traceback procedure in Smith-Waterman algorithm

Answer 5

1. Start with the highest value in the matrix.*
2. Trace back until a zero is found

*To break ties, pick the one that yields the longest local alignment.

Question 6

Explain the affine gap penalty scheme

Answer 6

In the affine gap penalty scheme, there is a different penalty for opening a gap and extending a gap.

Question 7

How would you check that a high alignment score you just calculated for two sequences did not happen by chance?

Answer 7

1. Create randomized versions of sequence 1.
2. Align sequence two against the randomized versions.
3. The fraction of randomized alignment scores that are bigger than the original gives the p-value.