CMB2000/L18 Bioinformatics I

Question 1

Explain sequence alignment.

Answer 1

Same set of sequences with zero or more gaps (-) inserted into them such that:
All sequences have the same length
No alignment position where every sequence contains a gap

Question 2

Explain pairwise alignment.

Answer 2

Optimal alignment for any pair of biological sequences

Question 3

Define global alignment and give an example of a software using this.

Answer 3

Aligning whole sequences end-to-end
E.g., Needle

Question 4

Define local alignment and give an example of a software using this.

Answer 4

Focuses of best matching part of sequences
E.g., Water

Question 5

What is the formula to calculate the number of comparisons in multiple alignment?

Answer 5

(n(n-1))/2

Question 6

Give a software which uses multiple sequence alignment.

Answer 6

JalView

Question 7

What are the 2 main classes of multiple sequence alignment?

Answer 7

Progressive
Iterative

Question 8

Why is multiple sequence alignment described as a heuristic approach?

Answer 8

It is more experimentation, evaluation and trial and error than optimal

Question 9

Give 4 algorithms using multiple sequence alignment.

Answer 9

Clustal (1992-2011)
T-Coffee (2000)
MAFFT (2002)
Muscle (2004)

Question 10

What are the 3 steps of the Clustal algorithm?

Answer 10

Compare sequences to obtain similarity matrix
Make a guide tree relating all sequences
Perform progressive alignments, adding new sequences according to guide tree

Question 11

Explain how a similarity matrix is obtained in Clustal MSA. (3)

Answer 11

Long vector alignment
Clustering using standard algorithms
Genetic distances between sequence pairs computed - no. mismatched positions/total number of matched positions

Question 12

Explain how a guide tree is made in Clustal MSA. (3)

Answer 12

Genetic distances used to form phylogenetic tree
Used to control order of adding sequences to multiple alignment
relative contributions of alignment weighted according to evolutionary positions

Question 13

Explain how progressive alignments are formed in Clustal MSA. (3)

Answer 13

Sequences aligned progressively
Most closely related pairs aligned first
Next closely related sequences added by aligning with existing alignment

Question 14

What does MAFFT stand for?

Answer 14

Multiple Alignment using Fast Fourier Transform

Question 15

Explain MAFFT. (3)

Answer 15

Flexible alignment method constructs progressive alignment then improves iteratively
(Hybrid between two main approaches)
uses subsitution matrix when adding new (protein) sequences to alignment

Question 16

Give 3 factors to consider when choosing which algorithm to use for MSA.

Answer 16

DNA/protein
Number of sequences to align
Accuracy vs. speed