This presentation covers the basic of Dynamic programing and pairwise sequence alignment

1. 1 November 2019 1

2. Introduction
Algorithm used in dynamic programing
• Needleman-Wunsch algorithm
• Smith- Waterman algorithm
Pairwise sequence alignment
• BLASTn
• BLASTp
Applications of pairwise sequence alignment
References
1 November 2019 2

3.  Dynamic programming is a computational method that is
used to align two proteins or nucleic acids sequences.
 This method is very important for sequence analysis because
it provides the very best or optimal alignment between
sequences.
 Alignment includes matched, mismatched characters and
gaps in the two sequences that positioned so that the
number of matches between identical or related character is
maximum as possible.
INTRODUCTION
1 November 2019 3

4. Needleman-wunsch Algorithm
Developed by Saul.b. needleman &
christian.d. wunsch
Referred as global alignment
Used in aligning 2 closely related
sequence
Compares the whole sequence
Tools:- EMBOSS-Needle, Specialised
BLAST
Smith-Waterman algorithm
Developed by Temple.F.Smith &
Michael. S. Waterman
Referred as local alignment
Used in aligning divergent
sequences
Compares a patch from the
sequence
Tools:-EMBOSS-Water, LALIGN
1 November 2019 4

5. Fig 1:- Comparison of Global and Local alignment in general
1 November 2019 5

6. Needleman-Wunsch algorithm
• Aligns protein or nucleic acid sequences
• Divides a large problem into a series of smaller
problems
• Uses the solution of smaller problem to
reconstruct a solution to the larger problems
1 November 2019 6

7. Constructing the matrix
We will have 2 matrices of 2D representation viz,
1. The score matrix
2. Traceback matrix
The N-W algorithm consists of 4 steps:-
1. Initialization of the score matrix
2. Filling up the matrix
3. Traceback
4. Alignment
1 November 2019 7

8. 1.Initializing the scoring matrix
G C A T G C
0 -1 -2 -3 -4 -5 -6
G -1
T -2
A -3
C -4
G -5
C -6
Match = 1
Mismatch. = -1
Gap. = -1
1 November 2019 8

9. 2. Filling the matrix
G
0 -1
G -1 X
For x :
This cell has 3 possible values
• Top :- (-1)+(-1) = -2
• Left :- (-1)+(-1) = -2
• Top-left :- (0)+(1) = 1
The highest value is 1 and thus
it is entered into the cell
i.e x = 1
G
0 -1
G -1 1
1 November 2019 9

10. Contd..
G C
0 -1 -2
G -1 1 X
C -2 Y
For X :
Top: (-2)+(-1) = (-3)
Left: (+1)+(-1) = (0)
Top-Left: (-1)+(-1) = (-2)
For Y :
Top: (1)+(-1) = (0)
Left: (-2)+(-1) = (-3)
Top-Left: (-1)+(-1) = (-2)
The highest value for X and Y is 0,
thus it is entered into the cell.
i.e X = O; Y = 0
G C
0 -1 -2
G -1 1 0
C -2 0
1 November 2019 10

11. 3. Traceback
1 November 2019 11

12. 4. Alignment
Rules :-
1. If arrow is vertical/horizontal assign a gap
and a character
:- Gaps and characters
Where to Assign
a gap and a character ?
Sequence
1 or 2
1 November 2019 12

13. Contd…
Ans) The gap will be assigned in the direction of
the arrow and the character will be assigned in
the opposite direction
2. If there is a diagonal arrow both the
characters will be assigned
:- Both characters
1 November 2019 13

14. Result of alignment
G C T A G C -
. .
G - T A C G C
1 November 2019 14

15. • S-W algorithm is modified version of
Needleman- Wunsch algorithm
• Negative scoring matrix cells are set to zero
• Traceback procedure starts at the highest
scoring matrix cells and procedure until a cell
with score zero is found
1 November 2019 15

16. Constructing the matrix
G C A T G C
0 0 0 0 0 0 0
G 0
C 0
A 0
T 0
G 0
C 0
Match = 1
Mismatch. = -1
Gap. = -1
1 November 2019 16

17. Contd..
G C
0 -1 -2
G -1 1 X
C -2 Y
For X :
Top: (-2)+(-1) = (-3)
Left: (+1)+(-1) = (0)
Top-Left: (-1)+(-1) = (-2)
For Y :
Top: (1)+(-1) = (0)
Left: (-2)+(-1) = (-3)
Top-Left: (-1)+(-1) = (-2)
The highest value for X and Y is 0,
thus it is entered into the cell.
i.e X = O; Y = 0
G C
0 -1 -2
G -1 1 0
C -2 0
1 November 2019 17

18. Traceback
1 November 2019 18

19. Alignment
Rules:
Same as of Needleman- Wunsch algorithm
1 November 2019 19

20. Difference between the procedure of S-W and N-W algorithm
1 November 2019 20

21. Example
1 November 2019 21

22. 1 November 2019 22

23. Fig :- Emboss homepage
1 November 2019 23

24. Fig 2:- Entering the sequence to be compared in N-W algorithm
1 November 2019 24

25. Fig 4:- Protein alignment result
1 November 2019 25

26. When comparing 2 sequences it is Pairwise
sequence alignment (nucleic acids or protein)
When comparing more than 2 sequence it is
Mulitiple sequence alignment (nucleic acids
or protein)
1 November 2019 26

27. Contd…
 Pairwise sequence alignment is concerned
with comparing 2 DNA or 2 Amino acids
sequences
For ex.
BLASTn :- for nucleotide sequence
BLASTp :- for protein sequence
1 November 2019 27

28.  BLAST is a Basic Local Alignment Search Tool.
 Used for comparing primary biological
information viz,
–Amino acid sequences of protein
–Nucleotide of DNA or RNA sequences
 BLASTn and BLASTp is particularly used for
comparing nucleotide sequence and protein
sequence respectively1 November 2019 28

29. 1 November 2019 29
Fig 6:- Result of Paralichthys olivaceus in BLASTn

30. 1 November 2019 30
Fig 7:- Sequence producing significant alignment

31. 1 November 2019 31
Fig 8:- Sequence alignment of Paralichthys olivaceus

32.  Searching large sequences for matches
 Characterize newly sequenced genes or gene
products
 Molecular distance of evolution between
species
1 November 2019 32

33. REFERENCE
 Introduction of Needleman-wunsch and smith
waterman algorithm
David Mount;“Bioinformatics sequence and
genome analysis”,chp 3;pp53
 Needleman,S.B.and wunsch,C.D.(1970), “A
general method applicable to the search for
similarities in the amino acid sequence of two
proteins”, J.Mol.Biol.,vol,48,pp 443-453.
1 November 2019 33

34. Contd..
 Smith, T.t.&Waterman, M.S.(1981), “Identification of
common molecular subsequences”, -
J.Mol.Biol.,vol.147,pp195-197
 Tools used for sequence alignment
(https://www.omictools.com)
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446
765/)
1 November 2019 34

35. 1 November 2019 35

36. 1 November 2019 36