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Lecture 4.1 and 4.2 Sequence Alignment (Global and Local)

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26 views14 pages

Lecture 4.1 and 4.2 Sequence Alignment (Global and Local)

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thehostsmm
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Sequence

Alignment
Lecture – 5

Department of CSE, DIU


CONTENTS

1. Sequence Alignment
- Why align sequences

2. Sequence Alignment Methods


- Pairwise Alignment
- Multiple Sequence Alignment

3. Pairwise Sequence Alignment Methods


-Global Alignment (Needleman-
Wunsch)
- Local Alignment (Smith-Waterman)
1. Sequence
Alignment
Why and how align sequences
Sequence
Alignment
A way of arranging the sequences of DNA,
RNA, or protein to identify regions of CTGTCG-CTGCACG
similarity that may be a consequence of
-TGC-CG-TG----
functional, structural, or evolutionary
relationships between the sequences
Why align sequences?

• Useful for discovering


• Functional
• Structural and
• Evolutionary relationship
– For example
• To find whether two (or more) genes or proteins are
evolutionarily related to each other
• Two proteins with similar sequences will probably be
structurally or functionally similar
2. Sequence Alignment
Methods
Pairwise and Multiple
Pairwise Sequence
Alignment

▹A pair of sequences as input

▹Align them in such a way that, for that particular


alignment the assumed region of similarity produces
higher score than all the other alignments
CTGTCGCTGCACG--
▹Methods
-------TGC-CGTG
- Global Alignment (Needleman-
Wunsch)
- Local Alignment (Smith-Waterman)
Pairwise Sequence
Alignment

• Idea:
Display one sequence above another with spaces inserted in
both to reveal similarity

A: C A T - T C A - C
| | | | |
B: C - T C G C A G C
Multiple Sequence
Alignment

• Three or more than three sequences as


input

• Align all the sequences altogether in


such a manner that the alignment
produces highest score
3. Pairwise Sequence
Alignment
Global and Local methods
Global Alignment (Needleman-
Wunsch)
3 Major Steps Trace back
-Create 2D Matrix - Start from Cell (Row,
-Trace back Col)
-Final Alignment - Go back up to Cell
(0,0)
Create 2D Matrix
- Row x Col 2D matrix draw (Row
Final Alignment
, Col size of seq1 and seq2
- Start from Cell (Row,
respectively)
Col)
- Place 2 seqs as Row and Column
- If then, place
Header
character in both seq
- Cell (0,0) = 0
- If or then
- Cell (0,1) to Cell (0,Column) and
character in start seq &
Cell (1,0) to Cell (Row,0) value =
gap in end seq
delete gap value from previous cell
value
- For other cell values, follow
equation in (1)
Global Alignment (Needleman-Wunsch) -
Example
Input
- seq1 = AAAC
-AGC A G C
- seq2 = AGC
AAAC 0 -2 -4 -6
Scoring Scheme Final
δ(x, x) = 1 (Match)
δ(x,-) = -2 (Gap)
Alignment
A -2 1 -1 -3
δ(x, y) = -1 (Mis
match)
A -4 -1 0 -2
A -6 -3 -2 -1
Eq. 1: Cell
Value
C -8 -5 -4 -1
Local Alignment (Smith-
Waterman)
3 Major Steps Trace back
-Create 2D Matrix - Start from each Cell which has the
-Trace back maximum value in the entire matrix
-Final Alignment - Go back up to the Cell where first time 0
occurs
Create 2D Matrix
- Row x Col 2D matrix draw (Row
Final Alignment
, Col size of seq1 and seq2
- Start from each Cell with max value
respectively)
- If then, place character in both
- Place 2 seqs as Row and Column
seq
Header
- If or then character in
- First Row, First Column all value
start seq & gap in end seq
=0
- For other cell values, follow
equation in (2)
Local Alignment (Smith-Waterman) - Example
Input
- seq1 = AAAC
-AAG A A G
- seq2 = AAG
AAAC 0 0 0 0
Scoring Scheme Final
δ(x, x) = 1 (Match)
δ(x,-) = -2 (Gap)
Alignment
A 0 1 1 0
δ(x, y) = -1 (Mis
match)
A 0 1 2 0
A 0 1 2 1
Eq. 2: Cell
Value
C 0 0 0 1

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