Scribd
Upload
35 views

Sequence Alignment: Lecture - 4

1. The lecture discusses sequence alignment methods including pairwise alignment techniques like global alignment using Needleman-Wunsch and local alignment using Smith-Waterman. 2. Multiple sequence alignment techniques like progressive and iterative methods are also covered. Progressive alignment first builds a guide tree before performing pairwise alignments while iterative alignment repeatedly realigns sequences. 3. Challenges in multiple sequence alignment include computational complexity, difficulty in scoring alignments, and placement of gaps between more divergent sequences.

Uploaded by

sk3 khan
Copyright
© © All Rights Reserved
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
35 views

Sequence Alignment: Lecture - 4

1. The lecture discusses sequence alignment methods including pairwise alignment techniques like global alignment using Needleman-Wunsch and local alignment using Smith-Waterman. 2. Multiple sequence alignment techniques like progressive and iterative methods are also covered. Progressive alignment first builds a guide tree before performing pairwise alignments while iterative alignment repeatedly realigns sequences. 3. Challenges in multiple sequence alignment include computational complexity, difficulty in scoring alignments, and placement of gaps between more divergent sequences.

Uploaded by

sk3 khan
Copyright
© © All Rights Reserved
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
You are on page 1/ 19

Sequence

Alignment
Lecture – 4

Nafis Neehal, Lecturer, Department of CSE, DIU


CONTENTS
1. Sequence Alignment

2. Sequence Alignment Methods


- Pairwise Alignment
- Multiple Sequence Alignment

3. Pairwise Sequence Alignment Methods


-Global Alignment (Needleman-Wunsch)
- Local Alignment (Smith-Waterman)

4. Multiple Sequence Alignment


- Progressive Method
- Iterative Method
- MSA Challenges
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
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
CTGTCGCTGCACG--
other alignments
-------TGC-CGTG
▹ Methods
- Global Alignment (Needleman-Wunsch)
- Local Alignment (Smith-Waterman)
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, Col)
-Trace back - Go back up to Cell (0,0)
-Final Alignment

Create 2D Matrix
- Row x Col 2D matrix draw (Row , Col
Final Alignment
size of seq1 and seq2 respectively)
- Start from Cell (Row, 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 Cell
character in start seq & gap in end
(1,0) to Cell (Row,0) value = delete
seq
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 maximum
-Trace back 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 , Col
Final Alignment
size of seq1 and seq2 respectively)
- Start from each Cell with max value
- Place 2 seqs as Row and Column
- If then, place character in both seq
Header
- If or then character in start
- First Row, First Column all value = 0
seq & gap in end seq
- 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
4. Multiple Sequence Alignment
Progressive, Iterative
Progressive Method
▹ Two major steps – Guide Tree build up
and Multiple Pairwise Alignment

▹ Steps
- Take each pair, align
- Generate consensus of that
alignment
- Align new sequence with the
consensus of the previous one
- Go back, Until all sequences are
finished
▹ Example
- Clustal ω
- MAFFT
- KALIGN
- T-COFFEE
Iterative Method

▹ Works similarly to progressive


methods
▹ Repeatedly realign the initial
sequences as well as add new
sequences to the growing MSA
▹ Example
- DIALIGN
- MUSCLE
- POA
MSA Challanges
▹ Computationally Expensive

▹ Difficult to score. Multiple comparison necessary in each


column of the MSA for a cumulative score

▹ Placement of gaps and scoring of substitution is more


difficult

▹ Difficulty increases with diversity

▹ Relatively easy for a set of closely related sequences.


Identifying the correct ancestry relationships for a set of
distantly related sequences is more challenging

▹ Even difficult if some members are more alike compared


to others
95%
Of Human DNA is identical to Chimpanzees

2 gm DNA
Can contain digital information of whole world

510 DNA Codes


Lost throughout human evolution

1.8 Meter
Long DNA is squeezed into a space of 0.09 µm
TO BE
CONT
INUED

Shocked?
Youtube Links
▹Global Alignment Part 1 - https://www.youtube.com/watch?v=vqxc2EfPWdk

▹Global Alignment Part 2 - https://www.youtube.com/watch?v=zwA-6_1bLgE

▹Local Alignment - https://www.youtube.com/watch?v=IatoWOsJ35Q

You might also like