DNA Sequence Alignment

A dynamic programming algorithm

Some ideas stole from Winter 1996 offering of 590BI at
http://www/education/courses/590bi/98wi/
See Lecture 2 by Prof. Ruzzo. Or try current quarter of CSE 527.
Those slides are more detailed and biologically accurate.
 DNA Sequence Alignment (aka
“Longest Common Subsequence”)
• The problem
– What is a DNA sequence?
– DNA similarity
– What is DNA sequence alignment?
– Using English words
• The Naïve algorithm
• The Dynamic Programming algorithm
• Idea of Dynamic Programming
 What is a DNA sequence
• DNA: string using letters A,C,G,T
– Letter = DNA “base”
– e.g. AGATGGGCAAGATA
• DNA makes up your “genetic code”
 DNA similarity
• DNA can mutate.
– Change a letter
• AACCGGTT  ATCCGGTT
– Insert a letter
• AACCGGTT  ATAACCGGTT
– Delete a letter
• AACCGGTT  ACCGGTT
• A few mutations makes sequences different, but
“similar”
Why is DNA similarity important
• New sequences compared to existing
sequences
• Similar sequences often have similar
function
• Most widely used algorithm in
computational biology tools
– e.g. BLAST at
http://www.ncbi.nlm.nih.gov/BLAST/
 What is DNA sequence
alignment?
• Match 2 sequences, with underscore ( _ )
wildcards.
• Best Alignment  minimum underscores
(slight simplification, but okay for 326)
• e.g. ACCCGTTT
TCCCTTT

Best alignment: A_CCCGTTT

(3 underscores) _TCCC_TTT
Moving to English words

zasha
ashes

zash__a
_ashes_
 Naïve algorithm
• Try every way to put in underscores
• If it works, and is best so far, record it.
• At end, return best solution.
 Naïve Algorithm – Running
Time
• Strings size M,N: ( 2 M  N )
 Dynamic Approach – A table
• Table(x,y): best alignment for first x letters
of string 1, and first y letters of string 2
• Decide what to do with the end of string,
then look up best alignment of remainder in
Table.
 e.g. ‘a’ vs. ‘s’
• “zasha” vs. “ashes”. 2 possibilities for last
letters:
– (1) match ‘a’ with ‘_’:
• best_alignment(“zash”,”ashes”)+1
– (2) match ‘s’ with ‘_’:
• best_alignment(“zasha”,”ashe”)+1
 best_alignment(“zasha”,”ashes”)
=min(best_alignment(“zash”,”ashes”)+1,
best_alignment(“zasha”,”ashe”)+1)
 An example
(empty) Z A S H A
(empty)
A
S
H
E
S
 Example with solution
(empty) Z A S H A
(empty) 0 1 2 3 4 5
A 1 2 1 2 3 4
S 2 3 2 1 2 3
H 3 4 3 2 1 2
E 4 5 4 3 2 3
S 5 6 5 4 3 4
zasha__
_ash_es
 Pseudocode (bottom-up)
Given: Strings X,Y , Table[0..x,0..y]

For i=1 to x do
Table[i,0]=i
For j=1 to y do
Table[0,j]=i
i=1, j=1
While i<=x and j<=y
If X[x]=Y[y] Then
// matches – no underscores
Table[x,y]=Table[x-1,y-1]
Else
Table[x,y]=min(Table[x-1,y],Table[x,y-1])+1
End If
i=i+1
If i>x Then
i=1
j=j+1
End If
 Pseudocode (top-down)
Given: Strings X,Y , Table[0..x,0..y]

BestAlignment (x,y)
Compute Table[x-1,y] if necessary
Compute Table[x,y-1] if necessary
Compute Table[x-1,y-1] if necessary

If X[x]=Y[y] Then
// matches – no underscores
Table[x,y]=Table[x-1,y-1]
Else
Table[x,y]=min(Table[x-1,y],Table[x,y-1])+1
End If
 Running time
• Every square in table is filled in once
• Filling it in is constant time
 (n2) squares
 alg is (n2)
Idea of dynamic Albert Q.
Dynamic
programming at Whisler
mountain

Picture from PhotoDisc.com

• Re-use expensive computations

– Identify critical input to problem (e.g. best
alignment of prefixes of strings)
– Store results in table, indexed by critical input
– Solve cells in table of other cells
• Top-down often easier to program