Sequence alignment

Gabor T. Marth

Department of Biology, Boston Collegemarth@bc.edu

BI420 – Introduction to Bioinformatics

Sequence alignment – Biology

http://bioinfo.pbi.nrc.ca:8090/EMBOSS/index.html

Biologically significant sequence alignment

Sequence alignment – Biology

http://bioinfo.pbi.nrc.ca:8090/EMBOSS/index.html

Biologically plausible sequence alignment

Sequence alignment – Biology

http://bioinfo.pbi.nrc.ca:8090/EMBOSS/index.html

Spurious alignment

Examples from: Biological sequence analysis. Durbin, Eddy, Krogh, Mitchison

Alignment types

Examples from: BLAST. Korf, Yandell, Bedell

How do we align the words: CRANE and FRAME?

CRANE || |FRAME

3 matches, 2 mismatches

How do we align words that are different in length?

COELACANTH || |||P-ELICAN--

COELACANTH || |||-PELICAN--

5 matches, 2 mismatches, 3 gaps

In this case, if we assign +1 points for matches, and -1 for mismatches or gaps, we get 5 x 1 + 1 x (-1) + 3 x (-1) = 0. This is the alignment score.

Finding the “best” alignment

COELACANTH || |||P-ELICAN--

COELACANTH | |||PE-LICAN--

COELACANTH || P-EL-ICAN-

COELACANTH PELICAN--

S=-2 S=-6 S=-10

S=0

Global alignment – Needleman-Wunsch

C O E L A C A N T H

0 -1 -2 -3 -4 -5 -6 -7 -8 -9 -10

P -1 -1 -2 -3 -4 -5 -6 -7 -8 -9 -10

E -2 -2 -2 -1 0 -3 -4 -5 -6 -7 -8

L -3 -3 -3 -2 -2 -1 -2 -3 -4 -5 -6

I -4 -4 -4 -3 -1 -1 -2 -1 -4 -5 -6

C -5 -3 -4 -4 -2 -2 0 -1 -2 -3 -4

A -6 -4 -4 -5 -3 -1 -1 -1 0 -1 -2

N -7 -5 -5 -5 -4 -2 -2 0 -2 -1 0

Local alignment – Smith-Waterman

C O E L A C A N T H

0 0 0 0 0 0 0 0 0 0 0

P 0 0 0 0 0 0 0 0 0 0 0

E 0 0 0 1 0 0 0 0 0 0 0

L 0 0 0 0 2 1 0 0 0 0 0

I 0 0 0 0 1 1 0 0 0 0 0

C 0 1 0 2 0 0 2 0 0 0 0

A 0 0 0 0 0 1 0 3 2 1 0

N 0 0 0 0 0 0 0 1 4 3 2

Visualizing pair-wise alignments

http://bioinfo.pbi.nrc.ca:8090/EMBOSS/index.html

Sequence similarity and scoring

Match-mismatch-gap penalties: e.g. Match = 1 Mismatch = -5 Gap = -10

Scoring matrices

Multiple alignments

Anchored multiple alignment