10 Multiple Sequence Alignment

10 Multiple Sequence Alignment - 1 Introduction to...

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1 Introduction to Bioinformatics/ Elements of Bioinformatics Multiple Sequence Alignment
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2 References Mount D.W. (2004) Bioinformatics: Sequence and Genome Analysis. 2 nd ed. Cold Spring Harbor Lab. Press, N.Y. Chapter 5 . Baxevanis, A.D., and Ouellette, B.F.F. (2005) Bioinformatics - A practical guide to the analysis of genes and proteins. 3 rd ed. John Wiley and Sons, NY. Chapter 12. • Higgins D. G. et. al. (1996) Using CLUSTAL for multiple sequence alignments. Methods in Enzymology 266: 383-402. • Notredame C. (2002) Recent progresses in multiple sequence alignment: a survey. Pharmacogenomics 3: 131-144.
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3 Multiple sequence alignment Multiple alignments improve the accuracy of alignment of weakly similar sequences
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4 Uses of multiple sequence alignment • Identify conserved and variable sites in a set of related sequences • As query to search database to identify members of a protein family • Phylogenetic studies • Protein modeling, structure prediction • etc.
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5 SL K R K Sequence Variation (and Disease) 45 C C C CS W C W CY Multiple sequence alignment of growth hormone receptor
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6 From: Davidson AR (2006) Methods Mol Biol 340: 171-181. Multiple sequence alignment as a guideline for protein engineering strategies Identification of a solubility enhancing substitution in the Cystic Fibrosis Transmembrane Conductance Regulator. F429S substitution increases soluble yield of human CFTR.
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7 Group of related sequences Multiple sequence alignment Identify conserved sequences Design PCR primers Application of multiple sequence alignment: Designing PCR primers
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8 Human ...T G T A T C G C T C. .. Rabbit ...T G T G T C G C T C. .. Chicken ...A G T C T C G T T C. .. Human ...T G T A T C G C T C. .. Rabbit ...T G T G T C G C T C. .. Human ...T G T A T C G C T C. .. Chicken ...A G T C T C G T T C. .. Rabbit ...T G T G T C G C T C. .. Chicken ...A G T C T C G T T C. .. Human Rabbit Chicken 0.5 0.5 1.0 1.5 Rabbit Chicken Human 1 3 Rabbit 3 Construction of a phylogenetic tree from a multiple sequence alignment
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9 Application of multiple sequence alignment: phylogeny and molecular epidemiology Dentist Patient C Patient A Patient G Patient B Patient E Patient A Dentist Control 1 Control 5 Control 4 Control 3 Control 2 Spread of SARS Case of Florida dentist
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10 Types of multiple alignment • Global alignment – alignment throughout the length of the entire sequence, e.g. ClustalW • Local alignment – statistical methods for the identification of conserved motifs from a set of unaligned DNA or protein sequences e.g. MEME (http://meme.sdsc.edu/meme/)
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11 Global vs local alignment From: Duret L. and Abdeddaim S.(2000). In Bioinformatics: Sequence, Structure and Databanks , Higgins D. and Taylor W. (ed.), OUP.
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This note was uploaded on 07/29/2010 for the course BIOC BIOC1805 taught by Professor Dr.brianwong during the Summer '09 term at HKU.

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10 Multiple Sequence Alignment - 1 Introduction to...

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