1 Multiple Sequence Alignment 暨南大學資訊工程學系 黃光璿 2004/05/31

2 What is a multiple alignment?

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4 An alignment of ten I-set immunoglobin superfamily

5 Motivation A multiple alignment may suggest a common structure of the protein products; a common function; a common evolutionary source.

6 Issues How to define meaningful scoring function for an alignment?  evolutionary correct alignment --- more difficult!  structure alignment How to find the best alignment?  by algorithms

7 Three types of alignment problems DNA protein  joined by disulfide bond RNA  more difficult due to long-range correlation We focus on alignment problems of sequences of DNAs or proteins.

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12 To prove that a computational problem is NP-hard, we need  to reduce an NP-complete (hard) problem to this problem.

13 When a computational problem is NP- hard, we deal with it by  heuristic: convince other people by experiments  approximation: how to analyze the performance?  randomization: how to design a reasonable algorithm

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20 Branch & bound heuristic for the DP algorithm of the Sum-of-pairs Carrillo & Lipman (1988) The idea was implemented in the famous problem MSA.  Lipman, Altshul, Kececiogly, 1989 MSA can align 6 sequences of length ~200 in reasonable time.

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35 參考資料及圖片出處 1. Biological Sequence Analysis – Probabilistic Models of Proteins and Nucleic Acids R. Durbin, S. Eddy, A. Krogh, and G. Mitchison, Cambridge University Press, Biological Sequence Analysis