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Multiple Sequence Alignment 多序列比对 Outline Introduction Method Tools Example 1. Why need MSA? Comparing a pair of sequences is not sufficient for many research purposes, mainly for evolutionary reconstructions and study functional similarities chite ADKPKRPLSAYMLWLNSARESIKRENPDFK-VTEVAKKGGELWRGLKD wheat --DPNKPKRAPSAFFVFMGEFREEFKQKNPKNKSVAAVGKAAGERWKSLSE trybr KKDSNAPKRAMTSFMFFSSDFRSKHSDLS-IVEMSKAAGAAWKELGP mouse KPKRPRSAYNIYVSESFQEAKDDS-AQGKLKLVNEAWKNLSP ***. ::: .: .. . : . . * . *: * chite AATAKQNYIRALQEYERNGG- wheat ANKLKGEYNKAIAAYNKGESA trybr AEKDKERYKREM mouse AKDDRIRYDNEMKSWEEQMAE * : .* . : Potential Uses of A Multiple Sequence Alignment? Extrapolation Motifs/Patterns Phylogeny Profiles Struc. Prediction Multiple Alignments Are CENTRAL to MOST Bioinformatics Techniques. protein sequences that are 30% identical often have the same structure and function Profiles谱 and motifs模体 一个序列模体是一段局部保守的区域或由一组序列共有的短的序列模式（pattern） A sequence motif is a locally conserved region of a sequence or a short sequence pattern shared by a set of sequences. 模体指用于预测分子功能、结构特征或家族关系的模式 The term motif refers to any sequence pattern that is predictive of a molecule’s function, a structural feature, or a family membership. Motifs can be detected in proteins, DNA and RNA sequences, but they most commonly refer to protein motifs. 模体可以表示为不同的形式因不同计算目的 Motifs can be represented for computational purposes as Flexible patterns [K,R]-R-P-C-x(11)-C-V-S (qualitative, unweighted; see the Prosite database at ) Position-specific scoring matrices (PSSM, see next page) Profile hidden Markov models (HMM). These are rigorous probabilistic formulation of a sequence profile. They contain the same probability information as PSSMs but can also account for gaps. Discovery of novel related sequences is efficiently done using multiple sequence alignments. This profile- or motif-based analysis uses knowldedge derived from alignments to construct and search for seq