生物信息学-06多序列比对和进化树分析

第一、

第六章多序列比对和分子系统发育分析

第一节序列间比对

DefinitionsPairwise alignmentThe process of lining up two sequences to achieve maximal levels of identity (and conservation, in the case of amino acid sequences) for the purpose of assessing the degree of similarity and the possibility of homology.

Pairwise sequence alignment programs

Multiple sequence alignment programsHow to get multiple sequences? Sequence BLAST Program

Two kinds of multiple sequence alignment resources[1] Databases of multiple sequence alignments Text-based searches of CDD, Pfam (profile HMMs), PROSITE Database searches with a query sequence with BLAST, CDD, PFAM[2] Multiple sequence alignment by manual input PileUp, CLUSTAL W, CLUSTAL X

Multiple sequence alignment programs AMAS Genedoc ClustalW ClustalX DIALIGN HMMT Match-Box MultAlin MSA Musca PileUp SAGA T-COFFEE

1. ClustalW in BioEdit(1)序列的输入 (2)序列alignment (3)格式调节 (4)输出到绘图内编辑

1. ClustalW in BioEdit

2. Clustal W online(1)序列的输入 (2)序列alignment

http://www.ebi.ac.uk/Tools/clustalw2/index.html

Multiple sequence alignment algorithms

Local Progressive

GlobalCLUSTAL PileUp other

PIMA

Iterative

DIALIGN

SAGA

PIMA

Strategy for assessment of alternative multiple sequence alignment algorithms[1] Create or obtain a database of protein sequences for which the 3D structure is known. Thus we can define“true” homologs using structural criteria.[2] Try making multiple sequence alignments with many different sets of proteins (very related, very distant, few gaps, many gaps, insertions, outliers).[3] Compare the answers.

BaliBase: comparison of multiple sequence alignment algorithms

Conclusions: assessment of alternative multiple sequence alignment algorithms[1] As percent identity among proteins drops, performance (accuracy) declines also. This is especially severe for proteins< 25% identity. Proteins<25% identity: 65% of residues align well Proteins<40% identity: 80% of residues align well

Conclusions: assessment of alternative multiple sequence alignment algorithms[2]“Orphan” sequences are highly divergent members of a family. Surprisingly, orphans do not disrupt alignments. Also surprisingly, global alignment algorithms outperform local.

Conclusions: assessment of alternative multiple sequence alignment algorithms

[3] Separate multiple sequence alignments can be combined (e.g. RBPs and lactoglobulins). Iterative algorithms (PRRP, SAGA) outperform progressive alignments (ClustalX)

Conclusions: assessment of alternative multiple sequence alignment algorithms

[4] When proteins have large N-terminal or C-terminal extensions, local alignment algorithms are superior. PileUp (global) is an exception.

Multiple sequence alignment programs1.新基因的鉴定 2.蛋白序列特殊氨基酸残基分析 3.分子系统发育分析的基础

第二节分子系统发育分析几

个慨念分子进化分析介绍系统发育树重建方法 MEGA4软件包在分子进化分析中的应用

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