04-Multiple_sequence_alignment(生物信息学国外教程2010版).ppt

Page 205 Note conserved regions: exons and regulatory sites (scale: 50,000 base pairs) regulatory Page 205 Multiple alignment of beta globin gene scale: 1,800 base pairs Page 205 Multiple alignment of beta globin gene scale: 55 base pairs This week: please download MEGA software and paste in a set of protein sequences. We’ll use MEGA next week to make phylogenetic trees. Download from * * * APDB ClustalW output:TCoffee can incorporate structural information into a MSA Protein Data Bank accession numbers Multiple sequence alignment: outline [1] Introduction to MSA Exact methods Progressive (ClustalW) Iterative (MUSCLE) Consistency (ProbCons) Structure-based (Expresso) Conclusions: benchmarking studies [2] Hidden Markov models (HMMs), Pfam and CDD [3] MEGA to make a multiple sequence alignment [4] Multiple alignment of genomic DNA Multiple sequence alignment: methods How do we know which program to use? There are benchmarking multiple alignment datasets that have been aligned painstakingly by hand, by structural similarity, or by extremely time- and memory-intensive automated exact algorithms. Some programs have interfaces that are more user-friendly than others. And most programs are excellent so it depends on your preference. If your proteins have 3D structures, use these to help you judge your alignments. For example, try Expresso at . Page 196 [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. Strategy for assessment of alternative multiple sequence alignment algorithms Page 196 BaliBase: comparison of multiple sequence alignment algorithms Page 196 Multiple sequence alignment: methods Benchmarking tests suggest that ProbCons, a consistency-based/progressive algorithm, per