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Comparative genomics. Structural Genomics. Comparative Genomics. Functional genomics. Pairwise alignment Exact algorithms Heuristic algorithms (FastA, Blast) Multiple alignments Exact algorithms Heuristic algorithms (clustalW) Profile searches
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Structural Genomics Comparative Genomics Functional genomics
Pairwise alignment • Exact algorithms • Heuristic algorithms (FastA, Blast) • Multiple alignments • Exact algorithms • Heuristic algorithms (clustalW) • Profile searches • Motif detection (improved multiple alignment for nucleotide sequences based on profiles)
Algorithms FastA Pairwise Alignment Dynamic programming Heuristic approaches Needleman Wunsch (global) Smith Waterman (local) Blast Database searches Chapter 1 Chapter 1
Algorithms HMM Multiple Alignment Dynamic Programming Heuristic Searches Pattern recognition Motif Searches Database searches Chapter 2
Introduction Multiple sequence alignment Features characteristic for the protein family Profile (HMM) Detect remote members of the family Phylogeny Reconstruct phylogenetic relationships
Introduction Multiple sequence alignment Features characteristic for the whole family How to represent the characteristic features? • Profile: captures the family characteristic features • regular expression, weight matrix, HMM profile
Introduction • Profile: captures the family characteristic features • Used to detect remote homologs of a family • In this course emphasis on nucleotide sequences Multiple sequence alignment Scan new sequence with the profile Construct profile Unaligned sequences
Overview Query Sequence Unknown Blast Blast Sequence to search for close homologs ClustalW PFAM PROSITE Make a multiple sequence alignment Search pFAM, Prosite for conserved motifs HMMer, PSSM PSI-blast Generate profile or HMM You detected homology with an annotated protein family Profile Search Search database for remote homologs