Medicago Genomics and Bioinformatics：苜蓿基因组学和生物信息学.pptVIP

Protein Domain Analysis Using Hidden Markov Models Liangjiang (LJ) Wang ljwang@ March 10, 2005 PLPTH 890 Introduction to Genomic Bioinformatics Lecture 17 Outline Basic concepts and biological problems. Search for protein domains: The Pfam database, Other domain/motif databases. Protein domain modeling: Hidden Markov Models (HMM), Construction of the Pfam protein domain models using HMMER. Biological Problem #1 You identified a new gene, which might be involved in a very interesting biological process. BLAST search in GenBank resulted in a few homologous sequences with unknown function. What else can you do to understand the function of the gene product and/or to localize the possible conserved domain in the protein? Biological Problem #2 Suppose there is a novel gene identified in mammals, C. elegans and Drosophila, but not yet in plants. This gene is involved in an interesting biological process (e.g., apoptosis). You are interested in finding the orthologous gene in Arabidopsis. However, BLAST search using each of the known sequences failed to identify an Arabidopsis homologue. What else can you try? Orthologs, Paralogs and Homologs X Y X X X1 X2 Y Y Ya Yb Ancestral organism Speciation A B A B X1 and X2 are orthologs with same function. Paralogs Ya and Yb may have different but related functions. Duplication Homologs Protein Domains Domains represent evolutionarily conserved amino acid sequences carrying functional and structural information of a protein. Domain analysis helps understand the biological function of a gene product. bZIP Protein Domain Analysis Using HMM Multiple Sequence Alignment HMMER Search Hidden Markov Models Your Sequence Set TC50726 AIKLNDVKSCQGTAFWMAPEVVRGKVKGYGLPADIWSLGCTVLEMLTGQVPYAPMECISAMFRIGKGELPPVPDTLSRDARDFILQCLKVNPDDRPTAAQLLDHKFVQRSFSQSSGSASPHIPRRS UFO_ARATH MDSTVFINNPSLTLPFSYTFTSSSNSSTTTSTTTDSSSGQWMDGRIWSKLPPPLLDRVIAFLPPPAFFRTRC Comparison of Search Approaches BLAST HMM Threading Sensitivity Speed Low