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Bioinformatics

Bioinformatics. Richard Tseng and Ishawar Hosamani. Outline. Homology modeling (Ishwar) Structural analysis Structure prediction Structure comparisons Cluster analysis Partitioning method Density-based method Phylogenetic analaysis. Structural Analysis. Overview Structure prediction

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Bioinformatics

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  1. Bioinformatics Richard Tseng and Ishawar Hosamani

  2. Outline • Homology modeling (Ishwar) • Structural analysis • Structure prediction • Structure comparisons • Cluster analysis • Partitioning method • Density-based method • Phylogenetic analaysis

  3. Structural Analysis • Overview • Structure prediction • Structural alignment • Similarity

  4. Tools for protein structure prediction • Protein • Secondary structure prediction: SSEA http://protein.cribi.unipd.it/ssea/ • Tertiary structure prediction: • Wurst: http://www.zbh.uni-hamburg.de/wurst/ • LOOPP: http://cbsuapps.tc.cornell.edu/loopp.aspx

  5. WURST( Torda et al. (2004) Wurst: A protein threading server with a structural scoring function, sequence profiles and optimized substitution matrices Nucleic Acids Res., 32, W532-W535) • Rationale • Alignment: Sequence to structure alignments are done with a Smith-Waterman style alignment and the Gotoh algorithm • Score function: fragment-based sequence to structure compatibility score and a pure sequence-sequence component substitution score • Library: Dali PDB90 (24599 srtuctures)

  6. Tools for structure comparison • Pair structures comparison: • TopMatch • Matras: (http://biunit.naist.jp/matras/) • Multiple structures comparison: • 3D-surfer • Matras: (http://biunit.naist.jp/matras/)

  7. TopMatch (Sippl & Wiederstein (2008) A note on difficult structure alignment problems. Bioinformatics 24, 426-427) • Rationale: • Structure alignment: http://www.cgl.ucsf.edu/home/meng/grpmt/structalign.html • Similarity measurement • Input format • PDB, SCOP and CATH code • PDB structure directly • Exercise: http://topmatch.services.came.sbg.ac.at/

  8. 3D-surfer (David La et al.  3D-SURFER: software for high throughput protein surface comparison and analysis. Bioinformatics , in press. (2009)) • Rationale • Define a surface function • Transform the surface function into a 3D Zernike description function • Input format • PDB and CATH code • PDB structure directly • Exercise: http://dragon.bio.purdue.edu/3d-surfer/

  9. Cluster analysis • Goal: • Grouping the data into classes or clusters, so that objects within a cluster have high similarity in comparison to one another but are very dissimilar to objects in other clusters. • Methods • Partitioning method: k-means • Density-based method: Ordering Points to Identify the Clustering Structure (OPTICS)

  10. k-means • Rationale: Partition n observations into k clusters in which each observation belongs to the cluster with the nearest mean • Exercise http://cgm.cs.ntust.edu.tw/etrex/kMeansClustering/kMeansClustering2.html

  11. OPTICS • Rationle: Partition observations based on the density of similar objects • Exercise http://www.dbs.informatik.uni-muenchen.de/Forschung/KDD/Clustering/OPTICS/Demo/

  12. Example: Folding of Trp-cage peptide

  13. Phylogenetic analysis • Overviews • Comparisons of more than two sequences • Analysis of gene families, including functional predictions • Estimation of evolutionary relationships among organisms

  14. Theoretical tree • Parsimony method • Distance matrix method • Maximum likelihood and Bayesian method • Invariants method

  15. Software • Collections of tools http://evolution.genetics.washington.edu/phylip/software.html • A web server version for tree construction and display • PHYLIP, http://bioweb2.pasteur.fr/phylogeny/intro-en.html • Interactive tree of life, http://itol.embl.de/ • Mostly common used stand alone software • PHYLIP, tool for evaluating similarity of nucleotide and amino acid sequences. http://evolution.gs.washington.edu/phylip.html • TreeView, tool for visualization and manipulation of family tree. http://taxonomy.zoology.gla.ac.uk/rod/treeview.html • Matlab - bioinformatics tool box

  16. Example: Alignment phylogenetic tree of Tubulin family • Searching homologous sequences of Tubulin (PDB code: 1JFF) from RCSB protein databank • Blast for pair sequence alignment • Clustalw for comparative sequence alignment • Evaluating protein distance matrix • using “Protdist” of PHYILIP (Particularly, Point Accepted Mutation (PAM) matrix is used) • Clustering proteins using “Neighbor” of PHYILIP (Neightboring-Joint method is considered)

  17. Example: n-distance phylogenetic tree • Evaluating n-distance matrix • n-distance method • Clustering proteins using “Neighbor” of PHYILIP (Neightboring-Joint method is considered) • 16S and 18S Ribosomal RNA sequenecs of 35 organisms

  18. Summary • Homology modeling • Tools for structure prediction and comparisons • Tools for phylogenetic tree construction Thanks for your attention!!

  19. Protein distance matrix

  20. Tubulin family tree

  21. n-distance method • Frequency count of “n-letter words” • n-dsiatnce matrix • Advantage: • Identify fully conservative words located at nearly the same sites • Effecient MREIVHIQAGQCGNQIGAKFWEVISDEHGIDPTGSYHGDSDLQLERINVYYNE

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