Bioinformatics

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Bioinformatics

• Richard Tseng and Ishawar Hosamani

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Outline

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

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Structural Analysis

• Overview
• Structure prediction
• Structural alignment
• Similarity

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• 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

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• 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)

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• 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/)

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• 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/
  

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• 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/

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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)

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• 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
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• OPTICS
• Rationle Partition observations based on the
  density of similar objects
• Exercise

http//www.dbs.informatik.uni-muenchen.de/Forschun
g/KDD/Clustering/OPTICS/Demo/
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• Example Folding of Trp-cage peptide

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Phylogenetic analysis

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

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

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• Software
• Collections of tools
• http//evolution.genetics.washington.edu/phylip/so
  ftware.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.htm
  l
• Matlab - bioinformatics tool box

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• 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)

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• 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

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Summary

• Homology modeling
• Tools for structure prediction and comparisons
• Tools for phylogenetic tree construction

Thanks for your attention!!
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• Protein distance matrix

1Z5V_A 3CB2_A 1JFF_B 1FFX_B 1TUB_B 1Z2B_B
1Z5V_A 0 0.000010 1.349411 1.349411 1.303115 1.345634
3CB2_A 0.000010 0 1.350506 1.350506 1.303115 1.346730
1JFF_B 1.349411 1.350506 0 0.000010 0.000010 0.010729
1FFX_B 1.349411 1.350506 0.000010 0 0.000010 0.010729
1TUB_B 1.303115 1.303115 0.000010 0.000010 0 0.006725
1Z2B_B 1.345634 1.346730 0.010729 0.010729 0.006725 0
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• Tubulin family tree

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• n-distance method
• Frequency count of n-letter words
• n-dsiatnce matrix
• Advantage
• Identify fully conservative words located at
  nearly the same sites
• Effecient

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YNE
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