Essential Bioinformatics and Biocomputing LSM2104: Section I Biological Databases and Bioinformatics

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Essential Bioinformatics and Biocomputing
(LSM2104 Section I) Biological Databases
andBioinformatics SoftwareProf. Chen Yu
ZongTel 6874-6877Email csccyz_at_nus.edu.sghttp
//xin.cz3.nus.edu.sgRoom 07-24, level 7, SOC1,
NUSJanuary 2003
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Lecture 5 Bioinformatics software

• Outline
• Types of bioinformatics software
• Sequence, pattern and domain
• Evolutionary analysis
• Visualization
• Modeling and prediction (sequence, structure and
  function)
• Data mining (bibliographic and text searches)
• Examples

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Types of Bioinformatics software

• Analysis of biological data/systems and
  characterization of molecules and sequences.
• Analysis and interpretation of experimental
  results
• Simulation of laboratory experiments, important
  for tackling large scale problems
• Predictions that lead to the design of
  experiments
• Bioinformatics software can be accessed via WWW,
  or through integrated software packages (such as
  Emboss, GCG, Staden, DNAstar, ). It may be
  coupled with databases, or may stand alone.

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Bioinformatics software

• Major sources
• Software package at ExPASy Molecular Biology
  Server http//www.expasy.org
  http//au.expasy.org
• Software at PBIL Bio-Informatique Lyonnais
  http//pbil.univ-lyon1.fr/
• Toolbox at EBI European Bioinformatics Institute
  http//www.ebi.ac.uk/Tools/index.html

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Bioinformatics software

• Major types of bioinformatics tools
• Sequence analysis tools
• Sequence comparison
• Pattern and domain search
• Evolutionary analysis
• Prediction of sequence structure and function
• Visualization of molecular structures
• Structure modeling
• Bibliographic and text searches
• Specialized and other tools

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Bioinformatics software

• Sequence analysis tools
• This kind of software focuses on extraction and
• comparison of properties in DNA and protein
  sequences
• Sequence analysis provides for identification of
  domains, structure, and function, and other
  properties
• The analysis of individual sequences helps with
  sequence comparison
• Textbook chapter 5, pages 81-93

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Bioinformatics software

• Sequence analysis tools
• This kind of software focuses on extraction and
• comparison of DNA and protein sequence
• properties such as
• composition of nucleotide or protein sequences
• codon usage in DNA
• translation and backtranslation
• Textbook chapter 5, pages 81-93

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Bioinformatics software

• Composition of nucleotide or protein sequences
• Composition (frequency of occurrence of a
  nucleotide or of an amino acid) is the most basic
  analysis. It can give us important functional and
  structural clues.
• For example, CG-rich regions called CpG islands
  are often found in promoters. A short region just
  before the splice site at the end of introns
  often has high CT content.

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Bioinformatics software

• Composition of protein and DNA sequences
• Web
• NPS_at_ Network Protein Sequence _at_nalysis
  http//npsa-pbil.ibcp.fr/ (Amino-acid
  composition)
• AA Composition http//molbiol.soton.ac.uk/compute/
  aacomp.html
• JEMBOSS (in our own laboratory)
• http//srs1.bic.nus.edu.sg/jnlp/ (nucleic,
  composition, compseq)

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Bioinformatics software
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Bioinformatics software
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Bioinformatics software

• Codon usage in DNA
• Web
• Count-codon program in Codon Usage Database
  http//www.kazusa.or.jp/codon/countcodon.html
  (needs start and stop codons at the start and the
  end of the sequence)
• Tool for Gene to Codon Usage Table
  http//www.entelechon.com/eng/genetocut.html
• (does not care about start and stop codons)
• JEMBOSS (in the laboratory)
• http//srs1.bic.nus.edu.sg/jnlp/ (nucleic, codon
  usage, cusp)
• DNA coding region should have only one stop codon

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Bioinformatics software
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Bioinformatics software
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Bioinformatics software

• Translation (DNA to protein) and back translation
  
• (protein to DNA)
• Web
• Translate tool at ExPASy http//au.expasy.org/tool
  s/dna.html (DNA to protein)
• JEMBOSS (in the laboratory)
• http//srs1.bic.nus.edu.sg/jnlp/ (DNA to protein
  and reverse)
• (nucleic, translation, transeq nucleic,
  translation, backtranseq)
• If we translate and back translate the same
  sequence we will typically
• not get the same sequence as the starting one.

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Bioinformatics Software

• Sequence comparison (the most important software)
  
• This will be taught next month by A/P Tan Tin
  Wee.
• Web
• Local alignment (BLAST, FASTA)
• http//www.ebi.ac.uk/fasta33/
• http//www.ncbi.nlm.nih.gov/BLAST/
• http//www.ebi.ac.uk/blast2/
• Multiple alignment (Clustal W)
• http//www.ebi.ac.uk/clustalw/index.html
• JEMBOSS (in the laboratory)
• http//srs1.bic.nus.edu.sg/jnlp/
• Local alignment Smith-Waterman (alignment,
  local, water)
• Global alignment Needleman-Wunsh (alignment,
  global, needle)

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Bioinformatics software

• Evolutionary analysis
• Multiple sequence alignments can be used as
  measures of evolutionary distance between
  proteins. The phylogeny systems are used to
  represent evolutionary distances between
  sequences.
• WebPhylip
• http//sdmc.krdl.org.sg8080/lxzhang/phylip/
• GeneBee
• http//www.genebee.msu.su/services/phtree_reduced.
  html
• Read textbook, page 83.

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Bioinformatics software
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Bioinformatics software

• Prediction of sequence structure and function
• Sequences that have similar structure often have
  similar function. For many sequences we can
  extract secondary and tertiary structure from the
  PDB database.
• What if our sequence is not in the PDB? We can
  predict structure of a biological sequence using
  appropriate software.
• There are several programs for prediction of
  secondary structure. For prediction of tertiary
  structure we can do modelling.
• http//npsa-pbil.ibcp.fr (PHD method for
  secondary structure prediction)

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Bioinformatics software

• Secondary structure prediction

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Bioinformatics software

• Secondary structure prediction
• The PHD program predicted four alpha helices in
  the human IL-2 (red). The number of helices is
  correct, but their lengths and boundaries are not
  correct (purple).
• When we make a prediction in bioinformatics, we
  must have an idea about the accuracy of
  prediction programs.
• To assess the accuracy of a program, we can test
  it with known data. Our test must have sufficient
  examples, so that we can make reasonable
  conclusions.

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Secondary structure prediction Bioinformatics
software

• alpha Lactalbumin PDB 1A4V
• http//npsa-pbil.ibcp.fr/cgi-bin/npsa_automat.pl?p
  age/NPSA/npsa_server.html

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Bioinformatics software

• We used nine different programs for prediction of
  secondary structure of alphaLactalbumin (PDB
  1A4V).
• The results show that the best predictions for
  this molecule were from Predator, while DSC was
  the laggard.
• This test does not mean that Predator is the best
  of the tested programs, nor that DSC is the
  worst. To make such conclusions we must make test
  set first. The test set should contain the
  examples from the family of proteins that our
  query protein belongs to.
• The learning point none of the prediction
  programs (and this applies across all
  bioinformatics software, not only secondary
  structure prediction) is 100 accurate. The users
  must be cautious when interpreting results from
  the predictive software.

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Bioinformatics software

• Common measure (other measures also exist)
• Sensitivity SETP/(TPFN)
• Specificity SPTN/(TNFP)
• For example, prediction of binding peptides to a
  particular receptor
• Experimental Predicted
  Class
• Example 1 Binder Binder
  True positive (TP)
• Example 2 Non-binder Non-binder
  True negative (TN)
• Example 3 Binder Non-binder
  False negative (FN)
• Example 4 Non-binder Binder
  False positive (FP)
• Prediction system that has SE0.8 and SP0.9 will
  correctly predict 8 of 10 experimental positives,
  and for each 10 experimental negatives it will
  make one false prediction. This prediction
  accuracy may be very good for prediction of
  peptide binding, but is not very good for some
  other predictions, for example gene prediction.

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Bioinformatics software

• Prediction of 3-D structure
• Various modelling programs
• comparative modelling, using known structures as
  templates
• ab initio modelling, using atomic simulation,
  residue statistics, etc.
• These methods will be covered later in the course
• An example of the comparative modelling software
  is SWISS-MODEL http//www.expasy.org/swissmod/SWIS
  S-MODEL.html
• This model is provided by email.
• This tool has the facility for assessing the
  quality of predictions

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Bioinformatics software
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Bioinformatics software
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Bioinformatics software
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Bioinformatics software

• Software for visualisation of 3-D structures.
  Provides different views to 3-D molecular
  structure, which will be taught by A/P Shoba.
• Chime, Rasmol (they use files in PDB format)
• Scorpion database uses Chime. Chime can be
  downloaded from http//www.mdli.com/downloads/dow
  nloads.html?uidkeyid1

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Bioinformatics software
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Bioinformatics software
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Bioinformatics software

• Text searches
• Text searching software is used associated with
  databases. Most commonly we search by keywords or
  combinations of keywords.
• Examples of PubMed searches
• Diabetes 181,672
  matches
• Diabetes AND IDDM 35,841
• Diabetes AND IDDM AND autoimmunity 1,109
• Diabetes OR autoimmunity 190,674
• DiabetesTitle/Abstract 114,624
• The last example is more advanced PubMed option
  preview/index

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Bioinformatics software Summary of Todays
lecture

• Why bioinformatics software?
• Types of software sequence, motif, evolution,
  visualization, structural modeling, simulation,
  test search.
• Examples of selected software
• Sequence composition
• DNA-protein sequence translation
• Evolutionary analysis
• Protein secondary structure prediction
• Comparative modeling
• Text search
• To be taught later Sequence comparison,
  visualization etc.

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Summary of the SectionBiological databases and
bioinformatics software

• We first focused on biological databases. We
  covered topics
• discussed types of biological databases
• briefly described popular databases
• structure of the GenBank and SWISS-PROT entries
• searching biological databases
• types of questions that can be answered by
  searching databases
• completeness and errors in the databases

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Summary of the SectionBiological databases and
bioinformatics software

• The second topic was bioinformatics software. We
  covered
• why do we need bioinformatics software?
• briefly described major types of bioinformatics
  software
• described software for sequence composition,
  codon usage, translation and backtranslation
• introduced the concept of sequence alignment,
  evolutionary analysis
• secondary and tertiary structure prediction,
  molecular visualization
• accuracy of prediction software
• text searching