Biological Information and Biological Databases

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Biological Information and Biological Databases

• Meena K Sakharkar
• Bioinformatics Centre
• National University of Singapore

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Biological Information
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Nature of Life Science Information

• Descriptive
• Classification and Nomenclatural
• Observational and Phenomenological
• Experimental
• Deduced/Computed
• Simulated?
• Theoretical?

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Descriptive
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Classify and Give Names

• Classification and Nomenclature
• Linnaeus - binomial nomenclature
• Group into kingdoms, phyla, classes, orders,
  families, genera, species, subspecies, strains,
  etc
• Associate descriptions to these classification
  schema, and classify according to description etc

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Observational/Phenomenological

• Like descriptive, yet more active
• Observe a lot of biological phenomenon
• Charles Darwin
• Gregor Mendel to McClintock
• Start to do some experiments

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Experimental

• From dissections to complex genetic engineering
  experiments

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BioInformatics

• Deduced/Computed
• Simulated?
• Theoretical?

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What is BioInformatics?

• Many related terms and buzzwords
• A multiplicity of names
• bioinformatics
  
• biocomputing
• biological computing
• computational biology
• computational genomics
• biological data mining

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Overview of the challenges of Molecular Biology
Computing

• The huge dataset problem
• automated DNA sequencers
• the Human Genome Project
• bulk sequencing of cDNAs (ESTs)

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Human Genome Project

• What is the Human Genome Project?
• 15-year effort formally begun in October 1990.
  coordinated by the U.S. Department of Energy and
  the National Institutes of Health.
• identify all the estimated 80,000 genes in human
  DNA,
• determine the sequences of the 3 billion chemical
  bases that make up human DNA,
• store this information in databases,
• develop tools for data analysis, and
• address the ethical, legal, and social issues
  (ELSI) that may arise from the project.

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• Who is head of the U.S. Human Genome Project?
• The DOE Human Genome Program is directed by Ari
  Patrinos, and Francis Collins directs the NIH
  Human Genome Program.
• Ari Patrinos also heads the Department of Energy
  Office of Biological and Environmental Research.
  

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• What are the comparative genome sizes of humans
  and other organisms being studied?

If compiled in books, the data would fill an
estimated 200 volumes the size of a Manhattan
telephone book (at 1000 pages each), and reading
it would require 26 years working around the
clock
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Informatics Data Collection and Interpretation

• HUMAN GENETIC DIVERSITY
• The Ultimate Human Genetic Database
• Any two individuals differ in about 3 x 106 bases
  (0.1).
• The population is now about 5 x 109.
• A catalog of all sequence differences would
  require 15 x 1015 entries.
• This catalog may be needed to find the rarest or
  most complex disease genes.

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Databases
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Basic Terminology

• What is a nucleotide/protein sequence database
  and
• databank?
• Database is a collection of Nucleotide/protein
  sequence and their Associated annotations.
• Databanks
• Groups which collect, compile, maintain and
  distribute the database.

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Fundamental Dogma
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Work from the Code of Life
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Deduced and Computed Information in the Era of
Computational Biology
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Databases

• What are the different kinds of databases and
  their formats?

Nucleic Acid Sequence EMBL at EBI.
GENBANK at NCBI. DDBJ at Japan.
Protein Sequence SWISS PROT NBRF(PIR)
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Database

• Protein structure databases
• PDB
• Information on the structural data for
  the proteins/nucleic acids.
• whose 3-D structure solved by X-ray
  crystallography/NMR
• PDB database
• NRL 3D Database
• NRL_3D is a sequence-structure database.
  
• Can be used in conjunction with PIR.
• PDB with PIR.

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GenBank Entry
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EMBL Entry
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SwissProt Entry
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Other databases

• Genome Databases
• GDB Genome Data Bank
• OMIM
• Pattern Databases
• Prosite
• TFD

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Usage of databases

• Annotation Searches - KW, Authors, Features.
• What is the protein sequence for human insulin?
• How does the 3D structure of calmodulin look
  like?
• What is the genetic location of cystic fibrosis
  gene?
• List all introns in rat?
• Homology Searches
• Is there any protein sequence that is similar to
  mine?
• Is this gene known in any other species?
• Has someone already cloned this sequence?

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Usage of databases

• Pattern searches
• Does my sequence contain any known motif (that
  can give me a clue about the function)?
• Which known sequences contain this motif?
• Is any part of my sequence recoganised by a
  transcription factor?
• List all known start, splice and stop signals in
  my genomic sequence
• Prediction - Use the database as knowledge
  database
• What may the structure of my protein be?
• Secondary structure prediction
• Modeling by homology
• What is the gene structure of my genomic
  sequence?
• Which parts of my protein have a high
  antigenicity?

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Usage of Databases

• Comparisons
• Gene Families
• Phylogenetic Trees

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GenBank Growth Chart
Bases
Year
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Evolutionary basis of Alignment

• Enable the researcher to determine if two
  sequences display sufficient similarity to
  justify the inference of homology.
• Similarity is an observable quantity that may be
  expressed as say identity or some other measure.
• Homology is a conclusion drawn from this data
  that the two genes share a common evolutionary
  history.

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Sequence Formats
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Fasta Format

• gtSANJAY REFORMAT of SANJAY.seq check 8826
  from 1 to 573 March 12, 1998
• MASSSVPPMITEEEARFEAEVSAVESWWRTDRFRLTRRPYSARDVVSLRG
  TLHHSYASDQ
• MAKKLWRTLKSHQSAGTASRTFGALDPVQVTMMAKHLDTIYVSGWQCSST
  HTATNEPGPD
• LADYPYNTVPNKVEHLFFAQLYHDRKQHEARVSMTREQRAKTPYVDYLRP
  IIADGDTGFG
• GATATVKLCKLFVERGAAGVHIEDQSSVTKKCGHMAGKVLVAVSEHINRL
  VAARLQFDVM
• GVETVLVARTDAVAATLIQSNVDLRDHQFILGATNPDFKRRSLAAVLSAA
  MAAGKTGAVL
• QAIEDDWLSRAGLMTFSDAVINGINRQLPEYEKQRRLNEWAAATEYSKCV
  SNEQGREIAE
• RLGAGEIFWDWDIARTREGFYRFRGSVEAAVVRGRAFAPHADLIWMETSS
  PDLVECGKFA
• QGMKASHPEIMLAYNLSPSFNWDAAGMTDEEMRDFIPRIAKMGFCWQFIT
  LGGFHADALV
• TDTFAREFAKQGMLAYVERIQREERNNGVDTLAHQKWSGANYYDRYLKTV
  QGGISSTAAM
• GKGVTEEQFKEESRTGTRGLDRGGITVNAKSRL

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GCG Format

• ckl.seq Length 473 September 15, 1999 1225
  Type P Check 8103 ..
• 1 MSTKYSASAE SASSYRRTFG SGLGSSIFAG
  HGSSGSSGSS RLTSRVYEVT
• 51 KSSASPHFSS HRASGSFGGG SVVRSYAGLG
  EKLDFNLADA INQDFLNTRT
• 101 NEKAELQHLN DRFASYIEKV RFLEQQNSAL
  TVEIERLRGR EPTRIAELYE
• 151 EEMRELRGQV EALTNQRSRV EIERDNLVDD
  LQKLKLRLQE EIHQKEEAEN
• 201 NLSAFRADVD AATLARLDLE RRIEGLHEEI
  AFLRKIHEEE IRELQNQMQE
• 251 SQVQIQMDMS KPDLTAALRD IRLQYEAIAA
  KNISEAEDWY KSKVSDLNQA
• 301 VNKNNEALRE AKQETMQFRH QLQSYTCEID
  SLKGTNESLR RQMSEDGGAA
• 351 GREAGGYQDT IARLEAEIAK MKDEMARHLR
  EYQDLLNVKM ALDVEIATYR
• 401 KLLEGEESRI SLPVQSFSSL SFRESSPEQH
  HHQQQQPQRS SEVHSKKTVL
• 451 IKTIETRDGE VVSESTQHQQ DVM

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Taxonomy Database
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Blast Results
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Examples of the New Biology

• 1. Full genome-genome comparisons
• 2. Rapid assessment of polymorphic genetic
  variations
• 3. Complete construction of orthologous or
  paralogous groups of genes
• 4. Structure determination of large
  macromolecular assemblies/complexes
• 5. Dynamically simulation of realistic oligomeric
  systems
• 6. Rapid structural/topological clustering of
  proteins
• 7. Prediction of unknown molecular structures
  Protein folding
• 8. Computer simulation of membrane structure and
  dynamic function
• 9. Simulation of genetic networks and the
  sensitivity of these pathways to component
  stoichiometry and kinetics
• 10. Integration of observations across scales of
  vastly different dimensions and organization to
  yield realistic environmental models for basic
  biology and societal needs

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Theoretical?

• The day will dawn when we will have sufficient
  information to understand how basic life
  functions are integrated into a living cell, and
  how such cells intercommunicate and interoperate
  to function as a living whole. Then maybe, we can
  start talking about theoretical biology

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Categories of BioDbs - by domain of information

• DNA
• RNA
• Protein
• Genomic Mapping
• Pathways
• Structure
• Bibliographic
• Biochemical/Molecular/Miscellaneous

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Other categories

• By category of species
• By families or superfamilies of molecules
• etc
• Demo
• http//www.infobiogen.fr/services/dbcat/

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Demonstration of BioDatabases

• Majority of Life Science databases are online,
  accessible with Web via Internet
• Catalogs of databases available
• Need for a Registry to keep track and offer
  quality control