Bioinformatic Databases

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Bioinformatic Databases

• Microbiology 343
• David Wishart
• david.wishart_at_ualberta.ca

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Objectives Outline

• The biological data explosion appreciating
  the size scope
• Different types of database knowing which
  database is right for the given job
• The web is your friend (on-line DBs)
• EcoCyc, PDB, Bind, BacMap, etc.
• Using PubMed

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The U of A Library

• 10.02 million total holdings
• 4.81 million books journals
• 3.69 million microfilms
• 1.39 million maps
• 39,141 journal subs
• 8,000 PhD dissertations
• 12 library bldngs
• 2 Terabytes of data

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The Library of Congress

• 120 million items in storage
• 54 million manuscripts
• 18 million books
• 12 million photographs
• 4.5 million maps
• 4.4 million technical reports
• 1.1 million PhD dissertations
• 20 Terabytes of data

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Some Numbers

• 3 scientific journals in 1750
• 120,000 scientific journals today
• 500,000 medical articles/year
• 4,000,000 scientific articles/year
• 14,000,000 abstracts in PubMed derived from 4600
  journals
• 10 billion web pages on Google
• 800,000,000,000,000 bytes on the Web

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Some Numbers

• A researcher would have to scan 130 different
  journals and read 27 papers per day to follow a
  single disease, such as breast cancer.
• Baasiri, R.A., Glasser, S.R., Steffen, D.L.
  Wheeler, D.A. Oncogene 18, 7958-7965 (1999)

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Some Graphs
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A Tidal Wave of Data
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Different Databases in Bioinformatics

• Sequence Databases
• SNP/mutation DBs
• Structure Databases
• Expression Databases
• Spectral Databases
• Metabolism Databases
• Drug Databases

• Cell/Strain Databases
• Organism Databases
• Interaction Databases
• Function/Ontology DBs
• Bibliographic DBs
• Disease Databases
• Databases of Databases

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Why So Many Databases?

• To collect and preserve valuable data
• To make data accessible and easily searched
• To standardize data representation or data
  formats
• To organize data into knowledge

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Different Types of Databases

• Public (web-accessible, downloadable)
• Local or Private (restricted to registered users
  or not web-accessible)
• Archival (anything goes)
• Curated (managed data submission)
• Specialty databases (special interest)
• General databases (wide interest)

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Where To Go For More Info?
Nucleic Acids Research Web Server Issue (every
Jan.)
http//nar.oupjournals.org/
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Sequence Databases

• GenBank
• www.ncbi.nlm.nih.gov/
• EMBL/trEMBL/UniProt
• www.ebi.ac.uk/trembl/
• DDBJ
• www.nig.ac.jp/
• PIR
• http//pir.georgetown.edu/
• SwissProt
• www.expasy.ch/sprot/

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Sequence Databases

• Some specialize in DNA sequence data (GenBank,
  DDBJ)
• Some specialize in protein sequence data (PIR,
  Swiss-Prot, UniProt)
• Some are specific for organisms or classes of
  organisms (yeast, fruitflies, human, certain
  bacteria)

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Sequence Annotation

• Most sequence databases usually include more
  information than just the raw sequence data
• This additional information is called
  annotation and it may be done either
  automatically or manually
• Annotations include information about
  gene/protein name, length, position, references,
  corrections, etc

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Different Levels of Annotation

• Sparse typical of most archival DNA sequence
  databases (GenBank, DDBJ)
• Moderate typical of more curated databases or
  protein-specific databases (PIR, trEMBL)
• Detailed typical of organism-specific databases
  or databases with a very high level of curation
  (Swiss-Prot, EcoCyc, BacMap)

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Different Levels of Database Annotation

• GenBank (large of sequences, minimal
  annotation)
• PIR (large of sequences, slightly better
  annotation)
• SwissProt (small of sequences, even better
  annotation)
• Organsim-specific DB (very small of sequences,
  best annotation)

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GenBank Annotation
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Swiss-Prot Annotation
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Organism-specific Databases

• Flybase
• http//flybase.harvard.edu/
• ENSEMBL (human)
• http//www.ensembl.org/
• CYGD (yeast)
• http//www.mips.biochem.mpg.de/proj/yeast/
• BacMap (all bacteria)
• http//wishart.biology.ualberta.ca/BacMap/
• EcoCyc (E. coli)
• http//ecocyc.org

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The EcoCyc Database
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The EcoCyc Database

• EcoCyc is a scientific database for the bacterium
  E. coli K12 MG1655
• The EcoCyc project assembles its data via
  literature-based curation of the entire genome
  along with information on transcriptional
  regulation, transporters, and metabolic pathways
• Actively developed since 1999

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The EcoCyc Database

• Users may query the database for E. coli
  sequences, pathways, genes, reactions, compounds,
  metabolic charts and gene expression data
• Supports sequence searches and interactive
  visualization of key genomic and proteomic
  features

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The EcoCyc Database

• EcoCyc supports the visualization of
• gene layouts within the E. coli chromosome
• individual biochemical reactions
• a complete biochemical pathway (with compound
  structures
• Users may display an enzyme, the reaction that
  the enzyme catalyzes, or the gene that encodes
  the enzyme

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EcoCyc Statistics
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Structure Databases

• RCSB-PDB
• http//www.rcsb.org/pdb/
• MSD
• http//www.ebi.ac.uk/msd/index.html
• CATH
• www.biochem.ucl.ac.uk/bsm/cath/
• SCOP
• www.scop.mrc-lmb.cam.ac.uk/scop/

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Sequences vs. Structures
200000
160000
120000
Sequences
Structures
80000
40000
0
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Protein DataBank (PDB)
http//www.rcsb.org/pdb/Welcome.do
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Looking at E. coli Trx (2trx)
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Homework

• Explore the PDB, click on some of the links, try
  the visualization tools
• Use the advanced search mode to find out how many
  proteins have been solved by NMR that have
  between 200 and 350 residues
• Find out how many structures are similar (lt3 Angs
  RMSD) to 2trx

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Metabolism Databases

• KEGG
• http//www.genome.ad.jp/kegg/metabolism.html
• Roche/Boeringer
• http//www.expasy.org/cgi-bin/search-biochem-index
  
• EcoCyc
• http//ecocyc.org/
• WIT
• http//wit.mcs.anl.gov/WIT2/

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Interaction Databases

• BIND
• http//www.bind.ca/
• DIP
• http//dip.doe-mbi.ucla.edu/
• PIM
• http//www.hybrigenics.fr/
• PathCalling
• http//portal.curagen.com/extpc/com.curagen.portal
  .servlet.Yeast

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Bibliographic Databases

• PubMed Medline
• http//www.ncbi.nlm.nih.gov/PubMed/
• Science Citation Index
• http//isi4.isiknowledge.com/portal.cgi
• Your Local eLibrary
• www.XXXX.ca
• Current Contents
• http//www.isinet.com/isi/

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Bibliographic Databases

• Research paper from author X
• Sequence from gene X in organism Y
• All information about organelle W in model
  organism Y
• All information about disease X caused by microbe
  Z
• Orthologs of disease gene Y in other model
  organisms

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Where to go? PubMed
http//www.ncbi.nlm.nih.gov/PubMed/
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PubMed

• Allows users to search by journal, key words,
  titles etc.
• Uses MeSH (Medical SubHeadings) to allow
  automated search of synonyms (renal transplant
  kidney transplantation)
• API available to query PubMed automatically and
  remotely
• Few users know how to use PubMed properly or to
  its full extent

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ouellette bf au AND yeast
Details
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MeSH Medical Subject Heading
("ouellette bf"au AND (("yeasts"MeSH Terms OR
"saccharomyces cerevisiae"MeSH Terms) OR
yeastText Word))
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Integrated Text/Sequence Searching with Entrez
Wishart DS au AND coli
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Results
Click Here!
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PubMed Icons
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Results
Click Here!
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How Do You Search Sequence Databases?

• Most kinds of non-biological databases are
  designed to be searched using exact matches of
  dates, keywords or numbers
• Sequence databases are different in that we only
  want to or only can query them with approximate
  or inexact matches this is a challenging
  problem
• Next Lecture Sequence Searching

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Sample Exam Question

• Which database(s) would you use to find out about
  E. colis pyruvate synthase
• A) structure
• B) reactions
• C) interacting partners
• D) enzymology
• E) sequence variations