Computational Microbiology

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Computational Microbiology

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

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Objectives

• Definition of computational microbiology
• Raise awareness of new kinds of database
  resources for learning about the molecular
  aspects of microbes
• Discussion of CCDB, BacMap, Basys and other tools
  (MIPS, CMR)

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What is Computational Microbiology?

• Microbiology on a laptop
• Using computers databases to aid in
  microbiological research and discovery
• Includes computational biology, bioinformatics,
  systems biology and biological simulation
• An (indispensable) adjunct to basic microbiology
  and key to microbial genomics, proteomics
  metabolomics

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The CCDB
http//redpoll.pharmacy.ualberta.ca/CCDB Or just
type CCDB and coli on Google
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The CCDB

• Assembled using a combination of both manual and
  automatic annotation methods
• Covers DNA, RNA, proteins, metabolites
• Uses many of the tools (sequence alignment,
  protein property prediction) weve already seen
  to help infer name, function, structure and other
  properties
• Builds from other databases on E. coli

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E. coli Alliance
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The CyberCell Database (CCDB)

• Most complete, current, quantitative collection
  of molecular data on E. coli
• Web accessible, Web browsable, self-updating
• Supports many kinds of query, viewing and
  browsing options
• Structured using ColiCards as in the GeneCards
  database
• Informatic foundation for coordinating
  integrating data collected for Project CyberCell

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CCDB ColiCard
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ColiCard Contents

• Functional info (predicted or known)
• Sequence information (sites, modifications, pI,
  MW, cleavage)
• Location information (in chromosome cell)
• Interacting partners (known predicted)
• Structure (2o, 3o, 4o, predicted)
• Enzymatic rate and binding constants
• Abundance, copy number, concentration
• Links to other sites viewing tools
• Integrated version of all major Dbs
• 70 fields for each entry

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CCDB Annotation
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CCDB Annotation
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Searching Capabilities

• Text search, BLAST search, SQL search
• Show all membrane proteins that are essential
  and have more than 6 membrane spanning regions
• Chemical Structure search
• Find all metabolites similar to this prospective
  drug structure

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How To Use CCDB

• Click on the Search button and type the name of
  your favorite E. coli protein
• Explore whats known about it by clicking on the
  corresponding links
• Learn about E. colis molecular details by
  clicking on Stats or E. coli in the menu bar
  at the top
• Key is to explore and click links not
  everything on E. coli is in CCDB proper

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BacMap

• Picking up where we left off with the CCDB
  (Google bacmap)
• Idea is to generate a visual atlas of all (not
  just Escherichia coli) bacterial chromosomes and
  plasmids but with links to extensive genome
  annotation
• Attempt to re-use annotation and graphing tools
  originally developed for the CCDB

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BacMap
http//wishart.biology.ualberta.ca/BacMap/
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BacMap
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Text Search Tools
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Sequence Search Tools
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Bacterial Biography Card
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Genome Statistics
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Proteome Statistics
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BacMap

• Each genome has a short description of the
  organism and sequence data
• Supports zoomable, hyperlinked, clickable map
  views of the genome
• Supports text search of gene names, protein names
  and synonyms
• Supports BLAST search and supplies genome-wide
  stats

Stothard P, et al. BacMap an interactive picture
atlas of annotated bacterial genomes. Nucleic
Acids Res. 2005 Jan 133 Database IssueD317-20.
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When To Use BacMap?

• Any time you need to find molecular biological
  information about a bacterium (DNA, RNA or
  protein)
• Any time you need to find general information
  about a bacterium
• Does not provide same detailed information as
  CCDB and does not support the advanced querying
  found in CCDB (no metabolic information)

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What if Your Organism or Genome isnt in BacMap?
http//wishart.biology.ualberta.ca/basys/
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BASys

• Bacterial Annotation System
• A publicly available web server that performs
  automated annotation of bacterial genomes given
  only the gene sequence of a chromosome or plasmid
• Takes about 24 hrs for an average genome (4
  megabases)
• Output includes images and annotation text (about
  70 fields for each gene)

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BASys

• Reads either a genome sequence (finds genes using
  Glimmer, performs translation) or a proteome
  sequence (multi-FASTA format)
• Performs BLAST search against CCDB to see if it
  can transfer annotations from this database first
• Performs BLAST search against SwissProt to see if
  it can transfer annotations from this DB second

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BASys

• For all remaining proteins and all remaining
  fields (MW, pI, structure, etc.) BASys calls on
  various internal prediction programs to predict
  or calculate these values
• A BASys text card is generated and a series of
  maps are prepared and posted on the website.
  Source and reliability of annotations is also
  provided

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Typical BASys Result
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BASys Output
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Other Microbial Resources
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MIPS (Munich Information Centre for Protein
Sequence)
http//mips.gsf.de/
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Programs Used By Pedant

• HMMER
• PSORT
• PREDATOR
• COILS
• FGENESH
• pI
• PROSEARCH
• TargetP

• SAPS
• NCBI-BLAST
• SEG
• InterProScan
• SignalP
• TMHMM
• tRNAscan-SE
• GENSCAN

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Databases Used By Pedant

• EMBL
• PIR-PSD
• SWISS-PROT
• Functional Cat
• PROSITE
• TrEMBL

• Blocks
• PDB
• SCOP
• COGs
• Pfam
• STRIDE

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Navigating in PEDANT
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TIGR CMR
http//www.tigr.org/tigr-scripts/CMR2/CMRHomePage.
spl
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The CMR

• A database and searching system that allows
  researchers to access all of the bacterial genome
  sequences completed to date
• Two kinds of annotation are displayed the
  Primary annotation taken from the genome
  sequencing center and the TIGR annotation
  generated by an automated annotation process at
  TIGR

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The CMR Genome Page
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CMR Page for A. pernix
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CMR Annotation
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Conclusion

• Content in these microbial resources is
  equivalent to an encyclopedia that is 8000 pages
  long just about that microbe alone
• Far more visual and far more detailed than what
  you can get in textbooks
• Still not quite as thorough as a well written
  book --- but were getting there!