Transcript EnsEmbl – Genome Browser - CBS

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”Resources of
Biomolecular Data:
Sequences,
Structures and
Functionality”
PhD course #27803
Nikolaj Blom
Center for Biological Sequence Analysis
BioCentrum-DTU
Technical University of Denmark
[email protected]
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Outline
Magnitudes and Scales
Resources: Data Sources & Tools
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Primary DNA sources
Sequence Repositories
Structure Repositories
Functional Categorization
Integration of Databases
The Human Genome
• Genome Browsers
• Prediction Tools
• Evaluation of Prediction Servers
Starting points
• Link collections
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Resources: Sources & Tools
There is A LOT OF
biomolecular
databases/sources
A LOT OF overlap of
information/redundancy
A LOT OF TOOLS
Personal
picks/preferences
• User-friendliness
• Update intervals
• Curation efforts / error
correction
• Linkage to other DBs
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Faster than Moore’s law...
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Human Genome
Published
HUGO: Nature,
15.feb.2001
Celera: Science,
16.feb.2001
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Magnitudes and Scales
Human genome
3,200,000,000 bp
• Single basepair  full
genome is 9 orders of
magnitude
Genome = Football field:
~3 billion leaves of grass
Single base A T G C (or
SNP) = 1 leaf of grass
Genome browsing
• Zooming from whole
stadium to single leaf
How we got the sequence
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Sanger chain termination method
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Primary DNA sources
Trace files repositories
Single read: 500-1000 bp (~golf ball size / jig saw puzzle)
Variable quality
• WashU-Merck Human EST Project / Trace files
• ”Base-calling” non-trivial
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Assembly is Non-trivial!
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Sequence repositories - GenBank
et al.
GenBank / EMBL / DDBJ
• Highly redundant (many versions of same gene)
• Cross-updated daily
• Version history is recorded
• Previous sequence records can be retrieved
• Contigs/HTGS (100-200 kb) finishing at
different stages
• Draft  Finished
• Includes genomic DNA, cDNA, ESTs, translated
peptides
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Non-redundant and Curated
databases
Non-redundant
• Manual or automatic curation
• DNA
• RefSeq (NCBI; semi-automated)
• Ensembl gene index (automated)
• Protein
• RefSeq (NCBI; semi-automated)
• TrEMBL (EMBL; automated)
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Curated database: UniProt/SwissProt
SIB - Swiss Institute of
Bioinformatics
Protein Knowledgebase /
Sequence Database
• Highly curated
• Experimental evidence
evaluated (e.g. modifications)
• All 80,000 entries checked by
Amos Bairoch himself ;-)
ExPASy - Expert Protein
Analysis System
• Proteomics tools: links + local
servers
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Structure databases / Protein Data
Bank (PDB)
X-ray , NMR biomolecular
structures
Protein Data Bank (PDB)
>22,000 structures
(April 2003)
http://www.rcsb.org/pdb/
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Functional Categorization
Gene Ontology
(GO)
• Hierarchical
• Controlled
vocabulary
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Functional Categorization
Gene Ontology (GO)
http://www.geneontology.org/
• Molecular Function - the tasks performed by
individual gene products; examples are
transcription factor and DNA helicase
• Biological Process - broad biological goals, such
as mitosis or purine metabolism, that are
accomplished by ordered assemblies of
molecular functions
• Cellular Component - subcellular structures,
locations, and macromolecular complexes;
examples include nucleus, telomere, and origin
recognition complex
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Integration of databases - Webs of websites
Links, links,
links...
SRS = Sequence
Retrieval
System
• Powerful,
complex query
language
BioDAS –
Distributed
Annotation
System
http://srs.ebi.ac.uk/
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For ’my gene’, how do I:
Get an overview of the sequence
information known? (GeneCards)
Examine the ’Genome Neighbourhood’?
(Genome Browsers)
Predict protein post-translational
modifications (PTMs)? (Prediction servers)
• (Evaluate the value of predicted features)
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GeneCards
http://nciarray.nci.nih.gov/cards/
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GeneCards-II
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GeneCards-III
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GeneCards-IV
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GeneCards-V
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Genetic/Medical Information
OMIM, Online Mendelian Inheritance in
Man (NCBI)
• The OMIM database is a catalog of human genes
and genetic disorders
• >13,000 entries (April, 2002)
• Examples: cystic fibrosis, prions, amyloid
precursor protein
• Condensed, highly curated descriptions of
genetics/disease/animal models/references
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OMIM-I
(http://www3.ncbi.nlm.nih.gov/Omim/)
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OMIM-II
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OMIM-III
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For ’my gene’, how do I:
Get an overview of the sequence
information known? (GeneCards)
Examine the ’Genome Neighbourhood’?
(Genome Browsers)
Predict protein post-translational
modifications (PTMs)? (Prediction servers)
• (Evaluate the value of predicted features)
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Genome Browsing
Three public
• Open access
• Use same genome build/assembly
• NCBI (U.S.)
• UCSC (Santa Cruz, U.S.)
• EnsEmbl (EBI, EU)
One private
• Restricted, commercial
• Academic, free usage: 1 Mbase/week
• Proprietary assembly
• Celera Genomics (U.S.)
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Celera Human/Mouse Genomes
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Genome Browsers
- Portals to the Genomic World
NCBI – National Center for Biotechnology
Information (U.S.)
• http://www.ncbi.nlm.nih.gov/Genomes/index.
html
UCSC – Univ. California – Santa Cruz (U.S.)
• http://genome.ucsc.edu/
EnsEmbl – European Molecular Biology
Laboratory (E.U.)
• http://www.ensembl.org/
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NCBI
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NCBI
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UCSC – Genome Browser
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UCSC – Genome Browser II
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EnsEmbl – Genome Browser
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EnsEmbl – Genome Browser
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EnsEmbl – Genome Browser
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EnsEmbl – Genome Browser
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EnsEmbl – Genome Browser
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EnsEmbl – Genome Browser
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For ’my gene’, how do I:
Get an overview of the sequence
information known? (GeneCards)
Examine the ’Genome Neighbourhood’?
(Genome Browsers)
Predict protein post-translational
modifications (PTMs) or Gene Structure?
(Prediction servers)
• ...and evaluate the reliability of prediction
methods
CBS Services/Toolbox
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http://www.cbs.dtu.dk/services/
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NetPhos – a prediction server
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http://www.cbs.dtu.dk/services/NetPhos/
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NetPhos – a prediction server
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Evaluating Prediction Servers
Performance on independent/crossvalidated data presented?
Published in peer-reviewed journal?
Cited by others?
• Science Citation Index
Linked to from credible web sites?
• Google Page-rank
• ”link:URL” search
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Evaluating Prediction Servers
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2can Bioinformatics Education
At EBI – European
Bioinformatics Institute
http://www.ebi.ac.uk/2
can/index.html
Tutorials, resource
links, etc.
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Starting Points
General Bioinformatics
• NCBI, National Center for Biotechnology
Information, U.S.
• EBI, European Bioinformatics Institute
Prediction Tools
• CBS, DK
• Expasy (Protein analysis), Switzerland
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Dynamic Resources
Pros
• Includes most recent developments
• Updated regularly
• User interface improves(usually)
Cons
• Difficult to keep pace
• Tutorials and lectures hard to recycle ;-(
• Difficult to use at irregular intervals
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Genome Browsers
- Portals to the Genomic World
Three main entry points:
• NCBI, UCSC, EnsEmbl
• Essentially contain same information
• High degree of linking to secondary databases
• Advisable to become familiar with only one genome
browser
• Learn to navigate and make queries
GeneCards and OMIM
• well suited for getting a quick overview of a
gene of interest
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Prediction Servers
Evaluate scientific ’soundness’
• Look for indications of quality (citations, etc.)
Remember that prediction servers
provide...well, predictions!
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The End