Other biological databases
and ontologies
Biological systems
Sequence data
Protein folding and 3D structure
Taxonomic data
Literature
Pathways and networks
Protein families and domains
Small molecules
Whole genome data
Ontologies -GO
Biological systems
Ontologies
• An ontology is a formal specification of terms and
relationships between them –widely used in biology and
boinformatics (e.g. taxonomy)
• The relationships are important and represented as graphs
• Ontology terms should have definitions
• Ontologies are machine-readable
• They are needed for ordering and comparing large data
sets
What’s in a name?
• What is a cell?
What’s in a name?
• What is a cell?
Ambiguities in naming
• The same name can be used to describe different
concepts, e.g:
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Glucose synthesis
Glucose biosynthesis
Glucose formation
Glucose anabolism
Gluconeogenesis
• All refer to the process of making glucose
• Makes it difficult to compare the information
• Solution: use Ontologies and Data Standards
Gene Ontology (GO)
http://www.geneontology.org
• Controlled vocabulary/ontology
• Introduced to provide standardised way of annotating
gene products (http://www.geneontology.org)
• Used for functional annotation of genes or proteins
GO ontologies
• Molecular function:
– tasks performed by gene product –e.g. G-protein coupled
receptor
• Biological process:
– broad biological goals accomplished by one or more gene
products –e.g. G-protein signaling pathway
• Cellular component:
– part(s) of a cell of which a gene product is a component;
includes extracellular environment of cells –e.g nucleus,
membrane etc.
GO term examples
• GO terms arranged
in DAG
• Relationships
between terms
How to annotate to GO
• See if gene product annotated already e.g. by
MOD or GOA
• Manual annotation –need evidence codes
• Blast2GO
• Using GO mapping files (e.g. InterPro, EC,
Swiss-Prot keyword)
Multiple GO
terms
Process mappings:
-Cell communication
(IPR2GO)
-GPCR pathways
(SPKW2GO)
-GPCR pathways (IDA)
Select most manual
first, then most specific
Finding existing GO annotation
• Small-scale –QuickGO or AmiGO browsers
• Large-scale:
– GOA FTP site
• GOA proteomes (>25% coverage)
• GOA human, mouse, rat, cow, zebrafish, Arabidopsis, etc.
• GOA UniProt
– Proteome Analysis
Searching GOA in QuickGO
• http://www.ebi.ac.uk/ego
Uses of GO annotation
Microarray data analysis
GO classification
Larkin JE et al, Physiol Genomics, 2004
Cunliffe HE et al, Cancer Res, 2003
Analysis of high-throughput data
Proteomics data analysis
GO classification
Open Biomedical Ontologies (OBO)
http://obo.sourceforge.net
• Central web location for accessing well-structured
CVs and ontologies for use in the biological and
medical sciences.
• Provides a simple format for ontologies that
encodes terms, relationships between terms and
definitions of terms (Not all OBO ontologies use
this format however).
Scope of OBO
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Anatomy
Animal natural history and life history
Chemical
Development
Ethology
Evidence codes
Experimental conditions
Genomic and proteomic
Metabolomics
OBO relationship types
Phenotype
Taxonomic classification
Vocabularies
Other Biological Databases
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Transcription factor binding sites -TRANSFAC
Protein structure databases- PDB, SCOP, CATH
Protein family databases- Pfam, Prints, PROSITE etc.
Chemicals and small molecules -ChEBI
Gene expression databases –GEO, ArrayExpress
Metabolic pathways - Reactome, KEGG
Genome Databases- Ensembl, FlyBase, WormBase etc.
Transcription factor binding sites
• TRANSFAC –database of eukaryotic transcription
factors: http://www.generegulation.com/pub/databases.html#transfac
• TESS –Transcription Element Search System –for
predicting transcription factor binding sites, uses
TRANSFAC: http://www.cbi.upenn.edu/tess
• TFsearch –for searching transcription factor binding
sites:
http://www.cbrc.jp/research/db/TFSEARCH.html
Protein structure databases
• Main resource is Protein Data Bank (PDB):
http://www.rcsb.org/pdb/
• Repository for solved structures
• Can search by PDB code
• Structural family databases based on PDB –SCOP
(http://scop.mrc-lmb.cam.ac.uk/scop/) and CATH
(http://www.biochem.ucl.ac.uk/bsm/cath/)
• Predicted structures in SWISS-MODEL
(http://swissmodel.expasy.org//SWISSMODEL.html)
Searching MSD
http://www.ebi.ac.uk/msd -Search by PDB code
Link to CATH
Protein family databases
• Databases that produce signatures for identifying
protein families or domains
• Used for functional classification of proteins
• E.g. Pfam, PROSITE, Prints, SMART,
TIGRFAMs etc.
• Integrated into single resource InterPro
(http://www.ebi.ac.uk/interpro)
InterProScan
sequence search
Stand-alone
version available
Results for
protein acc
Example
InterPro
entry
Chemicals and small molecules
• Chemical abstracts- http://www.cas.org/
• ChEBI- http://www.ebi.ac.uk/chebi
• KEGG –part of it includes chemicals
http://www.genome.jp/kegg
• ChemID plus -chemicals cited in NLM databases
http://chem2.sis.nlm.nih.gov/chemidplus/chemi
dlite.jsp
• MSD-Chem –ligands and chemicals in MSD
CheBI example entry
Hierarchy
for
chemicals
Gene expression databases
• NCBI Gene Expression Omnibus (GEO)
http://www.ncbi.nlm.nih.gov/geo/
• ArrayExpress http://www.ncbi.nlm.nih.gov/geo/
• Stanford microarray database http://genomewww5.stanford.edu/
• Can usually search for experiments or particular
expression profiles
GEO
search
page
Profiles search results
Specific
entry and
experiment
info
ArrayExpress
search results
Metabolic Pathways
• PATHGUIDE >200 pathways
• KEGG (Kyoto encyclopedia of genes and genomes):
http://www.genome.jp/kegg -includes:
– Database of chemicals, genes and networks (metabolic,
regulatory etc.)
– Well-curated and quite specific
• EcoCyc (Encyclopedia of E. coli K12 genes and
metabolism): http://ecocyc.org –curation of entries
genome
• Reactome –curated biological pathways:
http://www.reactome.org/
• GenMAPP –pathways contributed by users
Pathway in Reactome
Example of a pathway in BioCyc
Protein-protein interaction databases
• Protein-protein interaction databases store
pairwise interactions or complexes
• IntAct http://www.ebi.ac.uk/intact
• DIP (Database of Interacting Proteins)
http://dip.doe-mbi.ucla.edu/
• BIND (Biomolecular Interaction Network
Database) http://submit.bind.ca:8080/bind/
Protein-protein interactions
Genome browsers
• Integrate sequence & functional data for a genome
• Ensembl –genome browser for major eukaryotic genomes,
e.g. human, mouse etc. http://www.ensembl.org
• UCSC browser -http://genome.ucsc.edu/
• FlyBase –Drosophila genome database:
http://www.ebi.ac.uk/flybase
• WormBase –C. elegans: http://www.wormbase.org
• PlasmoDB –Plasmodium (malaria): http://plasmodb.org
• Etc.
Ensembl genome browser
Ensembl gene view 1
Ensembl
gene view 2
Gene within context on chromosome