Other biological databases and ontologies
Jan 09, 2016
Other biological databases and ontologies
Biological systems
Taxonomic data
Literature
Protein folding and 3D structure
Small molecules
Pathways and networks
Biological systems
Protein families and domains
Whole genome data
Sequence data
Ontologies -GO
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 is a cell?
What’s in a name?
What’s in a name?
• What is a cell?
Ambiguities in naming• The same name can be used to describe different
concepts, e.g:– 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
Microarray data analysis
Proteomics data analysis
Larkin JE et al, Physiol Genomics, 2004
Cunliffe HE et al, Cancer Res, 2003
GO classification
GO classification
Analysis of high-throughput data
Uses of GO annotation
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• 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
• 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.gene-regulation.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//SWISS-MODEL.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/chemidlite.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://genome-www5.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