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