An Automated System for An Automated System for Deep Proteome AnnotationDeep Proteome Annotation

Gary Van DomselaarSeptember 27, 2003

The ProblemThe Problem

• Most existing biological databases have a narrow biological aspect.– PDB: biomolecular coordinate data– Ensembl: human gene predictions– GO: Genome Ontology (process, function, location)

• Each has a custom interface• Each can answer questions in its own domain

but cannot answer question that span multiple domain boundaries. ‘Which human gene products located in the

endoplasmic reticulum have experimental coordinate data?’

The Solution: Integrated Biological The Solution: Integrated Biological Databases.Databases.

3 main approaches:1. Link Integration. Researchers begin their

query with one data source, then follow hypertext links to related information in other data sources. Example: DAS, NCBI link out.

2. View Integration. A ‘super interface’ is created that makes the source databases appear as one. Example: Kleisli.

3. Data Warehousing. All the data is brought under one roof. Example: Genecards, GeneMine, Cybercell database.

An Automated Proteome An Automated Proteome Annotation System for Proteome Annotation System for Proteome

AnalystAnalyst

• Proteome Analyst provides annotations in the form of a ‘PA Card’

An Automated Proteome An Automated Proteome Annotation System for Proteome Annotation System for Proteome

AnalystAnalyst

An Automated Proteome An Automated Proteome Annotation System for Proteome Annotation System for Proteome

AnalystAnalyst

• Proteome Analyst provides annotations in the form of a ‘PA Card’

• This system will provide a much fuller set of annotations

AnnotationsAnnotations• 2D_Gel_Image• Accession_No.• Alternate_Names• Availability• Centisome Position• Cofactors• Copy Number• Cys/Met_Content• EC_Number• Entry_ID• Following_Gene• Gene_Name• Gene_Ontology• Gene_Position• General_Function• General_Reaction• Gene_Sequence

• Quaternary_Structure• Resolution• Riley_Cell_Function• Riley_Gene_Function• RNA_Copy_No.• Secondary_Structure• Sequence• Similarity• Specific_Activity• Specific_Function• Specific_Reaction• Structure_CLASS• Substrates• SWISS_PROT_(AC_&_ID)• Theoretical_pI• Transmembrane• Upstream_100_bases

• Homologues• Important_Sites• Inhibitor• Interacting_Partners• Kcat_Value_[1/min]• Km_Value_[mM]• Location• Metabolic_Importance• Metals_Ions• Molecular_Weight• No._of_Amino_Acids• Other_Databases• Paralogues• Pfam_Domain/Function• Preceding_Gene• Products

• PROSITE_Motif

Concept Concept Genomic Sequence Data

Concept Concept Genomic Sequence Data

Genomic data analysis must be tailored to the major kingdoms:

•viruses

•prokaryotes

•Eukaryotes - Genscan

} Glimmer

Genomic Sequence Data

Concept Concept Genomic Sequence Data

Proteomic Sequence Data

Gene Identification

and Translation

Concept Concept Genomic Sequence Data

Proteomic Sequence Data Processing

Gene Identification

and Translation

Concept Concept Genomic Sequence Data

Proteomic Sequence Data Processing

Gene Identification

and Translation

Internal Processing

Concept Concept Genomic Sequence Data

Proteomic Sequence Data Processing

Gene Identification

and Translation

Internal Processing

Concept Concept Genomic Sequence Data

Proteomic Sequence Data Processing

Gene Identification

and Translation

•Secondary Structure

•Homology Modeling

•Mol. Wt

•pI

•Etc.

Internal Processing

Concept Concept Genomic Sequence Data

Proteomic Sequence Data Processing

Internal Processing

Gene Identification

and Translation

Internal DBs

Concept Concept Genomic Sequence Data

Proteomic Sequence Data Processing

Internal Processing

Gene Identification

and Translation

•CCDB: a deeply annotated database for E. coli.

•CCDB++ other deeply annotated model organisms from each kingdom

SWISS-PROT

PDB

Internal DBs

Cybercell (CCDB)Cybercell (CCDB)

• A comprehensive collection of detailed enzymatic, biological, chemical, genetic, and molecular biological data about E. coli (strain K12, MG1655).

Concept Concept

External DBs

Genomic Sequence Data

Proteomic Sequence Data Processing

External Processing

Internal Processing

Internal DBsGene Identification

and Translation

Data SourcesData Sources

• GenBank • SwissProt • Prosite • pI/MW Tool • Geneiz • PIR PEC/Shigen • Echobase • Wisconsin • ExpressDB • GeneOntology • GenProtEC • EcoGene • PsiPred

• EcoCyc • PDB • CATH • Swiss2D PAGE • SwissModel • BRENDA • TargetDB • Rosetta • PsortB • KEGG • Chemfinder • Babel

Concept Concept

External DBs

Genomic Sequence Data

Proteomic Sequence Data Processing

External Processing

Internal Processing

Internal DBs

Annotated Proteomic Sequence Data

Gene Identification

and Translation

Concept Concept

External DBs

Genomic Sequence Data

Proteomic Sequence Data Processing

External Processing

Internal Processing

Internal DBs

Annotated Proteomic Sequence Data

Viewing and Mining Software

Gene Identification

and Translation

Concept Concept

External DBs

Genomic Sequence Data

Proteomic Sequence Data Processing

External Processing

Internal Processing

Internal DBs

Annotated Proteomic Sequence Data

Viewing and Mining Software

Gene Identification

and Translation

Proteome

Analyst

Multiple

Protein

Extraction and

Report

System

Data Mining and VisualizationData Mining and Visualization

Data Mining and VisualizationData Mining and Visualization

Concept Concept

External DBs

Genomic Sequence Data

Proteomic Sequence Data Processing

External Processing

Internal Processing

Internal DBs

Annotated Proteomic Sequence Data

Viewing and Mining Software

Gene Identification

and Translation

Discoveries

ProgressProgress

• Curently working on H. Influenzae reference genome.

• Written modules for generating protein sequence data from gene predictions (using glimmer).

• Currently writing the analysis modules and automation scripts.

ProgressProgress

AcknowledgmentsAcknowledgments

P.I.sDavid WishartDwayne SzaffronPaul LuRussel Greiner

CyberCell DatabaseShan Sundararaj An Chi GuoBahram Habibi Nazhad

Proteome AnalystAlona FysheDavid MeeuwisRoman Eisner Brett PoulinZhiyong LuJohn AnvikCam Macdonnel

An Automated System for An Automated System for Deep Proteome AnnotationDeep Proteome Annotation

Gary Van DomselaarSeptember 27, 2003