Bio-Trac 25 (Proteomics: Principles and Methods)

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Tutorial Bioinformatics Resources

(http//pir.georgetown.edu/pirwww/workshop/bioinfo
_resource.html)

• Bio-Trac 25 (Proteomics Principles and Methods)
• October 5, 2007
• Zhang-Zhi Hu, M.D.
• Research Associate Professor
• Protein Information Resource, Department of
• Biochemistry and Molecular Cellular Biology
• Georgetown University Medical Center

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What is Bioinformatics?
computer mouse bioinformatics
(information) (biology)

• NIH Biomedical Information Science and Technology
  Initiative (BISTI) Working Definition (2000) -
  Research, development, or application of
  computational tools and approaches for expanding
  the use of biological, medical, behavioral or
  health data, including those to acquire, store,
  organize, archive, analyze, or visualize such
  data.

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Molecular Biology Database Collection
(http//nar.oxfordjournals.org/cgi/content/full/35
/suppl_1/D3/DC1)
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Database Collection in Nucleic Acids Res.
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2007
Online Access to Database Collection
http//pir.georgetown.edu/pirwww/workshop/2005_dat
abase_update.html
http//www.oxfordjournals.org/nar/database/cap/
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Overview
Database Contents, Search and Retrieval

1. Text search / Information retrieval
2. Sequence genomics databases
3. Protein family databases
4. Database of protein functions
5. Databases of protein structures
6. Proteomics databases

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Entrez Text Searches
(http//www.ncbi.nlm.nih.gov/Entrez/)
Lab
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PubMed Literature Database
(http//www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD
SearchDBPubMed)
Lab
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iProLINK Protein Literature Mining Resource
Text mining for protein phosphorylation
Gene/protein name thesaurus synonyms, ambiguous
names
http//pir.georgetown.edu/iprolink/
Lab
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BioThesaurus Gene/protein name searches -
synonyms, ambiguous names
Synonyms CRYAA crystallin, alpha A CRYA1 HSPB4
http//pir.georgetown.edu/iprolink/biothesaurus
Lab
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RLIMS-P Text mining for protein phosphorylation
http//pir.georgetown.edu/iprolink/rlimsp/
Lab
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UniProt Text Search
(http//www.pir.uniprot.org/cgi-bin/textSearch)
Google type search vs. Boolean searches AND,
OR, NOT
Lab
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PIR Text Search (I)
(http//pir.georgetown.edu/pirwww/search/textsearc
h.html)
Search alpha crystallin A chain that are in
protein families?
Search for synonyms
Lab
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PIR Text Search (II)
Search what crystallins are enzymes and what
families they belong to?
Can you find which crystallins have 3D structure
determined?
Lab
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I. Sequence Genomics Databases

• GenBank An annotated collection of all publicly
  available nucleotide and protein sequences.
• RefSeq NCBI non-redundant set of reference
  sequences, including genomic DNA, transcript
  (RNA), and protein products
• UniProt Consortium Database Universal protein
  resource, a central repository of protein
  sequence and function.
• Entrez Gene Gene-centered information at NCBI.
• UniGene Unified clusters of ESTs and full-length
  mRNA sequences .
• OMIM Online Mendelian inheritance in man a
  catalog of human genetic and genomic disorders.
• Model Organism Genome Databases MGD, RGD, SGD,
  Flybase
• GeneCards Integrated database of human genes,
  maps, proteins and diseases.
• SNP Consortium Database International HapMap
  Project Genes associated with human disease

(http//www.oxfordjournals.org/nar/database/cap/)
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UniProt Consortium Databases
Universal Protein Resource
http//beta.uniprot.org/
(http//www.uniprot.org)
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UniProt Sequence Report (I)
UniProtKB
Whats the difference between CRYAA_RABIT
CYRBAA?
(http//www.pir.uniprot.org/cgi-bin/unipEntry?idC
RYAA_RABIT)
Lab
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UniProt Report (II) UniRef100 90
UniRef100
(http//www.pir.uniprot.org/cgi-bin/unipEntry?idU
niRef100_P02489)
UniRef90
(http//www.pir.uniprot.org/cgi-bin/unipEntry?idU
niRef90_P02489)
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Entrez Gene Gene centric information
http//www.ncbi.nlm.nih.gov/entrez/query.fcgi?dbg
enecmdRetrievedoptGraphicslist_uids12954ubo
r0_RefSeq
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OMIM Online Mendelian inheritance in man
(http//www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?i
d123580)
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II. Protein Family Databases

• Whole Proteins
• PIRSF Network Classification Based on
  Evolutionary Relationship of Whole Protein
• COG (Clusters of Orthologous Groups) of Complete
  Genomes
• PANTHER Proteins Classified into
  Families/Subfamilies of Shared Function
• ProtoNet Automated Hierarchical Classification
  of Proteins
• Protein Domains
• Pfam Alignments and HMM Models of Protein
  Domains
• SMART Protein Domain Families
• CDD Conserved Domain Database
• Protein Motifs
• PROSITE Protein Patterns and Profiles
• BLOCKS Protein Sequence Motifs and Alignments
• PRINTS Compendium of Protein Fingerprints (a
  group of conserved motifs)
• Integrated Family Databases
• InterPro Integrate Pfam, PRINTS, PROSITES,
  ProDom, SMART, PIRSF, SuperFamily

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Protein Clustering
Initial version
COGs (http//www.ncbi.nlm.nih.gov/COG/)
New version Includes Eukaryotic Clusters - KOGs
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PIRSF Full Length Classification iProClass
Family Report
Lab
(http//pir.georgetown.edu/cgi-bin/ipcSF?idSF0022
80)
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Domain Classification Pfam Domain
(http//www.sanger.ac.uk/cgi-bin/Pfam/swisspfamget
.pl?nameCRYAA_RABIT)
(http//pir.georgetown.edu/cgi-bin/ipcEntry?idP02
493)
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Pfam Domain
(http//www.sanger.ac.uk/cgi-bin/Pfam/getacc?PF005
25)
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Protein Motifs PROSITE A database of protein
families and domains. It consists of biologically
significant sites, patterns and profiles.
(http//us.expasy.org/prosite/)
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Integrated Family Classification

• InterPro
• An integrated resource unifying PROSITE, PRINTS,
  ProDom, Pfam, SMART, and TIGRFAMs, PIRSF.
  (http//www.ebi.ac.uk/interpro/search.html)

Mapping of families
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III. Databases of Protein Functions

• Metabolic Pathways, Enzymes, and Compounds
• Enzyme Classification Classification and
  Nomenclature of Enzyme-Catalysed Reactions
  (EC-IUBMB)
• KEGG (Kyoto Encyclopedia of Genes and Genomes)
  Metabolic Pathways
• LIGAND (at KEGG) Chemical Compounds, Reactions
  and Enzymes
• EcoCyc Encyclopedia of E. coli Genes and
  Metabolism
• MetaCyc Metabolic Encyclopedia (Metabolic
  Pathways)
• BRENDA Enzyme Database
• UM-BBD Microbial Biocatalytic Reactions and
  Biodegradation Pathways
• Inter-Molecular interactions and Regulatory
  Pathways
• IntAct Protein interaction data from literature
  and user submission
• BIND Descriptions of interactions, molecular
  complexes and pathways
• DIP Catalogs experimentally determined
  interactions between proteins
• Reactome - A curated knowledgebase of biological
  pathways
• BioCarta Biological pathways of human and mouse
• GO Gene Ontology Consortium Database
• Pathway Resources - Pathguide

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Biological Pathway Resource Collection
http//www.pathguide.org/

• Protein-protein interactions
• Metabolic pathways
• Signaling pathways
• Pathway diagrams
• Transcription factors / gene regulatory networks
• Protein-compound interactions
• Genetic interaction networks

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KEGG Metabolic Regulatory Pathways
Lab

• KEGG is a suite of databases and associated
  software, integrating our current knowledge
• on molecular interaction networks, the
  information of genes and proteins, and of
  chemical
• compounds and reactions. (http//www.genome.ad.
  jp/kegg/kegg2.html)

(http//www.genome.ad.jp/dbget-bin/show_pathway?hs
a002204.3.2.1)
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BioCyc EcoCyc/MetaCyc Metabolic Pathways

• The BioCyc Knowledge Library is a collection of
  Pathway/Genome Databases (http//biocyc.org/)

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BioCarta Cellular Pathways
(http//www.biocarta.com/index.asp)
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Reactome http//www.reactome.org/

• Collaboration of CSHL, EBI and GO Consortium
• Curated resource of core pathways and reactions
  in human biology
• Authored by biological researchers of field
  experts
• Cross-referenced with NCBI, Ensembl and UniProt,
  HapMap, KEGG
• Inferred orthologous events in 22 non-human
  species (mouse, rat)

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Transforming Growth Factor (TGF) beta signaling
Homo sapiens
(http//reactome.org/cgi-bin/eventbrowser?DBgk_cu
rrentFOCUS_SPECIESHomo20sapiensID170834)
Reactome events and objects (including modified
forms and complex)
Event -gtREACT_6879.1 Activated type I receptor
phosphorylates R-SMAD directly Homo sapiens
Object -gt REACT_7364.1 Phospho-R-SMAD
cytosol Event -gt REACT_6760.1 Phospho-R-SMAD
forms a complex with CO-SMAD Homo
sapiens Object -gt REACT_7344.1
Phospho-R-SMADCO-SMAD complex cytosol Event -gt
REACT_6726.1 The phospho-R-SMADCO-SMAD
transfers to the nucleus Object -gt REACT_7382.2
Phospho-R-SMADCO-SMAD complex nucleoplasm
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Protein-Protein Interaction Database - IntAct
(http//www.ebi.ac.uk/intact/)
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Gene Ontology (GO)
(http//www.geneontology.org/)
- Molecular Function - Biological Process -
Cellular Component
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IV. Databases of Protein Structures

• Protein Structure
• PDB Structure Determined by X-ray
  Crystallography and NMR
• PDBsum Summaries and analyses of PDB structures
• MMDB NCBIs database of 3D structures, part of
  NCBI Entrez
• SWISS-MODEL Repository Database of annotated
  protein 3D models
• ModBase Annotated comparative protein structure
  models
• Structure Classification
• CATH Hierarchical Classification of Protein
  Domain Structures
• SCOP Familial and Structural Protein
  Relationships
• FSSP Protein Fold Classification Based on
  Structure--Structure Alignment

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PDB Experimental 3D Structure Repository
Rat gamma-crystallin (chain A, B.)
Can you do a text search at PIR to find this
(CRGE_RAT)?
(http//www.rcsb.org/pdb/)
Lab
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PDBsum
Pictorial Database to Provide Summary and
Analysis to PDB Entries
Search
3-D structure summary
2-D structure
(http//www.ebi.ac.uk/thornton-srv/databases/pdbsu
m/)
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Protein Structural Classification (1)
CATH Hierarchical domain classification of
protein structures (http//www.cathdb.info/latest/
index.html)
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Protein Structural Classification (2)
SCOP comprehensive description of structural
and evolutionary relationships between all
proteins whose structure is known.
(http//scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.ht
ml)
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SWISS-MODEL Repository
A database of annotated three-dimensional
comparative protein structure models
(http//swissmodel.expasy.org/repository/smr.php?s
ptr_acCRGE_RATjob2)
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VI. Proteomic Resources

• GELBANK (http//gelbank.anl.gov) 2D-gel patterns
  of species with completed genomes.
• SWISS-2DPAGE (http//www.expasy.org/ch2d/) index
  of 2D-gels
• PEP (http//cubic.bioc.columbia.edu/ pep/)
  Predictions for Entire Proteomes summarized
  analyses of protein sequences
• Integr8 (http//www.ebi.ac.uk/integr8/) A
  browser for information relating to completed
  genomes and proteomes, based on data contained in
  Genome Reviews and the UniProt proteome sets
• PRIDE (http//www.ebi.ac.uk/pride/) PRoteomics
  IDEntifications database Expression Profiling
  databases
• GPMdb (http//gpmdb.thegpm.org/) Mass Spec
  Proteomics Databases

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2D-Gel Image Databases
Lab
(http//us.expasy.org/ch2d/)
Part of WORLD-2DPAGE index to 2-D PAGE databases
and services
(http//us.expasy.org/swiss-2dpage/acP02489)
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GPMdb MS Data Search
(http//gpmdb.thegpm.org/)
Craig, et al., J Proteome Res. 2004, 31234-42.
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PRIDE centralized, standards compliant, public
data repository for proteomics data
http//www.ebi.ac.uk/pride/
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Lab

• Text search / Information retrieval
• Literature search and text mining
• Finding synonyms (BioThesaurus)
• Information extraction (e.g., protein
  phosphorylation sites)
• Find the sequence for the rabbit alpha crystallin
  A chain
• Find all alpha crystallin A chain classified in
  protein families
• Search crystallins that have active enzyme
  activities
• Find crystallins that have determined 3D
  structures
• Database contents (reports)
• Sequence genomics databases (UniProt)
• Protein family databases (PIRSF)
• Database of protein functions (KEGG)
• Databases of protein structures (PDB)
• Proteomics databases (Swiss-2D)

• Protein Examples
• Rabbit alpha crystallin A (UniProtKB
  CRYAA_RABIT/P02493)
• Delta crystallin II (Argininosuccinate lyase)
  (UniProtKB ARLY2_ANAPL/P24058)
• Any additional proteins of your interest for
  search and retrieval