Tutorial: Bioinformatics Resources

Presentation Transcript

(http://pir.georgetown.edu/pirwww/workshop/bioinfo_resource.html)

Bio-Trac 25 (Proteomics: Principles and Methods)

March 23, 2007

Zhang-Zhi Hu, M.D.

Research Associate Professor

Protein Information Resource, Department of

Biochemistry and Molecular & Cellular Biology

Georgetown University Medical Center

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 visualizesuch data.

--968 key databases of 14 categories

Molecular Biology Database Collection

(http://nar.oxfordjournals.org/cgi/content/full/35/suppl_1/D3/DC1)

Database Collection in Nucleic Acids Res.

2007

Online Access to Database Collection

http://pir.georgetown.edu/pirwww/workshop/2005_database_update.html

http://www.oxfordjournals.org/nar/database/cap/

Overview

Database Contents, Search and Retrieval

Text search / Information retrieval
Sequence & genomics databases
Protein family databases
Database of protein functions
Databases of protein structures
Proteomics databases

Entrez Text Searches

(http://www.ncbi.nlm.nih.gov/Entrez/)

PubMed Literature Database

(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=Search&DB=PubMed)

Literature mining

iProLINK: Protein Literature Mining Resource

Text mining for protein phosphorylation

Gene/protein name thesaurus: synonyms, ambiguous names…

http://pir.georgetown.edu/iprolink/

BioThesaurus:Gene/protein name searches - synonyms, ambiguous names…

Synonyms:

CRYAA

crystallin, alpha A

CRYA1

HSPB4…

http://pir.georgetown.edu/iprolink/biothesaurus

RLIMS-P: Text mining for protein phosphorylation

http://pir.georgetown.edu/iprolink/rlimsp/

UniProt Text Search

(http://www.pir.uniprot.org/cgi-bin/textSearch)

Googletype search vs.

Booleansearches: AND, OR, NOT

PIR Text Search (I)

(http://pir.georgetown.edu/pirwww/search/textsearch.html)

Search: alpha crystallin A chain that are in protein families?

Search for synonyms

PIR Text Search (II)

Search: what crystallins are enzymes and what families they belong to?

Can you find which crystallins have 3D structure determined?

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
UniProtConsortium 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 HapMapProject: Genes associated with human disease

(http://www.oxfordjournals.org/nar/database/cap/)

4.1 million

UniProt Consortium Databases

Universal Protein Resource

(http://www.uniprot.org)

UniProtKB UniRef UniParc

UniProt Sequence Report (I)

UniProtKB

What’s the difference between CRYAA_RABIT & CYRBAA?

(http://www.pir.uniprot.org/cgi-bin/unipEntry?id=CRYAA_RABIT)

UniProt Report (II): UniRef100 & 90

UniRef100

(http://www.pir.uniprot.org/cgi-bin/unipEntry?id=UniRef100_P02489)

UniRef90

(http://www.pir.uniprot.org/cgi-bin/unipEntry?id=UniRef90_P02489)

Entrez Gene – Gene centric information

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=12954#ubor0_RefSeq

OMIM:Online Mendelian inheritance in man

(http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=123580)

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…

Protein Clustering

Initial version

COGs:(http://www.ncbi.nlm.nih.gov/COG/)

New version: Includes Eukaryotic Clusters - KOGs

PIRSF: Full Length ClassificationiProClass Family Report

(http://pir.georgetown.edu/cgi-bin/ipcSF?id=SF002280)

Domain Classification – Pfam Domain

(http://www.sanger.ac.uk/cgi-bin/Pfam/swisspfamget.pl?name=CRYAA_RABIT)

(http://pir.georgetown.edu/cgi-bin/ipcEntry?id=P02493)

Pfam Domain

(http://www.sanger.ac.uk/cgi-bin/Pfam/getacc?PF00525)

Protein Motifs: PROSITE –A database of protein families and domains. It consists of biologically significant sites, patterns and profiles.

(http://us.expasy.org/prosite/)

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

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

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

KEGG Metabolic & Regulatory Pathways

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?hsa00220+4.3.2.1)

BioCyc: EcoCyc/MetaCyc Metabolic Pathways

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

BioCarta Cellular Pathways

(http://www.biocarta.com/index.asp)

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…)

Transforming Growth Factor (TGF) beta signaling [Homo sapiens]

(http://reactome.org/cgi-bin/eventbrowser?DB=gk_current&FOCUS_SPECIES=Homo%20sapiens&ID=170834&)

Reactome: events and objects (including modified forms and complex)

Event ->REACT_6879.1: Activated type I receptor phosphorylates R-SMAD directly [Homo sapiens]

Object -> REACT_7364.1: Phospho-R-SMAD [cytosol]

Event -> REACT_6760.1: Phospho-R-SMAD forms a complex with CO-SMAD [Homo sapiens]

Object -> REACT_7344.1: Phospho-R-SMAD:CO-SMAD complex [cytosol]

Event -> REACT_6726.1: The phospho-R-SMAD:CO-SMAD transfers to the nucleus

Object -> REACT_7382.2: Phospho-R-SMAD:CO-SMAD complex [nucleoplasm] ……

Protein-Protein Interaction Database - IntAct

(http://www.ebi.ac.uk/intact/)

Gene Ontology (GO)

(http://www.geneontology.org/)

- Molecular Function

- Biological Process

- Cellular Component

IV. Databases of Protein Structures

Protein Structure

PDB: Structure Determined by X-ray Crystallography and NMR
PDBsum: Summaries and analyses of PDB structures
MMDB: NCBI’s 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

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/)

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/pdbsum/)

Protein Structural Classification (1)

CATH: Hierarchical domain classification of protein structures (http://www.cathdb.info/latest/index.html)

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.html)

SWISS-MODEL Repository

A database of annotated three-dimensional comparative protein structure models(http://swissmodel.expasy.org/repository/smr.php?sptr_ac=CRGE_RAT&job=2)

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