Tutorial: Bioinformatics Resources (http://pir. georgetown Bio-Trac 25 (Proteomics: Principles and Methods) March 25, 2005 Zhang-Zhi Hu, M.D. Senior Bioinformatics Scientist Protein Information Resource National Biomedical Research Foundation, GUMC

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.

Molecular Biology Database Collection (http://nar. oupjournals -- 719 key databases of 14 categories

Database Collection in Nucleic Acids Res.

http://pir.georgetown.edu/~huz/class/2005_database_update.html

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

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

PIR Text Search (I) (http://pir.georgetown.edu/pirwww/search/textsearch.html) What’s different between CRAA_RABIT & CYRBAA? How about Search: Crystallin and SuperFamily?

PIR Text Search (II) Can you find which crystallin that has 3D structure determined using PIR text search?

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 knowledgebase, a central resource of protein sequence and function from Swiss-Prot, TrEMBL and PIR. 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

UniProt Consortium Database UniProtKB (knowledgebase) UniRef (100,90,50) UniParc (archive) (http://www.uniprot.org)

UniProt Sequence Report (I) (http://www.pir.uniprot.org/cgi-bin/unipEntry?id=CRAA_RABIT)

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

Entrez Gene 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: A Network Classification System of Protein Families COG (Clusters of Orthologous Groups) of Complete Genomes 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: Protein Sequence Motifs and Signatures Integrated Family Databases iProClass: Superfamilies/Families, Domains, Motifs, Rich Links InterPro: Integrate Pfam, PRINTS, PROSITES, ProDom, SMART, PIRSF, SuperFamily

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

KOGs: Eukaryotic Clusters (http://www.ncbi.nlm.nih.gov/COG/new/shokog.cgi?KOG3591)

Domain Classification (http://www.sanger.ac.uk/cgi-bin/Pfam/swisspfamget.pl?name=CRAA_RABIT) (http://pir.georgetown.edu/cgi-bin/ipcEntry?id=CRAA_RABIT)

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

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

PIRSF: Full Length Classification iProClass Family Report (http://pir.georgetown.edu/cgi-bin/ipcSF?id=SF002280)

Protein Motifs PROSITE is a database of protein families and domains. It consists of biologically significant sites, patterns and profiles. (http://us.expasy.org/prosite/)

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) WIT: Functional Curation and Metabolic Models BRENDA: Enzyme Database UM-BBD: Microbial Biocatalytic Reactions and Biodegradation Pathways Cellular Regulation and Gene Networks EpoDB: Genes Expressed during Human Erythropoiesis BIND: Descriptions of interactions, molecular complexes and pathways DIP: Catalogs experimentally determined interactions between proteins BioCarta: Biological pathways of human and mouse GO: Gene Ontology Consortium Database MetaCyc is a metabolic-pathway database. The database describes pathways, reactions, and enzymes of a variety of organisms, with a microbial focus.

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)

Protein-Protein Interaction: BIND (http://www.bind.ca/)

Gene Ontology (http://www.geneontology.org/) Three GOs: Molecular Function Biological Process Cellular Component

IV. Databases of Protein Structures 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 3D Structure Rat gamma-crystallin, chain A, B. Can you do a text search at PIR to find this? (http://www.rcsb.org/pdb/)

PDBsum: Summary and Analysis (http://www.biochem.ucl.ac.uk/bsm/pdbsum)

Protein Structural Classification (1) CATH: Hierarchical domain classification of protein structures (http://www.biochem. ucl.ac.uk/bsm/cath_new/)

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 from completed genomes; SWISS-2DPAGE (http://www.expasy.org/ch2d/) PEP: Predictions for Entire Proteomes: (http://cubic.bioc.columbia.edu/ pep/): Summarized analyses of protein sequences Proteome BioKnowledge Library: (http://www.proteome.com): Detailed information on human, mouse and rat proteomes Proteome Analysis Database (http://www.ebi.ac.uk/proteome/): Online application of InterPro and CluSTr for the functional classification of proteins in whole genomes Expression Profiling databases: GNF (http://expression.gnf.org/cgi-bin/index.cgi, human and mouse transcriptome), SMD (http://genome-www5.stanford.edu/MicroArray/SMD/, Stanford microarray data analysis), EBI Microarray Informatics (http://www.ebi.ac.uk/microarray/ index.html , managing, storing and analyzing microarray data)

2D-Gel Image Databases (1) (http://us.expasy.org/ch2d/2d-index.html) (http://us.expasy.org/cgi-bin/nice2dpage.pl?P02489)

2D-Gel Image Databases (2) (http://gelbank.anl.gov/2dgels/index.asp)

Expression Profiling (http://genome-www.stanford.edu/serum/) Human and Mouse Transcriptome (http://genome-www.stanford.edu/serum/) (http://expression.gnf.org/cgi-bin/index.cgi) (http://expression.gnf.org/cgi-bin/index.cgi/)

Lab: Choose additional protein IDs to browse the variety of molecular biology databases each sequence report links to. Delta crystallin II (Argininosuccinate lyase) (UniProt: CRD2_ANAPL) Alpha crystallin (UniProt: CRAA_RABIT)