MOLECULAR BIOLOGY DATABASES. Juan Carlos Sánchez Ferrero

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1 MOLECULAR BIOLOGY DATABASES Juan Carlos Sánchez Ferrero Centro Nacional de Biotecnología, CSIC July 2008

2 GROWING NUMBER OF DATA Molecular biology data explosion in the omics era: genome sequencing, high-throughput proteomics, structural genomics, functional genomics Protein structures (PDB) Nucleotide sequences (GenBank) Year Bioinformatics: to uncover relevant biological information hidden in the huge amount of biological data All that information (primary data and derived data) is stored in databases

3 Ouellette, 2000

4 PRIMARY BIOLOGICAL DATA SOURCES Genome sequencing projects: genome sequences Functional genomics: gene expression data Proteomics: protein catalogues, postranslational modifications Structural genomics: protein structures Functional interactions between cellular components: gene regulatory networks Physical interactions between proteins: protein interaction networks Diverse experimental data: non structured information=>publications

5 GROWING NUMBER OF DATABASES The number of molecular biology databases is also highly increasing Because of huge data amount and new types of biological data (less) Due to database specialization (most), e.g. by taxonomic group

6 Environmental genome shotgun sequencing of the Sargasso Sea. Venter et al. Science March billion nucleotides 1.2 million new genes 782 new rhodopsin like photoreceptors 1800 genomic species

7 HOW TO ACCESS DATABASES Databases are organized: As flat files with all the information in a single text file As relational databases (based on MySQL, Oracle, etc) Users can: Query a database through a web form and get the information on the screen (HTML) or download it as text (e.g. sequences) and other formats such as XML. Download all or the most relevant information of a database as text or XML

8 CLASSIFICATION OF MOLECULAR BIOLOGY DATABASES First classification scheme: Classification scheme based on the source of the database content (core data): Primary DBs: the content consists of experimentally obtained data Secondary DBs: the content is the result of analyses of data in primary DBs

9 CONTENT OF PRIMARY DATABASES Experimentally derived information: Nucleic acid sequences: complete genomes, cloned genome fragments, cdnas, ESTs, SNPs, small RNAs Protein or nucleic acid structures: atomic coordinates obtained by NMR and X-ray crystallography Transcript or protein expression data: obtained in microarray experiments and by proteomic approaches, respectively Cellular processes, such as experimentally determined metabolic or regulatory pathways

10 CONTENT OF SECONDARY DATABASES Predictions or interpretations based on information contained in primary databases Protein sequences, deduced from nucleotide sequences Alignments of protein or nucleic acid sequences Protein families, inferred by sequence similarity or by the presence of common motifs or domains Protein families, inferred by structural similarity Reconstructed (predicted) cellular processes, such as metabolic pathways

11 CLASSIFICATION OF MOLECULAR BIOLOGY DATABASES Second classification scheme: Follows the well known layout to describe the levels of organization of protein structures. Primary DBs: the content consists of SEQUENCES (primary structure of nucleic acids or proteins). Secondary DBs: the content consists of PATTERNS (regions of local regularity, for example, conserved motifs or domains). Structure DBs: the content consists of sets of ATOMIC COORDINATES (three-dimensional packing of secondary structure elements). This scheme applies only to biological molecules (for example, a database of results from micro-array expression experiments would not fit).

12 DATABASE CONTENT & ANNOTATIONS Additional information complementing the DB content information Annotations can refer to: Authorship of the entry Experimental conditions Source of the biological material Sub-cellular location Molecular function or cellular process Bibliographic references Cross-references: entry attributes that make reference to related entries in other databases. Some annotations consist of information of secondary type, since they are predictions, and some of them have been transferred from other databases

13 DATABASE SEARCHES: QUERY TYPES TEXT QUERIES These type of fixed form queries are searches performed against the ANNOTATIONS, which, almost by definition, consist of texts. It is usual to allow the combination of words with Boolean operators (and, or, not) the use of wild cards (*), and also, to specify the search field, for example: ponb and ayala* [AUTH] would result in a search with the word ponb, in any field, combined with a search of the word ayala* in the author field.

14 DATABASE SEARCHES: QUERY TYPES QUERIES by CONTENT This type of fixed form query refers to searches performed against the CONTENT or CORE DATA, which, almost by definition, consists in abstract representations: Strings of characters that represent nucleotide or protein sequences. Tables of atomic coordinates that represent three dimensional objects Bitmap files that represent 2D gel images.

15 DATABASE SEARCHES: QUERY TYPES QUERIES by CONTENT For example, in the case of a sequence database, we may be asking: Does a sequence exactly like: LLLIHRLH or similar to it, exists in the database? Because biological sequences change along time, or between individuals, this type of search is not a matter of finding exact matches in strings of characters. On the contrary, it must consider the principles of molecular evolution. A number of algorithms have been developed to cope with that task, and BLAST is the most popular.

16 NUCLEOTIDE DATABASES International collaboration among main three nucleotide sequence databases: NCBI GenBank, EMBL Nucleotide Sequence Database and DNA Data Bank of Japan (DDBJ) Every sequence that is cited in a publication must be submitted to one of these databases and made publicly available Submissions from individual laboratories and batch submissions from large-scale sequencing projects Daily exchange of information between databases

17 NUCLEOTIDE DATABASES GenBank Maintained at the National Center for Biotechnology Information (NCBI) More than 61 million nucleotide sequences from ~240,000 organisms Diverse sources: expressed sequence tag (EST), high throughput genomic (HTG), environmental sample (ENV), whole genome shotgun (WGS),... Features with biological significance such as coding regions and their translations, transcription units, repeat regions, and sites of mutations Complete bimonthly releases and daily updates Accessible through Entrez (NCBI's search and retrieval system) and FTP RefSeq: comprehensive, integrated, non-redundant set of sequences including genomic DNA, transcripts and proteins

18 NUCLEOTIDE DATABASES EMBL Nucleotide Sequence Database Maintained at the European Bioinformatics Institute (EBI) 80.5 million entries from ~260,000 organisms (as of Sept. 2006) Entry types include standard (STD), constructed (CON), third party annotation (TPA), whole genome shotgun (WGS), annotated constructed (ANN) and mass genome annotation library (MGA) Complete releases every three months Accessible through the EBI Sequence Retrieval System (SRS), other web services and FTP

19 GENOME DATABASES Ensembl Ensembl, EBI: mostly vertebrates Entrez Genome, NCBI: eukaryotes, prokaryotes and viruses UCSC Genome Browser: mostly animals The Institute for Genomics Research: bacteria, fungi, parasites, plants

20 GENOME DATABASES Ensembl Joint project between EMBL-EBI and the Sanger Institute Comprehensive source of annotation of (mostly) chordate genome sequences Automated annotation system of genes from unannotated species Currently 37 genomes (Feb. 2008) Features include: Chromosome maps Contig views Gene predictions Annotations Gene structures (exons-introns) Regulatory regions SNPs mrnas Peptides Comparative genomics and evolutionary trees Hubbard et al. (2007) Nucl. Acids Res. 35:D610-D617

21 GENOME DATABASES Entrez Genome Includes complete chromosomes, organelles and plasmids as well as draft genome assemblies Chromosome views, contig maps, sequence maps (NCBI Map Viewer) Integrated with Entrez Nucleotide and Entrez protein Entrez Genome Project: 22 eukaryotic and 646 prokaryotic complete genomes (Feb. 2008)

22 GENOME DATABASES OTHER SPECIALIZED DATABASES Rat Genome Database: laboratory rat, Rattus norvegicus VectorBase: invertebrate vectors of human pathogens (e.g. Anopheles) FlyBase: genus Drosophila BeetleBase: genus Tribolium WormBase: C. elegans and C. briggsae PlasmoDB: Plasmodium falciparum TAIR: Arabidopsis thaliana Candida Genome Database: Candida albicans Saccharomyces Genome Database, CYGD: Saccharomyces cerevisiae EcoCyc: Escherichia coli PBRC: family Poxviridae

23 GENE-CENTERED DATABASES Complete information about a gene: from genomic location to protein function Integrated with NCBI Entrez, contains genes from multiple genomes Only human genes, maintained by the Weizmann Institute of Science

24 GENE-CENTERED DATABASES Genomic context Transcripts and links to Entrez Nucleotide Proteins and links to Entrez Protein Functional information extracted from Pubmed Protein interactions Gene Ontology terms

25 PROTEIN DATABASES Non-redundant data from SwissProt, PIR, PDB, and translations of all coding sequences present in the EMBL/GenBank/DDBJ Sources: protein databases including SwissProt, PIR, PRF, PDB, and translations from annotated coding regions in GenBank and RefSeq

26 PROTEIN DATABASES Consortium by the European Bioinformatics Institute (EBI), the Protein Information Resource (PIR) and the Swiss Institute of Bioinformatics (SIB) The world's most comprehensive catalog of information on protein

27 PROTEIN DATABASES UniProtKB/Swiss-Prot Manually curated protein sequences from all organisms Functional information with bibliographic references Domains and sites Secondary and tertiary structures Posttranslational modifications 356,194 entries in UniProtKB/Swiss-Prot (Feb. 2008)

28 PROTEIN DATABASES UniProtKB/TrEMBL Translations of all coding sequences present in the EMBL/GenBank/DDBJ Automatic annotation and classification Proteins that get manually annotated go to UniProtKB/Swiss-Prot 5,395,414 entries in UniProtKB/TrEMBL (Feb. 2008)

29 STRUCTURE DATABASES Protein Data Bank RCSB PDB (USA), MSD-EBI (Europe), PDBj (Japan) and BMRB (USA) To maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available Protein and nucleic acid structures X-ray crystallography, NMR and electron microscopy More than structures (Feb 2008)

30 STRUCTURE DATABASES Protein structure classification databases Structural Classification of Proteins Folds, superfamilies and families of structural domains Classified by manual inspection Currently more than 34,000 PDB structures (Feb 2008) Hierarchical classification of protein domain structures Class(C), Architecture(A), Topology(T) and Homologous(H) superfamily Combination of automated and manual procedures More than 30,000 classified PDB structures (Feb 2008)

31 PROTEIN DOMAINS DATABASES Protein domains Elements that usually fold independently of the rest of the protein chain They often play an important role in the biological function of the protein Domains defined with sequence patterns and profiles Domains defined with hidden Markov models (HMM) Domains defined with HMMs, and Pfam domains Domain definitions from multiple databases Domain definitions from Pfam, SMART and COG

32 PROTEIN DOMAIN DATABASES Around ~9,300 protein families/domains Covers 73% of proteins in UniProtKB Tool for searching domains in protein sequences Domains are defined with HMM profiles Multiple sequence alignments Protein domain architectures Species distribution Cross-references with protein sequence and structure databases Maintained at the Sanger Institute

33 GENE EXPRESSION DATABASES Gene expression profiling studies, array comparative genomic hybridization, chromatin-immunoprecipitation on arrays (ChIP-chip) studies, etc Experiment-centered and gene-centered views ArrayExpress Maintained by NCBI More than 8,000 experiments Maintained by the EBI Around 3,300 experiments Link to Expression Profiler, an online data analysis tool

34 PROTEIN INTERACTION DATABASES Information on interaction partners, interaction type and experimental evidence Experimental protein-protein interactions (literature) Direct (physical) and indirect (functional) associations More than 62,000 proteins and 162,000 interactions Maintained at the EBI Known and predicted protein-protein interactions Direct and indirect associations More than 1.5 million proteins from 373 organisms At EMBL and UniZH

35 PATHWAY DATABASES Display metabolic and signaling pathways and how genes are functionally connected Comprehensive catalogue of genes and pathways at Kyoto University Human signaling pathways database by Nature and National Cancer Institute Metabolic pathways mostly in microorganisms and plants

36 BIBLIOGRAPHIC DATABASES Published experimental information Over 16 million citations from MEDLINE and other life science journals Links to full text articles Links to related articles Links to gene information and other NCBI databases US National library of Medicine

37 ONTOLOGIES IN MOLECULAR BIOLOGY Controlled and structured vocabularies, constructed with two purposes Proposing standard collections of terms for annotation Organizing the knowledge of a given field around its language Examples of ontologies Enzyme Commission Nomenclature: EC numbers for enzymes MeSH (Medical Subject Headings) terms: NLM controlled vocabulary Gene Ontology: controlled vocabulary to describe gene and gene product attributes in any organism

38 ONTOLOGIES IN MOLECULAR BIOLOGY Enzyme Commission Nomenclature. EC 1... Oxidoreductases. EC Acting on the CH OH group of donors. EC With NAD(+) or NADP(+) as acceptor. EC With a cytochrome as acceptor.

39 GENE ONTOLOGY Developed and maintained by the GO Consortium of laboratories and institutions involved in molecular biology database management Gene Ontology terms have been grouped in three ontologies: Molecular functions Biological processes Cellular components Most molecular biology databases have joined this initiative, and have included annotations following this standard

40 GENE ONTOLOGY Annotators Database curators Gene Ontology Annotation (GOA) database: central repository, - this controlled vocabulary to a non-redundant set of proteins GO browsers Search GO terms for a gene/protein Retrieve genes/proteins associated to a GO term applies

41 GenBank and EMBL GenBank and the EMBL nucleotide databases were founded in Contain ALL DNA sequences ever published. Submissions are made by the laboratories or centers that obtain them. Depositing sequences in GenBank / EMBL is a requisite of most journals to accept manuscripts in which new sequences are reported. In August 2003 they contained: 18, sequence files , nucleotides Every two months a new complete version of the database is published.

42 Organismal Divisions in GenBank PRI Primate ROD Rodent MAM Mammalian VRT Vertebrate INV Invertebrate PLN Plant BCT Bacterial RNA Structural VRL Viral PHG Phage SYN Synthetic UNA Unannotated Funcional Divisions in GenBank PAT Patent EST Expressed Sequence Tags STS Sequence Tagged Sites GSS Genome Survey Sequences HTG High Throughput Genome

43 Entrez is the indexing and data retrieval system developed by the NCBI The Entrez Global Query page searches NCBI Entrez databases, either individually or globally

44 MAIN DATABASES ACCESIBLE WITH ENTREZ PubMed: Bibliographic references in Molecular Biology and Medicine. Nucleotide: Composite database of DNA sequences from Genbank, EMBL and DDBJ, plus other databases or projects such as RefSeq. RefSeq contains nucleotide sequences from the Nucleotide database that have been curated or re annotated, by the NCBI. Protein: Proteins sequences derived from translation of DNA sequences in GenBank, EMBL y DDBJ, plus sequences from PIR, SWISSPROT and Protein Data Bank (PDB). Genome: Complete genomes, chromosomes, contig maps, physical maps.

45 MAIN DATABASES ACCESIBLE WITH ENTREZ Entrez Gene: locus centered database that integrates information from other databases (replaces LocusLink). Structure: (Molecular Modeling Database, MMDB) experimentally obtained structures from Protein Data Bank (PDB). Taxonomy: Names and taxonomy of organisms that have at least one sequence at the NCBI databases. OMIM: Online Mendelian Inheritance in Man, catalog of human mutations and associated diseases.

46 SEQUENCE FILES FLAT FILE FORMATS For sequence databases, the main formats are: FASTA GenBank EMBL and SwissPro

47 FASTA format > essential GI Accession.version Locus Additional information >gi emb X BSBOFCGEN B.subtilis bofc gene CTGCAGCGGCTGACAATAGCAGGCCGACAACGGTTGAGGTGTCAACAGCTGATTTTGTGATGAAGGATAA ACCGCATTTCTTTTTCCTTGAACGCTATAAGGATTCATATGAGGAGGAGATTCTCCGTTTTGCAGAAGCG ATCGGCACAAACCAGGAGACTCCCTGCACCGGCAATGACGGTTTACAGGCCGGGAGGATCGCCAGAGCAG CACAGCAATCGCTTGCTTTTGGCATGCCTGTTAGCATTGAGCACACTGAAAAAATCGCTTTTTAATCTAA CAGGATTACAATTCAGCAAGCTTGGGTATATACTCCATTGATACTTTAAGTAGGCGGTGGAGAAAATGAA TACAGTACATGCTAAAGGAAATGTTTTGAACAAAATCGGAATTCCTTCTCACATGGTTTGGGGTTATATT GGCGTTGTCATCTTTATGGTTGGAGACGGCCTCGAACAAGGCTGGCTGTCTCCTTTTCTCGTTGATCATG GTCTCAGTATGCAGCAATCCGCATCGTTATTTACCATGTACGGCATTGCTGTCACCATCTCAGCTTGGCT TTCAGGAACGTTTGTGGAAACTTGGGGGCCGAGAAAAACGATGACTGTCGGATTGCTTGCATTTATCCTC > CTGCAGCGGCTGACAATAGCAGGCCGACAACGGTTGAGGTGTCAACAGCTGATTTTGTGATGAAGGATAA ACCGCATTTCTTTTTCCTTGAACGCTATAAGGATTCATATGAGGAGGAGATTCTCCGTTTTGCAGAAGCG ATCGGCACAAACCAGGAGACTCCCTGCACCGGCAATGACGGTTTACAGGCCGGGAGGATCGCCAGAGCAG CACAGCAATCGCTTGCTTTTGGCATGCCTGTTAGCATTGAGCACACTGAAAAAATCGCTTTTTAATCTAA CAGGATTACAATTCAGCAAGCTTGGGTATATACTCCATTGATACTTTAAGTAGGCGGTGGAGAAAATGAA

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49 GBFF: HEADER LOCUS BSBOFCGEN 2664 bp DNA linear BCT 15 APR 1997 DEFINITION B.subtilis bofc, orf1, csbx, and orf4 genes. ACCESSION X93081 VERSION X GI: KEYWORDS bofc gene; csbx gene; ORF1; ORF4. SOURCE Bacillus subtilis ORGANISM Bacillus subtilis Bacteria; Firmicutes; Bacillales; Bacillaceae; Bacillus. REFERENCE 1 AUTHORS Gomez,M. and Cutting,S.M. TITLE BofC encodes a putative forespore regulator of the Bacillus subtilis sigma K checkpoint JOURNAL Microbiology 143 (Pt 1), (1997) MEDLINE PUBMED REFERENCE 2 (bases 1 to 2664) AUTHORS Cutting,S.M. TITLE Direct Submission JOURNAL Submitted (14 NOV 1995) S.M. Cutting, Dept. of Microbiology, University of Pennsylvania School of Medicine, 346 Johnson Pavillon, 3610 Hamilton Walk, Philadelphia, PA , USA

50 GBFF: FEATURES FEATURES source gene CDS gene CDS Location/Qualifiers /organism="bacillus subtilis" /strain="py79" /isolate="168" /db_xref="taxon:1423" /germline /gene="orf1" < /gene="orf1" /codon_start=3 /transl_table=11 /protein_id="caa " /db_xref="gi: " /db_xref="sptrembl:o05389" /translation="aaadnsrpttvevstadfvmkdkphffflerykdsyeeei EAIGTNQETPCTGNDGLQAGRIARAAQQSLAFGMPVSIEHTEKIAF" /gene="csbx" /gene="csbx" /note="sigma B transcribed gene" /codon_start=1

51 GBFF: SEQUENCE BASE COUNT 670 a 518 c 690 g 786 t ORIGIN 1 ctgcagcggc tgacaatagc aggccgacaa cggttgaggt gtcaacagct gattttgtga 61 tgaaggataa accgcatttc tttttccttg aacgctataa ggattcatat gaggaggaga 121 ttctccgttt tgcagaagcg atcggcacaa accaggagac tccctgcacc ggcaatgacg 181 gtttacaggc cgggaggatc gccagagcag cacagcaatc gcttgctttt ggcatgcctg 241 ttagcattga gcacactgaa aaaatcgctt tttaatctaa caggattaca attcagcaag 301 cttgggtata tactccattg atactttaag taggcggtgg agaaaatgaa tacagtacat 361 gctaaaggaa atgttttgaa caaaatcgga attccttctc acatggtttg gggttatatt 421 ggcgttgtca tctttatggt tggagacggc ctcgaacaag gctggctgtc tccttttctc 481 gttgatcatg gtctcagtat gcagcaatcc gcatcgttat ttaccatgta cggcattgct 541 gtcaccatct cagcttggct ttcaggaacg tttgtggaaa cttgggggcc gagaaaaacg 601 atgactgtcg gattgcttgc atttatcctc ggttcggccg cttttatcgg ctgggcgatt 661 cctcatatgt attatccggc tctcttgggc agctatgctc ttagaggctt gggatatccg 721 ctgtttgcat actcttttct cgtatgggtg tcatacagca cctctcaaaa tattcttgga 781 aaagccgtcg gctggttttg gtttatgttt acgtgcggcc ttaacgtgct cggtccgttc 841 tattccagct atgcagttcc ggcctttgga gaaatcaata cgctttggag cgctttactg 901 tttgtggcgg caggcggaat tcttgcctta ttttttaaca aagataaatt tactccgata 961 caaaaacaag atcagccgaa atggaaagaa ctgtcgaagg catttacgat tatgtttgaa 1021 aaccctaagg taggcatcgg cggagtggtc aagacgatta atgcgatagg acaatttgga 1081 tttgccatct ttcttcctac ttatttagca cgatacgggt attcggtttc ggaatggctg 1141 caaatatggg ggactctgtt ttttgtgaat // LOCUS BSOTHERGENE 4356 bp DNA linear BCT 15 APR 1997

52 EMBL AND SwissProt FORMAT The field name is specified by a TWO CHARACTER keyword, in the beginning of each line, what makes easier to parse the file to extract specific information. ID BSBOFCGEN standard; genomic DNA; PRO; 2664 BP. XX AC X93081; XX SV X XX DT 15-APR-1997 (Rel. 51, Created) DT 15-APR-1997 (Rel. 51, Last updated, Version 12) XX DE B.subtilis bofc, orf1, csbx, and orf4 genes XX KW bofc gene; csbx gene; ORF1; ORF4. XX OS Bacillus subtilis OC Bacteria; Firmicutes; Bacillales; Bacillaceae; Bacillus. XX

53 EMBL AND SwissProt FORMAT RN [1] RX MEDLINE; RX PUBMED; RA Gomez M., Cutting S.M.; RT "BofC encodes a putative forespore regulator RT of the Bacillus subtilis sigma K checkpoint"; RL Microbiology 143: (1997). XX XX DR GOA; O DR GOA; O DR GOA; O DR GOA; O DR SWISS-PROT; O05389; YRBE_BACSU. DR SWISS-PROT; O05390; CSBX_BACSU. DR SWISS-PROT; O05391; BOFC_BACSU. DR SWISS-PROT; O05392; RUVA_BACSU.

54 EMBL AND SwissProt FORMAT FT source FT /db_xref="taxon:1423" FT /germline FT /mol_type="genomic DNA" FT /organism="bacillus subtilis" FT /strain="py79" FT /isolate="168" FT CDS < FT /codon_start=3 FT /db_xref="goa:o05389" FT /db_xref="swiss-prot:o05389" FT /transl_table=11 FT /gene="orf1" FT /protein_id="caa " FT /translation="aaadnsrpttvevstadfvmkdkphfffl ERYKDSYEEEILRFAEFTAIGTNQETPCTGNDGLQAGRIARAA QQSLAFGMPVSIEHTEKIAF"

55 EMBL AND SwissProt FORMAT XX SQ Sequence 2664 BP; 670 A; 518 C; 690 G; 786 T; 0 other; ctgcagcggc tgacaatagc aggccgacaa cggttgaggt gtcaacagct gattttgtga 60 tgaaggataa accgcatttc tttttccttg aacgctataa ggattcatat gaggaggaga 120 ttctccgttt tgcagaagcg atcggcacaa accaggagac tccctgcacc ggcaatgacg 180 gtttacaggc cgggaggatc gccagagcag cacagcaatc gcttgctttt ggcatgcctg 240 ttagcattga gcacactgaa aaaatcgctt tttaatctaa caggattaca attcagcaag 300 cttgggtata tactccattg atactttaag taggcggtgg agaaaatgaa tacagtacat 360 gctaaaggaa atgttttgaa caaaatcgga attccttctc acatggtttg gggttatatt 420 ggcgttgtca tctttatggt tggagacggc ctcgaacaag gctggctgtc tccttttctc 480 //

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58 Sequence Retrieval System is a data warehouse developed by Lion and EBI It allows the connection of related information from many databases

59 SEQUENCE RETRIEVAL SYSTEM Developed at different successive institutions Started by Thure Etzold, at the EMBL EBI (Cambridge), financed in part by EMBnet Lion Biosciences. It is not a database. It is a data warehouse. SRS uses flat text file versions of many databases: EMBL, Swiss Prot, MEDLINE, etc., which are copied and indexed, to allow the connection of related information from several databases. There are many mirrors installed. The most popular is, probably, the one at the EBI. SRS offers access to more than 700 databases.

60 ACKNOWLEDGMENTS This presentation contains material from previous presentations by: - Manuel J. Gómez, Centro de Astrobiología, CSIC-INTA - Rodrigo López, European Bioinformatics Institute