Guide to data resources - European Bioinformatics Institute

The EMBL-European Bioinformatics InstituteGuide to data resources

Copyright © 2012 EMBL-European Bioinformatics InstituteCover image courtesy of Samuel Kerrien

The European Bioinformatics InstituteGuide to data resourcesContentsAbout this guide 2Genes and genomes 2Gene expression 3Proteins and proteomics 4Macromolecular structures 4Small molecules 5Enzymes and reactions 5Interactions, pathways and networks 6Patent sequences 6Literature and text mining 7Ontologies 7Tools 8

About usThe EMBL-European BioinformaticsInstitute (EMBL-EBI) maintains oneof the world’s most comprehensivecollections of freely availablebiological databases. Our free toolsallow you to analyse this informationand share it with the researchcommunity.Genes and genomesNext-generation sequencing has transformed the task of collecting DNAsequence data. We no longer sequence just single genomes but also sets ofrelated genomes in structured studies. This has made possible the 1000Genomes Project, an international initiative to build a comprehensivecatalogue of all common human variation. We also capture genetic variationof medical relevance. Such data require careful attention to access control,ensuring that only authorised scientists can use them, and that they do so in away that reflects the spirit of consent and confidentiality.About this guideThis document provides an overviewof EMBL-EBI’s core resources. Youcan find overviews of these resourcesin Train online.www.ebi.ac.uk/training/onlineSupportDetailed help documentationis available through each of theresources described here. You canalso find answers to some of yourquestions through our homepage:www.ebi.ac.uk/helpTrainingEMBL-EBI offers training at alllevels. Our hands-on training coursesare held regularly on the GenomeCampus in Hinxton, UK and at hostinstitutions throught the world.Train online guides you throughmany bioinformatics resources, inyour own time and at your own pace.www.ebi.ac.uk/trainingStay in touchYou can find EMBL-EBI news, serviceupdates and training opportunities onour website, Twitter and Facebook.www.ebi.ac.uk@emblebi/EMBLEBIEnsemblwww.ensembl.orgEnsembl Genomeswww.ensemblgenomes.orgEuropean NucleotideArchivewww.ebi.ac.uk/enaEuropean GenomephenomeArchivewww.ebi.ac.uk/egaMetagenomics Portalwww.ebi.ac.uk/metagenomicsEnsembl produces and maintains both automaticand manually curated annotation on selectedeukaryotic genomes. Automatic annotationis based on mRNA and protein information.Ensembl provides valuable insights into variationwithin and between species, and allows you tocompare whole genomes to identify conservedelements. It is integrated with several otherimportant molecular resources, for exampleUniProt, and can be accessed programmatically.Ensembl is developed as a joint project betweenEMBL-EBI and the Wellcome TrustSanger Institute.Ensembl Genomes is a portal to genome-scaledata from bacteria, protists, fungi, plants andinvertebrate metazoa, through a unified setof interactive and programmatic interfaces.Domain-centric resources (focused on particularareas of scientific interest) are developed incollaboration with the appropriate scientificcommunities, and integrated in the broadtaxonomic context through comparative analysisand standardised annotation.ENA, a member of the International SequenceDatabase Collaboration, contains all thenucleotide sequences in the public domainand consolidates data from EMBL-Bank, theEuropean Trace Archive and the Sequence ReadArchive. The EBI Search returns results fromselected annotated sections of the ENA.EGA allows you to explore datasets fromnumerous genotype experiments – includingcase-control, population and family studies –that are supplied by a range of data providers.Our Metagenomics service is an automatedpipeline for the analysis and archiving ofmetagenomic data, and provides insights into thefunctional and metabolic potential of a sample.2Search www.ebi.ac.ukOur search service is your gateway to a world of informationspanning DNA, genes, functional genomics, proteins, structures,small molecules, enzymes, interactions, pathways, scientificpublications and patent sequences.

Gene expressionGenome-wide expression assays, originally using microarrays and morerecently high-throughput sequencing, can answer specific biological questionsand provide reference data sets. The associated large-scale expression datasetscan be used to answer questions that might not be related to the study forwhich the data were originally generated. For example, a gene expressionstudy that reveals differentially expressed genes characteristic of a particulartype of cancer may also reveal candidate genes for therapeutics development.EMBL-EBI’s functional genomics resources provide easy access to geneexpression data and related information. Our visualisation tools collateinformation from multiple data sets and present it in an intuitive way.ArrayExpresswww.ebi.ac.uk/arrayexpressExpression Atlaswww.ebi.ac.uk/gxaR-Workbenchwww.ebi.ac.uk/Tools/rcloudThe MIAME-standard compliant ArrayExpressArchive stores functional genomics experimentsperformed using RNA-Seq/ChIP-Seq andarray-based technologies.The Expression Atlas allows you to search forgene expression changes measured in various celltypes, organism parts, disease states and manyother biological and experimental conditions.It represents a curated subset of the ArrayExpressAchive experiments, and can be downloaded forlocal use.The R-Workbench provides access to R andBioconductor in the EBI cloud, and rapid accessto data stored in EMBL-EBI databases such asArrayExpress. You can upload your own data anduse EMBL-EBI’s infrastructure to perform yourdata analyses.Leanne,discovery biologistLeanne works on discovery andvalidation of candidate drugtargets in a pharmaceuticalcompany. She explains: ‘I do a lotof cloning and expression analysis.I need to find published cDNAsequences and their orthologues, sothat I can find appropriate modelsin which to validate my targets.For discovery, I’d like a simple wayto search across all public-domainbiological information. A colleaguementioned a gene to me in passingrecently and I only caught thename of it. I’d like to be able to findout more about it without havingto forage around in lots ofdifferent publications.’EBI resources forLeanne:EBI Search for quick summaryreports on specific genes.BLAST to root outvector contamination.The Expression Atlas fortranscription profiles andfunctional genomics.UniProt to learn more aboutprotein function.ChEMBL for druggability oftarget molecules.3

Francesco,marine biologistProteins and proteomicsOur protein and nucleotide data are extensively linked, both at the level ofunderlying data and through the coordination of web resources. This helps uscapture, organise and interpret sequence-related data, providing informationfreely in a variety of formats including user-friendly web sites. Whereverpossible, we collaborate with other groups worldwide with similar aims.Francesco is Head of Departmentin a new collaborative centrefor marine biology. His group isdoing metagenomic studies ofextreme marine environments buthis department has just securedfunding to look for novel woundhealingcompounds in marinealgae. “We’re about to scale up oursequencing efforts severalfold. Weneed to put some pipelines in placethat will enable us to make sense ofall the data that we’re generating.The extremophile project is acollaborative effort, and we want tobe able to share information withour research network.”EBI resources forFrancesco:European Nucleotide Archivefor DNA barcodes to identifyorganisms in his samples.His team could set up a pipelineto submit their data to ENA andmake it publicly available.Ensembl and Ensembl Genomesto characterise organisms bycomparing them with a wealth ofinformation on the genomes ofmany fully sequenced organisms.InterProScan to help identifydomains and motifs in the novelsequences he is generating thatmay imply specific functions.UniMes, a repository specificallydeveloped for metagenomic andenvironmental data.Metagenomics Portal forpowerful analysis of samplescontaining a variety of organisms.Web Services to helpcreate pipelines.UniProtwww.uniprot.orgInterProwww.ebi.ac.uk/interproPRIDEwww.ebi.ac.uk/prideMacromolecular structuresThree-dimensional structures give us mechanistic insight into howmacromolecules work, and help explain how their functions are disrupted bymutation or interaction with small molecules. Our structural data resourcesare engineered to reflect the needs of a growing and diverse structuralbiology community.PDBewww.ebi.ac.uk/pdbePDBsumwww.ebi.ac.uk/pdbsumProFuncwww.ebi.ac.uk/profuncThis comprehensive resource organises proteinsequence information so that you can find splicevariants, functional information and links to relatedresources from a single entry. UniProt is a jointeffort with the Swiss Institute of Bioinfomatics andGeorgetown University. It comprises four components:the UniProt Knowledgebase (UniProtKB),Reference Clusters (UniRef), Archive (UniParc)and Metagenomic and Environmental Sequences(UniMES). UniProtKB is the hub for the collectionof functional information on proteins, with accurate,consistent and rich annotation.InterPro classifies proteins into families and predictsthe presence of important domains and sites.InterProScan allows you to query your sequenceagainst the database.The Proteomics Identifications Database is acentralised, standards-compliant, public repositoryfor proteomics data. It contains protein and peptideidentifications and their associated supportingevidence. PRIDE also captures details ofpost-translational modifications.The Protein Data Bank in Europe (PDBe), part of theWorldwide Protein Data Bank (wwPDB), allows youto search all the macromolecular structures in thepublic domain. Its tools help you perform sophisticatedanalyses of the data, including sub-structure searchesand structural comparisons. You can analyse detailedmolecular interactions and correlate them withsequence or structure patterns.This pictorial database provides an overview ofmacromolecular structures deposited in the ProteinData Bank archive.ProFunc allows you to identify the likely biochemcialfunction of a protein from its 3D structure.4

Small moleculesJohn,medicinal chemistEMBL-EBI’s cheminformatics resources help bridge the gap between smallmolecules and the macromolecules with which they interact in living systems.In addition to the resources listed below, PDBe offers small molecule servicesthat are associated with macromolecular structures.ChEBIwww.ebi.ac.uk/chebiChEMBLwww.ebi.ac.uk/chemblRESIDwww.ebi.ac.uk/RESIDMetaboLightswww.ebi.ac.uk/metabolightsChemical Entities of Biological Interest (ChEBI)is a manually annotated dictionary of smallmolecular entities, for example any constitutionallyor isotopically distinct atom, molecule, ion orradical. It provides a wide range of related chemicalinformation such as formulae, links to otherdatabases and a controlled vocabulary that describesthe ‘chemical space’.ChEMBL, a database of bioactive compounds,focuses on interactions between small molecules andtheir macromolecular targets, including medicinalchemistry, clinical development and therapeuticsdata. Pharmaceutically important gene families inChEMBL can be viewed in the GPCR and KinaseSARfari web portals.This collection of annotations and structures forprotein modifications includes amino-terminal,carboxy-terminal and peptide chainpost-translational modifications.MetaboLights is a database for metabolomicsexperiments and derived information. It iscross-species, cross-technique and covers metabolitestructures and their reference spectra as well as theirbiological roles, locations and concentrations, andexperimental data from metabolic experiments.Enzymes and reactionsThe Enzyme Portal helps you explore the biology of enzymes and proteinswith enzymatic activity. It integrates publicly available information aboutenzymes, such as small-molecule chemistry, biochemical pathways and drugcompounds. The Enzyme Portal summarises information from:••The UniProt knowledge base;••The Protein Data Bank in Europe;••Rhea (www.ebi.ac.uk/rhea), a database of enzyme-catalysed reactions;••Reactome, a database of biochemical pathways;••IntEnz (www.ebi.ac.uk/IntEnz), a resource with enzymenomenclature information;••ChEBI and ChEMB (see above);••Cofactor (www.ebi.ac.uk/thornton-srv/databases/CoFactor) andMACiE (www.ebi.ac.uk/thornton-srv/databases/MACiE) forhighly detailed, curated information about cofactors andreaction mechanisms.John is a medicinal chemistin a large, multinationalpharmaceutical company.“I’m constantly looking for newinformation, so searchabledatabases of existing chemicalliterature are very useful,” he says.“For hit and lead optimisation,new ideas that could get meinto novel chemical space wouldbe great. Information on mypharmacophore would be reallyuseful too; things like: is itlikely to be toxic? Or, can wepredict if analogues will bebiologically active?”EBI resources for John:ChEMBL for detailedinformation about over a millionbioactive compounds.Kinase SARfari, an integratedchemogenomics workbenchlinking kinase sequences withtheir structures, compounds thattarget them and screening data.GPCR SARfari for G-proteincoupledreceptors.ChEBI for information aboutsmall molecular entities andlinks to the macromolecules withwhich they interact.PDBe for 3D structures ofmacromolecules, includingprotein–ligand interactions.The Enzyme Portal covers a large number of species including the key modelorganisms, and provides a simple way to compare orthologues.EMBL-EBI also hosts the Catalytic Site Atlas, a resource of catalytic sites andresidues that have been identified in enzymes using structural data:www.ebi.ac.uk/thornton-srv/databases/CSA5

Leon,postdocInteractions, pathways& networksComputational systems biology takes us beyond the identification of molecular‘parts lists’ for living organisms and towards synthesising information togenerate and test new hypotheses about how biological systems work.Leon is a postdoc working onquorum sensing in bacteria. Hewants to understand what makesa normally harmless bacteriumpathogenic in the lungs of peoplewith cystic fibrosis. “I’m using acombination of transcriptomics,proteomics and metabolomicsto understand these pathogenicchanges better,” he says. “I end upwith big spreadsheets of protein orgene IDs and I’m trying to piecetogether which signalling pathwaysare involved in flipping to thepathogenic state. When I comeacross a gene or protein that’s notfamiliar to me, I want to be able tofind out about it quickly and putit in the context of other genes orproteins that are expressed at thesame time.”EBI resources for Leon:EBI Search for quick summaryreports of genes or proteins.Enzyme Portal to learn moreabout a particular enzyme thatswitches a pathway on or off.InterPro for uncharacterisedproteins or novel protein familiesand domains.UniProt for the function ofproteins in his lists of IDs.Gene Ontology to find outwhich ones are involved in thesame processes.Reactome to map gene andprotein lists to pathways.Leon could also submit histranscriptomics and proteomicsexperiments to ArrayExpressand PRIDE to analyse his resultsin the context of other similarexperiments.IntActwww.ebi.ac.uk/intactReactomewww.reactome.orgBioModelswww.ebi.ac.uk/biomodelsPATENTPatent sequencesThe IntAct molecular interaction database and analysissystem provides a central, standards-compliant repositoryof molecular interactions, including protein–protein,protein–small molecule and protein–nucleicacid interactions.Reactome is a database of human biological pathways builtfrom connected reactions that encompass all biologicalevents as well as classical biochemical events. Contentis authored by expert biologists and linked to scientificliterature that experimentally validates the steps in apathway. The goal is to represent the current biologicalconsensus of human pathways, as a free online referenceand a downloadable core dataset. Reactome offers tools forsearching and viewing pathways as interactive diagrams,and for analysing datasets by comparing them with otherpathways and overlaying expression or interaction data.Biomodels is a database of published mathematical modelsdescribing biological processes. You can simulate themodels online and use them to develop your own. Biologistscan store, search and retrieve published and annotatedmathematical models of biological interest.We offer free, unrestricted access to dedicated patent sequence databasesthat contain valuable information about patent family data, patentequivalents and ‘earliest priority’ dates. These databases also offer access tofull-text patent documents.Our non-redundant patent sequence databases help you search efficientlyand return de-duplicated results, saving valuable time and effort.Patent nucleotide and protein sequences are contributed by the EuropeanPatent Office (EPO), US Patent and Trademark Office, and the Japanese(JPO) and Korean (KIPO) patent offices, including World IntellectualProperty Organization (WIPO)-approved patents from these offices.Further agreements with patent offices from Brazil, Canada, China andMexico have been achieved or are in progress.www.ebi.ac.uk/patentdata/nr6

Literature and text miningJudith,plant geneticistWe develop free public resources based on the scientific literature, and leadthe development of UK PubMed Central. Our resources provide links tofull-text articles and maintain cross-references to biological databases such asUniProt, ENA, PDBe and InterPro. The CiteXplore search engine integratestext-mining functions to build links to biological concepts and the underlyingdatabases of proteins, genes and gene ontology.CiteXplorewww.ebi.ac.uk/citexploreUK PubMed Centralhttp://ukpmc.ac.ukOntologiesCiteXplore covers 25 million abstracts inlcudingPubMed, Agricola and patents. It combinesliterature search with text-mining tools,citation networks and cross references to otherbioinformatics resources.UKPMC contains over 2 million full text lifescience research articles, of which around 250 000are open access. Combined with the CiteXplorecontent and functions listed above, it providesintegrated text-mining tools as well asgrant-reporting services.The wide variations in terminology between different research communitiespose a challenge both for the researcher conducting a search and thecomputer executing it. Ontology services help identify the most usefulinformation by identifying functionally equivalent terms.Judith works for a plant-breedinginstitute that is using genomics toidentify new crop strains that areresistant to drought, salt and fungaldiseases. “We’re doing linkagestudies to find out which genes areinvolved in resistance to differenttypes of stress,” she explains. “Someof the crops we work on haven’tbeen sequenced yet. We’ve got a lotof data, both on genomic variantsand on differences in expressionlevels, that we need to map on towell-characterised plants to makesense of it. We also need to find outwhether any of our sequences haveassociated patents so that we don’twaste time and effort.”Gene Ontologywww.geneontology.orgGO Annotationwww.ebi.ac.uk/QuickGoChEBIwww.ebi.ac.uk/ChEBISystems BiologyOntologieswww.ebi.ac.uk/sboExperimentalFactor Ontologywww.ebi.ac.uk/EFOOntology LookupServicewww.ebi.ac.uk/ontology-lookupThe Gene Ontology Consortium provides a controlledvocabulary to describe gene and gene product attributesin any organism.GOA provides Gene Ontology assignments for proteinsfor all species in the UniProt Knowledge Base.The ChEBI chemistry ontology provides a controlledvocabulary to describe small molecules, including theirbiological and chemical roles.The SBO project develops controlled vocabularies andontologies for problems in systems biology. SBO is partof BioModels.net.EFO is used to describe experimental variables infunctional genomics experiments, and is crossreferencedto more than 20 species or domain-specificterminologies. It provides a way to integrate databasesusing different terminologies and is deployed insearching for the ArrayExpress Archive and ExpressionAtlas databases.OLS is a centralised query interface for ontology andcontrolled vocabulary lookup. It features interactivegraphics that clarify the relationships between terms.EBI resources forJudith:Ensembl Genomes forcomparative analysis andorthologue prediction.ArrayExpress to find relatedfunctional genomics data. Judithcould also submit her expressiondata to ArrayExpress.Expression Atlas to see whichgenes are expressed undersimilar conditions.Gene Ontology for matchingprocesses and functions to plantgenes and their products.Reactome to map genesto pathways.The EPO-EBI Non-redundantpatent databases to search forprior art.7

Ola,clinical researcherToolsWe provide a comprehensive range of bioinformatics tools. Here wehighlight a selection of those used most frequently, but you can find a moreextended list on our website (www.ebi.ac.uk/Tools).For programmatic access, take a look at our Web Services (SOAP or RESTAPIs): www.ebi.ac.uk/Tools/webservicesOla is an MD/PhD. When she’s notpractising as an oncologist, she’sworking on her research project.“I’m looking for proteomics-basedbiomarkers for the early detectionof bladder cancer, specificallypeptides from transitional-cellcarcinomas that are shed into theurine,” she explains. “I do mass specof samples from patients coming infor biopsies. I need to identify theproteins whose production is up- ordown-regulated. I’ve started lookingat post-translational modificationson these proteins, and have founda phosphoprotein that seems to beupregulated in some patients. I’dlike to know more about the cellularprocesses leading to this change.This might help us find noveltherapies, too.”EBI resources for Ola:PRIDE for proteomicsexperiments that have identifiedproteins from carcinoma cells.Ola could also submit her ownresearch results to PRIDE.UniProt to find out about thephosphorylation sites on hernew biomarker and whattype of kinase might catalysethese changes.IntAct to find evidence of otherproteins that interact with herprotein of interest.Nucleotide sequence searchYou can use these tools to searchnucleotide sequence databases,including ENA and resources for codingsequences, immunoglobulins and highthroughputsequences:••BLAST Nucleotide••ENA Sequence Search(Exonerate)Multiple sequence alignmentFor alignment of three or moresequences to identify regions ofconservation, which may indicatefunctional constraints and inferevolutionary relationships:••Clustal Omega••ClustalW2••WebPRANK••T-Coffee••MUSCLEProtein functional analysisFor identification of potential proteinfamilies, domains and functional sitesallowing the the function of a proteinsequence to be predicted:••InterProScan••Pratt••Phobius••RADARMolecular structure analysisThese tools help you determine andvisualise macromolecular structures:••PDBeFold••QuaternaryStructureProtein sequence searchYou can use these tools to searchprotein sequence databases includingUniProtKB, sequences derivedfrom macromolecular structures,immunoglobulins and sequencesfrom patents:••BLAST Protein••PSI-SearchPairwise sequence alignmentFor alignment of two sequences toidentify regions where the sequence isconserved:••Needle••LAlignFunctional genomics toolsTo explore data from gene expressionexperiments:••Expression Atlas••EFO Tools••EBI R-WorkbenchText miningFor analysis of text documents toidentify important terms and relate themto database entries and ontologies:••EBIMed••WhatizitData retrieval and ID mapping••dbfetch••ENA / SRA••ENA / EMBL-SVA••UniProt / UniSave••SRS••PICR8

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