EnVisioning Pathways
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This document summarizes a presentation about the EnVisioning Pathways project. It discusses: 1) The EnCORE integration platform developed by the ENFIN Network of Excellence to enable mining data across different biological domains, sources, formats and types through a standardized XML format and web services. 2) Examples of EnCORE services that retrieve interaction data from databases like IntAct and Pride, map between identifiers, and represent results in biological pathways in databases like Reactome. 3) Efforts to adapt EnCORE to utilize standards and create a federated system to integrate information from different biological domains. This includes building predefined and user-selected workflows between EnCORE services.
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EnVisioning Pathways
- 1. EnVisioning Pathways EMBRACE-ENFIN workshop, 5-6 October Rafael Jimenez rafael@ebi.ac.uk Updated: 30 September 2009 EnCORE tutorial 41 slides
- 2. Molecular Biology Database resources Human Genes and Diseases 13% Proteomics Resources 1% Other Molecular Biology Databases 3% Immunological databases 2% Plant databases 7% Organelle databases 2% Human and other Vertebrate Genomes 8% Nucleotide Sequence Databases 9% RNA sequence databases 5% Protein sequence databases 13% Structure Databases 9% , Genomics Databases non-vertebrate 19% Metabolic and Signaling Pathways 9% Nucleic Acids Research annual Database Issue and the NAR online Molecular Biology Database Collection in 2009. MY Galperin, GR Cochrane - Nucleic Acids Research, 2008 ~1440 resources
- 3. Molecular Biology Database resources • Metabolic and Signaling Pathways Enzymes and enzyme nomenclature 12% Metabolic pathways 21% Protein -protein Interactions 62% Signaling pathways 5% Nucleic Acids Research annual Database Issue and the NAR online Molecular Biology Database Collection in 2009MY Galperin, GR Cochrane - Nucleic Acids Research, ~122 resources
- 4. Biological pathway resources Pathguide • Categories Other 4% Protein -Protein Interactions 34% Metabolic Pathways 20%Pathway Diagrams 10% Transcription Factors / Gene Regulatory Networks 15% Protein -Compound Interactions 11% Protein Sequence Focused 6% http://www.pathguide.org ~303 resources
- 5. Centralized databases VS In-house databases DB GUI API WS Centralized database A AA A DB GUI API WS DB GUI API WS DB GUI API WS DB GUI API WS In-house databases A AA A A Annotator Database Graphical User Interface Application programming interface Web Services GUI API WS User Standard protocolSP
- 6. Utility of bioinformaticsScientificimpact Too little bioinformatics Too many databases Too diverse interfaces Tim Hubbard
- 7. Many databases VS Federation DB GUI API WS DB DB DB SP SP SP SP DB GUI API WS DB GUI API WS DB GUI API WS DB GUI API WS Many databases Federation Database Graphical User InterfaceGUI User Standard protocolSP
- 8. Utility of bioinformaticsScientificimpact Too little bioinformatics Too many databases Too diverse interfaces Integration of
- 9. Data integration • Combining data residing in different sources • … providing users with a unified view of these data. Main objective Requires • Share • Compare • Unify – Data from the same domain – Data from different domains • Federated systems • Standard formats • Mapping tools • Ontologies
- 10. Data integration • Federated systems – DAS – PSICQUIC – … • Standard formats – DAS – PSI-MI – BioPAX – SBML – CellML – … • Ontologies – OLS – … • Mapping tools – PICR – Uniprot API – Ensembl API – DAS – Biomart – … • Integration systems – Biomart – EnCORE – …
- 11. Standards development – international collaborations Genome annotation www.geneontology.org Genome annotation www.geneontology.org Microarray and Gene Expression Data (MGED) www.mged.org Microarray and Gene Expression Data (MGED) www.mged.org Protein sequence www.uniprot.org Protein sequence www.uniprot.org HUPO- Proteomics Standards Initiative (PSI) Psidev.sf.net HUPO- Proteomics Standards Initiative (PSI) Psidev.sf.net Protein structure www.wwpdb.org Protein structure www.wwpdb.org Cheminformatics www.ebi.ac.uk/chebi Cheminformatics www.ebi.ac.uk/chebi Pathways www.reactome.org www.biopax.org Pathways www.reactome.org www.biopax.org Systems modelling standards www.sbml.org Systems modelling standards www.sbml.orgMetabolomics Standards Initiative (MSI) www.metabolomicssociety.org Metabolomics Standards Initiative (MSI) www.metabolomicssociety.org Genomics Standards Consortium (GSC) gensc.org Genomics Standards Consortium (GSC) gensc.org Nucleotide sequence www.insdc.org Nucleotide sequence www.insdc.org
- 12. The Distributed Annotation System, 2001 Dowell et al; BMC Bioinformatics. 2001; 2: 7. Published online 2001 October 10. DAS, Architectural Overview illustration
- 13. DAS implementation Service broker Service consumer Service provider Service Contract ... ... Interact PublishFind DAS ... ... ... DAS Registry DAS Clients Annotation sources Reference source Alignment sources Alignment sources Alignment sources Annotation sources Annotation sources DAS Clients DAS Clients Protocol Service Oriented Architecture … 657 sources!
- 14. DAS servers and data types Genome sequence Sequence alignments Protein sequence Protein-protein interaction Gel 2D EMAP 3DM Protein structure Protein structure EMAP 3DM Protein-protein interaction Protein structure Gel 2D Mass spectrometry Epigenetics Phenotype Functional genomics Structural genomics Protein sequence Alignment servers Annotation servers Reference servers
- 16. PSICQUIC based on the PSI-MI standard for molecular interactions ….…. …..... ….…. …..... PSICQUIC PSICQUIC PSICQUIC Sample Observation error Interaction databases Publications PSICQUIC servers Annotation error Client
- 17. PSICQUIC implementation Service broker Service consumer Service provider Service Contract ... ... Interact PublishFind Service Oriented Architecture PSI-MI ... ... ... PSICQUIC Registry DAS ClientsDAS ClientsPSICQUIC Clients Format PSICQUIC sources PSICQUIC sources PSICQUIC sources
- 19. ENFIN Network of Excellence • Brings together experimentalists and computational biologists to develop the next generation of informatics resources for systems biology • Funded by the European Commission within its FP6 programme under the thematic area ‘Life sciences, genomics and biotechnology for health’ • 20 partners in 13 countries • www.enfin.org
- 20. EnCORE … Input EnXML Output EnXML Service EnCORE WS • ENFIN Platform to enable mining data across various domains, sources, formats and types • Integrates database resources and analysis tools across different disciplines
- 21. Diverse service world SOAP, REST, Java API, Perl API, FTP, GUI, … External data sources Different formats Access interfaces User ?integration • Multiple manual connections • Multiple technologies • Multiple result files which have to be combined manually • Much work to reproduce XML, CSV, Plain Text, JSON, …
- 22. Standardised EnCORE world Heterogeneous external world Standardised EnCORE world EnXML External data sources EnCORE services EnVISION pages API, WS access Standard EnXML format User input output
- 23. Standardised EnCORE world External data sources EnCORE services EnCORE workflows EnVISION pages WS, API WS API Web interface 21
- 24. EnCORE services From Inputs to Outputs Positive Negative Input/Query Output/Results Program/Service EnCORE dataset EnCORE results EnCORE webservice • Enfin-IntAct • Enfin-PRIDE • Enfin-Affy2UniProt • Enfin-PICR • Enfin-Reactome • Enfin-ArrayExpress • Enfin-UniProt • Enfin-BioModels • Enfin-KEGG • Enfin-G:GOSt • Enfin-CellMINT • Enfin-DOMAINATION • Database IDs • Sequences • Experiment: Identifies the result • Sets: Contains the structure of the result • Molecules: Includes the results • Features: Describe details of the result
- 25. EnCORE services Example Positive Negative Input/Query Output/Results Program/Service EnCORE dataset EnCORE results EnCORE webservice • Encore webservice Enfin-IntAct • Database ID (Uniprot ID) P37173 • Experiment: ID4 • Sets: (1)EBI-296235, (2)EBI-1033040, (3) EBI- 902913, EBI-902937, (4) EBI-296166, EBI-296246, (5)EBI-902913 • Molecules: (1)O35613, (2)P10600, (3)P07200, (4)Q9UER7, (5)Q99K41 • Features: No features
- 26. EnCORE services Example (Result on a table) Interactor A Interactor B Interaction IDs 1 P37173 O35613 EBI-296235 2 P37173 P10600 EBI-1033040 3 P37173 P07200 EBI-902913, EBI-902937 4 P37173 Q9UER7 EBI-296166, EBI-296246 5 P37173 Q99K41 EBI-902913 Input/Query Output/Results Program/Service Enfin-IntAct P37173
- 27. EnCORE services Building workflows Input Result Positive result Negative resultWebservice Input selection
- 28. Envison interface (example) • Results for Pride, Uniprot, Intact, Reactome, CellMint, PICR, Biomodels, … http://www.ebi.ac.uk/~rafael/enfin/presentations/EnVISION2_01.ppt http://www.enfin.org/dokuwiki/ EnCORE tutorial
- 29. EnVISION Pathways result Positive results Negative results Representation in a Pathway map
- 30. EnVISION dataset representation in Reactome
- 31. EnVISION dataset representation in Reactome
- 32. ~303 resources Integration of information from the same Molecular Biology Domain Domain 5 Domain …Domain 4 Domain 2 Domain 3Domain 1
- 33. Adapting EnCORE to Standards and Federation Domain 1 External data sources Federated systems / Standards EnVISION pages WS WS Web interface EnCORE wrapper
- 34. Adapting EnCORE to Standards and Federation Domain 5 Domain …Domain 4 Domain 2 Domain 3Domain 1
- 35. Adapting EnCORE to Standards and Federation • Integration of sources. • Filtering redundancy (whenever possible) • Interconnect results. Domain 5 Domain …Domain 4 Domain 2 Domain 3Domain 1
- 36. Predefined workflows Run different services on the same input Use the output of one service as an input of another service EnVISION EnVISION2
- 37. Predefined workflows and automated workflows • “Semantic Web” promises to use data sources and analysis tools to automatically build workflows that make sense to satisfy users’ requests. • Early stage of “Semantic Web”, not a practical solution to apply on our workflows. • Useful workflows require users to go though each step of the workflow. • Our problem using predefined workflows: – Explosion of results. – Workflow configuration is subjective. – We could come up with multiple predefined combinations. – Limitations to define its configuration.
- 38. User selection based workflow Query Results EnCORE WS Positive Negative User selection Query Results EnCORE WS Positive Negative User selection EnCORE WS Negative Positive Positive Negative Results EnCORE WS 1 2 3
- 39. Biological pathway resources Pathguide • Data Access Methods 0 50 100 150 200 250 Browsing / Canned queries Keyword searches Download in other format Download in BioPAX format Download in PSI format Download in SBML format SQL queries Download in CellML format Standards
- 40. Conclusions • Data integration – Adopting standards formats – Building a federated system of sources – Describing data with ontologies – Using standard identifiers – Mapping references from different domains
Editor's Notes
- Integration of biological data of various types and development of adapted bioinformatics tools represent critical objectives to enable research at the systems level. The European Network of Excellence ENFIN is engaged in developing an adapted infrastructure to connect databases, and platforms to enable both generation of new bioinformatics tools and experimental validation of computational predictions. Beyond the use of common standards to format individual datasets, there is a need for sophisticated informatics platforms to enable mining data across various domains, sources, formats and types. The aim of the EnCORE project is to integrate across different disciplines an extensive list of database resources and analysis tools in a computationally accessible and extensible manner, facilitating automated data retrieval and processing with a special focus on systems biology. The EnCORE platform is available as a collection of webservices with a common standard format easy to integrate in Workflow management software such as Taverna. Additionally EnCORE services are also accessible thought EnVISION, a web graphical user interface providing elaborated information such as molecular interaction, biological pathways and computational models of pathways.
- EBI has a comprehensive collection of databases. We are not alone. The latest “Molecular Biology Database Collection” published in NAR describes more than 1400 database resources.
- From these 1400, it describes more than 100 pathway databases.
- Pathguide lists more than 300 pathway resources. In general we can say there are lots of pathway resources available in different databases.
- As a biologist I would prefer to see all the information in one unique database. Centralized databases have this mission. The aim to collect all the information for one specific domain. However … Medium-size labs and organizations are capable to produce large amounts of data. The it becomes harder to submit data to centralized repositories. Moreover data producers like to control and structure their own databases, developing their own GUI and access protocols. For us, the users, it becomes harder to access the information. For one specific domain we might find different databases, using different GUIs. We might end up downloading data in different formats complicating the integration of results. After integration we might find a problem of high redundancy in our results.
- This integration problem is well defined by this chart. In bioinformatics before we didn’t have to much data available to help biologist Now we have the data but it is not very useful if it is difficult to find and difficult to access.
- Data producers have good reasons to have their own database. However among all of us have to think about ways to share our data and make it easily available to user. Federation provides an easy way to integrate data resources. 100% compatible with database providers continuing working with their own database structure, GUI, ...
- … Mapping tools to be able to work in the same identification space. …
- A protocol to exchange data. A network of biological resources A standard XML formal A federated system. Different distributed databases install the DAS protocol Now a client, a user can use the same query for the all these databases And all the database will return the results in the same standard XML format over the internet. For the client it is easy to put all the annotations together.
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- EnVISION2 (ENFIN tool) query for molecular interactions using PSICQUIC. It connects to the registry to find out what servers are available And query for molecular interaction for a list of Protein Acc (in this case two proteins interacting with each other). It merges results filtering redundancy and display the results in a table and in a interaction network.
- Let me talk about what we do in ENFIN in data integration ENFIN is a platform, a project that brings together experimentalist and computational biologist to help each other and develop bioinformatics resources for systems biology.
- The idea behind EnCORE is simplified in this picture Input (our query) is contained in a XML standard format called EnXML We can run different services over this input. We get results contained in the same EnXML format The Outputs can be use as inputs of other services.
- We are exposed to a very diverse service world
- EnCORE provides an easy way to build workflows since input and outputs share the same standard format
- This is a generic example of how an EnCORE service work
- An specific example The query is a protein Acc We run the Intact service We get the interactions result defined by the EnXML terminology
- The same results in a table
- EnCORE facilitates building workflows
- EnVISION is an EnCORE interface With just one click user can run different services get a quick overview for a dataset This example shows result for …
- Here an example of the potential of EnVISION In this example we used a dataset of more than 300 protein Acc. In this screenshot EnVISION was able to find more than 500 pathways for this dataset. EnVISION is capable to link and display positive results in a pathway map.
- UP: Reaction present in our dataset MIDDLE: Heatmap DOWN: Proteins from our dataset found in reactome reactions Heatmap displaying represented pathways in our dataset. Color identifies the better hits Red means there are more proteins from our dataset are present in the reaction.
- EnVISION results are nice, but do not forget our initial integration problem For one domain (protein interaction, pathways, protein sequence …) we might have several databases providing data
- EnCORE provides a great solution however it is not complete if it can not include more resources For EnCORE it is not feasible to develop and maintain so many wrappers. Nonetheless EnCORE can overcome this problem using standards and federated systems
- Right now EnCORE workflows are predifined. Two types of workflow. They are static, not very easy to adapt to user needs.
- Web semantics seems to be the solution to build intelligent workflows. However web semantics is in a early stage. Molecular biology to complicated for Web Semantics
- I personally think “user selection based workflows” is a better solution for developers and users as far as we keep it simple like it is in EnCORE.
- To conclude … I would like to see more database providers and users using standards. Just 20% of the DB described in PATHGUIDE use standards.
- Data integration and properly representation of pathway information will be possible if …
- Integration of biological data of various types and development of adapted bioinformatics tools represent critical objectives to enable research at the systems level. The European Network of Excellence ENFIN is engaged in developing an adapted infrastructure to connect databases, and platforms to enable both generation of new bioinformatics tools and experimental validation of computational predictions. Beyond the use of common standards to format individual datasets, there is a need for sophisticated informatics platforms to enable mining data across various domains, sources, formats and types. The aim of the EnCORE project is to integrate across different disciplines an extensive list of database resources and analysis tools in a computationally accessible and extensible manner, facilitating automated data retrieval and processing with a special focus on systems biology. The EnCORE platform is available as a collection of webservices with a common standard format easy to integrate in Workflow management software such as Taverna. Additionally EnCORE services are also accessible thought EnVISION, a web graphical user interface providing elaborated information such as molecular interaction, biological pathways and computational models of pathways.