Implementing chemistry platform for OpenPHACTS
•Transferir como PPTX, PDF•
1 gostou•517 visualizações
The Open PHACTS project delivers an online platform integrating a wide variety of data from across chemistry and the life sciences and an ecosystem of tools and services to query this data in support of pharmacological research, turning the semantic web from a research project into something that can be used by practising medicinal chemists in both academia and industry. In the summer of 2015 it was the first winner of the European Linked Data Award. At the Royal Society of Chemistry we have provided the chemical underpinnings to this system and in this talk we review its development over the past five years. We cover both our early work on semantic modelling of chemistry data for the Open PHACTS triplestore and more recent work building an all-purpose data platform, for which the Open PHACTS data has been an important test case, what has worked well, what's missing and where this is is likely to go in future.
Recomendados
Recomendados
Mais conteúdo relacionado
Mais procurados
Mais procurados (20)
Destaque
Destaque (19)
Semelhante a Implementing chemistry platform for OpenPHACTS
Semelhante a Implementing chemistry platform for OpenPHACTS (20)
Mais de Valery Tkachenko
Mais de Valery Tkachenko (20)
Último
Último (20)
Implementing chemistry platform for OpenPHACTS
- 1. Implementing chemistry platform for OpenPHACTS: Lessons learned Colin Batchelor, Alexey Pshenichnov, Jon Steele, Valery Tkachenko Royal Society of Chemistry ACS Spring 2016 San Diego, CA March 17th 2016
- 2. Open PHACTS Mission: Integrate Multiple Research Biomedical Data Resources Into A Single Open & Sustainable Access Point
- 3. info@openphactsfoundation.org @Open_PHACTS Open PHACTS Practical Semantics Acknowledgements GlaxoSmithKline – Coordinator Universität Wien – Managing entity Technical University of Denmark University of Hamburg, Center for Bioinformatics BioSolveIT GmBH Consorci Mar Parc de Salut de Barcelona Leiden University Medical Centre Royal Society of Chemistry Vrije Universiteit Amsterdam Novartis Merck Serono H. Lundbeck A/S Eli Lilly Netherlands Bioinformatics Centre Swiss Institute of Bioinformatics ConnectedDiscovery EMBL-European Bioinformatics Institute Janssen Esteve Almirall OpenLink Scibite The Open PHACTS Foundation Spanish National Cancer Research Centre University of Manchester Maastricht University Aqnowledge University of Santiago de Compostela Rheinische Friedrich-Wilhelms-Universität Bonn AstraZeneca Pfizer
- 4. Why is it so hard to…. Competitors? What’s the structure? Are they in our file? What’s similar? What’s the target?Pharmacology data? Known Pathways? Working On Now? Connections to disease? Expressed in right cell type? IP?
- 5. Literature PubChem Genbank Patents Databases Downloads Data Analysis Data Integration Firewalled Databases How do R&D companies use public data?
- 6. @gray_alasdair Big Data Integration 9
- 7. Patent annotations in Open PHACTS • Huge amount of knowledge hidden in patent corpus • Most of which will never be published elsewhere • Substantial lag between patent and scientific literature • SureChEMBL system already extracts chemical entities from full-text patent documents • Text (title, abstract, description, claims), images, molfiles • Complemented with gene and disease entity annotations • Using the Termite text-mining tool by SciBite • Relevance scoring to reduce noise • Tested for recall • Patent, compound, gene, disease info available via API
- 8. Open PHACTS Expanding EcoSystem Further Apps Data Warrior
- 9. • VM install of Open PHACTS – Docker Image is now available • Updating to ver 2.0 Open PHACTS • Allows you to customise and load your own data into the environment Want to load your data into Open PHACTS? Want to run Open PHACTS within your environment?
- 12. All Users by Sector Type
- 15. Explorer Explorer2 ChemBioNavigator Target Dossier Pharmatrek Helium MOE Collector Cytophacts Utopia Garfield SciBite KNIME Mol. Data Sheets PipelinePilot scinav.it Taverna
- 18. Nanopub Db VoID Data Cache (Virtuoso Triple Store) Semantic Workflow Engine Linked Data API (RDF/XML, TTL, JSON) Domain Specific Services Identity Resolution Service Chemistry Registration Normalisation & Q/C Identifier Management Service Indexing CorePlatform P12374 EC2.43.4 CS4532 “Adenosine receptor 2a” VoID Db Nanopub Db VoID Db VoID Nanopub VoID Public Content Commercial Public Ontologies User Annotations Apps
- 19. We integrate, standardize and host the chemical compound collection underpinning Open PHACTS. We have developed a structure validation and normalization platform (CVSP) to ensure chemical structures are normalized to rules derived from the FDA structure normalization guidelines and modified based on input from members of EFPIA. http://cvsp.chemspider.com/ The Royal Society of Chemistry’s role in Open PHACTS
- 20. Freely-available (requires logging in) chemical validation system for: • Structure validation: warning on query atoms, pseudoatoms, nonsensical or unclear stereo • Standardization workflows. CVSP and the Open Pharmacological Space Chemical Registration System (OPS CRS)
- 21. Chemical data sources Data source Number of records in source DrugBank 6828 PDB ligands 18681 MeSH (extracted by text mining) 24381 ChEBI 40503 HMDB 41494 ChEMBL 20 1456020 SureChEMBL 1.0 14228299
- 22. We generate RDF that: 1. Describes synonyms and identifiers 2. Provides linksets between our data sources and the OPS identifiers 3. Describes molecule–molecule relations of interest to the pharma industry 4. Delivers calculated physicochemical properties of compounds 5. Lists the validation and standardization issues found by CVSP. Royal Society of Chemistry data provided to Open PHACTS
- 23. • Use standard ontologies where possible (CHEMINF for cheminformatics properties, QUDT for units, OBO ontologies elsewhere) • Use an event-based pattern for cheminformatics outputs. This enables us to add arbitrary provenance information. Principles
- 24. Use the CHEMINF ontology: https://github.com/semanticchemistry Validated ChemSpider synonyms, Unvalidated ChemSpider synonyms, Validated database identifiers, Unvalidated database identifiers, InChI, InChIKey, SMILES, preferred ChemSpider name 1. Synonyms and identifiers
- 25. Metadata describing the RDF: • Can be used to build a directory of the RDF available • Find what’s there without having to download all of it first • Describes how Datasets are linked by the Linksets using SKOS. Recommendations here: http://www.openphacts.org/specs/2013/WD- datadesc-20130912/ 2. Linksets: Vocabulary of Interlinked Datasets
- 26. We relate molecules to “parent” forms, variously, those which are: • uncharged • not isotopically-specified • not stereochemically-specified • the preferred tautomer • the largest fragment • the “superparent” (all of the above) 3. Molecule–molecule relations in CHEMINF
- 27. log P, log D (at pH 5.5 and 7.4), bioconcentration factor, KOC (at pH 5.5 and 7.4), index of refraction, polar surface area, molar refractivity, molar volume, polarizability, surface tension, density at STP, flash point a 1 atm, enthalpy of vaporization at STP, vapour pressure at STP. 4. Calculated physicochemical properties
- 28. 5. Issues from validation and standardization We use the CHEMINF ontology again. We distinguish between information, warnings and errors. Only serious failures to process, such as a structure having an invalid atom, count as errors.
- 29. This is the world we live in
- 30. Data quality issue and CVSP – Robochemistry – Proliferation of errors in public and private databases • ChemSpider • PubChem • DrugBank • KEGG • ChEBI/ChEMBL – Automated quality control system
- 31. Chemistry Validation and Standardization Platform
- 32. Chemistry Validation and Standardization Platform
Notas do Editor
- Remember this, some of these questions are easier to answer than others
- Using available public data is critical to drug discovery
- 10 Can go get everything Open PHACTS not a repo of the world, specific sources
- 8
- Open PHACTS was developed to support the key questions of drug discovery Business questions have been at the heart of Open PHACTS and have driven the development of the platform Mx/psa, how calculated who did it? Mash up. With your data too, - top layer join together but need them all commercial Data provided by many publishers Originally in many formats: relational, SD files and RDF Worked closely with publishers Data licensing was a major issue Over 5 billion triples – 14 datasets & growing Hosted on beefy hardware; data in memory (aim) Extensive memcaching Pose complex queries to extract data
- 4 million full-text patent documents annotated • USPTO, WIPO, EPO – English language • Life-sciences relevant • Patents mapped to SureChEMBL IDs (e.g. EP-1339685-A2) • Title, publication date, classification codes • Compounds mapped to SCHEMBL IDs (e.g. SCHEMBL15064) • Genes mapped to HGNC symbols (e.g. FDFT1) • Diseases mapped to MeSH terms (e.g. D009765)
- Db Stds :which ones (later) Access (API). Driven by the API. Acelerate bulding if apps
- Open PHACTS discover platform is now supported by a Foundation
- Seen a growing usage of the platform both in volume and in registered applications API remains the cornerstone of the delivery
- Connected to different consumer groups
- Once users get connected to an API, they tend to stick with it. We are listening to this and will have a version independent URL
- Here we see the RSC dataset in Open PHACT’s data repository, which is running the open source Artifactory. The repository understands Maven metadata, and also maintain and verifies checksums of data artifacts. We see here it includes the suggested <dependency> setting for using the dataset from a different Maven project – while this would be a bit exotic perhaps, doing so would put the dataset directly on the classloader without any worrying about downloads or file paths. We can see the hierarchy of the dataset on the left – the repository has expanded the archive for us. The .ro folder contains the Research Object manifest, the void file is the Dataset description – the rest is the “actual data”. One power of Maven is the ease of setting up mirroring – the dataset above is actually from a mirror of the Maven repository of the build server in Manchester.
- All have probably seen this slide. Want to pick out some of the key changes and tomorrow will here more