RDF Workshop. Building an RDF representation of the the ChEMBL Database. Mark Davies. ChEMBL Group, Technical Lead 30/04/2014

Transcription

1 RDF Workshop Building an RDF representation of the the ChEMBL Database Mark Davies ChEMBL Group, Technical Lead 30/04/2014

2 Overview Brief introduction to ChEMBL database Approaches to mapping relational data to RDF data model based on ChEMBL experience New features in ChEMBL RDF (version 18) Future ChEMBL plans

3 What is ChEMBL? Open access database for drug discovery Freely available (searchable and downloadable) Content: Bioactivity data manually extracted from the primary medicinal chemistry literature from journals such as J. Med. Chem. Subset of data from PubChem Deposited data e.g. neglected disease screening, GSK kinase set Bioactivity data is associated with a biological target and a chemical structure Compounds are stored in a structure searchable format Protein targets are linked to protein sequences in UniProt Updated regularly with new data Secure searching ( )

4 ChEMBL ChEMBL 18 Release 1,359,508 compounds 12,419,715 activities 1,042,374 assays 9,414 targets 53,298 documents 19 bioactivity sources 6 compound-only sources

5 What does ChEMBL data look like? Compound Activity Assay Target Ref

6 How can I access ChEMBL data? Web Services Widgets Website Downloads Virtual Machine (mychembl) Semantic Web

7 ChEMBL + Semantic Web The creation of the RDF version of ChEMBL is funded by the Open PHACTS project - Migrate the ChEMBL relational data model to RDF based data model triplify everything RDF generation is part of official ChEMBL release process Identify and use ontologies important in the field of bioactivity data ChEMBL RDF to be made available through EBI RDF Platform

8 Goals of the ChEMBL RDF conversion Responding to the demands of the community Academic and more recently industry Semantic data conversion and querying Reasoning/inferencing - providing a starting point for the community Ensure the conversion is part of the ChEMBL release cycle ChEMBL data model is still evolving so almost impossible for external efforts to keep up to speed with changes

9 ChEMBL RDF Compound Bioactivity Assay Target Ref ftp://ftp.ebi.ac.uk/pub/databases/chembl/chembl-rdf/

10 Conversion process ChEMBL Relational Schema ChEMBL RDF Schema

11 Migrating a relational data model Where to start? What is your goal? How often will it be updated? Who is the audience? What tools to use? Do you write you own ontology? Which ontologies to use? Which format to use? Will it be made available to the public? Two approaches were used to convert the ChEMBL relational model to an RDF based model Approach 1: Semi-automated using the D2RQ Platform Approach 2: Manual model building

12 Approach 1: Semi-automated using the D2RQ Platform

13 D2RQ platform overview Query a non-rdf database using SPARQL Access the content of the database as Linked Data over the Web Create custom dumps of the database in RDF formats for loading into an RDF store Access information in a non- RDF database using the Apache Jena API

14 ChEMBL relational schema 3 core domains Compound Activity Target 52 tables (52 primary keys J ) 341 columns 4 data types (40 if length, scale and precision included) Many indexes, constraints, triggers..

15 D2RQ: Prerequisites Download the software from Java 1.5 or higher Oracle users will need to download database driver

16 D2RQ: Example usage Aims Create RDF representation of your relational data model Run and test SPARQL queries against your database Online data access and representation Process Generate D2R Mapping File Start up D2R Server using D2R Mapping File Refine model Support databases Oracle, SQL Server, PostgreSQL, MySQL, HSQLDB,

17 D2RQ: Mapping File Creation Command used to generate D2R Mapping File (you just need a database connection string): $>./generate-mapping -o example_d2r_mapping.ttl \! -u <USER> \! -p <PASSWORD> \! -d oracle.jdbc.driver.oracledriver jdbc:oracle:thin:@<server>:<port>:<database>! Command above will inspect database and create RDF based definitions of tables and relationships between tables Possible to skip/restrict schemas/tables/columns with additional argument useful for Oracle

18 D2RQ: Mapping file map: db: vocab: rdf: rdfs: xsd: d2rq: jdbc: < map:database a d2rq:database;! d2rq:jdbcdriver "oracle.jdbc.driver.oracledriver";! d2rq:jdbcdsn "jdbc:oracle:thin:@<server>:<port>:<database>";! d2rq:username "<USER>";! d2rq:password "<PASSWORD>";!.!! # Table CHEMBL_18.ACTION_TYPE! map:chembl_18_action_type a d2rq:classmap;! d2rq:datastorage map:database;! d2rq:uripattern "CHEMBL_18/ACTION_TYPE/@@CHEMBL_18.ACTION_TYPE.ACTION_TYPE urlify@@";! d2rq:class vocab:chembl_18_action_type;! d2rq:classdefinitionlabel "CHEMBL_18.ACTION_TYPE";!.! map:chembl_18_action_type label a d2rq:propertybridge;! d2rq:belongstoclassmap map:chembl_18_action_type;! d2rq:property rdfs:label;! d2rq:pattern "ACTION_TYPE #@@CHEMBL_18.ACTION_TYPE.ACTION_TYPE@@";!.! map:chembl_18_action_type_action_type a d2rq:propertybridge;! d2rq:belongstoclassmap map:chembl_18_action_type;! d2rq:property vocab:chembl_18_action_type_action_type;! d2rq:propertydefinitionlabel "ACTION_TYPE ACTION_TYPE";! d2rq:column "CHEMBL_18.ACTION_TYPE.ACTION_TYPE";!.! map:chembl_18_action_type_description a d2rq:propertybridge;! d2rq:belongstoclassmap map:chembl_18_action_type;! d2rq:property vocab:chembl_18_action_type_description;! d2rq:propertydefinitionlabel "ACTION_TYPE DESCRIPTION";! d2rq:column "CHEMBL_18.ACTION_TYPE.DESCRIPTION";!.! map:chembl_18_action_type_parent_type a d2rq:propertybridge;! d2rq:belongstoclassmap map:chembl_18_action_type;! d2rq:property vocab:chembl_18_action_type_parent_type;! d2rq:propertydefinitionlabel "ACTION_TYPE PARENT_TYPE";! d2rq:column "CHEMBL_18.ACTION_TYPE.PARENT_TYPE";!.!

19 D2R Server SPARQL endpoint and explorer Browsing database contents Resolvable URIs Content negotiation Downloading contents of BLOBs/CLOBs Serving the vocabulary Publishing metadata Command used to start D2R server (assuming you have generated mapping file): $>./d2r-server example_d2r_mapping.ttl!

20 D2R Server

21 D2R Server

22 (Quick) D2RQ Demo

23 D2RQ: Data modeling It is possible to model data and also create more meaningful class and property names Approach 1 Edit the mapping file using advanced features of the D2RQ query language: Approach 2 Create mapping file based on restricted set of database objects e.g. users, schemas, views, materialised views modeling within the database

24 D2RQ: Optimisations Review D2R server deployment Increase D2R server heap space Review configurations settings, such as page sizes, resultset limits Use latest built-in D2RQ optimisations, by specifying d2rq:usealloptimizations (or --fast flag on server startup) Use D2RQ s dump-rdf command to export RDF representation of database Exported RDF can then be imported into a triplestore, e.g. Virtuoso

25 D2RQ: Limitations General limitations Integration of multiple databases not possible achieved within the database Read only access update extension is available Limited inferencing available Named graphs not supported Users tend to end up creating weird mapping files Database models are often not perfect or clean, which complicates mapping file creation process Just mapping to RDF is not enough

26 Approach 2: Manual model building

27 Approach 2 outline Building a basic ontology and instantiate with data Steps: Define entities in data source Define relationships between entities Define properties of the entities Identify and use external ontologies

28 Model building considerations Review available technologies/languages Preferred may not have good RDF support/libs RDF data formats e.g. rdf, ttl, n3 All are interchangeable, but some are considered more readable and offer reduced size

29 ChEMBL relational schema revisited References Activities Targets Assays Molecules Binding Sites MOAs Drugs

30 ChEMBL Entities/Classes Journal Source Target- Component Document Assay Protein- Classification Substance Activity Target Bio- Component ChEMBL 17 classes

31 ChEMBL class definition An OWL based ontology used to define ChEMBL classes OWL snippet used to define ChEMBL : < :Assay! rdf:type owl:class ;! rdfs:label "ChEMBL Assay Class"^^xsd:string ;! rdfs:subclassof :ChEMBL.! Tools available to help build and write ontologies, e.g. Protégé and TopBraid Composer

32 Entity RDF representation Entity names become classes, which allow you to type your data! chembl_assay:chembl a cco:assay.! chembl_assay: and cco: are prefixes and a is a turtle shorthand for rdf:type

33 ChEMBL Entity relationships Journal Source Target- Component Document Assay Protein- Classification Substance Activity Target Bio- Component

34 Relationship RDF representation Relationships defined between instances of your entities are object properties! chembl_assay:chembl a cco:assay ;! cco:hastarget chembl_target:chembl ;! cco:hasactivity chembl_activity:chembl_act_ !

35 ChEMBL assay attributes Identify attributes from database you want to include in RDF model Map attribute types e.g. integers, strings, Booleans Some attributes map to external resources/ontologies see later Denormalisation of relational data, e.g. FKs

36 Attribute RDF representation Attributes you define for your classes are datatype properties! chembl_assay:chembl a cco:assay ;! cco:hastarget chembl_target:chembl ;! cco:hasactivity chembl_activity:chembl_act_ ;! rdfs:label "CHEMBL615672" ;! cco:chemblid "CHEMBL615672" ;! cco:assaytype "Functional" ;! cco:assaycelltype "3LL cell line" ;! cco:organismname "Mus musculus.!! Good practice to add a rdfs:label to all instances

37 More examples ChEMBL Entity properties Substance Target Activity TopBraid Composer (Free Edition)

38 Mapping to external ontologies Examples of ontologies/taxonomies mapped to in ChEMBL RDF include: BioAssay Ontology (BAO) ChEBI Chemical Infomation Ontology (CHEMINF) Bibliographic Ontology Unit Ontology (UO) QUDT Ontology Semantic Science Ontology (SIO) Cell Line Ontology (CLO) Experimental Factor Ontology (EFO)

39 External ontologies/taxonomies Identification of relevant external ontologies Community consensus + recommendations BioPortal - Ontology Lookup Service -

40 ChEMBL assay data Journal Source Target- Component Document Assay Protein- Classification Substance Activity Target Bio- Component

41 ChEMBL assay annotation The assay is the central component to the ChEMBL data model Current model not ideal Single category - binding, functional, ADMET, physchem Unstructured/free text used to describe assay Many assay parameters not captured although often not available Ontologies are now being used to improve ChEMBL assay annotations - ChEMBL_17 onwards Mappings to BAO bioassays, assay_format, endpoints

42 BioAssay Ontology Bioassay parent class, 92 descendant classes How do we map to all these BAO assay classes?

43 External ontology mapping process In many cases mapping is straight forward Use common bridging identifier e.g. UniProt Simple text based conversion e.g. units - actually units not so straight forward in ChEMBL Some mappings require complex rules e.g. assay details Multiple database parameters Complex text processing Manual curation Tools available to assist with mapping process BioPortal Annotator ( Zooma ( ChEMBL Assay Annotator

44 BioPortal Annotator ChEMBL Assay Description Restricted to Ontology interest (optional) Results API available

45 BioPortal Annotator Example CHEMBL assay description Induction of apoptosis in human Jurkat T cells overexpressing Neo assessed as loss in mitochondrial membrane potential at 30 ug/ml after 36 hrs by DiO6-based flow cytometry (Rvb = 5.4%) More information here: Now use BioPortal Annotator to annotate

46 ChEMBL Assay Annotator ChEMBL Assay Annotator developed by Samuel Croset Aim is to map ChEMBL assays to BAO assay classes Tailored mapping rules developed

47 External mapping representation In this example defining assay_format:! chembl_assay:chembl a cco:assay ;! cco:hastarget chembl_target:chembl ;! cco:hasactivity chembl_activity:chembl_act_ ;! rdfs:label "CHEMBL615672" ;! cco:chemblid "CHEMBL615672" ;! cco:assaytype "Functional" ;! cco:assaycelltype "3LL cell line" ;! cco:organismname "Mus musculus ;! bao:bao_ bao:bao_ !!! BAO_ = has_assay_format BAO_ = Cell based

48 ChEMBL Core Ontology (CCO) The skeleton schema used to store ChEMBL classes, object properties and datatype properties The file is also RDF, so can be queried independent of an instances ftp://ftp.ebi.ac.uk/pub/databases/chembl/chembl-rdf/18.0/ cco.ttl.gz Namespace: Initial focus on Substance (Molecule) and Target Classification In future an additional mapping file may be provided, which maps/aligns ChEMBL classes and properties to external resources

49 ChEMBL Core Ontology (CCO) Classes Substance Classes Target Classes

50 ChEMBL RDF schema

51 The (raw) end result

52 Querying ChEMBL data Need to load files into triplestore (Virtuoso Open Source) CCO ChEMBL SPARQL Interface/LD Browser Reactome Triplestore UniProt Triplestore ChEMBL Data ChEMBL Triplestore External Ontos e.g. BAO Bio2RDF

53 Using external RDF data sources Questions to think about when using external RDF data sources Who creates resource and the RDF representation? When was the resource last updated? When was RDF last updated? Does the data model make sense? Basic queries work? Shared entities and ontologies? Any data licensing issues?

54 VoID can help VoID = Vocabulary of Interlinked Datasets Acts a bridge between publishers and users EBI RDF resources provide a VoID (just an extra RDF file) Information contained in VoID Creation timestamps Publisher details Versioning Ontologies/vocabularies used Licensing Data formats available and where they live (not just RDF) More complex information such as Subsets and Linksets

55 Quick look at the ChEMBL VoID

56 Model building recommendations Technology review URIs should resolve and be future proofed Ensure the correct external namespaces are being used Add rdfs:label to everything Consider using identifiers for ontology names instead of textual descriptions As small descriptive ontology grows consistent naming conventions can breakdown Not used for CCO, but may consider future format switch e.g. CCO_ = ChEMBL Activity, CCO_ = ChEMBL Assay and so on

57 Technology stack Triple Processing Groovy OpenRDF Sesame Java API ( Rapper useful command line utility Triplestore/Storage Virtuoso Open Source Edition (Upgrade to Version 7 planned) Raw.ttl files available to download from ChEMBL FTP site ftp://ftp.ebi.ac.uk/pub/databases/chembl/chembl-rdf/ Domain/class specific.ttl files created helps processing and loading

58 New features ChEMBL 18 RDF More data, now 409,989,782 triples New types of data Binding sites, cell lines, mechanism of action New properties Molecule hierarchy mappings Target complex mappings Assay parameters Improved mappings to the BAO ontology assay_format, e.g. biochemical, physiochemical, cell based, Some example queries now follow ->

59 Example query 1 Get all human cell-lines: PREFIX rdfs: < PREFIX dcterms: < PREFIX bao: < PREFIX cco: < SELECT?cellLine?cellName! WHERE {!?cellline a cco:cellline ;! cco:taxonomy < ;! rdfs:label?cellname.! }!

60 Example query 2 Get all compounds that have been tested in a cell-based (bao:bao_ ) toxicity assay in HepG2 cells: PREFIX rdfs: < PREFIX dcterms: < PREFIX bao: < PREFIX cco: < SELECT?mol?assayDesc! WHERE {!?mol?p cco:substance ;! cco:substancetype?moltype ;! cco:hasactivity?activity.!?activity cco:hasassay?assay.!?assay cco:assaycelltype 'HepG2' ;! cco:assaytype 'Toxicity' ;! bao:bao_ bao:bao_ ;! dcterms:description?assaydesc.! }!

61 Example query 3 Get all concentration response assays (bao:bao_ ) for monoamine receptor targets (CHEMBL_PC_1266): PREFIX rdfs: < PREFIX dcterms: < PREFIX bao: < PREFIX cco: < SELECT distinct?assay?assaydesc! WHERE{! < cco:hastargetdescendant?target.!?target cco:hasassay?assay.!?assay cco:hasactivity?activity ;! dcterms:description?assaydesc.!?activity bao:bao_ ?endpoint.!?endpoint rdfs:subclassof bao:bao_ ! }!

62 Example query 4 Get the number of ADME assays carried out in organismbased (bao:bao_ ) format for FDA approved drugs: PREFIX rdfs: < PREFIX dcterms: < PREFIX bao: < PREFIX cco: < SELECT?molname?mol (count(distinct?assay) as?assay_count)! WHERE{!?assay a cco:assay ;! cco:assaytype 'ADME' ;! bao:bao_ bao:bao_ !?assay cco:hasactivity?activity.!?activity cco:hasmolecule?mol.!?mol cco:highestdevelopmentphase 4 ;! rdfs:label?molname.! }! GROUP BY?molname?mol! ORDER BY DESC(count(distinct?assay))!

63 Example query 5 Get all cell-lines that have been used in physical property assays (bao:bao_ ): PREFIX rdfs: < PREFIX dcterms: < PREFIX bao: < PREFIX cco: < SELECT?cellLine?assay! WHERE {!?cellline a cco:cellline ;! cco:iscelllineforassay?assay.!?assay cco:hasactivity?activity.!?activity bao:bao_ ?endpoint.!?endpoint rdfs:subclassof bao:bao_ ! }!

64 Example query 6 Get all Protein Kinase (CHEMBL_PC_1100) inhibitor binding sites: PREFIX rdfs: < PREFIX dcterms:< PREFIX bao: < PREFIX cco:< SELECT?target?bindingSite?siteName?inhibitor! WHERE{!?bindingSite a cco:bindingsite ;! cco:bindingsitename?sitename ;! cco:hastarget?target.! < cco:hastargetdescendant?target.!?target rdfs:label?targetname ;! cco:istargetformechanism?mechanism.!?mechanism cco:mechanismactiontype 'INHIBITOR' ;! cco:mechanismdescription?mechanismdesc ;! cco:hasmolecule?molecule.!?molecule rdfs:label?inhibitor.! }!

65 Future Plans: SureChEMBL December 2013 EMBL-EBI acquired SureChem a leading chemistry patent mining product from Digital Science, Macmillan Group SureChem provides a live (updated daily) view chemical patent space Rebranded SureChEMBL

66 Open PHACTS extension Open PHACTS project is keen to include patent data in future extensions to the project ENSO approved - funding to include SureChEMBL data in Open PHACTS RDF conversion, target indexing and API development EBI-RDF project benefit from RDF conversion SureChEMBL is updated daily, compared to quarterly ChEMBL updates Interesting challenge for us creating exports and systems loading SureChEMBL

67 Open PHACTS Platform Apps Core Platform Identity Resolution Service Identifier Management Service Adenosine receptor 2a P12374 EC CS4532 Linked Data API (RDF/XML, TTL, JSON) Semantic Workflow Engine Data Cache (Virtuoso Triple Store) Chemistry Registration Normalisation & Q/C Domain Specific Services Indexing VoID VoID VoID VoID VoID Nanopub Nanopub Nanopub Public Ontologies Db Db Public Content Db Commercial Db User Annotations (slide author: Lee Harland)

68 Summary Review of the ChEMBL database Two approaches used to modeling ChEMBL data Approach 2 used to build RDF representation of ChEMBL New features included in ChEMBL_18 release Model enhancements More data Plans for the future Patents Open PHACTS

69 Acknowledgements Groups and people involved in the RDF representation of ChEMBL include: ChEMBL Group Anna Gaulton Samual Croset John Overington EBI-RDF Group Andy Jenkinson Simon Jupp James Malone Open PHACTS Alasdair Gray Antonis Loizou Lee Harland Egon Willighagen