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Intervet Chemicals Directory (ICD) - A Framework Combining Accelrys Pipeline Pilot and Symyx Isentris

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Frank Oellien
Frank Oellien

Chemical Normalization ? Isentris Registration PP ?

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Intervet Chemicals Directory (ICD) A Framework Combining Accelrys Pipeline Pilot and Symyx Isentris Frank Oellien 10/26/2010 Accelrys European User Group Meeting, Barcelona
Outline ? Motivation ICD project (historical review) ? Technical Implementation (2003) ? ICD Today (Enhancements in the last years) ? Technical limitations of the Isentris approach ? Solution: Combining Symyx Isentris & Accelrys PP C Structure Registration, Synchronization C Database Cleaning C Property-Calculations SP Intervet Chemicals Directory (ICD) 10/26/2010 2
Motivation ? Start of the ICD project 2003 ? Company was still young ? BioChemInformatics group (more precisely the cheminformatics branch) started its work on regular basis C C C C Ligand- and Structure-based Virtual Screening (LO and Hit2Lead projects) Property and Descriptor Calculations QSAR Substructure- and Similarity Searches ★ Access to many in-house data sources especially structures required ★ Many exchange formats used (including Excel and SD files) ★ Many diverse tools and applications used SP Intervet Chemicals Directory (ICD) 10/26/2010 3
Pre-ICD Time (before Q2 2003) SP Intervet Chemicals Directory (ICD) 10/26/2010 4
The Idea C A Central Data Source Other Data Sources In-house Databases Supplier Data SD SD SD SD SD SD ICD CompLog BCI Applications Medicinal Chemists SP Intervet Chemicals Directory (ICD) 10/26/2010 5
Requirements ? Standard data source for all BCI tasks ? Merged data source including in-house structures, supplier structures and other data sources ? Dynamically updated ? Structure database with unique structure identifier ? Standardized and Normalized data (including chemical normalization) ? Extendable system that can store other BCI-relevant information (e.g. virtual screening data) Ask other Scientists in the Drug Discovery department ? Storing supplier catalogues and other supplier information ? Data source for compound ordering ? Accessible by other scientists (especially medicinal chemists) ? Storage of physico-chemical properties for research projects SP Intervet Chemicals Directory (ICD) 10/26/2010 6
Implementation: Reasons for Isentris (2003) ? Not many systems available in 2003 (Auspyx, Acorrd, Isentris) ? Isentris used many technolgies that were already available in-house (MDL Direct, Oracle) ? Chemical Normalization available: Cheshire ? Advanced J2EE architecture and API that allows a good customization and extension ? CoRe: already an existing project based on Isentris C Intervet was an early adopter of Isentris C No additional software costs C Synergy effects (e.g. chemical business rules) SP Intervet Chemicals Directory (ICD) 10/26/2010 7
Implementation Overview SD Files ? supplier catalogs Chemical Rules ? TORE Updates (in-house) File syntax normalisation of SD files Generation of salt information and ParentHash codes (CheckAndFix_Main.cct) MDL Isentris (Client-Server) prepared SD Files CACTVS (Linux) ADME data Java application registration Java applications (Windows) Oracle SQLLoader (phys-chem properties) chemical normalisation ICD SP Intervet Chemicals Directory (ICD) 10/26/2010 8
Implementation: SD File Syntax Standardisation ? Based on CACTVS application (by Xemistry) ? SD file can have different inputs ? 2 generic scripts (supplier-specific, in-house specific) to standardize the format of the input SD files and supplier-specific configuration files ? SDF fields for supplier-related files: SupplierName, OrderNo, CatalogName, CatalogType, CatalogRelease, Confidential, CompoundName, IsSalt, Salt, Quantity, Purity ? SDF fields for in-house data: AHNO, CompoundName, IsSalt, Salt ? Calculation of structural hash codes (parent structure hash code) Insensitive hash codes: isotope, salt, tautomer, stereochemistry ? Automatically knowledge-based identification of salts ★ 174 different salts can be determined SP Intervet Chemicals Directory (ICD) 10/26/2010 9
Implementation: Chemical Normalisation ? Based on Cheshire (part of the Isentris framework) ? JavaScript clone ? Valence checks, Ion2kov, nitro group, transition metals, queries, geometries, stereo chemistry,´ ? 99 rules C 45 correction functions C 29 warnings functions C 25 error functions ? Used by CoRe and ICD applications ? Import: molfile string ? Output: molfile string and message string ★ Category; No of changes???list of descriptions SP Intervet Chemicals Directory (ICD) 10/26/2010 10
Implementation: Registration ? Based on Symyx Isentris Java Client (now Accelrys Isentris) ? Using Isentris Data Sources (Data Source Factory) ? 3 Java applications (in-house structures, supplier, virtual screening) ★ 31 java classes, ~9.500 lines code ? Run types: command line, GUI, batch mode ? Chem. Normalisation, duplicate check, registration logic * * ICD Supplier Registration * Version null * Frank Oellien, Intervet Innovation GmbH * 1:10:21 PM INFO: Chemical Normalization status: 304334 records without changes 4685 records fixed 11 records fixed but still have warnings 200 records with warnings 2 records with errors 1:10:21 PM INFO: Chemical Registration status: 1:10:21 PM INFO: New supplier has been registered. 309230 records to register 309222 records passed registration 8 records failed registration 180284 new structues registered 128938 structues already found in the DB 1:10:21 PM INFO: Closing Cheshire environment... 1:10:22 PM INFO: Releasing the ICD datasource resources ... 1:10:22 PM INFO: Closing the ICD DataSourceFactory... 1:10:22 PM INFO: Logout... 1:10:22 PM INFO: All resources released. SP Intervet Chemicals Directory (ICD) 10/26/2010 11
ICD Today - Datasheet ? ~ 11,500,000 structures ? 237 different catalogues (including screening libraries, focused data sets) ? 60 suppliers ? A broad range of standard pysicochemical properties ? Intervet¨s in-house database ? Specific Intervet data sets ? References to external sources (PubChem) SP Intervet Chemicals Directory (ICD) 10/26/2010 12
ICD Today C Change of Relevance ? Still the main data source for the BCI group, although almost all other BCI technologies have changed in the meantime ? Moreover, has become a key technology platform for the whole Drug Discovery process C Almost all compound logistic activities are based on the ICD (Applications for compound ordering) C Stores specific essential information for CompLog C Important database for Hit2Lead and LO projects (contains decision-critical properties) C Has become the most important structure-database for medicinal chemists ? Isentris upgrade to 3.1 ★ re-design of the ICD Isentris part necessary ? New demands by BCI and others had to be implemented ★ could not be realized with former setup because of limitations ? Solution: Combination with Pipeline Pilot SP Intervet Chemicals Directory (ICD) 10/26/2010 13
Limitations of the original Isentris Setup From the Beginning ? Starting with Isentris 1.1, early adopters ? Hard to implement: large, over-designed J2EE API, no developer guides, only some small code snippets ? Limited and complicated functions C e.g. no support for very large structure files ? Re-design of applications was necessary, because of Isentris updates ? No automation, everything is done in user context! Regarding recent Demands ? Missing Automation was still most critical issue: C Synchronisation C Adding non-structural data ? Elaborate database cleaning mechanisms SP Intervet Chemicals Directory (ICD) 10/26/2010 14
Registration of Supplier Cataloges SD Files Chemical Rules (CheckAndFix_Main.cct) structural normalisation of SD files Generation of salt information and ParentHash codes CACTVS (Linux) MDL Isentris (Client-Server) prepared SD Files chemical normalisation registration Java applications (Windows) ICD SP Intervet Chemicals Directory (ICD) 10/26/2010 15
Registration of in-house Structures by PP I in-house database structural normalisation of SD files Chemical Rules (CheckAndFix_Main.cct) Generation of salt information and ParentHash codes CACTVS called by PP Synchronisation by Pipeline Pilot (Linux) chemical normalisation registration Cheshire PP Component ICD SP Intervet Chemicals Directory (ICD) 10/26/2010 16
Registration of in-house Structures by PP II Retrieve structures from database Call CACTVS application Chemical Normalisation & Registration SP Intervet Chemicals Directory (ICD) 10/26/2010 17
Cheshire PP Component (Java) ? Implemented as PP Java component ? Based on Cheshire Java API ? Calls Cheshire core library (shared object files called by JNI) SP Intervet Chemicals Directory (ICD) 10/26/2010 18
Cheshire PP Component (Java) ? Implemented as PP Java component ? Based on Cheshire Java API ? Calls Cheshire core library (shared object files called by JNI) SP Intervet Chemicals Directory (ICD) 10/26/2010 19
Cheshire PP Component (Java) SP Intervet Chemicals Directory (ICD) 10/26/2010 20
Importing physico-chemical Properties I ADME data Oracle SQLLoader (phys-chem properties) Java application ICD SP Intervet Chemicals Directory (ICD) 10/26/2010 21
Importing physico-chemical Properties I External application 2 (descriptos) External ADME data application 3 (phys-chem (descriptos) properties) External application 4 (descriptos) External application 1 (standardize) Retrieval of structures without properties Oracle SQLLoader Java application Internal PP components (descriptors) ICD Import properties Managed by Pipeline Pilot (Linux) SP Intervet Chemicals Directory (ICD) 10/26/2010 22
Importing physico-chemical Properties II SP Intervet Chemicals Directory (ICD) 10/26/2010 23
Database Maintenance SP Intervet Chemicals Directory (ICD) 10/26/2010 24
Isentris PP Components @ SP Intervet ? Isentris Cheshire PP ? Converter: C C C C Chime string to Molecule Chime string to CTAB Molecule to Chime string CTAB to Chime string SP Intervet Chemicals Directory (ICD) 10/26/2010 25
Acknowledgement Information Management ? Werner Schl┨ter ? Thomas Fischer BioChemInformatics ? Richard Marh?fer ? Andreas Krasky ? (J?rg Cramer) ? J?rg Schr?der ? Paul M. Selzer Thank you SP Intervet Chemicals Directory (ICD) 10/26/2010 26

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Intervet Chemicals Directory (ICD) - A Framework Combining Accelrys Pipeline Pilot and Symyx Isentris

  • 1. Intervet Chemicals Directory (ICD) A Framework Combining Accelrys Pipeline Pilot and Symyx Isentris Frank Oellien 10/26/2010 Accelrys European User Group Meeting, Barcelona
  • 2. Outline ? Motivation ICD project (historical review) ? Technical Implementation (2003) ? ICD Today (Enhancements in the last years) ? Technical limitations of the Isentris approach ? Solution: Combining Symyx Isentris & Accelrys PP C Structure Registration, Synchronization C Database Cleaning C Property-Calculations SP Intervet Chemicals Directory (ICD) 10/26/2010 2
  • 3. Motivation ? Start of the ICD project 2003 ? Company was still young ? BioChemInformatics group (more precisely the cheminformatics branch) started its work on regular basis C C C C Ligand- and Structure-based Virtual Screening (LO and Hit2Lead projects) Property and Descriptor Calculations QSAR Substructure- and Similarity Searches ★ Access to many in-house data sources especially structures required ★ Many exchange formats used (including Excel and SD files) ★ Many diverse tools and applications used SP Intervet Chemicals Directory (ICD) 10/26/2010 3
  • 4. Pre-ICD Time (before Q2 2003) SP Intervet Chemicals Directory (ICD) 10/26/2010 4
  • 5. The Idea C A Central Data Source Other Data Sources In-house Databases Supplier Data SD SD SD SD SD SD ICD CompLog BCI Applications Medicinal Chemists SP Intervet Chemicals Directory (ICD) 10/26/2010 5
  • 6. Requirements ? Standard data source for all BCI tasks ? Merged data source including in-house structures, supplier structures and other data sources ? Dynamically updated ? Structure database with unique structure identifier ? Standardized and Normalized data (including chemical normalization) ? Extendable system that can store other BCI-relevant information (e.g. virtual screening data) Ask other Scientists in the Drug Discovery department ? Storing supplier catalogues and other supplier information ? Data source for compound ordering ? Accessible by other scientists (especially medicinal chemists) ? Storage of physico-chemical properties for research projects SP Intervet Chemicals Directory (ICD) 10/26/2010 6
  • 7. Implementation: Reasons for Isentris (2003) ? Not many systems available in 2003 (Auspyx, Acorrd, Isentris) ? Isentris used many technolgies that were already available in-house (MDL Direct, Oracle) ? Chemical Normalization available: Cheshire ? Advanced J2EE architecture and API that allows a good customization and extension ? CoRe: already an existing project based on Isentris C Intervet was an early adopter of Isentris C No additional software costs C Synergy effects (e.g. chemical business rules) SP Intervet Chemicals Directory (ICD) 10/26/2010 7
  • 8. Implementation Overview SD Files ? supplier catalogs Chemical Rules ? TORE Updates (in-house) File syntax normalisation of SD files Generation of salt information and ParentHash codes (CheckAndFix_Main.cct) MDL Isentris (Client-Server) prepared SD Files CACTVS (Linux) ADME data Java application registration Java applications (Windows) Oracle SQLLoader (phys-chem properties) chemical normalisation ICD SP Intervet Chemicals Directory (ICD) 10/26/2010 8
  • 9. Implementation: SD File Syntax Standardisation ? Based on CACTVS application (by Xemistry) ? SD file can have different inputs ? 2 generic scripts (supplier-specific, in-house specific) to standardize the format of the input SD files and supplier-specific configuration files ? SDF fields for supplier-related files: SupplierName, OrderNo, CatalogName, CatalogType, CatalogRelease, Confidential, CompoundName, IsSalt, Salt, Quantity, Purity ? SDF fields for in-house data: AHNO, CompoundName, IsSalt, Salt ? Calculation of structural hash codes (parent structure hash code) Insensitive hash codes: isotope, salt, tautomer, stereochemistry ? Automatically knowledge-based identification of salts ★ 174 different salts can be determined SP Intervet Chemicals Directory (ICD) 10/26/2010 9
  • 10. Implementation: Chemical Normalisation ? Based on Cheshire (part of the Isentris framework) ? JavaScript clone ? Valence checks, Ion2kov, nitro group, transition metals, queries, geometries, stereo chemistry,´ ? 99 rules C 45 correction functions C 29 warnings functions C 25 error functions ? Used by CoRe and ICD applications ? Import: molfile string ? Output: molfile string and message string ★ Category; No of changes???list of descriptions SP Intervet Chemicals Directory (ICD) 10/26/2010 10
  • 11. Implementation: Registration ? Based on Symyx Isentris Java Client (now Accelrys Isentris) ? Using Isentris Data Sources (Data Source Factory) ? 3 Java applications (in-house structures, supplier, virtual screening) ★ 31 java classes, ~9.500 lines code ? Run types: command line, GUI, batch mode ? Chem. Normalisation, duplicate check, registration logic * * ICD Supplier Registration * Version null * Frank Oellien, Intervet Innovation GmbH * 1:10:21 PM INFO: Chemical Normalization status: 304334 records without changes 4685 records fixed 11 records fixed but still have warnings 200 records with warnings 2 records with errors 1:10:21 PM INFO: Chemical Registration status: 1:10:21 PM INFO: New supplier has been registered. 309230 records to register 309222 records passed registration 8 records failed registration 180284 new structues registered 128938 structues already found in the DB 1:10:21 PM INFO: Closing Cheshire environment... 1:10:22 PM INFO: Releasing the ICD datasource resources ... 1:10:22 PM INFO: Closing the ICD DataSourceFactory... 1:10:22 PM INFO: Logout... 1:10:22 PM INFO: All resources released. SP Intervet Chemicals Directory (ICD) 10/26/2010 11
  • 12. ICD Today - Datasheet ? ~ 11,500,000 structures ? 237 different catalogues (including screening libraries, focused data sets) ? 60 suppliers ? A broad range of standard pysicochemical properties ? Intervet¨s in-house database ? Specific Intervet data sets ? References to external sources (PubChem) SP Intervet Chemicals Directory (ICD) 10/26/2010 12
  • 13. ICD Today C Change of Relevance ? Still the main data source for the BCI group, although almost all other BCI technologies have changed in the meantime ? Moreover, has become a key technology platform for the whole Drug Discovery process C Almost all compound logistic activities are based on the ICD (Applications for compound ordering) C Stores specific essential information for CompLog C Important database for Hit2Lead and LO projects (contains decision-critical properties) C Has become the most important structure-database for medicinal chemists ? Isentris upgrade to 3.1 ★ re-design of the ICD Isentris part necessary ? New demands by BCI and others had to be implemented ★ could not be realized with former setup because of limitations ? Solution: Combination with Pipeline Pilot SP Intervet Chemicals Directory (ICD) 10/26/2010 13
  • 14. Limitations of the original Isentris Setup From the Beginning ? Starting with Isentris 1.1, early adopters ? Hard to implement: large, over-designed J2EE API, no developer guides, only some small code snippets ? Limited and complicated functions C e.g. no support for very large structure files ? Re-design of applications was necessary, because of Isentris updates ? No automation, everything is done in user context! Regarding recent Demands ? Missing Automation was still most critical issue: C Synchronisation C Adding non-structural data ? Elaborate database cleaning mechanisms SP Intervet Chemicals Directory (ICD) 10/26/2010 14
  • 15. Registration of Supplier Cataloges SD Files Chemical Rules (CheckAndFix_Main.cct) structural normalisation of SD files Generation of salt information and ParentHash codes CACTVS (Linux) MDL Isentris (Client-Server) prepared SD Files chemical normalisation registration Java applications (Windows) ICD SP Intervet Chemicals Directory (ICD) 10/26/2010 15
  • 16. Registration of in-house Structures by PP I in-house database structural normalisation of SD files Chemical Rules (CheckAndFix_Main.cct) Generation of salt information and ParentHash codes CACTVS called by PP Synchronisation by Pipeline Pilot (Linux) chemical normalisation registration Cheshire PP Component ICD SP Intervet Chemicals Directory (ICD) 10/26/2010 16
  • 17. Registration of in-house Structures by PP II Retrieve structures from database Call CACTVS application Chemical Normalisation & Registration SP Intervet Chemicals Directory (ICD) 10/26/2010 17
  • 18. Cheshire PP Component (Java) ? Implemented as PP Java component ? Based on Cheshire Java API ? Calls Cheshire core library (shared object files called by JNI) SP Intervet Chemicals Directory (ICD) 10/26/2010 18
  • 19. Cheshire PP Component (Java) ? Implemented as PP Java component ? Based on Cheshire Java API ? Calls Cheshire core library (shared object files called by JNI) SP Intervet Chemicals Directory (ICD) 10/26/2010 19
  • 20. Cheshire PP Component (Java) SP Intervet Chemicals Directory (ICD) 10/26/2010 20
  • 21. Importing physico-chemical Properties I ADME data Oracle SQLLoader (phys-chem properties) Java application ICD SP Intervet Chemicals Directory (ICD) 10/26/2010 21
  • 22. Importing physico-chemical Properties I External application 2 (descriptos) External ADME data application 3 (phys-chem (descriptos) properties) External application 4 (descriptos) External application 1 (standardize) Retrieval of structures without properties Oracle SQLLoader Java application Internal PP components (descriptors) ICD Import properties Managed by Pipeline Pilot (Linux) SP Intervet Chemicals Directory (ICD) 10/26/2010 22
  • 23. Importing physico-chemical Properties II SP Intervet Chemicals Directory (ICD) 10/26/2010 23
  • 24. Database Maintenance SP Intervet Chemicals Directory (ICD) 10/26/2010 24
  • 25. Isentris PP Components @ SP Intervet ? Isentris Cheshire PP ? Converter: C C C C Chime string to Molecule Chime string to CTAB Molecule to Chime string CTAB to Chime string SP Intervet Chemicals Directory (ICD) 10/26/2010 25
  • 26. Acknowledgement Information Management ? Werner Schl┨ter ? Thomas Fischer BioChemInformatics ? Richard Marh?fer ? Andreas Krasky ? (J?rg Cramer) ? J?rg Schr?der ? Paul M. Selzer Thank you SP Intervet Chemicals Directory (ICD) 10/26/2010 26