Chemical Database Projects Delivered by RSC eScience


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This presentation is an overview of some of the projects we are involved with at RSC eScience. The presentation was given at the FDA Meeting regarding the “Development of a Freely Distributable Data System for the Registration of Substances

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  • The result of processing is a list of records with validation messages in the middle. If record was standardized then “Standardized” column is present with the structure.
  • Here is the bigger DrugBank dataset we have processed. Some warnings are shown in the dropdown list. Warnings about metals, stereo, enol presence, etc.
  • DrugBank data set was used as Guinea pig in this case and passed through CVSP and several issues were found. OF course, issues are marked as warnings or errors arbitrarily, but they correlate with the level of attention that depositors need to pay attention when reviewing their submission. There were 2 records where non aromatic query bonds were used, 3 records with invalid atoms (e.g. ”A” in polymers). About 70 records had issues: mostly radicals, inorganics, and coordination compounds have unusual valences. But these are records that experts in inorganic chemistry or coordination chemistry need to look at and have their verdict.
  • First example is where InChI shows known stereo on double bonds but structure doesn’t. Second example is where neither the InChI nor the name match the structure. This is an example where the primary data – in this case original DrugBank dataset – with these inconsistencies have propagated to few big databases. It would be beneficial if original dataset owners pass their data through validation and fix them. We would be happy to assist in this adventure to anybody that is interested in quality of their data sets.
  • Chemical Database Projects Delivered by RSC eScience

    1. 1. Chemical Database Projects Delivered by RSC eScience at the FDA Meeting “Development of a Freely Distributable Data System for the Registration of Substances” Antony Williams
    2. 2. RSC eScience What was once just ChemSpider is much more…  ChemSpider Reactions  Chemicals Validation and Standardization Platform  Learn Chemistry Wiki  National Chemical Database Service  Open PHACTS  PharmaSea  Global Chemistry Hub
    3. 3. We are known for ChemSpider… The Free Chemical Database A central hub for chemists to source information  >28 million unique chemical records  Aggregated from >400 data sources  Chemicals, spectra, CIF files, movies, images, podcasts, links to patents, publications, predictions A central hub for chemists to deposit & curate data
    4. 4. We Want to Answer Questions Questions a chemist might ask…  What is the melting point of n-heptanol?  What is the chemical structure of Xanax?  Chemically, what is phenolphthalein?  What are the stereocenters of cholesterol?  Where can I find publications about xylene?  What are the different trade names for Ketoconazole?  What is the NMR spectrum of Aspirin?  What are the safety handling issues for Thymol Blue?
    5. 5. I want to know about “Vincristine”
    6. 6. Vincristine: Identifiers and Properties
    7. 7. Vincristine: Vendors and Sources
    8. 8. Vincristine: Articles
    9. 9. How did we build it? We deal in Molfiles or SDF files – with coordinates Deposit anything that has an InChI – we support what InChI can handle, good and bad Standardization based on “InChI standardization” InChIs aggregate (certain) tautomers
    10. 10. The InChI Identifier
    11. 11. Downsides of InChI Good for small molecules – but no polymers, issues with inorganics, organometallics, imperfect stereochemistry. ChemSpider is “small molecules” InChI used as the “deduplicator” – FIRST version of a compound into the database becomes THE structure to deduplicate against…
    12. 12. Side Effects of InChI Usage
    13. 13. SMILES by comparison…
    14. 14. Side Effects of InChI Usage
    15. 15. Searches: The INTERNET
    16. 16. Search by InChI
    17. 17. ChemSpider Google Search
    18. 18. How did we build it? We deal in Molfiles or SDF files – with coordinates Deposit anything that has an InChI – we support what InChI can handle, good and bad Standardization based on “InChI standardization” InChIs aggregate (certain) tautomers We deal with “various forms” of data
    19. 19. Crowdsourced “Annotations” Users can add  Descriptions/Syntheses/Commentaries  Links to PubMed articles  Links to articles via DOIs  Add spectral data  Add Crystallographic Information Files  Add photos  Add MP3 files  Add Videos
    20. 20. ChemSpider : Spectra Linked
    21. 21. ChemSpider ID 24528095 H1 NMR
    22. 22. ChemSpider ID 24528095 HHCOSY
    23. 23. How did we build it? We deal in Molfiles or SDF files – with coordinates Deposit anything that has an InChI – we support what InChI can handle, good and bad Standardization based on “InChI standardization” InChIs aggregate (certain) tautomers We deal with “various forms” of data We are challenged with the complexities of chemical names
    24. 24. Antony Williams vs Identifiers Passport ID Dad, Tony, others5 email addresses LicenseChemSpiderman (blog, SSNTwitter account,Facebook, Friendfeed)OpenID…. Green Card
    25. 25. Aspirin names and synonyms • Text searches depend on correct association • >300 suggested identifiers for Aspirin just on PubChem • Disambiguation dictionaries are necessary, not just for authors!
    26. 26. The Final Search Strategy
    27. 27. All Those Names, One Structure
    28. 28. Curated Dictionaries Matter
    29. 29. Crowdsourcing ChemSpider ChemSpider is crowdsourced Community deposition, annotation and curation Anyone can “Leave Feedback” Registered users can add data
    30. 30. “Curate” Identifiers
    31. 31. “Curate” Identifiers
    32. 32. “Curate” Identifiers
    33. 33. Success Depends on Dictionaries
    34. 34. Vincristine: Identifiers and Properties
    35. 35. Vincristine: PatentsLinked by Name
    36. 36. Validated Names for Searching…
    37. 37. And yes..there are challenges
    38. 38. Licensing Data is Tough…
    39. 39. Data Licensing, Open Data The use of CAS data in third party Data Mining Tools is permitted as long as CAS Records are downloaded via STN® AnaVist™. All of these new "freedoms" are aimed at further enabling the dissemination of scientific information and the advancement of scientific research. CAS does not permit the building of Databases that have wide and general availability and no longer fulfill the purpose of individual or team research that CAS permits but instead serve as a substitute for the use of CAS Databases.
    40. 40. A Comment on Quality For >28 million chemical compounds there are some errors:  “Incorrect” structure representations  Mismatched name-structure relationships  Experimental properties (the values, the units)  Real vs. virtual compounds – text-mining and conversion  We have deprecated a LOT of data…
    41. 41. Identifier Dictionaries Reciprocal curation processes…share curation with each other. If a database has a compound already then use InChiKeys to match “suggested” validation against the compound. A series of “added” and “removed” synonyms against InChIKeys for matching.
    42. 42. Federated Data Curation SharingWho wants to work with us?
    43. 43. Structure Validation using feed Look for approved synonyms Compare feed InChIKey with database InChIKey If different, flag for inspection
    44. 44. Many Problems Can be Solved… Clean up databases – structure validation, structure standardization Warn about  Valency, charge balance, depiction issues, bond types, absent stereo, and another 100 rules (or so…) Standardize  Agree community rules to “Standardize”
    45. 45. Structure Validation
    46. 46. Structure Validation - Fixed
    47. 47. What needs to happen? If we could validate  Catch errors in databases (and clean)  Proactively catch errors in publications/patents  Reduce junk in the ether – improve QUALITY! If we standardized  Interlinking should improve
    48. 48. CVSP: result of processing
    49. 49. NCATS Dataset
    50. 50. DrugBank dataset (6516 records) Marked as Errors (arbitrary)  2 records with query bonds  3 records with invalid atoms (asterisk in polymers)  Unusual valence: ~70 (oxygen 3, sulfur 3 and 5, Mg 4, B 5, etc.) Warnings  INCHI not matching structure (100+)  SMILES not matching structure (100+)
    51. 51.  DrugBank ID: DB00755 InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18- 17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3, (H,21,22)/b9-6+,12-11+,15-8+,16-14+ DrugBank ID: DB00614
    52. 52. Connecting Chemistry across the web So much of what is seen on ChemSpider is retrieved in real time using services
    53. 53. Connecting Chemistry across the web
    54. 54. Online Predictions
    55. 55. Web Services Open Up Collaboration Agilent, Bruker, Waters and Thermo all use our web-based services for compound lookup Many academic sites integrating directly – metabonomics, name lookup, semantic markup Mobile app integration Commercial structure drawing packages
    56. 56. Web Services
    57. 57. ChemSpider Everywhere: Spectral Game
    58. 58. ChemSpider EverywhereCrowdsourced Curation of Spectra
    59. 59. Web Services Integrate INTERNAL Projects Integration between ChemSpider and…  Our publishing platform for structure display  ChemSpider SyntheticPages  LearnChemistry Wiki  National Chemical Database Service  And….a growing list….
    60. 60. What ChemSpider Does Not Handle Polymers Markush structures Organometallics Many Inorganics Materials Reactions…but….
    61. 61. ChemSpider Reactions
    62. 62. DERA Digitally Enabling the RSC Archive…back to 1841  Extracting data and making available via appropriate platform  Chemicals  Reactions  Analytical Data  Figures
    63. 63. Chemical Database Service
    64. 64. Data for life sciences IP? IP? What’s the What’s the structure? structure? Are they in Are they in our file? our file? What’s What’s similar? similar? What’s the What’s the Pharmacology Pharmacology target? target? data? data? Known Known Pathways? Pathways? Competitors? Competitors? Working On Working On Connections Connections Now? Now? to disease? to disease? Expressed in Expressed in right cell type? right cell type?
    65. 65. OpenPHACTS Open PHACTS is an Innovative Medicines Initiative (IMI) – 3 years project To reduce the barriers to drug discovery in industry, academia and for small businesses To build an open platform, integrating chemistry and biology data from public domain resources Semantic web platform Open Standards, Open Data and Open Source
    66. 66.  Crowdsourcing across drug discovery Open PHACTS : partnership between European Community and European Pharma Companies 22 partners, 8 pharmaceutical companies, 3 biotechs working together for 3 years Freely accessible for knowledge discovery and verification.  Data on chemistry and biology  Pharmacological profiles  Proprietary and public data sources.
    67. 67. PharmaSea• FP7 Initiative. PharmaSea: increasing value and flow in the marine biodiscovery pipeline (2012-2017)• Improve the quality, volume and value of active agents discovered in the marine environment and increase the speed at which they can be delivered• RSC: Providing dereplication via ChemSpider, analytical data algorithms, integration with computer-assisted structure elucidation algorithms
    68. 68. Conclusions RSC eScience supporting increasing number of grant-based projects ChemSpider grows daily – community depositions and data from RSC Content with a focus on expanding data while improving quality ChemSpider is an integration platform for MANY projects through web services CVSP processing is available to use and provide feedback – will be available as a service also We believe in curation sharing - who wants to collaborate?
    69. 69. Thank youEmail: williamsa@rsc.orgTwitter: ChemConnectorBlog: Blog: www.chemconnector.comSLIDES: