The document discusses the challenges in navigating the vast amounts of data in online chemistry, highlighting the need for better data organization and standards. It emphasizes the importance of crowd-sourced curation and collaboration in improving the accuracy of chemistry databases. The goal is to create a robust semantic integration hub to support drug discovery and enhance access to validated data.

1. Improving Online Chemistry – One Structure at a Time Antony Williams AstraZeneca, February 10 th 2012

2. We Have …Too Much Data!!!

3. It is so difficult to navigate… 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? Competitors? IP?

4. Pharma Information..and the web… Literature Patents News Pipeline SAR CSRs Safety In vivo Etc

5. The World of Online Chemistry Property databases Compound aggregators Screening assay results Scientific publications Encyclopedic articles (Wikipedia) Metabolic pathway databases ADME/Tox data – eTOX for example Blogs/Wikis and Open Notebook Science Contributing Open Source code to projects

6. PubChem

7. ChEMBL

8. Collaborative Knowledge Management

9. e-Science and Primary Data How much data generated in a lab, that COULD go public, is lost forever?

10. e-Science and Primary Data How much data generated in a lab, that COULD go public, is lost forever? Public Domain reference databases of value? Syntheses Properties Spectra CIFs Images

11. e-Science and Primary Data How much data generated in a lab, that COULD go public, is lost forever? Public Domain reference databases of value? Syntheses Properties Spectra CIFs Images Much of chemistry is chemical structure-based – where and how could we host these data?

12. RSC’s ChemSpider

13. 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?

14. Available Information… Linked to vendors, safety data, toxicity, metabolism

15. Available Information….

16. 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

18. Spectra

19. Data on the Web

21. Chemistry Data online is messy We have inherited errors All public compound databases, including ours, have errors “ Incorrect” structures – assertions, timelines etc “ Incorrect” names associated with structures Properties Links Publications ENORMOUS CHALLENGE

22. What could create change? Harvard Business Review (2010) “ One change would make a substantial difference [ to drug R&D ] : the creation of agreed-upon standards for digitally representing drug assets. ” Consider drug structures ONLY…

23. The Structure of Vitamin K?

24. MeSH A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants , VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K

25. The Structure of Vitamin K1?

26. What is the Structure of Vitamin K1?

27. CAS’s Common Chemistry

28. Wikipedia

31. ChEBI – Manual Curation

35. “ 2-methyl-3-(3,7,11,15-tetramethyl hexadec-2-enyl)naphthalene-1,4-dione” Variants of systematic names on PubChem 2-methyl-3-[(E,7R,11R)-3,7,11,15-tetramethyl 2-methyl-3-[(E,7S,11R)-3,7,11,15-tetramethyl 2-methyl-3-[(E,7R,11S)-3,7,11,15-tetramethyl 2-methyl-3-[(E,7S,11S)-3,7,11,15-tetramethyl 2-methyl-3-[(E,11S)-3,7,11,15-tetramethyl 2-methyl-3-[(E)-3,7,11,15-tetramethyl 2-methyl-3-(3,7,11,15-tetramethyl 2-methyl-3-[(E)-3,7,11,15-tetramethyl

36. What’s Methane?

37. What’s Methane?

38. What ELSE is Methane???

40. EPA’s DailyMed

41. EPA’s DailyMed

42. EPA’s DailyMed

43. With Great Fanfare…

44. NPC Browser http://tripod.nih.gov/npc/

45. NPC Browser http://tripod.nih.gov/npc/

47. Openness and Quality Issues Williams and Ekins, DDT, 16: 747-750 (2011) Science Translational Medicine 2011

48. Content is King and Quality Costs Curated Chemistry “content” is expensive to create Patent searching Structures and properties Drug databases Literature databases Chemical Abstracts Service (CAS), the “Gold Standard” in Chemistry related information 104 years of content >50 million substances Proprietary platform

49. The EXPERTS must get it right?!

50. Wikipedia, C&E News, PubChem C&E News (from ACS)

51. Feedback from Steve Ritter “ Although CAS and C&EN are both part of the ACS Publications Division, we at C&EN still have to pay for our SciFinder access, strangely enough.” “ It would be nice to have an authoritative web-based source of standard, well-drawn structures for chemists to go to so they can freely cut and paste structures into their papers, PowerPoint presentations, and anything else they might need. Maybe Wikipedia will be that source one day .”

52. Public Domain Databases Our databases are a mess… Non-curated databases are proliferating errors We source and deposit data between databases Original sources of errors hard to determine Curation is time-consuming and challenging

53. Stop Whining – Fix it

54. Crowdsourced Curation Crowd-sourced curation: identify/tag errors, edit names, synonyms, identify records to deprecate

55. Search “Vitamin H”

56. “ Curate” Identifiers

57. “ Curate” Identifiers

58. “ Curate” Identifiers

59. Standards : Structure Standardization

60. Standards : Structure Standardization

61. Standards : Structure Standardization

62. What needs to happen? Standards Standardization of structures ChEBI/PubChem sharing InChI adoption

63. The InChI Identifier

64. Multiple Layers

65. InChIStrings Hash to InChIKeys

66. Vancomycin – Search the Internet

67. Vancomycin Search Molecular SKELETON Search Full Molecule

68. Full Skeleton Search: 104 Hits

69. Full Molecule Search: 4 Hits

70. Crowdsourcing Works >130 people have deposited data and participated in data curation Different level curators check each other More curators and depositors are encouraged!

71. What needs to happen? Standards Standardization of structures ChEBI/PubChem sharing InChI adoption Collaboration Stop reinventing the wheel Share data, share efforts and speed the process

72. Antony Williams vs Identifiers Passport ID Dad, Tony, others SSN Green Card License 5 email addresses ChemSpiderman (blog, Twitter account, Facebook, Friendfeed) OpenID … .

73. Aspirin names and synonyms Text searches depend on correct association 335 suggested identifiers for Aspirin just on PubChem! Disambiguation dictionaries are necessary, not just for authors!

75. The Final Search Strategy

76. All Those Names, One Structure

77. Curated Dictionaries Matter

78. Success Depends on Dictionaries

79. Validated Name-Structure Dictionaries Chemical name dictionaries are used for: Text-mining (publications, patents) Used to index PubMed and link to Google Patents Linking to other databases – think Biology! When structures are not available drug names link Searching the web Names link to structures link to InChIs

80. I want to know about “Vincristine” If all algorithms work then everything on the page is correct by default except the name-structure relationship!

81. Vincristine: Identifiers and Properties

82. Vincristine: Patents Linked by Name

83. Vincristine: Articles Linked by Name

84. ChemSpider Everywhere: What do computers want? Web services

85. Mass Spec Analysis

86. ChemSpider Interface

88. Tinuvin 328

89. Position sorted by references

90. Position 1 only

91. Web Services

92. 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

93. ChemSpider Everywhere : Embed

94. ChemSpider Everywhere: Spectral Game

95. ChemSpider Everywhere Crowdsourced Curation of Spectra

96. ChemSpider Everywhere : ChemMobi

97. Structure Database Lookup

98. ChemSpider Resources for Chemistry

99. It is so difficult to navigate… 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? Competitors? IP?

100. Open PHACTS Project Develop a set of robust standards… Implement the standards in a semantic integration hub Deliver services to support drug discovery programs in pharma and public domain 22 partners, 8 pharmaceutical companies, 3 biotechs 36 months project Guiding principle is open access, open usage, open source - Key to standards adoption -

102. The Future Commercial Software Pre-competitive Data Open Science Open Data Publishers Educators Open Databases Chemical Vendors Small organic molecules Undefined materials Organometallics Nanomaterials Polymers Minerals Particle bound Links to Biologicals Internet Data

103. The Future of Chemistry on the Web? Public compound databases federate & build a linked environment of validated data! Data validation needs are not ignored Publishers layer on information to make publications discoverable Public-Private databases can be linked Open Data proliferate The “ Semantic Web ” in action

104. Acknowledgments The ChemSpider team Our data providers, depositors, collaborators and curators Software providers – OpenEye, ChemDoodle, ACD/Labs, GGA Software, Open Source (Jmol, JSpecView, OpenBabel)

105. Thank you Email: williamsa@rsc.org Twitter: ChemConnector Blog: www.chemspider.com/blog Personal Blog: www.chemconnector.com SLIDES: www.slideshare.net/AntonyWilliams