Applying Royal Society of Chemistry
Cheminformatics Skills to Support
the PharmaSea Project
Antony Williams, Alexey Psheni...
Cancer Deaths Worldwide
Top Treatments for Cancer
• Over half of all drugs introduced between
1940 and 2006 were of natural origin or
inspired by natural compounds
Importan...
Natural Products for all of us!
We Are Doomed I Tell You!!!
We Are Doomed I Tell You!!!
The Dangers of Algal Blooms!
Nature’s Little Pharmacy
O
O
O
O
O
O
O
O
O
O
O
O
O
CH2
CH3
OH
CH3
CH3
CH3
CH3
CH3
CH3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
We Are Doomed I Tell You!!!
Antibiotic resistance
Discovery Curve Decay
RSC and Natural Products
Focus on Marine Natural Products
• RSC cheminformatics support to include:
• Deliver “PharmaSea website”
• Provide access ...
http://www.pharma-sea.eu/
The PharmaSea Website
• RSC is open-sourcing a chemical registry
system as a result of Open PHACTS
• Chemical Registry sys...
The PharmaSea Website
The PharmaSea Website
The PharmaSea Website
New Repository Architecture
doi: 10.1007/s10822-014-9784-5
New Repository Architecture
Compounds Reactions Spectra Materials Documents
Compounds
API
Reactions
API
Spectra
API
Materi...
Compounds
Reactions
Analytical data
Crystallography data
Deposition of Data
Extending PharmaSea Site
• PharmaSea website will be extended
• Spectral data handling: Support Dereplication
Identifying novel compounds
• Compounds are collected from the ocean
• Extraction via chromatography
• Analytical sciences...
Is this already known or not??
4 Me singlets
4 Me doublets
1 OMe singlet
Aromatic protons
Identifying novel compounds
Identifying novel compounds
2D NMR data will give details
regarding substitutions and
this information can be used in
the ...
What we need is…
• If we could have:
• A DB containing known marine natural products
• This would give formula and mass fo...
RSC Acquires Marinlit
• All Marinlit chemical compounds in ChemSpider
• Marinlit developers are dereplication experts
• Index literature related to marine natural
products: 26K articles and growing
• Structure searchable database
• Data inc...
PharmaSea Dereplication
• Work in progress:
• Produce “dereplication widget” to embed in
the PharmaSea website
• Generate ...
CASE-based Elucidation
• Computers can elucidate structures today
with greater efficiency and success than
many scientists...
1D & 2D NMR Synchronized
Processing
The Software displays correlations for assigned spectra and structures, and highlights...
ChemSpider supporting CASE
RSC delivered entire ChemSpider structure dataset
for inclusion into the Structure Elucidator s...
CASE vs Microscopy?
DOI: 10.1002/anie.201203960
Single Molecule AFM
CASE vs Microscopy?
DOI: 10.1002/anie.201203960
Next:Tagging Natural Products
Next:Tagging Natural Products
Next:Tagging Natural Products
Next:Tagging Natural Products
Future Plans
• Roll out tagging on ChemSpider to crowdsource
marine natural products subset
• Implement tagging for furthe...
Future Plans – MS Fragmenter
Future Plans – MS Fragmenter
Future Plans
Modern NMR Approaches To The Structure Elucidation
of Natural Products
Volume 1: Instrumentation and Software
Volume 2: Da...
To be published: 2015 (Springer)
Computer-based Structure Elucidation from
Spectral Data
Will include a functional demo ve...
Acknowledgments
• Alexey Pshenichnov, Ken Karapapetyan and
Valery Tkachenko (RSC – US Cheminformatics)
• Marcel Jaspars (U...
Thank you
Email: williamsa@rsc.org
ORCID: 0000-0002-2668-4821
Twitter: @ChemConnector
Personal Blog: www.chemconnector.com...
Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project
Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project
Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project
Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project
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Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project

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The collaborative project PharmaSea brings European researchers to some of the deepest, coldest and hottest places on the planet. Scientists from the UK, Belgium, Norway, Spain, Ireland, Germany, Italy, Switzerland and Denmark are working together to collect and screen samples of mud and sediment from huge, previously untapped, oceanic trenches. The large-scale, four-year project is backed by almost 10 million euros of funding and brings together 24 partners from 13 countries from industry, academia and non-profit organisations. The PharmaSea project focuses on biodiscovery research and the development and commercialisation of new bioactive compounds from marine organisms, including deep-sea sponges and bacteria, to evaluate their potential as novel drug leads or ingredients for nutrition or cosmetic applications. The Royal Society of Chemistry is responsible for developing a number of capabilities to support the Pharmasea project including a chemical registration system for new compounds, dereplication technologies to assist in the identification of new compounds and search techniques for mass spectrometrists within the project. This presentation will provide an overview of the project and our progress to contributing chemical information technologies to support the effort.

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  • MarinLit is ‘article-centric’ and not compound centric. Compounds are only indexed when they are newly discovered, revised, or new to marine.
    All compound records link to the paper they were first mentioned. They are not linked to subsequent articles that describe them.
  • Transcript of "Applying Royal Society of Chemistry cheminformatics skills to support the PharmaSea project"

    1. 1. Applying Royal Society of Chemistry Cheminformatics Skills to Support the PharmaSea Project Antony Williams, Alexey Pshenichnov, Valery Tkachenko, Ken Karapetyan, David Sharpe ACS San Francisco August 2014
    2. 2. Cancer Deaths Worldwide
    3. 3. Top Treatments for Cancer
    4. 4. • Over half of all drugs introduced between 1940 and 2006 were of natural origin or inspired by natural compounds Importance of Natural Products
    5. 5. Natural Products for all of us!
    6. 6. We Are Doomed I Tell You!!!
    7. 7. We Are Doomed I Tell You!!!
    8. 8. The Dangers of Algal Blooms!
    9. 9. Nature’s Little Pharmacy O O O O O O O O O O O O O CH2 CH3 OH CH3 CH3 CH3 CH3 CH3 CH3 H H H H H H H H H H H H H H H
    10. 10. We Are Doomed I Tell You!!!
    11. 11. Antibiotic resistance
    12. 12. Discovery Curve Decay
    13. 13. RSC and Natural Products
    14. 14. Focus on Marine Natural Products • RSC cheminformatics support to include: • Deliver “PharmaSea website” • Provide access to natural products subset • Develop “dereplication techniques” • Searching NMR features against database • Develop advanced searches for MS data • Host Open Data from the PharmaSea project and make available to the community
    15. 15. http://www.pharma-sea.eu/
    16. 16. The PharmaSea Website • RSC is open-sourcing a chemical registry system as a result of Open PHACTS • Chemical Registry system used to underpin the PharmaSea website – behind login • Will be enhanced with data deposition capabilities and “dereplication”
    17. 17. The PharmaSea Website
    18. 18. The PharmaSea Website
    19. 19. The PharmaSea Website
    20. 20. New Repository Architecture doi: 10.1007/s10822-014-9784-5
    21. 21. New Repository Architecture Compounds Reactions Spectra Materials Documents Compounds API Reactions API Spectra API Materials API Documents API Compounds Widgets Reactions Widgets Spectra Widgets Materials Widgets Documents Widgets Data tier Data access tier User interface components tier Analytical Laboratory application User interface tier (examples) Electronic Laboratory Notebook Paid 3rd party integrations (various platforms – SharePoint, Google, etc) Chemical Inventory application
    22. 22. Compounds
    23. 23. Reactions
    24. 24. Analytical data
    25. 25. Crystallography data
    26. 26. Deposition of Data
    27. 27. Extending PharmaSea Site • PharmaSea website will be extended • Spectral data handling: Support Dereplication
    28. 28. Identifying novel compounds • Compounds are collected from the ocean • Extraction via chromatography • Analytical sciences including: • UV-Vis data (Lambda-max) • Mass spectrometry (formula/mass) • NMR spectroscopy (HNMR/2D) • Utilized for dereplication,,,
    29. 29. Is this already known or not??
    30. 30. 4 Me singlets 4 Me doublets 1 OMe singlet Aromatic protons Identifying novel compounds
    31. 31. Identifying novel compounds 2D NMR data will give details regarding substitutions and this information can be used in the dereplication process
    32. 32. What we need is… • If we could have: • A DB containing known marine natural products • This would give formula and mass for searching • The DB has all spectral data available for each compound • If experimental data are not available then use the compound to COMPUTE spectral features
    33. 33. RSC Acquires Marinlit • All Marinlit chemical compounds in ChemSpider • Marinlit developers are dereplication experts
    34. 34. • Index literature related to marine natural products: 26K articles and growing • Structure searchable database • Data includes taxonomy, location and literature • “Spectral features” generated algorithmically • Utilize the spectral features for dereplication
    35. 35. PharmaSea Dereplication • Work in progress: • Produce “dereplication widget” to embed in the PharmaSea website • Generate “structure features” file for every new compound deposited to PharmaSea • Ideal would be to utilize spectral data directly to elucidate structures – “Computer Assisted Structure Elucidation”. ACD/Labs….
    36. 36. CASE-based Elucidation • Computers can elucidate structures today with greater efficiency and success than many scientists – see Patrick Wheeler’s talk • Natural products specifically can be very challenging and CASE is well-proven • ACD/Labs have delivered their CASE- system (ACD/Structure Eludicator) to the project
    37. 37. 1D & 2D NMR Synchronized Processing The Software displays correlations for assigned spectra and structures, and highlights correlations that are likely to be erroneous.
    38. 38. ChemSpider supporting CASE RSC delivered entire ChemSpider structure dataset for inclusion into the Structure Elucidator software.
    39. 39. CASE vs Microscopy? DOI: 10.1002/anie.201203960
    40. 40. Single Molecule AFM
    41. 41. CASE vs Microscopy? DOI: 10.1002/anie.201203960
    42. 42. Next:Tagging Natural Products
    43. 43. Next:Tagging Natural Products
    44. 44. Next:Tagging Natural Products
    45. 45. Next:Tagging Natural Products
    46. 46. Future Plans • Roll out tagging on ChemSpider to crowdsource marine natural products subset • Implement tagging for further details onto PharmaSea website • Collaborate with other natural product sources • Mass spectrometry fragmentation prediction
    47. 47. Future Plans – MS Fragmenter
    48. 48. Future Plans – MS Fragmenter
    49. 49. Future Plans
    50. 50. Modern NMR Approaches To The Structure Elucidation of Natural Products Volume 1: Instrumentation and Software Volume 2: Data Acquisition and Applications to Compound Classes Edited by Antony Williams, RSC, Gary Martin, Merck and David Rovnyak, Bucknell University To be published: 2015 (RSC)
    51. 51. To be published: 2015 (Springer) Computer-based Structure Elucidation from Spectral Data Will include a functional demo version of the ACD/Structure Elucidator software to teach the basic approaches to computer-assisted structure elucidation Authored by Mikhail Elyashberg, Kirill Blinov and Antony Williams
    52. 52. Acknowledgments • Alexey Pshenichnov, Ken Karapapetyan and Valery Tkachenko (RSC – US Cheminformatics) • Marcel Jaspars (University of Aberdeen) • John Blunt and Murray Munro (Marinlit) • Serin Dabb (RSC, Marinlit) • Patrick Wheeler and David Hardy (ACD/Labs)
    53. 53. Thank you Email: williamsa@rsc.org ORCID: 0000-0002-2668-4821 Twitter: @ChemConnector Personal Blog: www.chemconnector.com SLIDES: www.slideshare.net/AntonyWilliams
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