applying royal society of chemistry cheminformatics skills to support the pharmasea project
DESCRIPTION
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.TRANSCRIPT
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
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
Importance of Natural Products
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
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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 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
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”
The PharmaSea Website
The PharmaSea Website
The PharmaSea Website
New Repository Architecturedoi: 10.1007/s10822-014-9784-5
New Repository Architecture
Compounds Reactions Spectra Materials Documents
CompoundsAPI
ReactionsAPI
SpectraAPI
MaterialsAPI
DocumentsAPI
CompoundsWidgets
ReactionsWidgets
SpectraWidgets
MaterialsWidgets
DocumentsWidgets
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
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 including:• UV-Vis data (Lambda-max)• Mass spectrometry (formula/mass)• NMR spectroscopy (HNMR/2D)• Utilized for dereplication,,,
Is this already known or not??
4 Me singlets4 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 dereplication process
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
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 includes taxonomy, location and literature
• “Spectral features” generated algorithmically
• Utilize the spectral features for dereplication
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….
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
1D & 2D NMR Synchronized Processing
The Software displays correlations for assigned spectra and structures, and highlights correlations that are likely to be erroneous.
ChemSpider supporting CASERSC delivered entire ChemSpider structure dataset for inclusion into the Structure Elucidator software.
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 further details onto PharmaSea website
• Collaborate with other natural product sources
• Mass spectrometry fragmentation prediction
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: 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)
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
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)
Thank you
Email: [email protected]: 0000-0002-2668-4821 Twitter: @ChemConnectorPersonal Blog: www.chemconnector.com SLIDES: www.slideshare.net/AntonyWilliams