Transcript HELM notation

Pistoia Alliance HELM Project
An Open Standard for the Representation of Complex Biomolecules
Best Practices in Personalized And Translational Medicine
Molecular Med Tri-Conference 2015
Sergio H. Rotstein, Ph.D.
February 16, 2015
Background
• Pfizer Goal
– “Top-tier biotherapeutics company”
• But supporting informatics infrastructure lacking
• Biomolecules Team Goal
– Working on therapeutic oligonucleotides since 2008
– Build on this work to support additional entities for
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Registration
Visualization
Analysis and design
Workflows
• HELM is one result of this initiative
© Pistoia Alliance
– Make biomolecules “first-class citizens” of the informatics tool
portfolio
What is a “Biomolecule”
ASOs
siRNAs
Peptides
Therapeutic
Proteins
Antibodies
ADCs
Vaccines
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Biomolecule: Anything that is not a small molecule
Stuck in the middle…
Small Molecule Tools
Sequence-Based Tools
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Sequences
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Biomolecules
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Small
Molecules
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“Fit-for-Purpose” Structure Representation
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MTTSASSHLNKGIKQVYMSLPQGEKVQAMYIWIDGTGEGLRCKTRTLDSEPKCVEELPEWNFDGSSTLQSEGSNSDM
YLVPAAMFRDPFRKDPNKLVLCEVFKYNRRPAETNLRHTCKRIMDMVSNQHPWFGMEQEYTLMGTDGHPFGWPSN
GFPGPQGPYYCGVGADRAYGRDIVEAHYRACLYAGVKIAGTNAEVMPAQWEFQIGPCEGISMGDHLWVARFILHRVC
EDFGVIATFDPKPIPGNWNGAGCHTNFSTKAMREENGLKYIEEAIEKLSKRHQYHIRAYDPKGGLDNARRLTGFHETSNI
NDFSAGVANRSASIRIPRTVGQEKKGYFEDRRPSANCDPFSVTEALIRTCLLNETGDEPFQYKN
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Hierarchical Editing Language for Macromolecules
• Hierarchical
– Supports multi-level structures
• Complex Polymer ⇒ Simple Polymer ⇒ Monomer ⇒ Atom
• Extensible
– Allows addition of new polymer types
• E.g. Polysaccharides
• Able to handle entity complexity
– Unnatural amino acids
– Bioconjugates
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• Oligonucleotide hybridization
• Chemically modified Biologics
Examples
HELM notation
RNA1{R(G)P.R(G)P.R(C)P.R(A)P.R(C)P.R(U)P.R(U)P.R(C)P.R(G)P.R(G)P.R(U)P.R(G)P.R(C)P.R(C)
}$$RNA1,RNA1,11:pair-32:pair|RNA1,RNA1,5:pair-38:pair|RNA1,RNA1,14:pair29:pair|RNA1,RNA1,8:pair-35:pair|RNA1,RNA1,2:pair-41:pair$$
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HELM notation
PEPTIDE1{A.R.G.[dF].C.K.[meA].E.D.A}$$$$
HELM at Pfizer: Drawing
Centralized Monomer DB
(smiles, InChI, mol)
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Editor
HELM at Pfizer: Registration
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Compound Registration
PFRED
PFRED: A computational tool for siRNA and antisense design. Simon Xi, Qing Cao, Christine Lawrence,
Tianhong Zhang, Simone Sciabola, Sergio Rotstein, Jason Hughes, Daniel Caffrey, and Robert Stanton,
PLOS ONE, Submitted
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HELM at Pfizer: Analysis & Design
Antibody
Linker Payload
ADC
Workflow
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HELM at Pfizer: Workflow
The Pistoia Alliance
31st October 2014
Presentation title
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The Pistoia Alliance is a global, nonprofit alliance of life science companies,
vendors, publishers, and academic
groups that work together to solve
common problems and lower barriers to
innovation in R&D
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Pistoia HELM Project Goal
• Transition HELM technology from Pfizer
proprietary to Open Source
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– Provide an industry-wide standard for data exchange
within and between organizations
– Reduce software development costs by minimizing
the need for companies to develop similar
functionality
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Specification
Documentation
Tutorials
Link to source code
Please join our mailing list!
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OpenHelm.Org
HELM Editor
API
GitHub
HELM Notation Toolkit
Source Code
HELM Drawing Applet
https://github.com/PistoiaHELM
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HELM For You: Different strokes…
Biomolecule Data
Exchange Mechanism
Level of Adoption
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Foundation for your biomolecule
informatics infrastructure
• Registration
• Visualization
• Analysis and design
• Workflows
The HELM Ecosystem
• Pharma / Biotech / Institutes
– BMS, GSK, Lundbeck, Merck,
Novartis, Pfizer, Roche
• Software vendors
– ACD/Labs, Arxspan, Biochemfusion,
BioMax, Biovia, ChemAxon,
NextMove, Scilligence
• Content / Service Providers
– EBI (ChEMBL), eMolecules, quattro
– e.g. FDA
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• Active discussions on-going with
others
Recent Developments
PEPTIDE1{G.[[*]N[C@@H](C=O)C([*])=O |$_R1;;;;;;_R2;$|].C}$$$$
In-Line HELM Notation
Exchangeable HELM
Roche Antibody Editor
Search POC
ChEMBL v20
UNIVERSITY OF
CAMBRIDGE
Andreas Bender GroupPeter MacCallum, Andrea Chlebikova
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HELM Phase 2
• Started in November
• Areas of focus (prioritized by steering committee)
– Continued dissemination and adoption
– Technical work to maximize utility and adoptability
• Management of ambiguity
• Mitigate dependencies on commercial libraries
– Graphing
– Chemical toolkit
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• Search
Best Practices
• Share the wealth
– Does your organization have “shareable” assets that others
could benefit from?
• Don’t go it alone
– “NIH Syndrome” is a luxury none of us can afford
• Volunteer army, paid sergeant(s)
– It has to be someone’s job to keep things moving
• Time’s fun when you’re having flies -- Kermit the Frog
31st October 2014
Presentation title
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– Everything works much better when the atmosphere is kept
light and friendly
HELM Team Members
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Akos Papp (ChemAxon)
Alex Allardyce (ChemAxon)
Alex Drijver (ChemAxon)
Andrey Yerin (ACD labs)
Dana Vanderwall (BMS)
Ed Currie (InfoSys)
Edvard Buki (ChemAxon)
Hans de Bie (ACDLabs)
Ian Stott (Unilever)
Jerry Winter (Unilever)
Jinbo Lee (Scilligence)
John Smith (GSK)
John Wise (Pistoia)
Keith Taylor (Ladera)
Kirti Jindal (InfoSys)
Matthias Nolte (BMS)
Michael Cui (GSK)
Mike Travers (CDD)
Rama Bhamidpati (GSK)
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Roland Knispel (ChemAxon)
Roland Molnar (ChemAxon)
Sergio Rotstein (Pfizer)
Stefan Klostermann (Roche)
Ted Slater (OpenBEL)
Tianhong Zhang (Pfizer)
Tony Yuan (Scilligence)
Our Steering Committee
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John Wise (Pistoia Alliance)
Margret Assfalg (Roche)
Leah O'Brien (GSK)
Ramesh Durvasula (BMS)
Sergio Rotstein (Pfizer)
Alex Drijver (ChemAxon)
Chris Waller (Merck)
Our Excellent Project Manager
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Claire Bellamy
Special thanks to ChemAxon for their generous contribution of software development resources!!
Special thanks to Pfizer for their unwavering support and contribution of in-kind project resources!!
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Our team Members (Subteam leads)
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www.OpenHelm.org
[email protected]