Roland Knispel
BIOMOLECULE TOOLKIT
www.amgenscience.com
JChem
www.amgenscience.com
JChem
www.amgenscience.com
Biomolecule Toolkit
• API (Java and REST-ful) for
– Standardization
– Centralized DB storage
– Registration of entities and batches with custom
business logic
– Search by sequence/chemical structure/metadata
– Conversion to/from Mol/FASTA/HELM
– Property calculations
• Integrates with
– Almost there: InstantJChem, planned: Plexus
Connect
– Texelia BioScity, planned: IDBS E-Workbook
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
Regulative authorities
• Acceptable format for substance submissions
under ISO11238 implementation guidelines (FDA
and others)
6
CASE STUDY: CHEMBL V21
Tools for getting started with HELM, and content curation
CHEMBL v21
• 19773 peptide
biotherapeutics with
associated activity data
• Molecules served as HELM
or chemical structure file
• ChEMBL interface:
searchable by CompoundID,
chemical structure or select
metadata
Standardize
Ungroup S-groups, Strip
salts/solvents, Remove
explicit hydrogens,
Neutralize structure,
Aromatize, Standardize
functional groups
Tools used
- KNIME
- Standardizer node
Convert
Canonicalize
Store/Search
CHEMBL297610
Standardize
Convert
Canonicalize
Store/Search
CHEMBL223118
- 3 wrong
conversions in
ChEMBL data set
identified
correct
wrong
Tools used
- KNIME
- Biomolecule Toolkit
- BioEddie for image
rendering
PEPTIDE1{E.C.G.[X1091]}$$$$
PEPTIDE1{E}|PEPTIDE2{C.G.[X10
91]}$PEPTIDE1,PEPTIDE2,1:R31:R1$$$
Standardize
Convert
Canonicalize
Store/Search
CHEMBL412009
- 864 HELM
notations in
ChEMBL changed
- Allows direct
comparison of
HELM notations
Tools used
- KNIME
- Biomolecule Toolkit
Before:
PEPTIDE1{[ac].[dE].[Phe(4-Cl)].[d3Pal]}|PEPTIDE2{D.R.[dNal].L.K}|PEPT
IDE3{P.[dDpr].[am]}$PEPTIDE2,PEPT
IDE3,5:R21:R1|PEPTIDE2,PEPTIDE1,5:R32:R3|PEPTIDE1,PEPTIDE2,4:R21:R1|PEPTIDE3,PEPTIDE2,2:R31:R3$$$
CHEMBL42623
After:
PEPTIDE1{[ac].[dE].[Phe(4-Cl)].[d3Pal].D.R.[dNal].L.K.P.[dDpr].[am]}$PEPTI
DE1,PEPTIDE1,11:R35:R3|PEPTIDE1,PEPTIDE1,9:R32:R3$$$
Before:
PEPTIDE1{G.Y.G.F}$PEPTIDE1,PEPTID
E1,4:R2-1:R1$$$
After:
PEPTIDE1{F.G.Y.G}$PEPTIDE1,PEPTID
E1,4:R2-1:R1$$$
Standardize
Search by:
- Sequence (incl.
wildcards)
- Chemical structure
- Modifications
- Metadata
Tools used
- Biomolecule Toolkit
Convert
Canonicalize
Store/Search
USE CASE: ANTIBODY REGISTRATION
Using Instant JChem/MiniReg + Biomolecule Toolkit
Antibody registration
Customer specification of an antibody:
• VL sequence / sequence (EIVLWQSPGT…)
• VH sequence / sequence (QVQIVQSGAE…)
• Fv backbone (scaffold) / text field (“CBr6”)
Delivered to the customer
-
Antibody definitions registered from file template
Duplicate check and batch handling
Assay data uploading
Form views and reporting
BIOMOLECULE TOOLKIT AS A
PLATFORM
Architecture
Registration Client
Web
Since 16.8.1
Biomolecule Toolkit
Instant JChem
Java API
Q4
Plexus Connect
REST-ful WS
2017
JChem for Office
Registration DB
Your application
Files (e.g. MOL,
FASTA, HELM)
Since v16.8.1: Biomolecules in IJC
- Create new project
pointing to
Biomolecule Toolkit
DB
- Grid view with
molecule
visualization
Since v16.8.1: Biomolecules in IJC
- Create new project
pointing to
Biomolecule Toolkit
DB
- Grid view with
molecule visualization
- Form views with
additional data
- Querying
Mockups only!!! – POC development won‘t be possible til UGM
HELM (auto-generated): untitled_molecule_file3.mol
HELM (auto-generated):
untitled_mole...
IDBS EWB Web – bringing HELM support into an ELN
Proof of concept – to be delivered to customers 2017
Mockups only!!! – POC development won‘t be possible til UGM
HELM (auto-generated): untitled_molecule_file3.mol
HELM (auto-generated):
untitled_mole...
IDBS EWB Web – bringing HELM support into an ELN
Proof of concept – to be delivered to customers 2017
BIOEDDIE
A JS-based HELM editor for the web
BioEddie
- Easy structure/
sequence editing
- Supports nostructure
components
- Native HELM support
- Multi-level
annotations
- Clear visualisation
- Customizable views
- JS application
BioEddie
Beta tests running now
Contact [email protected]
to sign up
Release in September
- Standalone
- Bundled with
Biomolecule Toolkit
ROADMAP
Roadmap
Q4
2016
• Biomolecule support
in Plexus Suite
• Rule-based bulk
import/editing of
biomolecules
• BioEddie product
release
Q1/2
2017
• Design/developability
assessment/SAR
analysis
2017
• Biomolecule support
in JChem for Office
applications
• IDBS E-Workbook
integration
SUMMARY
Summary
• Curation and standardization of existing
content
• Structure management á la JChem/Marvin incl.
registration
• Biomolecule and bio-asset data management
platform for desktop and web
• New BioEddie (JS-based HELM editor)
THANK YOU
Roland Knispel