BIOMOLECULES IN R&D INFORMATICS - ChemAxon...More on this by Jarrod Medeiros, IDBS IDBS EWB Web...
Transcript of BIOMOLECULES IN R&D INFORMATICS - ChemAxon...More on this by Jarrod Medeiros, IDBS IDBS EWB Web...
BIOMOLECULES IN
R&D INFORMATICS
Roland Knispel
Cyclosporin A
Draw or useName to Structure:Ciclosporin
In default monomer set Not in default monomer set
AALLVTAGLVL
Sequence
Chemical structure
Co
nve
rsio
n
BIOEDDIE
A JS-based HELM editor for the web
Eddie
- JS application for all
major browsers
- Easy editing
- No-structure
components
- Native support for
MOL/HELM/sequence
BioEddie
BioEddie
- JS application for all
major browsers
- Easy editing
- No-structure
components
- Native support for
MOL/HELM/sequence
- Customizable views
- Multi-level annotations
- JS application for all
major browsers
- Easy editing
- No-structure
components
- Native support for
MOL/HELM/sequence
- Customizable views
- Multi-level annotations
- NEW: sequence
domain support (Abs)
BioEddie
BioEddie: Oxytocin from sequence or MOL file
• API (Java and REST-ful) for
– Native HELM support (HELM, HELM2, xHELM)
– 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
– Since v16.8.1: Instant JChem, planned: Plexus Connect
– Texelia BioScity, planned: IDBS E-WorkBook
Biomolecule Toolkit
CASE STUDY: CHEMBL V21
Tools for getting started with HELM, and content curation
• 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
CHEMBL v21
- KNIME
- Standardizer node
Ungroup S-groups, Strip
salts/solvents, Remove
explicit hydrogens,
Neutralize structure,
Aromatize, Standardize
functional groups
Standardize Convert Canonicalize Store/Search
CHEMBL297610
Tools used
- KNIME
- Biomolecule Toolkit
- BioEddie for image
rendering
- 3 wrong
conversions in
ChEMBL data set
identified
Standardize Convert Canonicalize Store/Search
PEPTIDE1{E.C.G.[X1091]}$$$$
wrong
PEPTIDE1{E}|PEPTIDE2{C.G.[X10
91]}$PEPTIDE1,PEPTIDE2,1:R3-
1:R1$$$
correct
Tools used
CHEMBL223118
- KNIME
- Biomolecule Toolkit
- 864 HELM
notations in
ChEMBL changed
- Allows direct
comparison of
HELM notations
Standardize Convert Canonicalize Store/Search
Tools used
Before:
PEPTIDE1{[ac].[dE].[Phe(4-Cl)].[d3-
Pal]}|PEPTIDE2{D.R.[dNal].L.K}|PEPT
IDE3{P.[dDpr].[am]}$PEPTIDE2,PEPT
IDE3,5:R2-
1:R1|PEPTIDE2,PEPTIDE1,5:R3-
2:R3|PEPTIDE1,PEPTIDE2,4:R2-
1:R1|PEPTIDE3,PEPTIDE2,2:R3-
1: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$$$
After:
PEPTIDE1{[ac].[dE].[Phe(4-Cl)].[d3-
Pal].D.R.[dNal].L.K.P.[dDpr].[am]}$PEPTI
DE1,PEPTIDE1,11:R3-
5:R3|PEPTIDE1,PEPTIDE1,9:R3-
2:R3$$$
CHEMBL412009
CHEMBL42623
- Biomolecule Toolkit
Search by:
- Sequence (incl.
wildcards)
- Chemical structure
- Modifications
- Metadata
Standardize Convert Canonicalize Store/Search
Tools used
Query # hits
Molecules containing „Oxytocin“ in name
field2
Molecules with the natural analogue
sequence of Oxytocin18
Oxytocin-like sequences with non-standard
amino acids17
Oxytocin derivatives containing the
chemical structure of penicillamine3
Oxytocin derivatives containing the L-
penicillamine monomer2
USE CASE: ANTIBODY REGISTRATION
Using Instant JChem/MiniReg + Biomolecule Toolkit
Customer specification of an antibody:
• VL sequence / sequence (EIVLWQSPGT…)
• VH sequence / sequence (QVQIVQSGAE…)
• Fv backbone (scaffold) / text field (“CBr6”)
- Antibody definitions registered from file template
- Duplicate check and batch handling
- Assay data uploading
- Form views and reporting
Antibody registration
Delivered to the customer
BIOMOLECULE TOOLKIT AS A
PLATFORM
Registration DB
Architecture
Biomolecule Toolkit
Java API
REST-ful WS
Files (e.g. MOL,
FASTA, HELM)
Registration Client
Web
JChem for Office
Plexus Connect
Instant JChemSince 16.8.1
Q4
Your application
- Create new project
pointing to
Biomolecule Toolkit
DB
- Grid view with
molecule visualization
Since v16.8.1: Biomolecules in Instant JChem
- Create new project
pointing to
Biomolecule Toolkit
DB
- Grid view with
molecule visualization
- Form views with
additional data
- Querying
Since v16.8.1: Biomolecules in Instant JChem
Texelia BioScity - Data management/tracking and inventory for the Bio/Chem lab
BioScity
More on this by Jarrod Medeiros, IDBS
IDBS EWB Web – bringing HELM support into an ELN
Mockups only!!! – POC development won‘t be possible til UGM
HELM (auto-generated): untitled_molecule_file3.mol
HELM (auto-generated):
untitled_mole...
Proof of concept – to be delivered to customers 2017
IDBS EWB Web – bringing HELM support into an ELN
Mockups only!!! – POC development won‘t be possible til UGM
HELM (auto-generated): untitled_molecule_file3.mol
HELM (auto-generated):
untitled_mole...
ROADMAP
Q1/2 2017
• Sequence domains in BioEddie
• Library manager tool
• Oracle support
• KNIME/PP nodes (experimental)
Q3/4 2017
• ADC support in BioEddie
• Genealogy tracking
• Entity batches
• Sequence similarity search
Roadmap
THANK YOU
Roland Knispel