ChEMBL and KNIME provide an ideal match of open data with open tools. This is a quick overview of how to access ChEMBL data resources and web services (ChEMBL, UniChem, Beaker, myChEMBL, SureChEMBL) via the KNIME platform.

1. ChEMBL resources and KNIME
George Papadatos
georgep@ebi.ac.uk

2. Outline
• ChEMBL data
• ChEMBL nodes
• Web services v2.0
• UniChem
• Cheminformatics utilities
• myChEMBL
• SureChEMBL and Open PHACTS

3. Bioactivity data
Compound
Assay/Target
>Thrombin
MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLE
RECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGT
NYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYT
TDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVT
THGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGY
CDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLF
EKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDR
WVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWR
ENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTA
NVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGG
PFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE
3. Insight, tools and resources for translational drug discovery
2. Organization, integration, curation and standardization of pharmacology data
1. Scientific facts
Ki = 4.5nM
APTT = 11 min.
ChEMBL: Data for drug discovery

4. Bioactivity data
Compound
Assay/Target
>Thrombin
MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLE
RECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGT
NYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYT
TDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVT
THGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGY
CDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLF
EKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDR
WVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWR
ENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTA
NVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGG
PFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE
3. Insight, tools and resources for translational drug discovery
2. Organization, integration, curation and standardization of pharmacology data
1. Scientific facts
Ki = 4.5nM
APTT = 11 min.
ChEMBL: Data for drug discovery

5. KNIME at the EBI
• Access ChEBI and ChEMBL databases via KNIME nodes
• Trusted community nodes
• Algorithms development
• Document classification
• Share example workflows and use cases
• Provide KNIME training to scientists and researchers
• Wellcome Trust drug discovery courses, EMBL courses
• CDK community nodes development
h"p://tech.knime.org/book/embl-­‐ebi-­‐nodes

6. ChEMBL nodes

7. ChEMBL KNIME nodes

8. Example: All bioactivities for hERG
All
bioac9vi9es
for
hERG
Ac9vity
value,
assay
descrip9on,
compound,
reference

9. Example: Compound searching in ChEMBL
Query
List
of
NNs

10. Example: Polypharmacology profile
Compounds
Query
Find
NNs
Retrieve
bioac9vi9es
Filter,
summarise
&
pivot

11. Web services v2.0
• Many more entities à granularity
• Pagination, filtering, ordering

12. UniChem integration

13. EMBL-EBI chemistry resources
RDF
and
REST
API
interfaces
REST
API
Interface
-­‐
h"ps://www.ebi.ac.uk/unichem/
Atlas
Ligand
induced
transcript
response
750
PDBe
Ligand
structures
from
structurally
defined
protein
complexes
15K
ChEBI
Nomenclature
of
primary
and
secondary
metabolites.
Chemical
Ontology
24K
SureChEMBL
Chemical
structures
from
patent
literature
~17M
ChEMBL
Bioac9vity
data
from
literature
and
deposi9ons
1.5M
UniChem
–
InChI-­‐based
chemical
resolver
(full
+
relaxed
‘lenses’)
>90M
3rd
Party
Data
ZINC,
PubChem,
ThomsonPharma
DOTF,
IUPHAR,
DrugBank,
KEGG,
NIH
NCC,
eMolecules,
FDA
SRS,
PharmGKB,
Selleck,
….
~70M

14. Novelty checking with UniChem
h"ps://www.ebi.ac.uk/unichem/

15. Cheminformatics utilities

16. Cheminformatics utilities (aka ‘Beaker’)
• Chemical format conversions
• Dynamic image generation
• Image processing (via OSRA)
• Descriptors and property calculations
• Chemical modifications and standardization
https://www.ebi.ac.uk/chembl/api/utils/docs

17. Example: Image to Structure
image URL

18. myChEMBL integration

21. Accessing local data with myChEMBL

22. Using KNIME to connect to myChEMBL
SELECT mr.*, md.chembl_id,
cp.full_mwt, cp.alogp
from mols_rdkit mr,
molecule_dictionary md,
compound_properties cp
where
mr.m @> '$${SMolecule}$$'::qmol
and
mr.molregno = md.molregno
and
md.molregno = cp.molregno;

23. SureChEMBL and Open PHACTS

24. SureChEMBL and Open PHACTS
SureChEMBL
SciBite
Termite
Open
PHACTS
API
https://dev.openphacts.org/docs/develop
https://github.com/openphacts/OPS-Knime/

25. http://rdf.ebi.ac.uk/resource/surechembl/patent/US-8877786-B2
Substituted
carbamoylmethylamino acetic
acid derivatives as novel NEP
inhibitors
US-8877786-B2
Most relevant targets and diseases
MCS scaffold

26. Most relevant diseases
Most relevant targets
Patent publication date histogra
http://rdf.ebi.ac.uk/resource/surechembl/molecule/SCHEMBL371804
Foretinib, a kinase inhibitor in clinical phase II
Found in 89 EP,
WO and US
patents

27. Summary
• KNIME: democratizes access to data and tools
• Access public domain structure and bioactivity data and
services with KNIME
• ChEMBL KNIME Nodes
• UniChem
• Cheminformatics services
• myChEMBL
• SureChEMBL

28. Publications

29. Acknowledgements
• Francis Atkinson
• Louisa Bellis
• Jon Chambers
• Michał Nowotka
• Anne Hersey
• Stefan Beisken
• Edmund Duesbury
• Daniela Digles
• Thorsten Meinl
• KNIME
• KNIME community
All
workflow
examples
are
available
on
request.

30. ChEMBL resources and KNIME
George Papadatos
georgep@ebi.ac.uk