ChEMBL+KNIME

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
[email protected]

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
K
i
= 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
K
i
= 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/embl3ebi3nodes6

6. ChEMBL nodes

7. ChEMBL KNIME nodes

8. Example: All bioactivities for hERG
All6bioac9vi9es6for6hERG6
Ac9vity6value,6assay6
descrip9on,6compound,6
reference6

9. Example: Compound searching in ChEMBL
Query6
List6of6NNs6

10. Example: Polypharmacology profile
Compounds
Query6
Find6NNs6
Retrieve6
bioac9vi9es6
6
Filter,6summarise6&6pivot6
6

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

12. UniChem integration

13. EMBL-EBI chemistry resources
RDF6and6REST6API6interfaces6
REST6API6Interface636h"ps://www.ebi.ac.uk/unichem/6
Atlas6
6
6
6
Ligand6
induced6
transcript6
response6
7506
PDBe6
6
6
6
Ligand6
structures6
from6
structurally6
defined6
protein6
complexes6
6
15K6
ChEBI6
6
6
6
Nomenclature6
of6primary6and6
secondary6
metabolites.6
Chemical6
Ontology6
6
24K6
SureChEMBL6
6
6
6
6
Chemical6
structures6
from6patent6
literature6
6
~17M%
ChEMBL6
6
6
6
Bioac9vity6
data6from6
literature6
and6
deposi9ons6
6
1.5M6
UniChem6–6InChI3based6chemical6resolver6(full6+6relaxed6‘lenses’)6>90M6
3
rd
6Party6Data6
6
ZINC,6PubChem,6
ThomsonPharma6
DOTF,6IUPHAR,6
DrugBank,6KEGG,6
NIH6NCC,6
eMolecules,6FDA6
SRS,6PharmGKB,6
Selleck,6….6
6
~70M6

14. Novelty checking with UniChem
h"ps://www.ebi.ac.uk/unichem/6

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 histogram
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
All6workflow6examples6are6available6on6request.66

30. ChEMBL resources and KNIME




George Papadatos
[email protected]