chembl resources and knime - openphacts€¦ · chembl knime nodes . example: all bioactivities for...
TRANSCRIPT
![Page 2: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/2.jpg)
Outline
• ChEMBL data
• ChEMBL nodes
• Web services v2.0
• UniChem
• Cheminformatics utilities
• myChEMBL
• SureChEMBL and Open PHACTS
![Page 3: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/3.jpg)
Bioactivity data
Compound
Ass
ay/T
arge
t
>Thrombin MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE
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
![Page 4: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/4.jpg)
Bioactivity data
Compound
Ass
ay/T
arge
t
>Thrombin MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE
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
![Page 5: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/5.jpg)
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
![Page 6: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/6.jpg)
ChEMBL nodes
![Page 7: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/7.jpg)
ChEMBL KNIME nodes
![Page 8: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/8.jpg)
Example: All bioactivities for hERG
All bioac9vi9es for hERG
Ac9vity value, assay descrip9on, compound, reference
![Page 9: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/9.jpg)
Example: Compound searching in ChEMBL
Query
List of NNs
![Page 10: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/10.jpg)
Example: Polypharmacology profile
Compounds
Query
Find NNs
Retrieve bioac9vi9es
Filter, summarise & pivot
![Page 11: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/11.jpg)
Web services v2.0
• Many more entities à granularity
• Pagination, filtering, ordering
![Page 12: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/12.jpg)
UniChem integration
![Page 13: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/13.jpg)
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
![Page 14: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/14.jpg)
Novelty checking with UniChem h"ps://www.ebi.ac.uk/unichem/
![Page 15: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/15.jpg)
Cheminformatics utilities
![Page 16: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/16.jpg)
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
![Page 17: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/17.jpg)
Example: Image to Structure
image URL
![Page 18: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/18.jpg)
myChEMBL integration
![Page 19: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/19.jpg)
![Page 20: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/20.jpg)
![Page 21: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/21.jpg)
Accessing local data with myChEMBL
![Page 22: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/22.jpg)
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;
![Page 23: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/23.jpg)
SureChEMBL and Open PHACTS
![Page 24: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/24.jpg)
SureChEMBL and Open PHACTS
SureChEMBL
SciBite Termite
Open PHACTS API
https://dev.openphacts.org/docs/develop https://github.com/openphacts/OPS-Knime/
![Page 25: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/25.jpg)
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
![Page 26: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/26.jpg)
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
![Page 27: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/27.jpg)
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
![Page 28: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/28.jpg)
Publications
![Page 29: ChEMBL resources and KNIME - OpenPHACTS€¦ · ChEMBL KNIME nodes . Example: All bioactivities for hERG All6bioac9vi9es6for6hERG6 Ac9vity6value,6assay6 descripon,compound,6 reference](https://reader033.vdocuments.us/reader033/viewer/2022042613/5fa29521fb8d2f5b3471cf7f/html5/thumbnails/29.jpg)
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.