This presentation was a webinar update to the Open PHACTS community regarding the release of the OPen PHACTS open source components of the Chemical Registration System and, more specifically, the Chemical validation and Standardization Platform. The need for a community set of rules was driven home with the Chemical validation and Standardization Platform potentially being an example platform for the rules.

1. Open PHACTS - Chemistry
Platform Update and learnings
Antony Williams and Valery Tkachenko
ORCID ID:0000-0002-2668-4821

2. @gray_alasdair Big Data Integration 2
OpenPHACTS and CRS Diagram

3. The Chemical Registration Service
Chemistry processing
•Validation
•Standardization
•Properties generation
•Properties retrieval
Export
•RDF
•SDF
API
•Domain-specific searches
•Chemical visualization
•Properties
•Conversions

5. Subsystems
• “CVSP” (frontend, backend, database)
• Compounds (frontend, database)
• OpenPHACTS API (frontend, database)
• Datasources registry (frontend, database)
• Processing farm (optional)

6. Structure-Based Database linking
• Open PHACTS, and many other projects
requiring the linking of structure databases,
depend on mappings
• Different databases use different processes
for standardization prior at deposition
• Examples: PubChem, EBI databases,
ChemSpider, etc.

7. DrugBank
• ~60 records can’t be dearomatized unambiguously
• ~40 records where InChIs did not match structure
• 2 records where SMILES, InChI and name did not
match the structure
• 7 records with 2 stereo bonds at chiral atoms
DB04283 DB04462

8. Standardizers
• EBI Standardizer:
https://wwwdev.ebi.ac.uk/chembl/extra/francis/sta
/
• PubChem Standardizer: https://
pubchem.ncbi.nlm.nih.gov/standardize/standardi
• NCGC Standardizer: https://tripod.nih.gov/?
p=61
• The CVSP Standardizer work in Open
PHACTS http://cvsp.chemspider.com/

10. Standardization Rules
• Available from: http://tinyurl.com/hwapem3
• Use the SRS as guidance for standardization
• Adjust as necessary to our needs

11. Nitro groups

12. Salt and Ionic Bonds

13. The CVSP System
http://cvsp.chemspider.com

14. Supports various file formats

15. Comptox Chemistry Dashboard
Prior to deposition check a deposition…

16. >3450 compounds in one SDF

17. 98 Errors, 1571 Warnings

18. Review Errors

19. Validation Rule Set

20. Various Rules Sets Available

21. CVSP – My own custom rules

22. ChEMBL Validation Review
(of 1.3 million records)
• 11,020 records with 4 bonds and zero charge, e.g.
CHEMBL501101 or CHEMBL501973
• 271 records with hypervalent oxygen (e.g. ,
CHEMBL2219679), carbon (e.g. 1005895), boron,
chlorine, iodine or phosphine
• 6,177 records where direction of bond makes no
sense, e.g. CHEMBL12760 and CHEMBL34704

23. Chemical Validation first…
Standardization Second
• Chemical Validation detects errors –
Standardization FIXES them according to rules
• SMIRKS transformations are based on both
InChI Normalization and FDA SRS rules

24. Standardization SMIRKS
Examples of InChI normalization
[*;H+:1]>>[*;H:1]
[O,S,Se,Te:1]=[O+,S+,Se+,Te+:2][C-;v3:3]>>[O,S,Se,Te:1]=[O,S,Se,Te:2]=[C:3]
[N-,P-,As-,Sb-:1]=[C+;v3:2]>>[N,P,As,Sb:1]#[C:2]
Examples of FDA SRS rules
[n:1]=[O:2]>>[n+:1][O-:2]
[*:1]=[N:2]#[N:3]>>[*:1]=[N+:2]=[N-:3]
[N+0;H3:1].[C:3](=[O:4])[O:5][H:6]>>[N+1;H4:1].[C:3](=[O:4])[O-:5]
Thiopurine [H:1][S:2][c:3]1[n:8][c:7]([H,*:13])[n:6][c:5]2[c:4]1[n:11][c:10]
([H,*:12])[n:9]2>>[H:1][N:8]1[C:7]([H,*:13])=[N:6][C:5]2=[C:4]([N:11]=[C:10]
([H,*:12])[N:9]2)[C:3]1=[S:2]

25. Examples of Standardization
Double bond with adjacent wiggly single bond
Collapser hydrogen atoms with no stereo bonds

26. Examples of Standardization
Remove symmetric stereocenters
Turn off chiral flag if no up or down bonds

27. Defining a Community Rule Set
• There are multiple standardizers, each with
their own rules set
• Can we decide on a default community rules
set, like Standard InChI, that could be used
by ALL Standardizers?
• A joint meeting between the Research Data
Alliance (RDA), IUPAC and ACS Division of
Chemical Information discussed the value
and possibilities of this approach (July 2016)

28. EPA is investigating CVSP
• EPA is investigating CVSP as a validation
and standardization platform
• Considering the API aspects of CVSP to
integrate to our registration system
• CVSP is a reference implementation and
“starting point” for a community rules set

29. CVSP code is now Open Source
• Open Source CVSP code now released
• Code is hosted on Open PHACTS Github
https://github.com/openphacts/ops-crs
• Valery Tkachenko will offer future support
• Hoping for additional community engagement
and support
• Some details of availability….

30. Virtual Machines
• OPS_FRONT (all websites and API)
• OPS_BACK (all heavy-lifting)
• OPS_DB (databases)
• VMs are VMware images
• Can be converted to other hypervisors

31. Thank you
Emails: tony27587@gmail.com and tkachenko.valery@gmail.com
SLIDES: www.slideshare.net/AntonyWilliams