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.
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
10. Standardization Rules
• Available from: http://tinyurl.com/hwapem3
• Use the SRS as guidance for standardization
• Adjust as necessary to our needs
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]
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
Open PHACTS was developed to support the key questions of drug discovery
Business questions have been at the heart of Open PHACTS and have driven the development of the platform
Mx/psa, how calculated who did it?
Mash up. With your data too,
- top layer join together but need them all
commercial
Data provided by many publishers
Originally in many formats: relational, SD files and RDF
Worked closely with publishers
Data licensing was a major issue
Over 5 billion triples – 14 datasets & growing
Hosted on beefy hardware; data in memory (aim)
Extensive memcaching
Pose complex queries to extract data