Talk delivered at Vermont Code Camp 2014 by Mitch Miller

1. Geek Meets Science: ChemIDplus,
an Example of Scientific Thinking
Mitch Miller
Scientific Thinking

2. Overview
➲Introduce myself
➲My definition of a scientific geek consultant
➲An fast overview of Cheminformatics
➲Overview of the ChemIDplus project
➲The scientific geek's role in ChemIDplus

3. Introduction: who am I?
➲Ph.D. chemist with 20+ years of experience in
scientific information management
➲Currently independent consultant
➲Application developer, database person,
requirements analyst, application first-aid
➲Main areas of focus:
●Chemical structure database management
●Managing data from high-throughput
research

4. The perspective of the scientific-geek-
consultant
➲Is the scientific-geek-consultant's perspective on
technology different from other geeks'?
➲Learn new technologies/frameworks/paradigms
and take them in stride
➲What gets me excited is seeing a user able to do
something that the user could not do yesterday
➲This talk is about one project in scientific
information management and what I've done to
give users access to what they could not do
before

5. Quick Introduction to Chemical Databases

6. Representing Chemical Structures
➲This discussion is restricted to 2 dimensional (2D)
structures which establish identity
➲Chemical structures can be represented graphically
in a variety of ways.
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➲To make structures searchable, you need a
mathematical representation of the atoms and bonds:
a connection table

7. Searching for structures
➲Search for matches based on a graphic
chemical system
●Start with a chemical of interest
●Find others like it
➲Several definitions of what makes one structure
like another
●Exact match: find same molecule user input
●Substructure
●'Similarity' fuzzy match
➲Analogy: Word search for 'store'

8. Substructure matches for Aspirin
➲Each of these
➲structures contains
➲the query structure
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➲Word analogy results:
●Store
●drugstore
●stores
●stored
●restore

9. Non-matching structure
➲4-(acetyloxy)-benzoic acid is not a substructure match
for aspirin because it does not contain the same
arrangement of atoms and bonds
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➲Non-hits for Word search analogy:
●story
●storm
●'stoor'
➲Can be found using similarity search

10. Structure search software
➲Standalone programs
●Ran on server or desktop
➲Client-server architectures
➲Database cartridges
●Provide chemical structure searching within a relational
database
●Commercially available
●Add operators to store, search, retrieve and transform
chemical structures within SQL
●e.g. SELECT ID, MOLDEPICTION(STRUCT) FROM
OUR_STRUCTURE_TABLE WHERE SUBSTRUCT(STRUCT,
'CC(=O)Oc1ccccc1C(=O)O') =1
●Client application must have a tool that can display connection
tables as graphic chemical structures

11. Structure database operations
➲Data stored in tables
➲Data loading typically requires specialized
software
➲Indexing is non-typical
➲Search operators are specific to the cartridge

12. How can you search a million
chemical structures in seconds?
➲Chemical databases have sizes in 100's of thousands or
millions
➲Comparing atoms and bonds takes time!
➲Users want answers quickly.
➲Solution: rapid screen-out step before looking at atom and
bonds.
●Based on structure 'fingerprints'
●Analyze input structures for features such as rings,
atoms, connection patterns (O-X-X-N).
●Create a bit string
●Compare bit string of query structure with bit strings in
database.
●Bit string comparisons are very fast

13. The ChemIDplus project

14. ChemIDplus
➲“Dictionary of over 400,000 chemicals (names,
synonyms, and structures) … (with) links to
NLM and other databases and resources”
➲Maintained by the Division of Specialized
Information Services within the National Library
of Medicine within National Institutes of Health
➲Used by people in industry, academia and
government who handle drugs and chemicals
and access environmental and safety data plus
other biomedical information

15. ChemIDplus
➲Part of a system of databases called 'Toxnet' at
National Library of Medicine http://toxnet.nlm.nih.gov/
➲Focus:
●Chemical Information
●Environmental Health and Toxicology
●HIV / AIDS
●Disaster Information
➲Available on the web in 3 'flavors':
●Full: http://chem.sis.nlm.nih.gov/chemidplus/
●'Lite:' http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp
●Ultralite: http://druginfo.nlm.nih.gov/drugportal/drugportal.jsp
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16. ChemIDplus Team
➲George (Mike) Hazard – team leader
➲Shannon Jordan
➲Michael Chambers - developer
➲Chuchu Lan – system administrator/DBA
➲Jenny Fang
➲Stefanie Publicker
➲Larry Callahan, Frank Switzer – FDA liaisons

17. Historical Note
➲ChemIDplus was one of the first structure-searchable
databases on the worldwide web
➲Started in 1998
➲Original developer

18. Server Architecture
Tomcat Server
Servlets, JSPs,
JS libraries
Database Server
Chemical
Data Cartridge
Database
(Oracle)
Structures
Names
Links
Properties

19. And now, the demo...

20. Scientific Geek's role in ChemIDplus
➲Developer of the original system in 1998-9 in a since-retired technology
➲Database administrator for structures
●Upgrade between versions of the chemical search software
●Periodic reindexing of the structures for performance
●Batch updates
●Help clean up invalid data
➲Tester
●Performed load testing when the application was migrated to Java
servlets
➲Liaison with other governmental agencies
●Share structures with NCI, PubChem
➲Structure orientation application
●Tool to help ensure that series of chemical compounds look similar
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21. Structure table synchronization
The old way
➲Monthly manual process
●Query structures recently added or
changed
●Extract to disk files
●Generated data based on structure: InChI,
SMILES, 3D coordinates
●Registered each item separately
➲Took a couple of hours each month
➲This was repetitious work

22. New system
➲Database trigger detects a change when a value is
inserted or updated to a chemical structure field
➲Computes and stores InChI and SMILES immediately
➲Submits a batch job (DBMS_JOB package) for 3D
●Deletes old 3D structure
●Writes 2D structure to disk
●Invokes Corina (Molecular Networks) program
to generate 3D structure
●Reads 3D structure into separate table

23. Orienting Structures Consistently
➲Databases often contain 'families' of related
compounds
➲Example molecule and hits
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➲Manually manipulating
structures takes time!
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24. Solution: 'StructClean' Utility
➲Accepts a template structure + molecular weight
●Locates all molecules in the DB that contain
the template under the molecular weight cutoff
●Without the cutoff, you'd might have huge
molecules that contain a small template
➲All hits are oriented to match the template
➲User reviews hits
●Selects/deselects items
●Commits changes
➲Utility is a Java servlet

25. Conclusion
➲ChemIDplus is a valuable resource to those
looking for chemical information on the web
➲Scientific-geek-consultants use a variety of
technologies to provide service to research clients
➲We are similar to regular geeks in many ways
➲The differences are interesting!