Evaluating the Quality andPerformance of Automatic AtomMapping AlgorithmsACS National Meeting, Philadelphia, USA 20th Augu...
What is Atom-Mapping?MappingalgorithmACS National Meeting, Philadelphia, USA 20th August 2012
Why Perform Atom-Mapping?• Assigning roles to reagents• Normalization of reactions for registrationACS National Meeting, P...
Why Perform Atom-Mapping?• More precise database searches– Solvents/catalysts can be distinguished fromreactants– Allows t...
ExampleACS National Meeting, Philadelphia, USA 20th August 2012• I want to find reactions converting an alkeneto a cyclopr...
Why Perform Atom-Mapping?• Identifying suspect reactions:ACS National Meeting, Philadelphia, USA 20th August 2012
Qualities to look for in an atommapping algorithm• Chemically plausible atom mappings• Ability to distinguish genuine reac...
Algorithms EvaluatedACS National Meeting, Philadelphia, USA 20th August 2012Vendor:Program VersionAccelrys:Pipeline Pilot ...
MethodologyACS National Meeting, Philadelphia, USA 20th August 2012Test set ReactionsPharmaceutical ELN subset 18,244ChemR...
Methodology-cont.• Reaction SMILES were used as input andoutput for all algorithms bar ICMAP• Input and output was convert...
Ability to map all product atomsACS National Meeting, Philadelphia, USA 20th August 2012
c-c bonds brokenACS National Meeting, Philadelphia, USA 20th August 2012
Speed ComparisonACS National Meeting, Philadelphia, USA 20th August 20121.7 3.6 1.6 4.0Averagereagents perreaction
Simple mappingsACS National Meeting, Philadelphia, USA 20th August 2012Marvin/ChemDraw/Indigo/ICMAP
Simple mappingsACS National Meeting, Philadelphia, USA 20th August 2012Marvin/ChemDraw/Indigo/ICMAP
More complicated MappingsACS National Meeting, Philadelphia, USA 20th August 2012ChemDrawMarvin
More complicated MappingsACS National Meeting, Philadelphia, USA 20th August 2012ICMAPIndigo
Reuse of reactantsACS National Meeting, Philadelphia, USA 20th August 2012
Reuse of reactantsACS National Meeting, Philadelphia, USA 20th August 2012Marvin
Reuse of reactantsACS National Meeting, Philadelphia, USA 20th August 2012ChemDraw
Reuse of reactantsACS National Meeting, Philadelphia, USA 20th August 2012Indigo
Reuse of reactantsACS National Meeting, Philadelphia, USA 20th August 2012ICMAP
Single Atom MappingACS National Meeting, Philadelphia, USA 20th August 2012ICMAP/MarvinChemDraw/Indigo
Bugs and quirks• Marvin– 2 unsuccessful mappings produced uncheckedexceptions rather than checked exceptions• ChemDraw– Hy...
Bugs and quirks• ICMAP– Single atom products are interpreted as emptymolecules or occasionally replaced by a productfrom a...
conclusions• ICMAP produced the best quality mappings onthe tested sets• Atom mapping isn’t as simple as finding amaximum ...
acknowledgements• Ed Griffen and Nick Tomkinson, AstraZeneca.• Andrew Wooster, GSK.• Hans Kraut, InfoChem• Thank you for y...
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Evaluating the Quality and Performance of Automatic Atom Mapping Algorithms

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Presented by Daniel Lowe at the ACS National Meeting Philadelphia Fall 2012

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Evaluating the Quality and Performance of Automatic Atom Mapping Algorithms

  1. 1. Evaluating the Quality andPerformance of Automatic AtomMapping AlgorithmsACS National Meeting, Philadelphia, USA 20th August 2012Daniel Lowe and Roger SayleNextMove SoftwareCambridge, UK
  2. 2. What is Atom-Mapping?MappingalgorithmACS National Meeting, Philadelphia, USA 20th August 2012
  3. 3. Why Perform Atom-Mapping?• Assigning roles to reagents• Normalization of reactions for registrationACS National Meeting, Philadelphia, USA 20th August 2012
  4. 4. Why Perform Atom-Mapping?• More precise database searches– Solvents/catalysts can be distinguished fromreactants– Allows the relationship between the reactantatoms and product atoms to be made explicitACS National Meeting, Philadelphia, USA 20th August 2012
  5. 5. ExampleACS National Meeting, Philadelphia, USA 20th August 2012• I want to find reactions converting an alkeneto a cyclopropane so I search for C=C>>C1CC1
  6. 6. Why Perform Atom-Mapping?• Identifying suspect reactions:ACS National Meeting, Philadelphia, USA 20th August 2012
  7. 7. Qualities to look for in an atommapping algorithm• Chemically plausible atom mappings• Ability to distinguish genuine reactants fromsolvents/catalysts• Support for unbalanced reactions– Side product not specified– Reactant stoichiometry > 1• Fast run-timeACS National Meeting, Philadelphia, USA 20th August 2012
  8. 8. Algorithms EvaluatedACS National Meeting, Philadelphia, USA 20th August 2012Vendor:Program VersionAccelrys:Pipeline Pilot 8.5.0.200ChemAxon:Marvin 5.10.1GGA:Indigo 1.1InfoChem:ICMAP 5.10PerkinElmer:ChemDraw Ultra 12.0
  9. 9. MethodologyACS National Meeting, Philadelphia, USA 20th August 2012Test set ReactionsPharmaceutical ELN subset 18,244ChemReact68 database 67,926SPRESI database subset 5,230Reactions extracted from 2008-2011 USPTO patent applications*562,872* Lowe, D. M. Automated Extraction of Reactions from the Patent Literature.243rd ACS National Meeting & Exposition, San Diego, CA, March 27, 2012.
  10. 10. Methodology-cont.• Reaction SMILES were used as input andoutput for all algorithms bar ICMAP• Input and output was converted to and fromRDF for use with ICMAP• Indigo was ran with its default configurationand more lenient settings for matchingvalences, charges and bond orders• Marvin was configured to use its bestquality mapping strategyACS National Meeting, Philadelphia, USA 20th August 2012
  11. 11. Ability to map all product atomsACS National Meeting, Philadelphia, USA 20th August 2012
  12. 12. c-c bonds brokenACS National Meeting, Philadelphia, USA 20th August 2012
  13. 13. Speed ComparisonACS National Meeting, Philadelphia, USA 20th August 20121.7 3.6 1.6 4.0Averagereagents perreaction
  14. 14. Simple mappingsACS National Meeting, Philadelphia, USA 20th August 2012Marvin/ChemDraw/Indigo/ICMAP
  15. 15. Simple mappingsACS National Meeting, Philadelphia, USA 20th August 2012Marvin/ChemDraw/Indigo/ICMAP
  16. 16. More complicated MappingsACS National Meeting, Philadelphia, USA 20th August 2012ChemDrawMarvin
  17. 17. More complicated MappingsACS National Meeting, Philadelphia, USA 20th August 2012ICMAPIndigo
  18. 18. Reuse of reactantsACS National Meeting, Philadelphia, USA 20th August 2012
  19. 19. Reuse of reactantsACS National Meeting, Philadelphia, USA 20th August 2012Marvin
  20. 20. Reuse of reactantsACS National Meeting, Philadelphia, USA 20th August 2012ChemDraw
  21. 21. Reuse of reactantsACS National Meeting, Philadelphia, USA 20th August 2012Indigo
  22. 22. Reuse of reactantsACS National Meeting, Philadelphia, USA 20th August 2012ICMAP
  23. 23. Single Atom MappingACS National Meeting, Philadelphia, USA 20th August 2012ICMAP/MarvinChemDraw/Indigo
  24. 24. Bugs and quirks• Marvin– 2 unsuccessful mappings produced uncheckedexceptions rather than checked exceptions• ChemDraw– Hydrogen on aromatic atoms missing in SMILESoutput• Indigo– Calculation of valency fails for aromatic sulfurACS National Meeting, Philadelphia, USA 20th August 2012
  25. 25. Bugs and quirks• ICMAP– Single atom products are interpreted as emptymolecules or occasionally replaced by a productfrom a previous reaction (bug reported)– Input files must be < 2gb and use dos line endingsACS National Meeting, Philadelphia, USA 20th August 2012
  26. 26. conclusions• ICMAP produced the best quality mappings onthe tested sets• Atom mapping isn’t as simple as finding amaximum common subgraph mapping• In all the algorithms there were aspects thatcould be improved to yield appreciablebenefitsACS National Meeting, Philadelphia, USA 20th August 2012
  27. 27. acknowledgements• Ed Griffen and Nick Tomkinson, AstraZeneca.• Andrew Wooster, GSK.• Hans Kraut, InfoChem• Thank you for your time.ACS National Meeting, Philadelphia, USA 20th August 2012
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