What are chemical structures and their relations? Janna Hastings 1 , Colin Batchelor 2 , Christoph Steinbeck 1  and Stefan...
What are chemical entities? 20.10.10 Molecules Substances
A chemical ontology <ul><li>Ch emical  E ntities of  B iological  I nterest </li></ul><ul><li>Focused on ‘small’ chemical ...
What are chemical relations? 20.10.10
Mind and reality 20.10.10 REALITY mostly harmless MIND contents:  concepts infinitely  subjective,  impossible to ensure t...
What is information? 20.10.10 INFORMATION? mostly harmless <ul><li>Information ‘decorates’ or ‘is about’ reality, relative...
What is the problem with this? 20.10.10
<ul><li>What is a ‘molecular structure’? </li></ul><ul><li>And whatever it is, is ‘caffeine’ a kind of it? </li></ul>20.10...
The chemical graph formalism 20.10.10 hydrogen atoms may be  implicit paracetamol
20.10.10 ATP Front view (3D) Side view (3D)
Formal derivation, systematic nomenclature <ul><li>‘ Formal derivation’ (IUPAC) </li></ul><ul><ul><li>parent hydride </li>...
(Accurately) Predicted molecules <ul><li>Computational chemistry  and drug discovery work with chemical graph models of mo...
20.10.10
Impossible molecules 20.10.10 Impossible cubane Graphs can be drawn for molecules which are  chemically infeasible
Chemical graphs as information instances <ul><li>We can interpret chemical graphs as information entities (instances) whic...
Chemical graphs as information types  <ul><li>Rather than regarding chemical graphs as instances of the broader informatio...
Plan specification <ul><li>We can interpret the chemical graph as a special kind of information type, that is, a  plan spe...
<ul><li>We seem to be missing something </li></ul>20.10.10
Graphs are underexplained as information <ul><li>Are chemical graphs  solely  informational, like names, or database cross...
Mathematical objects <ul><li>The graph which specifies the way the parts of a molecule are connected is a kind of mathemat...
The nature of chemical structures <ul><li>We now have three ontologically interesting categories </li></ul><ul><ul><li>The...
Structural relations <ul><li>Subsumption </li></ul><ul><ul><li>can be defined in terms of graph specialization </li></ul><...
Conclusion <ul><li>Classes of chemical entities can be defined in terms of chemical graphs as specifications </li></ul><ul...
Acknowledgements <ul><li>Special thanks to Kirill Degtyarenko, Marcus Ennis, Larry Hunter and Martin Boeker, as well as th...
Thank you for your attention
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Chemical Structures and Relations

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Presentation at the 2010 Formal Ontology in Information Systems conference

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  • The ontology is concerned with representing types of entities of these kinds, the individuals are the real ones in the world
  • These relations are expressed at the type level in the ontology and their interpretation at the instance level may be problematic
  • Chemical Structures and Relations

    1. 1. What are chemical structures and their relations? Janna Hastings 1 , Colin Batchelor 2 , Christoph Steinbeck 1 and Stefan Schulz 3 1 EBI Cheminformatics and Metabolism, UK 2 Royal Society of Chemistry, Cambridge, UK 3 University Medical Center, Freiburg, Germany
    2. 2. What are chemical entities? 20.10.10 Molecules Substances
    3. 3. A chemical ontology <ul><li>Ch emical E ntities of B iological I nterest </li></ul><ul><li>Focused on ‘small’ chemical entities: no proteins or nucleic acids </li></ul><ul><li>Scope (material entities): mainly molecules, but also salts, polymers, atoms, electrons, groups, residues </li></ul><ul><li>Scope (dependent entities): chemical role, biological role, application </li></ul><ul><li>Access ChEBI at http://www.ebi.ac.uk/chebi/ </li></ul>20.10.10
    4. 4. What are chemical relations? 20.10.10
    5. 5. Mind and reality 20.10.10 REALITY mostly harmless MIND contents: concepts infinitely subjective, impossible to ensure that different people agree contents: objects descriptions are objective, disagreements between different people can be resolved by empirical investigation
    6. 6. What is information? 20.10.10 INFORMATION? mostly harmless <ul><li>Information ‘decorates’ or ‘is about’ reality, relative to human understanding </li></ul><ul><li>Information has to be stored somewhere </li></ul><ul><li>An example of an information entity is a name </li></ul><ul><li>A name is not a property of the thing it is a name of </li></ul>
    7. 7. What is the problem with this? 20.10.10
    8. 8. <ul><li>What is a ‘molecular structure’? </li></ul><ul><li>And whatever it is, is ‘caffeine’ a kind of it? </li></ul>20.10.10
    9. 9. The chemical graph formalism 20.10.10 hydrogen atoms may be implicit paracetamol
    10. 10. 20.10.10 ATP Front view (3D) Side view (3D)
    11. 11. Formal derivation, systematic nomenclature <ul><li>‘ Formal derivation’ (IUPAC) </li></ul><ul><ul><li>parent hydride </li></ul></ul><ul><ul><li>functional parent </li></ul></ul><ul><li>Used for naming chemical entities systematically </li></ul>20.10.10 has parent hydride hexafluorobenzene benzene
    12. 12. (Accurately) Predicted molecules <ul><li>Computational chemistry and drug discovery work with chemical graph models of molecules which </li></ul><ul><li>may or may not be synthesised </li></ul><ul><li>depending on the outcome of computational calculations of their properties </li></ul><ul><li>These ‘candidate’ chemicals can be fully described in terms of their constituent parts and the connectivity between them </li></ul>20.10.10
    13. 13. 20.10.10
    14. 14. Impossible molecules 20.10.10 Impossible cubane Graphs can be drawn for molecules which are chemically infeasible
    15. 15. Chemical graphs as information instances <ul><li>We can interpret chemical graphs as information entities (instances) which are about molecular entities, concretized in the files stored in computers Beta-farnesene ⊑ Farnesene </li></ul><ul><li>beta-farnesene-CG ∈ CG ⊑ InformationContentEntity </li></ul><ul><li>beta-farnesene-CG ∈ ( CG ⊓  is_about . Beta-farnesene ) </li></ul><ul><li>But we can’t </li></ul><ul><ul><li>have hierarchies of graphs (each one is an instance) </li></ul></ul><ul><ul><li>easily account for the ‘aboutness’ of predicted molecules or the ‘wrongness’ of impossible graphs </li></ul></ul>20.10.10 We borrow ‘information entity’ from IAO, code.google.com/p/ information - artifact - ontology
    16. 16. Chemical graphs as information types <ul><li>Rather than regarding chemical graphs as instances of the broader information entity type, we can regard chemical graphs as special types of information, with many instances in individual files </li></ul><ul><li>Beta-farnesene-CG ⊑ Farnesene-CG ⊑ CG ⊑ InformationContentEntity </li></ul><ul><li>Now we can express hierarchical relationships between graphs </li></ul><ul><li>But we still cannot account for the ‘aboutness’ of predicted molecules... </li></ul>20.10.10
    17. 17. Plan specification <ul><li>We can interpret the chemical graph as a special kind of information type, that is, a plan specification: </li></ul><ul><ul><li>“ the information content specifies a process which has to be followed in order to bring about some goal or objective.” </li></ul></ul><ul><li>Material output has_specification plan specification </li></ul><ul><li>The ‘aboutness’ of graphs for predicted molecules is the chemical synthesis plan which can be generated </li></ul><ul><li>But this cannot explain predicted molecules for which no reliable synthesis mechanism is yet known </li></ul>20.10.10
    18. 18. <ul><li>We seem to be missing something </li></ul>20.10.10
    19. 19. Graphs are underexplained as information <ul><li>Are chemical graphs solely informational, like names, or database cross references? </li></ul><ul><li>Names are truly decorative </li></ul><ul><ul><li>Glucose would still be glucose even if we named it Patches </li></ul></ul><ul><ul><li>Glucose would still be glucose even if the cat was also named Glucose </li></ul></ul><ul><li>On the other hand, chemical graphs formalise essential structural features of molecules </li></ul><ul><li>You cannot structurally modify the graph while it still remains about the same molecule </li></ul>ChEBI ontology 20.10.10
    20. 20. Mathematical objects <ul><li>The graph which specifies the way the parts of a molecule are connected is a kind of mathematical object </li></ul><ul><li>It obeys rules of compositionality which correspond to the feasibility of real molecules </li></ul><ul><li>Chemical graphs on computers are ‘about’ this mathematical object , which inheres in chemical entities by virtue of their structural arrangement </li></ul><ul><li>We will call this ‘ connectivity ’ </li></ul>20.10.10
    21. 21. The nature of chemical structures <ul><li>We now have three ontologically interesting categories </li></ul><ul><ul><li>The chemical entity (Material object) </li></ul></ul><ul><ul><li>The chemical graph description (Information object) </li></ul></ul><ul><ul><li>The connectivity (Mathematical object) </li></ul></ul><ul><li>The information objects are about connectivities </li></ul><ul><li>The existence of connectivity depends on chemical feasibility, not the existence of real molecules </li></ul><ul><li>We can account for the aboutness of predicted molecules and the lack of aboutness of impossible molecules </li></ul>20.10.10
    22. 22. Structural relations <ul><li>Subsumption </li></ul><ul><ul><li>can be defined in terms of graph specialization </li></ul></ul><ul><li>Mereology </li></ul><ul><ul><li>can be defined in terms of subgraph relations </li></ul></ul><ul><li>Formal derivation Benzene-name  ( Name ⊓  is_about . Benzene ); </li></ul><ul><li>Fluorobenzene-name  ( Name ⊓  is_about . Fluorobenzene ); Benzene-CG  ( CG ⊓  is_about . Benzene-connectivity ); Fluorobenzene-CG  ( CG ⊓  is_about . Fluorobenzene-connectivity ); Fluorobenzene-name ⊑  is_derived_from . Benzene-name; and Benzene-CG ⊑  is_hydride_graph_of . Fluorobenzene-CG </li></ul>20.10.10
    23. 23. Conclusion <ul><li>Classes of chemical entities can be defined in terms of chemical graphs as specifications </li></ul><ul><li>Some of the relations which chemists use refer mainly to graphs rather than material entities </li></ul><ul><li>Our approach distinguishes material entities from information and mathematical entities </li></ul><ul><li>We address a specific problem in the ontology of chemistry, with a view to adequately defining the terms and relations which chemists already use rather than suggesting new terms and relations they should adopt </li></ul>20.10.10 Dispositions and chemistry
    24. 24. Acknowledgements <ul><li>Special thanks to Kirill Degtyarenko, Marcus Ennis, Larry Hunter and Martin Boeker, as well as the rest of the ChEBI team. </li></ul><ul><li>This work was funded by the BBSRC, grant agreement number BB/G022747/1 within the ‘Bioinformatics and biological resources’ fund. </li></ul>
    25. 25. Thank you for your attention

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