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Chemical biology and drug discovery seek to uncover the relationship between chemical structure and function. In the context of the emerging life science semantic web, we have previously investigated multiple strategies for the representation and reasoning of chemical structure, functional groups and chemical attributes using RDF, OWL, SWRL and so-called Description Graphs. Here, we continue our investigation on the representation of molecular structure using class-based approach to infer molecular symmetry and specialization of atomic connectivity. This work provides new design patterns towards representing and reasoning about structured objects
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Molecular symmetry and specialization of atomic connectivity by class-based
reasoning of chemical structure
1
Michel Dumontier, Ph.D.
Associate Professor of Bioinformatics Department of Biology, School of Computer Science, Institute of Biochemistry, Carleton
University Ottawa Institute of Systems Biology
Ottawa-Carleton Institute of Biomedical Engineering Professeur Associé, Université Laval
OWLED2012::Dumontier
chemical structure: molecules consist of atoms connected by bonds
caffeine
single bond
double bond
Carbon atom
Hydrogen atom
Nitrogen atom Oxygen atom
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First attempt: class-based representation of chemical functional groups
HydroxylGroup equivalentTo: CarbonGroup that (hasSingleBondWith some ( OxygenAtom that hasSingleBondWith some HydrogenAtom))
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Describing chemical functional groups in OWL-DL for the classification of chemical compounds. Natalia Villanueva-Rosales and Michel Dumontier. OWL: Experiences and Directions (OWLED 2007).
automatic classification of chemical functional groups
28 OC
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Problems
1. Descriptions started at an arbitrary central atom, so all descriptions needed to “specialize these”
2. Not possible to describe a chemical functional groups that are graph-like
e.g. contains a cycle
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OWL representation
We really need to represent and reason over structured objects
Without structure-based representation, all parts must be explicitly asserted
(combinatorial explosion for larger molecules)
But the structure of complex molecules breaks the OWL Tree Model requirement
does not have a model in the shape of a tree
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Description Graphs
• A decidable extension to OWL 2 allowing expression of complex structures as graphs within the ontology
• strong separation requirement: atomic properties used as graph edges have to be different to those used in axioms in the main OWL ontology
• Rules can be used to enhance OWL with the capacity to express if – then constructions
• Using OWL, Description Graphs and Rules we could represent and reason over (classify) chemical structures at the class level.
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Representing Chemicals using OWL, Description Graphs and Rules. J Hastings, M Dumontier, D Hull, M Horridge, C Steinbeck, U Sattler, R Stevens, T Horne, and K Britz. OWLED 2010.
OWL + DG + Rules = Chemical Classification
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Before After
So, what can we do with just OWL?
• generate connectivity descriptions for every atom to every other atom – overcome the central atom problem – exponential part list
• reason at different levels of granularity – we could describe atoms in terms of 1. the types of atoms they are connected to 2. the exact set of atoms they are connected to 3. the only atoms they are connected to
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Dataset
A) butane, B) pentane, C) iso-butane, D) iso-pentane, E) cyclobutane and F) cyclohexane
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HermiT
Method
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Protégé 4.2
SDF
PHP-based OWLAPI
SDF2OWL
OWL
Inference
formalization
reasoning
Explanation Workbench
Formalization separates the chemical graph from the molecule
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`fully connected atom M` equivalentTo `atom type` and `has bond with` exactly 1 `fully connected atom N` and ...
`atom X from molecule A` equivalentTo `fully connected atom M` and `is component part of` some `molecule Y`
Symmetry
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equivalence among 2,3 and 4 as every peripheral atom is connected to the central atom (1)
1
4 3
2
Symmetry
• For iso-pentane, we get equivalence between atoms 4 & 5 because they are both connected to atoms 1
• we get a different relationship – one of subsumption - between atoms 2 and 4 and atoms 2 and 5
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3
1
4 5
2
Atomic specialization
Basically, atom 2 has a bond to atom 1, as do atoms 4 and 5, but it also has a bond to atom 3
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1
4 5
2 3
Symmetry in butane
• Equivalence between atoms 1 & 3 as they both share connectivity to atoms 2 & 4, and vice versa.
• No equivalence among all atoms, however.
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1
2
3
4
But not in cyclohexane
• No 2 atoms are connected to the same pair of atoms.
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Conclusion
• We investigated class-based representation where class descriptions consisted of fully qualified cardinality restrictions to other fully-connected atoms.
• We found instances of equivalence (symmetry) and specialization (additional bonding), all within a single molecule
• Next, we’ll be looking at reasoning across different molecules, but this requires some equivalence between atoms of different molecules.
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dumontierlab.com [email protected]
19 EBI2011::Dumontier
Website: http://dumontierlab.com Presentations: http://slideshare.com/micheldumontier
