Class-based reasoning (OWLED2012)

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 michel_dumontier@carleton.ca

19 EBI2011::Dumontier

Website: http://dumontierlab.com Presentations: http://slideshare.com/micheldumontier