Automated compound classification using a chemical ontology by Claudia Bobach, Timo Böhme, Ulf Laube, Anett Püschel and Lutz Weber. (Journal of Cheminformatics 2012, 4:40 doi:10.1186/1758-2946-4-40)
Abstract:
Background
Classification of chemical compounds into compound classes by using structure derived descriptors is a well-established method to aid the evaluation and abstraction of compound properties in chemical compound databases. MeSH and recently ChEBI are examples of chemical ontologies that provide a hierarchical classification of compounds into general compound classes of biological interest based on their structural as well as property or use features. In these ontologies, compounds have been assigned manually to their respective classes. However, with the ever increasing possibilities to extract new compounds from text documents using name-to-structure tools and considering the large number of compounds deposited in databases, automated and comprehensive chemical classification methods are needed to avoid the error prone and time consuming manual classification of compounds.
Results
In the present work we implement principles and methods to construct a chemical ontology of classes that shall support the automated, high-quality compound classification in chemical databases or text documents. While SMARTS expressions have already been used to define chemical structure class concepts, in the present work we have extended the expressive power of such class definitions by expanding their structure based reasoning logic. Thus, to achieve the required precision and granularity of chemical class definitions, sets of SMARTS class definitions are connected by OR and NOT logical operators. In addition, AND logic has been implemented to allow the concomitant use of flexible atom lists and stereochemistry definitions. The resulting chemical ontology is a multi-hierarchical taxonomy of concept nodes connected by directed, transitive relationships.
Conclusions
A proposal for a rule based definition of chemical classes has been made that allows to define chemical compound classes more precisely than before. The proposed structure based reasoning logic allows to translate chemistry expert knowledge into a computer interpretable form, preventing erroneous compound assignments and allowing automatic compound classification. The automated assignment of compounds in databases, compound structure files or text documents to their related ontology classes is possible through the integration with a chemistry structure search engine. As an application example, the annotation of chemical structure files with a prototypic ontology is demonstrated.
While creating an ontology to assist with compound classification, the authors concede the literature contains much semantic diversity:
Chemists use a variety of expressions to create compound class terms from a specific compound name – for example “backbone”, “scaffold”, “derivative”, “compound class” are often used suffixes or “substituted” is a common prefix that generates a class term. Unfortunately, the meaning of different chemical class terms is often not defined precisely and their usage may differ significantly due to historic reasons and depending on the compound class. For example, 2-ethyl-imidazole 1 belongs without doubt to the class of compounds having a imidazole scaffold, backbone or being an imidazole derivative or substituted imidazole. In contrast, pregnane 2 illustrates a more complicated case – as in case of 2-ethyl-imidazole this compound could be considered a 17-ethyl-derivative of the androstane scaffold 3. However, this would suggest a wrong compound classification as pregnanes are not considered to be androstane derivatives – although 2 contains androstane 3 as a substructure (Figure 1). This particular, structurally illogical naming convention goes back to the fundamentally different biological activities of specific compounds with a pregnane or androstane backbone, resulting in the perception that androstanes and pregnanes do not show a parent–child relation but are rather sibling concepts at the same hierarchical level. Thus, any expert chemical ontology will appreciate this knowledge and the androstane compound class structural definition needs to contain a definition that any androstane shall NOT contain a carbon substitution at the C-17 position. (emphasis added)
Not that present day researchers would create a structurally illogical naming convention in the view of future researchers.