Improving the classification of cardinality phenotypes using collections

Abstract

Motivation: Phenotypes are observable characteristics of an organism and they can be highly variable. Information about phenotypes is collected in a clinical context to characterize disease, and is also collected in model organisms and stored in model organism databases where they are used to understand gene functions. Phenotype data is also used in computational data analysis and machine learning methods to provide novel insights into disease mechanisms and support personalized diagnosis of disease. For mammalian organisms and in a clinical context, ontologies such as the Human Phenotype Ontology and the Mammalian Phenotype Ontology are widely used to formally and precisely describe phenotypes. We specifically analyze axioms pertaining to phenotypes of collections of entities within a body, and we find that some of the axioms in phenotype ontologies lead to inferences that may not accurately reflect the underlying biological phenomena.

Results: We reformulate the phenotypes of collections of entities using an ontological theory of collections. By reformulating phenotypes of collections in phenotypes ontologies, we avoid potentially incorrect inferences pertaining to the cardinality of these collections. We apply our method to two phenotype ontologies and show that the reformulation not only removes some problematic inferences but also quantitatively improves biological data analysis.

Keywords: Cardinality phenotypes; Genotype–phenotype associations; Phenotype ontologies.