An ASP application in integrative biology: Identification of functional gene units

Abstract

Integrating heterogeneous knowledge is necessary to elucidate the regulations in biological systems. In particular, such an integration is widely used to identify functional units, that are sets of genes that can be triggered by the same external stimuli, as biological stresses, and that are linked to similar responses of the system. Although several models and algorithms shown great success for detecting functional units on well-known biological species, they fail in identifying them when applied to more exotic species, such as extremophiles, that are by nature unrefined. Indeed, approved methods on unrefined models suffer from an explosion in the number of solutions for functional units, that are merely combinatorial variations of the same set of genes. This paper overcomes this crucial limitation by introducing the concept of "genome segments". As a natural extension of recent studies, we rely on the declarative modeling power of answer set programming (ASP) to encode the identification of shortest genome segments (SGS). This study shows, via experimental evidences, that SGS is a new model of functional units with a predictive power that is comparable to existing methods. We also demonstrate that, contrary to existing methods, SGS are stable in (i) computational time and (ii) ability to predict functional units when one deteriorates the biological knowledge, which simulates cases that occur for exotic species. © 2013 Springer-Verlag.