A bi-objective network design approach for discovering functional modules linking Golgi apparatus fragmentation and neuronal death

Abstract

Experimental records show the existence of a biological linkage between neuronal death and Golgi apparatus fragmentation. The comprehension of such linkage should help to understand the dynamics undergoing neurological damage caused by diseases such as Alzheimer’s disease or amyotrophic lateral sclerosis. In this paper, the bi-objective minimum cardinality bottleneck Steiner tree problem along with an ad-hoc exact algorithm are proposed to study such phenomena. The proposed algorithm is based on integer programming and the so-called ϵ-constraint method. A key feature of the devised approach is that it allows an efficient integer programming formulation of the problem. The obtained results show that it is possible to obtain additional evidence supporting the hypothesis that alterations of the Golgi apparatus structure and neuronal death interact through the biological mechanisms underlying the outbreak and progression of neurodegenerative diseases. Moreover, the function of cellular response to stress as a biological linkage between these phenomena is also further investigated. Complementary, computational results on a synthetic dataset are also provided with the aim of reporting the performance of the proposed algorithm.