TY - JOUR A1 - Videla, Santiago A1 - Guziolowski, Carito A1 - Eduati, Federica A1 - Thiele, Sven A1 - Gebser, Martin A1 - Nicolas, Jacques A1 - Saez-Rodriguez, Julio A1 - Schaub, Torsten H. A1 - Siegel, Anne T1 - Learning Boolean logic models of signaling networks with ASP JF - Theoretical computer science N2 - Boolean networks provide a simple yet powerful qualitative modeling approach in systems biology. However, manual identification of logic rules underlying the system being studied is in most cases out of reach. Therefore, automated inference of Boolean logical networks from experimental data is a fundamental question in this field. This paper addresses the problem consisting of learning from a prior knowledge network describing causal interactions and phosphorylation activities at a pseudo-steady state, Boolean logic models of immediate-early response in signaling transduction networks. The underlying optimization problem has been so far addressed through mathematical programming approaches and the use of dedicated genetic algorithms. In a recent work we have shown severe limitations of stochastic approaches in this domain and proposed to use Answer Set Programming (ASP), considering a simpler problem setting. Herein, we extend our previous work in order to consider more realistic biological conditions including numerical datasets, the presence of feedback-loops in the prior knowledge network and the necessity of multi-objective optimization. In order to cope with such extensions, we propose several discretization schemes and elaborate upon our previous ASP encoding. Towards real-world biological data, we evaluate the performance of our approach over in silico numerical datasets based on a real and large-scale prior knowledge network. The correctness of our encoding and discretization schemes are dealt with in Appendices A-B. (C) 2014 Elsevier B.V. All rights reserved. KW - Answer set programming KW - Signaling transduction networks KW - Boolean logic models KW - Combinatorial multi-objective optimization KW - Systems biology Y1 - 2015 U6 - https://doi.org/10.1016/j.tcs.2014.06.022 SN - 0304-3975 SN - 1879-2294 VL - 599 SP - 79 EP - 101 PB - Elsevier CY - Amsterdam ER -