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Bioinformatics has always been a prolific domain for generating complex satisfiability and optimization problems. For instance, the synthesis of multi-scale models of biological networks has recently been associated with the resolution of optimization problems mixing Boolean logic and universally quantified linear constraints (OPT+qLP), which can be benchmarked on real-world models. In this paper, we introduce a Counter-Example-Guided Abstraction Refinement (CEGAR) to solve such problems efficiently. Our CEGAR exploits monotone properties inherent to linear optimization in order to generalize counter-examples of Boolean relaxations. We implemented our approach by extending Answer Set Programming (ASP) solver Clingo with a quantified linear constraints propagator. Our prototype enables exploiting independence of sub-formulas to further exploit the generalization of counter-examples. We evaluate the impact of refinement and partitioning on two sets of OPT+qLP problems inspired by system biology. Additionally, we conducted a comparison with the state-of-the-art ASP solver Clingolpx that handles non-quantified linear constraints, showing the advantage of our CEGAR approach for solving large problems.
Thuillier et al. (Sun,) studied this question.