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Answer Set Programming (ASP) allows us to address knowledge-intensive search and optimization problems in a declarative way due to its integrated modeling, grounding, and solving workflow. A problem is modeled using a rule based language and then grounded and solved. Solving results in a set of stable models that correspond to solutions of the modeled problem. In this thesis, we present the design and implementation of the clingo system---perhaps, the most
widely used ASP system. It features a rich modeling language originating from the field of knowledge representation and reasoning, efficient grounding algorithms based on database evaluation techniques, and high performance solving algorithms based on Boolean satisfiability (SAT) solving technology.
The contributions of this thesis lie in the design of the modeling language, the design and implementation of the grounding algorithms, and the design and implementation of an Application Programmable Interface (API) facilitating the use of ASP in real world applications and the implementation of complex forms of reasoning beyond the traditional ASP workflow.
Proposing relevant perturbations to biological signaling networks is central to many problems in biology and medicine because it allows for enabling or disabling certain biological outcomes. In contrast to quantitative methods that permit fine-grained (kinetic) analysis, qualitative approaches allow for addressing large-scale networks. This is accomplished by more abstract representations such as logical networks. We elaborate upon such a qualitative approach aiming at the computation of minimal interventions in logical signaling networks relying on Kleene's three-valued logic and fixpoint semantics. We address this problem within answer set programming and show that it greatly outperforms previous work using dedicated algorithms.
Proposing relevant perturbations to biological signaling networks is central to many problems in biology and medicine because it allows for enabling or disabling certain biological outcomes. In contrast to quantitative methods that permit fine-grained (kinetic) analysis, qualitative approaches allow for addressing large-scale networks. This is accomplished by more abstract representations such as logical networks. We elaborate upon such a qualitative approach aiming at the computation of minimal interventions in logical signaling networks relying on Kleene's three-valued logic and fixpoint semantics. We address this problem within answer set programming and show that it greatly outperforms previous work using dedicated algorithms.
Logical modeling has been widely used to understand and expand the knowledge about protein interactions among different pathways. Realizing this, the caspo-ts system has been proposed recently to learn logical models from time series data. It uses Answer Set Programming to enumerate Boolean Networks (BNs) given prior knowledge networks and phosphoproteomic time series data. In the resulting sequence of solutions, similar BNs are typically clustered together. This can be problematic for large scale problems where we cannot explore the whole solution space in reasonable time. Our approach extends the caspo-ts system to cope with the important use case of finding diverse solutions of a problem with a large number of solutions. We first present the algorithm for finding diverse solutions and then we demonstrate the results of the proposed approach on two different benchmark scenarios in systems biology: (1) an artificial dataset to model TCR signaling and (2) the HPN-DREAM challenge dataset to model breast cancer cell lines.