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Metabolic networks play a crucial role in biology since they capture all chemical reactions in an organism. While there are networks of high quality for many model organisms, networks for less studied organisms are often of poor quality and suffer from incompleteness. To this end, we introduced in previous work an answer set programming (ASP)-based approach to metabolic network completion. Although this qualitative approach allows for restoring moderately degraded networks, it fails to restore highly degraded ones. This is because it ignores quantitative constraints capturing reaction rates. To address this problem, we propose a hybrid approach to metabolic network completion that integrates our qualitative ASP approach with quantitative means for capturing reaction rates. We begin by formally reconciling existing stoichiometric and topological approaches to network completion in a unified formalism. With it, we develop a hybrid ASP encoding and rely upon the theory reasoning capacities of the ASP system dingo for solving the resulting logic program with linear constraints over reals. We empirically evaluate our approach by means of the metabolic network of Escherichia coli. Our analysis shows that our novel approach yields greatly superior results than obtainable from purely qualitative or quantitative approaches.

plasp 3
(2019)

We describe the new version of the Planning Domain Definition Language (PDDL)-to-Answer Set Programming (ASP) translator plasp. First, it widens the range of accepted PDDL features. Second, it contains novel planning encodings, some inspired by Satisfiability Testing (SAT) planning and others exploiting ASP features such as well-foundedness. All of them are designed for handling multivalued fluents in order to capture both PDDL as well as SAS planning formats. Third, enabled by multishot ASP solving, it offers advanced planning algorithms also borrowed from SAT planning. As a result, plasp provides us with an ASP-based framework for studying a variety of planning techniques in a uniform setting. Finally, we demonstrate in an empirical analysis that these techniques have a significant impact on the performance of ASP planning.

In a recent line of research, two familiar concepts from logic programming semantics (unfounded sets and splitting) were extrapolated to the case of epistemic logic programs. The property of epistemic splitting provides a natural and modular way to understand programs without epistemic cycles but, surprisingly, was only fulfilled by Gelfond's original semantics (G91), among the many proposals in the literature. On the other hand, G91 may suffer from a kind of self-supported, unfounded derivations when epistemic cycles come into play. Recently, the absence of these derivations was also formalised as a property of epistemic semantics called foundedness. Moreover, a first semantics proved to satisfy foundedness was also proposed, the so-called Founded Autoepistemic Equilibrium Logic (FAEEL). In this paper, we prove that FAEEL also satisfies the epistemic splitting property something that, together with foundedness, was not fulfilled by any other approach up to date. To prove this result, we provide an alternative characterisation of FAEEL as a combination of G91 with a simpler logic we called Founded Epistemic Equilibrium Logic (FEEL), which is somehow an extrapolation of the stable model semantics to the modal logic S5.

Although Boolean Constraint Technology has made tremendous progress over the last decade, the efficacy of state-of-the-art solvers is known to vary considerably across different types of problem instances, and is known to depend strongly on algorithm parameters. This problem was addressed by means of a simple, yet effective approach using handmade, uniform, and unordered schedules of multiple solvers in ppfolio, which showed very impressive performance in the 2011 Satisfiability Testing (SAT) Competition. Inspired by this, we take advantage of the modeling and solving capacities of Answer Set Programming (ASP) to automatically determine more refined, that is, nonuniform and ordered solver schedules from the existing benchmarking data. We begin by formulating the determination of such schedules as multi-criteria optimization problems and provide corresponding ASP encodings. The resulting encodings are easily customizable for different settings, and the computation of optimum schedules can mostly be done in the blink of an eye, even when dealing with large runtime data sets stemming from many solvers on hundreds to thousands of instances. Also, the fact that our approach can be customized easily enabled us to swiftly adapt it to generate parallel schedules for multi-processor machines.

We introduce an approach to detecting inconsistencies in large biological networks by using answer set programming. To this end, we build upon a recently proposed notion of consistency between biochemical/genetic reactions and high-throughput profiles of cell activity. We then present an approach based on answer set programming to check the consistency of large-scale data sets. Moreover, we extend this methodology to provide explanations for inconsistencies by determining minimal representations of conflicts. In practice, this can be used to identify unreliable data or to indicate missing reactions.

The course timetabling problem can be generally defined as the task of assigning a number of lectures to a limited set of timeslots and rooms, subject to a given set of hard and soft constraints. The modeling language for course timetabling is required to be expressive enough to specify a wide variety of soft constraints and objective functions. Furthermore, the resulting encoding is required to be extensible for capturing new constraints and for switching them between hard and soft, and to be flexible enough to deal with different formulations. In this paper, we propose to make effective use of ASP as a modeling language for course timetabling. We show that our ASP-based approach can naturally satisfy the above requirements, through an ASP encoding of the curriculum-based course timetabling problem proposed in the third track of the second international timetabling competition (ITC-2007). Our encoding is compact and human-readable, since each constraint is individually expressed by either one or two rules. Each hard constraint is expressed by using integrity constraints and aggregates of ASP. Each soft constraint S is expressed by rules in which the head is the form of penalty (S, V, C), and a violation V and its penalty cost C are detected and calculated respectively in the body. We carried out experiments on four different benchmark sets with five different formulations. We succeeded either in improving the bounds or producing the same bounds for many combinations of problem instances and formulations, compared with the previous best known bounds.

Deciphering the functioning of biological networks is one of the central tasks in systems biology. In particular, signal transduction networks are crucial for the understanding of the cellular response to external and internal perturbations. Importantly, in order to cope with the complexity of these networks, mathematical and computational modeling is required. We propose a computational modeling framework in order to achieve more robust discoveries in the context of logical signaling networks. More precisely, we focus on modeling the response of logical signaling networks by means of automated reasoning using Answer Set Programming (ASP). ASP provides a declarative language for modeling various knowledge representation and reasoning problems. Moreover, available ASP solvers provide several reasoning modes for assessing the multitude of answer sets. Therefore, leveraging its rich modeling language and its highly efficient solving capacities, we use ASP to address three challenging problems in the context of logical signaling networks: learning of (Boolean) logical networks, experimental design, and identification of intervention strategies. Overall, the contribution of this thesis is three-fold. Firstly, we introduce a mathematical framework for characterizing and reasoning on the response of logical signaling networks. Secondly, we contribute to a growing list of successful applications of ASP in systems biology. Thirdly, we present a software providing a complete pipeline for automated reasoning on the response of logical signaling networks.

Biology has made great progress in identifying and measuring the building blocks of life. The availability of high-throughput methods in molecular biology has dramatically accelerated the growth of biological knowledge for various organisms. The advancements in genomic, proteomic and metabolomic technologies allow for constructing complex models of biological systems. An increasing number of biological repositories is available on the web, incorporating thousands of biochemical reactions and genetic regulations. Systems Biology is a recent research trend in life science, which fosters a systemic view on biology. In Systems Biology one is interested in integrating the knowledge from all these different sources into models that capture the interaction of these entities. By studying these models one wants to understand the emerging properties of the whole system, such as robustness. However, both measurements as well as biological networks are prone to considerable incompleteness, heterogeneity and mutual inconsistency, which makes it highly non-trivial to draw biologically meaningful conclusions in an automated way. Therefore, we want to promote Answer Set Programming (ASP) as a tool for discrete modeling in Systems Biology. ASP is a declarative problem solving paradigm, in which a problem is encoded as a logic program such that its answer sets represent solutions to the problem. ASP has intrinsic features to cope with incompleteness, offers a rich modeling language and highly efficient solving technology. We present ASP solutions, for the analysis of genetic regulatory networks, determining consistency with observed measurements and identifying minimal causes for inconsistency. We extend this approach for computing minimal repairs on model and data that restore consistency. This method allows for predicting unobserved data even in case of inconsistency. Further, we present an ASP approach to metabolic network expansion. This approach exploits the easy characterization of reachability in ASP and its various reasoning methods, to explore the biosynthetic capabilities of metabolic reaction networks and generate hypotheses for extending the network. Finally, we present the BioASP library, a Python library which encapsulates our ASP solutions into the imperative programming paradigm. The library allows for an easy integration of ASP solution into system rich environments, as they exist in Systems Biology.

Answer Set Programming (ASP) emerged in the late 1990s as a new logic programming paradigm, having its roots in nonmonotonic reasoning, deductive databases, and logic programming with negation as failure. The basic idea of ASP is to represent a computational problem as a logic program whose answer sets correspond to solutions, and then to use an answer set solver for finding answer sets of the program. ASP is particularly suited for solving NP-complete search problems. Among these, we find applications to product configuration, diagnosis, and graph-theoretical problems, e.g. finding Hamiltonian cycles. On different lines of ASP research, many extensions of the basic formalism have been proposed. The most intensively studied one is the modelling of preferences in ASP. They constitute a natural and effective way of selecting preferred solutions among a plethora of solutions for a problem. For example, preferences have been successfully used for timetabling, auctioning, and product configuration. In this thesis, we concentrate on preferences within answer set programming. Among several formalisms and semantics for preference handling in ASP, we concentrate on ordered logic programs with the underlying D-, W-, and B-semantics. In this setting, preferences are defined among rules of a logic program. They select preferred answer sets among (standard) answer sets of the underlying logic program. Up to now, those preferred answer sets have been computed either via a compilation method or by meta-interpretation. Hence, the question comes up, whether and how preferences can be integrated into an existing ASP solver. To solve this question, we develop an operational graph-based framework for the computation of answer sets of logic programs. Then, we integrate preferences into this operational approach. We empirically observe that our integrative approach performs in most cases better than the compilation method or meta-interpretation. Another research issue in ASP are optimization methods that remove redundancies, as also found in database query optimizers. For these purposes, the rather recently suggested notion of strong equivalence for ASP can be used. If a program is strongly equivalent to a subprogram of itself, then one can always use the subprogram instead of the original program, a technique which serves as an effective optimization method. Up to now, strong equivalence has not been considered for logic programs with preferences. In this thesis, we tackle this issue and generalize the notion of strong equivalence to ordered logic programs. We give necessary and sufficient conditions for the strong equivalence of two ordered logic programs. Furthermore, we provide program transformations for ordered logic programs and show in how far preferences can be simplified. Finally, we present two new applications for preferences within answer set programming. First, we define new procedures for group decision making, which we apply to the problem of scheduling a group meeting. As a second new application, we reconstruct a linguistic problem appearing in German dialects within ASP. Regarding linguistic studies, there is an ongoing debate about how unique the rule systems of language are in human cognition. The reconstruction of grammatical regularities with tools from computer science has consequences for this debate: if grammars can be modelled this way, then they share core properties with other non-linguistic rule systems.