Revisiting the Training of Logic Models of Protein Signaling Networks with a Formal Approach based on Answer Set Programming

A fundamental question in systems biology is the construction and training to data of mathematical models. Logic formalisms have become very popular to model signaling networks because their simplicity allows us to model large systems encompassing hundreds of proteins. An approach to train (Boolean) logic models to high-throughput phospho-proteomics data was recently introduced and solved using optimization heuristics based on stochastic methods. Here we demonstrate how this problem can be solved using Answer Set Programming (ASP), a declarative problem solving paradigm, in which a problem is encoded as a logical program such that its answer sets represent solutions to the problem. ASP has significant improvements over heuristic methods in terms of efficiency and scalability, it guarantees global optimality of solutions as well as provides a complete set of solutions. We illustrate the application of ASP with in silico cases based on realistic networks and data

Simplest random K-satisfiability problem

We study a simple and exactly solvable model for the generation of random satisfiability problems. These consist of $\gamma N$ random boolean constraints which are to be satisfied simultaneously by $N$ logical variables. In statistical-mechanics language, the considered model can be seen as a diluted p-spin model at zero temperature. While such problems become extraordinarily hard to solve by local search methods in a large region of the parameter space, still at least one solution may be superimposed by construction. The statistical properties of the model can be studied exactly by the replica method and each single instance can be analyzed in polynomial time by a simple global solution method. The geometrical/topological structures responsible for dynamic and static phase transitions as well as for the onset of computational complexity in local search method are thoroughly analyzed. Numerical analysis on very large samples allows for a precise characterization of the critical scaling behaviour.Comment: 14 pages, 5 figures, to appear in Phys. Rev. E (Feb 2001). v2: minor errors and references correcte

Learning Tuple Probabilities

Learning the parameters of complex probabilistic-relational models from labeled training data is a standard technique in machine learning, which has been intensively studied in the subfield of Statistical Relational Learning (SRL), but---so far---this is still an under-investigated topic in the context of Probabilistic Databases (PDBs). In this paper, we focus on learning the probability values of base tuples in a PDB from labeled lineage formulas. The resulting learning problem can be viewed as the inverse problem to confidence computations in PDBs: given a set of labeled query answers, learn the probability values of the base tuples, such that the marginal probabilities of the query answers again yield in the assigned probability labels. We analyze the learning problem from a theoretical perspective, cast it into an optimization problem, and provide an algorithm based on stochastic gradient descent. Finally, we conclude by an experimental evaluation on three real-world and one synthetic dataset, thus comparing our approach to various techniques from SRL, reasoning in information extraction, and optimization

Proving Finite Satisfiability of Deductive Databases

It is shown how certain refutation methods can be extended into semi-decision procedures that are complete for both unsatisfiability and finite satisfiability. The proposed extension is justified by a new characterization of finite satisfiability. This research was motivated by a database design problem: Deduction rules and integrity constraints in definite databases have to be finitely satisfiabl