Logic Integer Programming Models for Signaling Networks

We propose a static and a dynamic approach to model biological signaling networks, and show how each can be used to answer relevant biological questions. For this we use the two different mathematical tools of Propositional Logic and Integer Programming. The power of discrete mathematics for handling qualitative as well as quantitative data has so far not been exploited in Molecular Biology, which is mostly driven by experimental research, relying on first-order or statistical models. The arising logic statements and integer programs are analyzed and can be solved with standard software. For a restricted class of problems the logic models reduce to a polynomial-time solvable satisfiability algorithm. Additionally, a more dynamic model enables enumeration of possible time resolutions in poly-logarithmic time. Computational experiments are included

Small Resolution Proofs for QBF using Dependency Treewidth

In spite of the close connection between the evaluation of quantified Boolean formulas (QBF) and propositional satisfiability (SAT), tools and techniques which exploit structural properties of SAT instances are known to fail for QBF. This is especially true for the structural parameter treewidth, which has allowed the design of successful algorithms for SAT but cannot be straightforwardly applied to QBF since it does not take into account the interdependencies between quantified variables. In this work we introduce and develop dependency treewidth, a new structural parameter based on treewidth which allows the efficient solution of QBF instances. Dependency treewidth pushes the frontiers of tractability for QBF by overcoming the limitations of previously introduced variants of treewidth for QBF. We augment our results by developing algorithms for computing the decompositions that are required to use the parameter

Network-Based Biomarker Discovery : Development of Prognostic Biomarkers for Personalized Medicine by Integrating Data and Prior Knowledge

Advances in genome science and technology offer a deeper understanding of biology while at the same time improving the practice of medicine. The expression profiling of some diseases, such as cancer, allows for identifying marker genes, which could be able to diagnose a disease or predict future disease outcomes. Marker genes (biomarkers) are selected by scoring how well their expression levels can discriminate between different classes of disease or between groups of patients with different clinical outcome (e.g. therapy response, survival time, etc.). A current challenge is to identify new markers that are directly related to the underlying disease mechanism

Analyzing Satisfiability and Refutability in Selected Constraint Systems

This dissertation is concerned with the satisfiability and refutability problems for several constraint systems. We examine both Boolean constraint systems, in which each variable is limited to the values true and false, and polyhedral constraint systems, in which each variable is limited to the set of real numbers R in the case of linear polyhedral systems or the set of integers Z in the case of integer polyhedral systems. An important aspect of our research is that we focus on providing certificates. That is, we provide satisfying assignments or easily checkable proofs of infeasibility depending on whether the instance is feasible or not. Providing easily checkable certificates has become a much sought after feature in algorithms, especially in light of spectacular failures in the implementations of some well-known algorithms. There exist a number of problems in the constraint-solving domain for which efficient algorithms have been proposed, but which lack a certifying counterpart. When examining Boolean constraint systems, we specifically look at systems of 2-CNF clauses and systems of Horn clauses. When examining polyhedral constraint systems, we specifically look at systems of difference constraints, systems of UTVPI constraints, and systems of Horn constraints. For each examined system, we determine several properties of general refutations and determine the complexity of finding restricted refutations. These restricted forms of refutation include read-once refutations, in which each constraint can be used at most once; literal-once refutations, in which for each literal at most one constraint containing that literal can be used; and unit refutations, in which each step of the refutation must use a constraint containing exactly one literal. The advantage of read-once refutations is that they are guaranteed to be short. Thus, while not every constraint system has a read-once refutation, the small size of the refutation guarantees easy checkability