Towards automatic cost model discovery for combinatorial interaction testing

We present an automated approach for cost model discovery in configuration spaces. Given a configuration space, a quality assurance (QA) task of interest, and a means of measuring the cost of carrying out the QA task, the proposed approach systematically sample the configuration space by using a traditional covering array, carry out the QA task in each of the selected configurations, measure the costs, and fit a generalized linear regression model to the observed costs. The resulting model is then used to estimate the cost of performing the QA task in a possibly previously unseen configuration. The results of our empirical studies conducted on two highly configurable and widely used software systems, strongly support our basic hypothesis that the proposed approach can efficiently and effectively discover reliable cost models

Systems approaches and algorithms for discovery of combinatorial therapies

Effective therapy of complex diseases requires control of highly non-linear complex networks that remain incompletely characterized. In particular, drug intervention can be seen as control of signaling in cellular networks. Identification of control parameters presents an extreme challenge due to the combinatorial explosion of control possibilities in combination therapy and to the incomplete knowledge of the systems biology of cells. In this review paper we describe the main current and proposed approaches to the design of combinatorial therapies, including the empirical methods used now by clinicians and alternative approaches suggested recently by several authors. New approaches for designing combinations arising from systems biology are described. We discuss in special detail the design of algorithms that identify optimal control parameters in cellular networks based on a quantitative characterization of control landscapes, maximizing utilization of incomplete knowledge of the state and structure of intracellular networks. The use of new technology for high-throughput measurements is key to these new approaches to combination therapy and essential for the characterization of control landscapes and implementation of the algorithms. Combinatorial optimization in medical therapy is also compared with the combinatorial optimization of engineering and materials science and similarities and differences are delineated.Comment: 25 page

Dagstuhl Reports : Volume 1, Issue 2, February 2011

Online Privacy: Towards Informational Self-Determination on the Internet (Dagstuhl Perspectives Workshop 11061) : Simone Fischer-Hübner, Chris Hoofnagle, Kai Rannenberg, Michael Waidner, Ioannis Krontiris and Michael Marhöfer Self-Repairing Programs (Dagstuhl Seminar 11062) : Mauro Pezzé, Martin C. Rinard, Westley Weimer and Andreas Zeller Theory and Applications of Graph Searching Problems (Dagstuhl Seminar 11071) : Fedor V. Fomin, Pierre Fraigniaud, Stephan Kreutzer and Dimitrios M. Thilikos Combinatorial and Algorithmic Aspects of Sequence Processing (Dagstuhl Seminar 11081) : Maxime Crochemore, Lila Kari, Mehryar Mohri and Dirk Nowotka Packing and Scheduling Algorithms for Information and Communication Services (Dagstuhl Seminar 11091) Klaus Jansen, Claire Mathieu, Hadas Shachnai and Neal E. Youn

Genetic programming in data mining for drug discovery

Genetic programming (GP) is used to extract from rat oral bioavailability (OB) measurements simple, interpretable and predictive QSAR models which both generalise to rats and to marketed drugs in humans. Receiver Operating Characteristics (ROC) curves for the binary classier produced by machine learning show no statistical dierence between rats (albeit without known clearance dierences) and man. Thus evolutionary computing oers the prospect of in silico ADME screening, e.g. for \virtual" chemicals, for pharmaceutical drug discovery

Improving Efficiency and Scalability of Sum of Squares Optimization: Recent Advances and Limitations

It is well-known that any sum of squares (SOS) program can be cast as a semidefinite program (SDP) of a particular structure and that therein lies the computational bottleneck for SOS programs, as the SDPs generated by this procedure are large and costly to solve when the polynomials involved in the SOS programs have a large number of variables and degree. In this paper, we review SOS optimization techniques and present two new methods for improving their computational efficiency. The first method leverages the sparsity of the underlying SDP to obtain computational speed-ups. Further improvements can be obtained if the coefficients of the polynomials that describe the problem have a particular sparsity pattern, called chordal sparsity. The second method bypasses semidefinite programming altogether and relies instead on solving a sequence of more tractable convex programs, namely linear and second order cone programs. This opens up the question as to how well one can approximate the cone of SOS polynomials by second order representable cones. In the last part of the paper, we present some recent negative results related to this question.Comment: Tutorial for CDC 201