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

Optimal Topology Design for Disturbance Minimization in Power Grids

The transient response of power grids to external disturbances influences their stable operation. This paper studies the effect of topology in linear time-invariant dynamics of different power grids. For a variety of objective functions, a unified framework based on $H_2$ norm is presented to analyze the robustness to ambient fluctuations. Such objectives include loss reduction, weighted consensus of phase angle deviations, oscillations in nodal frequency, and other graphical metrics. The framework is then used to study the problem of optimal topology design for robust control goals of different grids. For radial grids, the problem is shown as equivalent to the hard "optimum communication spanning tree" problem in graph theory and a combinatorial topology construction is presented with bounded approximation gap. Extended to loopy (meshed) grids, a greedy topology design algorithm is discussed. The performance of the topology design algorithms under multiple control objectives are presented on both loopy and radial test grids. Overall, this paper analyzes topology design algorithms on a broad class of control problems in power grid by exploring their combinatorial and graphical properties.Comment: 6 pages, 3 figures, a version of this work will appear in ACC 201

Ant colony optimization for design of water distribution systems

During the last decade, evolutionary methods such as genetic algorithms have been used extensively for the optimal design and operation of water distribution systems. More recently, ant colony optimization algorithms ~ACOAs!, which are evolutionary methods based on the foraging behavior of ants, have been successfully applied to a number of benchmark combinatorial optimization problems. In this paper, a formulation is developed which enables ACOAs to be used for the optimal design of water distribution systems. This formulation is applied to two benchmark water distribution system optimization problems and the results are compared with those obtained using genetic algorithms ~GAs!. The findings of this study indicate that ACOAs are an attractive alternative to GAs for the optimal design of water distribution systems, as they outperformed GAs for the two case studies considered both in terms of computational efficiency and their ability to find near global optimal solutions.Holger R. Maier, Angus R. Simpson, Aaron C. Zecchin, Wai Kuan Foong, Kuang Yeow Phang, Hsin Yeow Seah and Chan Lim Ta

The General Combinatorial Optimization Problem: Towards Automated Algorithm Design

This paper defines a new combinatorial optimisation problem, namely General Combinatorial Optimisation Problem (GCOP), whose decision variables are a set of parametric algorithmic components, i.e. algorithm design decisions. The solutions of GCOP, i.e. compositions of algorithmic components, thus represent different generic search algorithms. The objective of GCOP is to find the optimal algorithmic compositions for solving the given optimisation problems. Solving the GCOP is thus equivalent to automatically designing the best algorithms for optimisation problems. Despite recent advances, the evolutionary computation and optimisation research communities are yet to embrace formal standards that underpin automated algorithm design. In this position paper, we establish GCOP as a new standard to define different search algorithms within one unified model. We demonstrate the new GCOP model to standardise various search algorithms as well as selection hyper-heuristics. A taxonomy is defined to distinguish several widely used terminologies in automated algorithm design, namely automated algorithm composition, configuration and selection. We would like to encourage a new line of exciting research directions addressing several challenging research issues including algorithm generality, algorithm reusability, and automated algorithm design