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

Combinatorial optimization and metaheuristics

Today, combinatorial optimization is one of the youngest and most active areas of discrete mathematics. It is a branch of optimization in applied mathematics and computer science, related to operational research, algorithm theory and computational complexity theory. It sits at the intersection of several fields, including artificial intelligence, mathematics and software engineering. Its increasing interest arises for the fact that a large number of scientific and industrial problems can be formulated as abstract combinatorial optimization problems, through graphs and/or (integer) linear programs. Some of these problems have polynomial-time (“efficient”) algorithms, while most of them are NP-hard, i.e. it is not proved that they can be solved in polynomial-time. Mainly, it means that it is not possible to guarantee that an exact solution to the problem can be found and one has to settle for an approximate solution with known performance guarantees. Indeed, the goal of approximate methods is to find “quickly” (reasonable run-times), with “high” probability, provable “good” solutions (low error from the real optimal solution). In the last 20 years, a new kind of algorithm commonly called metaheuristics have emerged in this class, which basically try to combine heuristics in high level frameworks aimed at efficiently and effectively exploring the search space. This report briefly outlines the components, concepts, advantages and disadvantages of different metaheuristic approaches from a conceptual point of view, in order to analyze their similarities and differences. The two very significant forces of intensification and diversification, that mainly determine the behavior of a metaheuristic, will be pointed out. The report concludes by exploring the importance of hybridization and integration methods

A memetic ant colony optimization algorithm for the dynamic travelling salesman problem

Copyright @ Springer-Verlag 2010.Ant colony optimization (ACO) has been successfully applied for combinatorial optimization problems, e.g., the travelling salesman problem (TSP), under stationary environments. In this paper, we consider the dynamic TSP (DTSP), where cities are replaced by new ones during the execution of the algorithm. Under such environments, traditional ACO algorithms face a serious challenge: once they converge, they cannot adapt efficiently to environmental changes. To improve the performance of ACO on the DTSP, we investigate a hybridized ACO with local search (LS), called Memetic ACO (M-ACO) algorithm, which is based on the population-based ACO (P-ACO) framework and an adaptive inver-over operator, to solve the DTSP. Moreover, to address premature convergence, we introduce random immigrants to the population of M-ACO when identical ants are stored. The simulation experiments on a series of dynamic environments generated from a set of benchmark TSP instances show that LS is beneficial for ACO algorithms when applied on the DTSP, since it achieves better performance than other traditional ACO and P-ACO algorithms.This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) of UK under Grant EP/E060722/01 and Grant EP/E060722/02

A controlled migration genetic algorithm operator for hardware-in-the-loop experimentation

In this paper, we describe the development of an extended migration operator, which combats the negative effects of noise on the effective search capabilities of genetic algorithms. The research is motivated by the need to minimize the num- ber of evaluations during hardware-in-the-loop experimentation, which can carry a significant cost penalty in terms of time or financial expense. The authors build on previous research, where convergence for search methods such as Simulated Annealing and Variable Neighbourhood search was accelerated by the implementation of an adaptive decision support operator. This methodology was found to be effective in searching noisy data surfaces. Providing that noise is not too significant, Genetic Al- gorithms can prove even more effective guiding experimentation. It will be shown that with the introduction of a Controlled Migration operator into the GA heuristic, data, which repre- sents a significant signal-to-noise ratio, can be searched with significant beneficial effects on the efficiency of hardware-in-the- loop experimentation, without a priori parameter tuning. The method is tested on an engine-in-the-loop experimental example, and shown to bring significant performance benefits

System optimization by multiobjective genetic algorithms and analysis of the coupling between variables, constraints and objectives

This paper presents a methodology based on Multiobjective Genetic Algorithms (MOGA’s) for the design of electrical engineering systems. MOGA’s allow to optimize multiple heterogeneous criteria in complex systems, but also simplify couplings and sensitivity analysis by determining the evolution of design variables along the Pareto-optimal front. A rather simplified case study dealing with the optimal dimensioning of an inverter – permanent magnet motor – reducer – load association is carried out to demonstrate the interest of the approach

Meta-heuristic algorithms in car engine design: a literature survey

Meta-heuristic algorithms are often inspired by natural phenomena, including the evolution of species in Darwinian natural selection theory, ant behaviors in biology, flock behaviors of some birds, and annealing in metallurgy. Due to their great potential in solving difficult optimization problems, meta-heuristic algorithms have found their way into automobile engine design. There are different optimization problems arising in different areas of car engine management including calibration, control system, fault diagnosis, and modeling. In this paper we review the state-of-the-art applications of different meta-heuristic algorithms in engine management systems. The review covers a wide range of research, including the application of meta-heuristic algorithms in engine calibration, optimizing engine control systems, engine fault diagnosis, and optimizing different parts of engines and modeling. The meta-heuristic algorithms reviewed in this paper include evolutionary algorithms, evolution strategy, evolutionary programming, genetic programming, differential evolution, estimation of distribution algorithm, ant colony optimization, particle swarm optimization, memetic algorithms, and artificial immune system

State-of-the-art in aerodynamic shape optimisation methods

Aerodynamic optimisation has become an indispensable component for any aerodynamic design over the past 60 years, with applications to aircraft, cars, trains, bridges, wind turbines, internal pipe flows, and cavities, among others, and is thus relevant in many facets of technology. With advancements in computational power, automated design optimisation procedures have become more competent, however, there is an ambiguity and bias throughout the literature with regards to relative performance of optimisation architectures and employed algorithms. This paper provides a well-balanced critical review of the dominant optimisation approaches that have been integrated with aerodynamic theory for the purpose of shape optimisation. A total of 229 papers, published in more than 120 journals and conference proceedings, have been classified into 6 different optimisation algorithm approaches. The material cited includes some of the most well-established authors and publications in the field of aerodynamic optimisation. This paper aims to eliminate bias toward certain algorithms by analysing the limitations, drawbacks, and the benefits of the most utilised optimisation approaches. This review provides comprehensive but straightforward insight for non-specialists and reference detailing the current state for specialist practitioners