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Search algorithms as a framework for the optimization of drug combinations.

ABSTRACT: Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms -- originally developed for digital communication -- modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs using only one-third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.

SUBMITTER: Calzolari D

PROVIDER: S-EPMC2590660 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Search algorithms as a framework for the optimization of drug combinations.

Calzolari Diego D Bruschi Stefania S Coquin Laurence L Schofield Jennifer J Feala Jacob D JD Reed John C JC McCulloch Andrew D AD Paternostro Giovanni G

PLoS computational biology 20081226 12

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms -- originally developed for digital communication -- modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, ...[more]

PMID: 19112483

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Project description:The efficiency of a metaheuristic algorithm for global optimization is based on its ability to search and find the global optimum. However, a good search often requires to be balanced between exploration and exploitation of the search space. In this paper, a new metaheuristic algorithm called Ringed Seal Search (RSS) is introduced. It is inspired by the natural behavior of the seal pup. This algorithm mimics the seal pup movement behavior and its ability to search and choose the best lair to escape predators. The scenario starts once the seal mother gives birth to a new pup in a birthing lair that is constructed for this purpose. The seal pup strategy consists of searching and selecting the best lair by performing a random walk to find a new lair. Affected by the sensitive nature of seals against external noise emitted by predators, the random walk of the seal pup takes two different search states, normal state and urgent state. In the normal state, the pup performs an intensive search between closely adjacent lairs; this movement is modeled via a Brownian walk. In an urgent state, the pup leaves the proximity area and performs an extensive search to find a new lair from sparse targets; this movement is modeled via a Levy walk. The switch between these two states is realized by the random noise emitted by predators. The algorithm keeps switching between normal and urgent states until the global optimum is reached. Tests and validations were performed using fifteen benchmark test functions to compare the performance of RSS with other baseline algorithms. The results show that RSS is more efficient than Genetic Algorithm, Particles Swarm Optimization and Cuckoo Search in terms of convergence rate to the global optimum. The RSS shows an improvement in terms of balance between exploration (extensive) and exploitation (intensive) of the search space. The RSS can efficiently mimic seal pups behavior to find best lair and provide a new algorithm to be used in global optimization problems.

Dataset Information

Search algorithms as a framework for the optimization of drug combinations.

Publications

Search algorithms as a framework for the optimization of drug combinations.

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