Adaptive reference update (ARU) algorithm. A stochastic search algorithm for efficient optimization of multi-drug cocktails.
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BACKGROUND: Multi-target therapeutics has been shown to be effective for treating complex diseases, and currently, it is a common practice to combine multiple drugs to treat such diseases to optimize the therapeutic outcomes. However, considering the huge number of possible ways to mix multiple drugs at different concentrations, it is practically difficult to identify the optimal drug combination through exhaustive testing. RESULTS: In this paper, we propose a novel stochastic search algorithm, called the adaptive reference update (ARU) algorithm, that can provide an efficient and systematic way for optimizing multi-drug cocktails. The ARU algorithm iteratively updates the drug combination to improve its response, where the update is made by comparing the response of the current combination with that of a reference combination, based on which the beneficial update direction is predicted. The reference combination is continuously updated based on the drug response values observed in the past, thereby adapting to the underlying drug response function. To demonstrate the effectiveness of the proposed algorithm, we evaluated its performance based on various multi-dimensional drug functions and compared it with existing algorithms. CONCLUSIONS: Simulation results show that the ARU algorithm significantly outperforms existing stochastic search algorithms, including the Gur Game algorithm. In fact, the ARU algorithm can more effectively identify potent drug combinations and it typically spends fewer iterations for finding effective combinations. Furthermore, the ARU algorithm is robust to random fluctuations and noise in the measured drug response, which makes the algorithm well-suited for practical drug optimization applications.
