Even as the clinical impact of drug combinations continues to accelerate, no consensus on how to quantify drug synergy has emerged. Rather, surveying the landscape of drug synergy reveals the persistence of historical fissures regarding the appropriate domains of conflicting synergy models - fissures impacting all aspects of combination therapy discovery and deployment. Herein we chronicle the impact of these divisions on: (i) the design, interpretation, and reproducibility of high-throughput combination screens; (ii) the performance of algorithms to predict synergistic mixtures; and (iii) the search for higher-order synergistic interactions. Further progress in each of these subfields hinges on reaching a consensus regarding the long-standing rifts in the field.

中文翻译：

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绘制药物协同作用的碎片化景观。


尽管药物组合的临床影响不断加速，但关于如何量化药物协同作用尚未达成共识。相反，调查药物协同作用的前景揭示了关于相互冲突的协同模型的适当领域的历史裂缝的持续存在——影响联合治疗发现和部署的各个方面的裂缝。在此，我们记录了这些划分对以下方面的影响：（i）高通量组合屏幕的设计、解释和再现性； (ii) 预测协同混合物的算法的性能； (iii) 寻找更高阶的协同相互作用。每个子领域的进一步进展取决于就该领域长期存在的分歧达成共识。