通过拮抗作用改善网络性能：从合成救援到多种药物组合
Improved Network Performance via Antagonism: From Synthetic Rescues to Multi-drug Combinations
摘要：
最近的研究表明，一个有缺陷的或次优运行的代谢网络通常可以通过有针对性地去除酶编码基因来挽救--这与传统基因治疗的建议完全相反。预测甚至断言，某些基因敲除可以恢复原本无法存活的基因缺陷细胞的生长。这一发现带来了许多问题：潜在的机制是什么？这种效应有多普遍？有哪些潜在的应用？在这里，我将从网络补偿扰动的角度来探讨这些问题。将绘制这样的合成救援和反应失活的自然发生的级联，以及它们在物理和其他生物网络的类似物之间的关系。我将特别讨论救援相互作用如何导致对抗耐药性的拮抗药物组合的合理设计，以及它们如何照亮癌症，抗生素和代谢疾病的医学研究。
英文摘要：
Recent research shows that a faulty or sub-optimally operating metabolic network can often be rescued by the targeted removal of enzyme-coding genes--the exact opposite of what traditional gene therapy would suggest. Predictions go as far as to assert that certain gene knockouts can restore the growth of otherwise nonviable gene-deficient cells. Many questions follow from this discovery: What are the underlying mechanisms? How generalizable is this effect? What are the potential applications? Here, I will approach these questions from the perspective of compensatory perturbations on networks. Relations will be drawn between such synthetic rescues and naturally occurring cascades of reaction inactivation, as well as their analogues in physical and other biological networks. I will specially discuss how rescue interactions can lead to the rational design of antagonistic drug combinations that select against resistance and how they can illuminate medical research on cancer, antibiotics, and metabolic diseases.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
