基于质谱的组学技术越来越多地用于微扰研究，通过识别重要的分子事件将药物效应映射到生物途径。显着性受到每个分子参数的倍数变化和变化的影响，而且还受到多次测试校正的影响。虽然倍数变化很大程度上由生物系统决定，但变化是由实验工作流程决定的。此处，表明先前传代培养的记忆效应可以影响使用两种结肠癌细胞系 SW480 和 HCT116 的扰动曲线的变化。这些记忆效应很大程度上是由微扰实验中持续存在的生长状态差异驱动的。在 SW480 细胞中，记忆效应与适度的治疗效果相结合，放大了多个组学水平的变化，包括二十碳组学、蛋白质组学和磷酸蛋白质组学。正如 HCT116 细胞中所证明的，治疗效果越强，记忆效应就越不明显。通过实时监测细胞生长来控制传代培养的同质性。受控同质传代培养产生了基于组合蛋白质组和磷酸蛋白质组数据的 321 个因果猜想的扰动网络，相比之下，在 SW480 细胞中不控制传代培养同质性时仅产生 58 个因果猜想。仅当考虑到这些记忆效应时，一些细胞反应和调节事件才被确定为延长三氧化二砷 (ATO) 的作用模式。受控的先前传代培养导致发现 ATO 与硫氧还蛋白还原酶 1 抑制剂金诺芬的协同组合治疗，这可能在 NRF2 介导的耐药机制的管理中有用。

Mass spectrometry-based omics technologies are increasingly used in perturbation studies to map drug effects to biological pathways by identifying significant molecular events. Significance is influenced by fold change and variation of each molecular parameter, but also by multiple testing corrections. While the fold change is largely determined by the biological system, the variation is determined by experimental workflows. Here, it is shown that memory effects of prior subculture can influence the variation of perturbation profiles using the two colon carcinoma cell lines SW480 and HCT116. These memory effects are largely driven by differences in growth states that persist into the perturbation experiment. In SW480 cells, memory effects combined with moderate treatment effects amplify the variation in multiple omics levels, including eicosadomics, proteomics, and phosphoproteomics. With stronger treatment effects, the memory effect was less pronounced, as demonstrated in HCT116 cells. Subculture homogeneity was controlled by real-time monitoring of cell growth. Controlled homogeneous subculture resulted in a perturbation network of 321 causal conjectures based on combined proteomic and phosphoproteomic data, compared to only 58 causal conjectures without controlling subculture homogeneity in SW480 cells. Some cellular responses and regulatory events were identified that extend the mode of action of arsenic trioxide (ATO) only when accounting for these memory effects. Controlled prior subculture led to the finding of a synergistic combination treatment of ATO with the thioredoxin reductase 1 inhibitor auranofin, which may prove useful in the management of NRF2-mediated resistance mechanisms.