The formation of protein complexes and the co-regulation of the cellular concentrations of proteins are essential mechanisms for cellular signaling and for maintaining homeostasis. Here we use isobaric-labeling multiplexed proteomics to analyze protein co-regulation and show that this allows the identification of protein-protein associations with high accuracy. We apply this 'interactome mapping by high-throughput quantitative proteome analysis' (IMAHP) method to a panel of 41 breast cancer cell lines and show that deviations of the observed protein co-regulations in specific cell lines from the consensus network affects cellular fitness. Furthermore, these aberrant interactions serve as biomarkers that predict the drug sensitivity of cell lines in screens across 195 drugs. We expect that IMAHP can be broadly used to gain insight into how changing landscapes of protein-protein associations affect the phenotype of biological systems.

中文翻译：

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通过高通量蛋白质组学检测失调的蛋白质关联网络可预测癌症的脆弱性。

蛋白质复合物的形成和蛋白质细胞浓度的共同调节是细胞信号传导和维持体内平衡的重要机制。在这里，我们使用等压线标记的多重蛋白质组学来分析蛋白质的共调节，并表明这可以高度准确地鉴定蛋白质与蛋白质的结合。我们将这种“通过高通量定量蛋白质组分析进行相互作用的作图”（IMAHP）方法应用于一组41个乳腺癌细胞系，并显示在特定细胞系中观察到的蛋白质共调控与共识网络的偏离会影响细胞适应性。此外，这些异常的相互作用还可以作为生物标志物，在195种药物的筛选中预测细胞系的药物敏感性。