蛋白质-蛋白质相互作用 (PPI) 在细胞功能和疾病表现中发挥着至关重要的作用，PPI 网络的功能障碍提供了压力源和表型之间的直接联系。功能失调的蛋白质-蛋白质相互作用组（dfPPI）平台，以前称为表层组学，是一种新开发的化学蛋白质组学方法，旨在检测疾病状态下应激诱导的细胞扰动下 PPI 网络系统水平的动态变化。本综述对 dfPPI 进行了概述，强调了新颖的方法、数据分析以及在疾病研究中的应用。 dfPPI 在癌症研究中得到应用，它可以识别维持恶性表型所必需的功能障碍，并发现增强当前疗法疗效的策略。在神经退行性疾病中，dfPPI 揭示了细胞过程中的关键功能障碍和应激源特异性脆弱性。讨论了挑战，包括数据复杂性以及与其他组学数据集集成的潜力。 dfPPI 平台是通过直接告知 PPI 网络功能障碍来剖析疾病系统生物学的有力工具，并有望推进疾病识别和治疗。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Protein-protein interactions (PPIs) play a crucial role in cellular function and disease manifestation, with dysfunctions in PPI networks providing a direct link between stressors and phenotype. The dysfunctional Protein-Protein Interactome (dfPPI) platform, formerly known as epichaperomics, is a newly developed chemoproteomic method aimed at detecting dynamic changes at the systems level in PPI networks under stressor-induced cellular perturbations within disease states. This review provides an overview of dfPPIs, emphasizing the novel methodology, data analytics, and applications in disease research. dfPPI has applications in cancer research, where it identifies dysfunctions integral to maintaining malignant phenotypes and discovers strategies to enhance the efficacy of current therapies. In neurodegenerative disorders, dfPPI uncovers critical dysfunctions in cellular processes and stressor-specific vulnerabilities. Challenges, including data complexity and the potential for integration with other omics datasets are discussed. The dfPPI platform is a potent tool for dissecting disease systems biology by directly informing on dysfunctions in PPI networks and holds promise for advancing disease identification and therapeutics.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.