BIOGRID CURATED DATA FOR PUBLICATION: DSBSO-Based XL-MS Analysis of Breast Cancer PDX Tissues to Delineate Protein Interaction Network in Clinical Samples.

Protein-Protein, Genetic, and Chemical Interactions for Jiao F (2024):DSBSO-Based XL-MS Analysis of Breast Cancer PDX Tissues to Delineate Protein Interaction Network in Clinical Samples. curated by BioGRID (https://thebiogrid.org); ABSTRACT: Protein-protein interactions (PPIs) are fundamental to understanding biological systems as protein complexes are the active molecular modules critical for carrying out cellular functions. Dysfunctional PPIs have been associated with various diseases including cancer. Systems-wide PPI analysis not only sheds light on pathological mechanisms, but also represents a paradigm in identifying potential therapeutic targets. In recent years, cross-linking mass spectrometry (XL-MS) has emerged as a powerful tool for defining endogenous PPIs of cellular networks. While proteome-wide studies have been performed in cell lysates, intact cells and tissues, applications of XL-MS in clinical samples have not been reported. In this study, we adopted a DSBSO-based in vivo XL-MS platform to map interaction landscapes from two breast cancer patient-derived xenograft (PDX) models. As a result, we have generated a PDX interaction network comprising 2,557 human proteins and identified interactions unique to breast cancer subtypes. Interestingly, most of the observed differences in PPIs correlated well with protein abundance changes determined by TMT-based proteome quantitation. Collectively, this work has demonstrated the feasibility of XL-MS analysis in clinical samples, and established an analytical workflow for tissue cross-linking that can be generalized for mapping PPIs from patient samples in the future to dissect disease-relevant cellular networks.

蛋白质-蛋白质、遗传学以及化学相互作用数据集（Jiao F，2024年）：基于DSBSO的XL-MS分析乳腺癌PDX组织，以描绘临床样本中的蛋白质相互作用网络。由BioGRID（https://thebiogrid.org）整理；摘要：蛋白质-蛋白质相互作用（PPIs）是理解生物系统的基础，蛋白质复合体作为执行细胞功能的活性分子模块，对生物系统的运行至关重要。功能失调的PPIs与多种疾病，包括癌症，有关。系统的PPI分析不仅揭示了病理机制，而且在确定潜在治疗靶点方面具有典范意义。近年来，交联质谱分析（XL-MS）已作为一种强大的工具崭露头角，用于定义细胞网络的内在PPIs。尽管已在对细胞裂解物、完整细胞和组织的全蛋白质组研究中应用，但XL-MS在临床样本中的应用尚未报道。在本研究中，我们采用基于DSBSO的体内XL-MS平台，从两个乳腺癌患者来源的异种移植（PDX）模型中绘制相互作用景观。结果，我们构建了一个包含2,557个人类蛋白质的PDX相互作用网络，并确定了乳腺癌亚型特有的相互作用。有趣的是，观察到的PPIs差异与由TMT基蛋白质组定量确定的蛋白质丰度变化密切相关。综上所述，本研究证明了XL-MS分析在临床样本中的可行性，并建立了一种适用于组织交联的分析方法，该法可推广用于未来从患者样本中绘制PPIs，以解析与疾病相关的细胞网络。