ABSTRACT

Introduction

Many pathologies, including cancer, have been associated with aberrant phosphorylation-mediated signaling networks that drive altered cell proliferation, migration, metabolic regulation, and can lead to systemic inflammation. Phosphoproteomics, the large-scale analysis of protein phosphorylation sites, has emerged as a powerful tool to define signaling network regulation and dysregulation in normal and pathological conditions.

Areas Covered

We provide an overview of methodology for global phosphoproteomics as well as enrichment of specific subsets of the phosphoproteome, including phosphotyrosine and phospho-motif enrichment of kinase substrates. We review quantitative methods, advantages and limitations of different mass spectrometry acquisition formats, and computational approaches to extract biological insight from phosphoproteomics data. Throughout, we discuss various applications and their challenges in implementation.

Expert opinion

Over the past 20 years the field of phosphoproteomics has advanced to enable deep biological and clinical insight through the quantitative analysis of signaling networks. Future areas of development include Clinical Laboratory Improvement Amendments (CLIA)-approved methods for analysis of clinical samples, continued improvements in sensitivity to enable analysis of small numbers of rare cells and tissue microarrays, and computational methods to integrate data resulting from multiple systems-level quantitative analytical methods.

中文翻译：

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磷酸蛋白质组学：揭示癌细胞中分子信号传导的宝贵工具

摘要

介绍

许多病理，包括癌症，都与异常磷酸化介导的信号网络有关，这些信号网络驱动细胞增殖、迁移、代谢调节的改变，并可能导致全身炎症。磷酸化蛋白质组学是对蛋白质磷酸化位点的大规模分析，已成为定义正常和病理条件下信号网络调节和失调的有力工具。

涵盖的领域

我们概述了全球磷酸化蛋白质组学的方法以及磷酸化蛋白质组特定子集的富集，包括磷酸酪氨酸和激酶底物的磷酸基序富集。我们回顾了不同质谱采集格式的定量方法、优点和局限性，以及从磷酸蛋白质组学数据中提取生物学洞察力的计算方法。在整个过程中，我们讨论了各种应用程序及其在实施中的挑战。

专家意见

在过去的 20 年中，磷酸蛋白质组学领域取得了进展，通过对信号网络的定量分析实现了深入的生物学和临床洞察力。未来的发展领域包括临床实验室改进修正案 (CLIA) 批准的用于分析临床样本的方法、持续提高灵敏度以分析少量稀有细胞和组织微阵列，以及整合来自多个系统级的数据的计算方法定量分析方法。