Top-down proteomics: challenges, innovations, and applications in basic and clinical research.
Top-down proteomics: challenges, innovations, and applications in basic and clinical research.
复制标题
DOI：
10.1080/14789450.2020.1855982
复制
发表时间：
2020-10
影响因子：
3.4
通讯作者：
Ge Y
中科院分区：
文献类型：
--
作者：
Brown KA;Melby JA;Roberts DS;Ge Y
更好地了解疾病的潜在分子机制对于开发更有效的诊断工具和精准医学治疗方法至关重要。然而，要阐明疾病的复杂本质，仍然存在许多挑战。蛋白质亚型表达和翻译后修饰 (PTM) 的变化因其在潜在疾病机制中的作用而得到认可。基于自上而下的质谱 (MS) 的蛋白质组学越来越被认为是综合表征基础和临床研究中可变剪接事件和/或 PTM 产生的蛋白质形式的重要方法。在这里，我们回顾了利用自上而下的蛋白质组学来阐明蛋白质组变化的挑战、技术创新和最新研究，重点是其在研究心脏疾病方面的用途。蛋白质型解析的信息可以极大地有助于理解各种疾病背后的分子机制，并有助于识别新的蛋白质型靶点，从而更好地开发精准医学的治疗方法。尽管对完整蛋白质进行测序存在挑战，但自上而下的蛋白质组学已经提供了有关蛋白质亚型转换和 PTM 变化的大量信息。样品制备、完整蛋白质分离和自上而下 MS 仪器的不断发展扩大了其在日益全球化的范围内表征一系列样品的蛋白质形式的能力。
A better understanding of the underlying molecular mechanism of diseases is critical for developing more effective diagnostic tools and therapeutics towards precision medicine. However, many challenges remain to unravel the complex nature of diseases. Changes in protein isoform expression and post-translation modifications (PTMs) have gained recognition for their role in underlying disease mechanisms. Top-down mass spectrometry (MS)-based proteomics is increasingly recognized as an important method for the comprehensive characterization of proteoforms that arise from alternative splicing events and/or PTMs for basic and clinical research. Here, we review the challenges, technological innovations, and recent studies that utilize top-down proteomics to elucidate changes in the proteome with an emphasis on its use to study the diseases of the heart. Proteoform-resolved information can substantially contribute to the understanding of the molecular mechanisms underlying various diseases and for the identification of novel proteoform targets for better therapeutic development toward precision medicine. Despite the challenges of sequencing intact proteins, top-down proteomics has enabled a wealth of information regarding protein isoform switching and changes in PTMs. Continuous developments in sample preparation, intact protein separation, and instrumentation for top-down MS have broadened its capabilities to characterize proteoforms from a range of samples on an increasingly global scale.
登录
查看更多内容
影响因子：
7.4
作者：
Chen B;Brown KA;Lin Z;Ge Y
通讯作者：
Ge Y
影响因子：
7.4
作者：
Blackwell, Anne E.;Dodds, Eric D.;Wysocki, Vicki H.
通讯作者：
Wysocki, Vicki H.
影响因子：
4
作者：
Dautant A;Meier T;Hahn A;Tribouillard-Tanvier D;di Rago JP;Kucharczyk R
通讯作者：
Kucharczyk R
DOI：
10.1073/pnas.0607719103
发表时间：
2006-10-31
影响因子：
11.1
作者：
Carroll, Joe;Fearnley, Ian M.;Walker, John E.
通讯作者：
Walker, John E.
影响因子：
4.4
作者：
Cleland, Timothy P.;DeHart, Caroline J.;Brodbelt, Jennifer S.
通讯作者：
Brodbelt, Jennifer S.