蛋白质组学
蛋白质组
计算生物学
翻译后修饰
自上而下的蛋白质组学
功能(生物学)
数据科学
化学
计算机科学
纳米技术
质谱法
生物
串联质谱法
生物化学
选择性反应监测
细胞生物学
色谱法
基因
酶
材料科学
作者
Jake A. Melby,David S. Roberts,Eli J. Larson,Kyle Brown,Elizabeth F. Bayne,Song Jin,Ying Ge
标识
DOI:10.1021/jasms.1c00099
摘要
Top-down mass spectrometry (MS)-based proteomics is a powerful technology for comprehensively characterizing proteoforms to decipher post-translational modifications (PTMs) together with genetic variations and alternative splicing isoforms toward a proteome-wide understanding of protein functions. In the past decade, top-down proteomics has experienced rapid growth benefiting from groundbreaking technological advances, which have begun to reveal the potential of top-down proteomics for understanding basic biological functions, unraveling disease mechanisms, and discovering new biomarkers. However, many challenges remain to be comprehensively addressed. In this Account & Perspective, we discuss the major challenges currently facing the top-down proteomics field, particularly in protein solubility, proteome dynamic range, proteome complexity, data analysis, proteoform-function relationship, and analytical throughput for precision medicine. We specifically review the major technology developments addressing these challenges with an emphasis on our research group's efforts, including the development of top-down MS-compatible surfactants for protein solubilization, functionalized nanoparticles for the enrichment of low-abundance proteoforms, strategies for multidimensional chromatography separation of proteins, and a new comprehensive user-friendly software package for top-down proteomics. We have also made efforts to connect proteoforms with biological functions and provide our visions on what the future holds for top-down proteomics.
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