Top-down proteomics in health and disease: challenges and opportunities.
Proteomics is essential for deciphering how molecules interact as a system and for understanding the functions of cellular systems in human disease; however, the unique characteristics of the human proteome, which include a high dynamic range of protein expression and extreme complexity due to a plethora of PTMs and sequence variations, make such analyses challenging. An emerging "top-down" MS-based proteomics approach, which provides a "bird's eye" view of all proteoforms, has unique advantages for the assessment of PTMs and sequence variations. Recently, a number of studies have showcased the potential of top-down proteomics for the unraveling of disease mechanisms and discovery of new biomarkers. Nevertheless, the top-down approach still faces significant challenges in terms of protein solubility, separation, and the detection of large intact proteins, as well as underdeveloped data analysis tools. Consequently, new technological developments are urgently needed to advance the field of top-down proteomics. Herein, we intend to provide an overview of the recent applications of top-down proteomics in biomedical research. Moreover, we will outline the challenges and opportunities facing top-down proteomics strategies aimed at understanding and diagnosing human diseases.
Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, Madison, WI, USA; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Zachery R
ZR
Gregorich
Ying
Y
Ge
D015415:Biomarkers / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism*; D003141:Communicable Diseases / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D009369:Neoplasms / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics; D049490:Systems Biology
D015415:Biomarkers; D020543:Proteome
Human disease; Mass spectrometry; PTMs; Proteomics; Systems biology