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Review

Mass-Spectrometry-Based Functional Proteomic and Phosphoproteomic Technologies and Their Application for Analyzing Ex Vivo and In Vitro Models of Hypertrophic Cardiomyopathy

by 1,2,3 and 1,2,*
1
Center for Network Systems Biology, Boston University School of Medicine, Boston, MA 02118, USA
2
Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA
3
MD-PhD Program, Boston University School of Medicine, Boston, MA 02118, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Manuel Vázquez-Carrera
Int. J. Mol. Sci. 2021, 22(24), 13644; https://doi.org/10.3390/ijms222413644
Received: 15 November 2021 / Revised: 10 December 2021 / Accepted: 15 December 2021 / Published: 20 December 2021
(This article belongs to the Special Issue Genetic and Molecular Mechanisms of Hypertrophic Cardiomyopathy)
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease thought to be principally caused by mutations in sarcomeric proteins. Despite extensive genetic analysis, there are no comprehensive molecular frameworks for how single mutations in contractile proteins result in the diverse assortment of cellular, phenotypic, and pathobiological cascades seen in HCM. Molecular profiling and system biology approaches are powerful tools for elucidating, quantifying, and interpreting dynamic signaling pathways and differential macromolecule expression profiles for a wide range of sample types, including cardiomyopathy. Cutting-edge approaches combine high-performance analytical instrumentation (e.g., mass spectrometry) with computational methods (e.g., bioinformatics) to study the comparative activity of biochemical pathways based on relative abundances of functionally linked proteins of interest. Cardiac research is poised to benefit enormously from the application of this toolkit to cardiac tissue models, which recapitulate key aspects of pathogenesis. In this review, we evaluate state-of-the-art mass-spectrometry-based proteomic and phosphoproteomic technologies and their application to in vitro and ex vivo models of HCM for global mapping of macromolecular alterations driving disease progression, emphasizing their potential for defining the components of basic biological systems, the fundamental mechanistic basis of HCM pathogenesis, and treating the ensuing varied clinical outcomes seen among affected patient cohorts. View Full-Text
Keywords: functional proteomics; mass spectrometry; cardiac disease modeling; hypertrophic cardiomyopathy functional proteomics; mass spectrometry; cardiac disease modeling; hypertrophic cardiomyopathy
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MDPI and ACS Style

Moore, J.; Emili, A. Mass-Spectrometry-Based Functional Proteomic and Phosphoproteomic Technologies and Their Application for Analyzing Ex Vivo and In Vitro Models of Hypertrophic Cardiomyopathy. Int. J. Mol. Sci. 2021, 22, 13644. https://doi.org/10.3390/ijms222413644

AMA Style

Moore J, Emili A. Mass-Spectrometry-Based Functional Proteomic and Phosphoproteomic Technologies and Their Application for Analyzing Ex Vivo and In Vitro Models of Hypertrophic Cardiomyopathy. International Journal of Molecular Sciences. 2021; 22(24):13644. https://doi.org/10.3390/ijms222413644

Chicago/Turabian Style

Moore, Jarrod, and Andrew Emili. 2021. "Mass-Spectrometry-Based Functional Proteomic and Phosphoproteomic Technologies and Their Application for Analyzing Ex Vivo and In Vitro Models of Hypertrophic Cardiomyopathy" International Journal of Molecular Sciences 22, no. 24: 13644. https://doi.org/10.3390/ijms222413644

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