Advances and Utility of the Human Plasma Proteome
- Eric W. Deutsch*Eric W. Deutsch*Email: [email protected]. Tel: 206-732-1200. Fax: 206-732-1299.Institute for Systems Biology, Seattle, Washington 98109, United StatesMore by Eric W. Deutsch
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- Gilbert S. OmennGilbert S. OmennInstitute for Systems Biology, Seattle, Washington 98109, United StatesDepartments of Computational Medicine & Bioinformatics, Internal Medicine, and Human Genetics and School of Public Health, University of Michigan, Ann Arbor, Michigan 48109-2218, United StatesMore by Gilbert S. Omenn
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- Zhi Sun
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- Michal MaesMichal MaesInstitute for Systems Biology, Seattle, Washington 98109, United StatesMore by Michal Maes
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- Maria PernemalmMaria PernemalmDepartment of Oncology and Pathology/Science for Life Laboratory, Karolinska Institutet, 171 65 Stockholm, SwedenMore by Maria Pernemalm
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- Krishnan K. PalaniappanKrishnan K. PalaniappanFreenome, 259 East Grand Avenue, South San Francisco, California 94080, United StatesMore by Krishnan K. Palaniappan
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- Natasha LetunicaNatasha LetunicaMurdoch Children’s Research Institute, 50 Flemington Road, Parkville 3052, Victoria, AustraliaMore by Natasha Letunica
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- Yves VandenbrouckYves VandenbrouckUniversité Grenoble Alpes, CEA, Inserm U1292, Grenoble 38000, FranceMore by Yves Vandenbrouck
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- Virginie BrunVirginie BrunUniversité Grenoble Alpes, CEA, Inserm U1292, Grenoble 38000, FranceMore by Virginie Brun
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- Sheng-ce TaoSheng-ce TaoKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, B207 SCSB Building, 800 Dongchuan Road, Shanghai 200240, ChinaMore by Sheng-ce Tao
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- Xiaobo YuXiaobo YuState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences-Beijing (PHOENIX Center), Beijing Institute of Lifeomics, Beijing 102206, ChinaMore by Xiaobo Yu
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- Philipp E. GeyerPhilipp E. GeyerOmicEra Diagnostics GmbH, Behringstr. 6, 82152 Planegg, GermanyMore by Philipp E. Geyer
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- Vera IgnjatovicVera IgnjatovicMurdoch Children’s Research Institute, 50 Flemington Road, Parkville 3052, Victoria, AustraliaDepartment of Paediatrics, The University of Melbourne, 50 Flemington Road, Parkville 3052, Victoria, AustraliaMore by Vera Ignjatovic
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- Robert L. MoritzRobert L. MoritzInstitute for Systems Biology, Seattle, Washington 98109, United StatesMore by Robert L. Moritz
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- Jochen M. Schwenk*Jochen M. Schwenk*Email: [email protected]Affinity Proteomics, Science for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, Tomtebodavägen 23, SE-171 65 Solna, SwedenMore by Jochen M. Schwenk
Abstract

The study of proteins circulating in blood offers tremendous opportunities to diagnose, stratify, or possibly prevent diseases. With recent technological advances and the urgent need to understand the effects of COVID-19, the proteomic analysis of blood-derived serum and plasma has become even more important for studying human biology and pathophysiology. Here we provide views and perspectives about technological developments and possible clinical applications that use mass-spectrometry(MS)- or affinity-based methods. We discuss examples where plasma proteomics contributed valuable insights into SARS-CoV-2 infections, aging, and hemostasis and the opportunities offered by combining proteomics with genetic data. As a contribution to the Human Proteome Organization (HUPO) Human Plasma Proteome Project (HPPP), we present the Human Plasma PeptideAtlas build 2021-07 that comprises 4395 canonical and 1482 additional nonredundant human proteins detected in 240 MS-based experiments. In addition, we report the new Human Extracellular Vesicle PeptideAtlas 2021-06, which comprises five studies and 2757 canonical proteins detected in extracellular vesicles circulating in blood, of which 74% (2047) are in common with the plasma PeptideAtlas. Our overview summarizes the recent advances, impactful applications, and ongoing challenges for translating plasma proteomics into utility for precision medicine.
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(6)
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(4)
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(2)
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(43)
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(12)
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(1)
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(1)
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(3)
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(2)
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(5)
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- Chen Li, Juan Xiao, Shihua Wu, Lu Liu, Xuemei Zeng, Qiang Zhao, Zhiwei Zhang. Clinical application of serum-based proteomics technology in human tumor research. Analytical Biochemistry 2023, 663 , 115031. https://doi.org/10.1016/j.ab.2022.115031
- Natalia Frankowska, Ewa Bryl, Tamas Fulop, Jacek M. Witkowski. Longevity, Centenarians and Modified Cellular Proteodynamics. International Journal of Molecular Sciences 2023, 24
(3)
, 2888. https://doi.org/10.3390/ijms24032888
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(4)
, 3420. https://doi.org/10.3390/ijms24043420
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- Yan Zhou, Rui Sun, Sainan Li, Xiao Liang, Liujia Qian, Liang Yue, Tiannan Guo. High-Throughput and In-Depth Proteomic Profiling of 5 μL Plasma and Serum Using TMTpro 16-Plex. 2023, 81-92. https://doi.org/10.1007/978-1-0716-2978-9_6
- Haoyun Fang, David W. Greening. An Optimized Data-Independent Acquisition Strategy for Comprehensive Analysis of Human Plasma Proteome. 2023, 93-107. https://doi.org/10.1007/978-1-0716-2978-9_7
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(29-30)
, 8191-8200. https://doi.org/10.1007/s00216-022-04355-2
- Bo He, Zhao Huang, Canhua Huang, Edouard C. Nice. Clinical applications of plasma proteomics and peptidomics: Towards precision medicine. PROTEOMICS – Clinical Applications 2022, 16
(6)
, 2100097. https://doi.org/10.1002/prca.202100097
- Xiaobo Yu, Jochen M. Schwenk, Ping Xu, Joshua LaBaer. Advances in plasma proteomics: Moving from technology to precision medicine. PROTEOMICS – Clinical Applications 2022, 16
(6)
, 2200083. https://doi.org/10.1002/prca.202200083
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(10)
, 2387. https://doi.org/10.3390/biomedicines10102387
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(07)
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- Yi‐Ting Chen, Wan‐Rou Liao, Hsueh‐Ting Wang, Hsiao‐Wei Chen, Sung‐Fang Chen. Targeted protein quantitation in human body fluids by mass spectrometry. Mass Spectrometry Reviews 2022, 9 https://doi.org/10.1002/mas.21788
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(3)
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(2)
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- Yi Yang, Ling Lin, Liang Qiao. Deep learning approaches for data-independent acquisition proteomics. Expert Review of Proteomics 2021, 18
(12)
, 1031-1043. https://doi.org/10.1080/14789450.2021.2020654
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(24)
, 13537. https://doi.org/10.3390/ijms222413537