Protein biomarker discovery and validation: the long and uncertain path to clinical utility

2006 ◽  
Vol 24 (8) ◽  
pp. 971-983 ◽  
Author(s):  
Nader Rifai ◽  
Michael A Gillette ◽  
Steven A Carr
Keyword(s):  
Clinical Utility ◽  
Biomarker Discovery ◽  
Protein Biomarker

Accelerating protein biomarker discovery and translation from proteomics research for clinical utility

Bioanalysis ◽  
2020 ◽  
Vol 12 (20) ◽  
pp. 1469-1481
Author(s):  
Jiwen Chen ◽  
Naiyu Zheng
Keyword(s):  
Clinical Utility ◽  
Biomarker Discovery ◽  
Clinical Applications ◽  
Clinical Perspective ◽  
Significant Progress ◽  
Clinical Implementation ◽  
Protein Biomarkers ◽  
Protein Biomarker ◽  
The Past ◽  
Proteomics Research

Discovery proteomics research has made significant progress in the past several years; however, the number of protein biomarkers deployed in clinical practice remains rather limited. There are several scientific and procedural gaps between discovery proteomics research and clinical implementation, which have contributed to poor biomarker validity and few clinical applications. The complexity and low throughput of proteomics approaches have added additional barriers for biomarker assay translation to clinical applications. Recently, targeted proteomics have become a powerful tool to bridge the biomarker discovery to clinical validation. In this perspective, we discuss the challenges and strategies in proteomics research from a clinical perspective, and propose several recommendations for discovery proteomics research to accelerate protein biomarker discovery and translation for future clinical applications.

scholarly journals L-Carnitine and Acylcarnitines: Mitochondrial Biomarkers for Precision Medicine

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 51
Author(s):  
Marc R. McCann ◽  
Mery Vet George De la Rosa ◽  
Gus R. Rosania ◽  
Kathleen A. Stringer
Keyword(s):  
Precision Medicine ◽  
Inborn Errors Of Metabolism ◽  
Clinical Utility ◽  
Biomarker Discovery ◽  
Genetic Disorders ◽  
Acid Oxidation ◽  
Inborn Errors ◽  
Therapeutic Decisions ◽  
Literature Evidence ◽  
Clinical Biomarker

Biomarker discovery and implementation are at the forefront of the precision medicine movement. Modern advances in the field of metabolomics afford the opportunity to readily identify new metabolite biomarkers across a wide array of disciplines. Many of the metabolites are derived from or directly reflective of mitochondrial metabolism. L-carnitine and acylcarnitines are established mitochondrial biomarkers used to screen neonates for a series of genetic disorders affecting fatty acid oxidation, known as the inborn errors of metabolism. However, L-carnitine and acylcarnitines are not routinely measured beyond this screening, despite the growing evidence that shows their clinical utility outside of these disorders. Measurements of the carnitine pool have been used to identify the disease and prognosticate mortality among disorders such as diabetes, sepsis, cancer, and heart failure, as well as identify subjects experiencing adverse drug reactions from various medications like valproic acid, clofazimine, zidovudine, cisplatin, propofol, and cyclosporine. The aim of this review is to collect and interpret the literature evidence supporting the clinical biomarker application of L-carnitine and acylcarnitines. Further study of these metabolites could ultimately provide mechanistic insights that guide therapeutic decisions and elucidate new pharmacologic targets.

scholarly journals Cerebrospinal fluid extracellular vesicle enrichment for protein biomarker discovery in neurological disease; multiple sclerosis

2017 ◽  
Vol 6 (1) ◽  
pp. 1369805 ◽  
Author(s):  
Joanne L. Welton ◽  
Samantha Loveless ◽  
Timothy Stone ◽  
Chris von Ruhland ◽  
Neil P. Robertson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Disease ◽  
Biomarker Discovery ◽  
Extracellular Vesicle ◽  
Protein Biomarker

scholarly journals Tutorial: best practices and considerations for mass-spectrometry-based protein biomarker discovery and validation

2021 ◽  
Author(s):  
Ernesto S. Nakayasu ◽  
Marina Gritsenko ◽  
Paul D. Piehowski ◽  
Yuqian Gao ◽  
Daniel J. Orton ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Best Practices ◽  
Biomarker Discovery ◽  
Protein Biomarker

Protein biomarker discovery for head and neck cancer

2010 ◽  
Vol 73 (10) ◽  
pp. 1790-1803 ◽  
Author(s):  
Tieneke B.M. Schaaij-Visser ◽  
Ruud H. Brakenhoff ◽  
C. René Leemans ◽  
Albert J.R. Heck ◽  
Monique Slijper
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Biomarker Discovery ◽  
Protein Biomarker

Proteome Analysis of Isolated Perfused Organ Effluent as a Novel Model for Protein Biomarker Discovery

2006 ◽  
Vol 5 (1) ◽  
pp. 177-182 ◽  
Author(s):  
John M. Koomen ◽  
Christopher R. Wilson ◽  
Patrick Guthrie ◽  
Matthew J. Androlewicz ◽  
Ryuji Kobayashi ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Proteome Analysis ◽  
Protein Biomarker ◽  
Novel Model

scholarly journals Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers

2018 ◽  
Vol 1 (2) ◽  
pp. e201800042 ◽  
Author(s):  
Tiannan Guo ◽  
Li Li ◽  
Qing Zhong ◽  
Niels J Rupp ◽  
Konstantina Charmpi ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Specific Antigen ◽  
Proteome Analysis ◽  
Tissue Microarrays ◽  
Protein Biomarker ◽  
Pressure Cycling ◽  
Pressure Cycling Technology ◽  
New Perspective ◽  
High Degree ◽  
Independent Cohort

It remains unclear to what extent tumor heterogeneity impacts on protein biomarker discovery. Here, we quantified proteome intra-tissue heterogeneity (ITH) based on a multi-region analysis of prostate tissues using pressure cycling technology and Sequential Windowed Acquisition of all THeoretical fragment ion mass spectrometry. We quantified 6,873 proteins and analyzed the ITH of 3,700 proteins. The level of ITH varied depending on proteins and tissue types. Benign tissues exhibited more complex ITH patterns than malignant tissues. Spatial variability of 10 prostate biomarkers was validated by immunohistochemistry in an independent cohort (n = 83) using tissue microarrays. Prostate-specific antigen was preferentially variable in benign prostatic hyperplasia, whereas growth/differentiation factor 15 substantially varied in prostate adenocarcinomas. Furthermore, we found that DNA repair pathways exhibited a high degree of variability in tumorous tissues, which may contribute to the genetic heterogeneity of tumors. This study conceptually adds a new perspective to protein biomarker discovery: it suggests that recent technological progress should be exploited to quantify and account for spatial proteome variation to complement biomarker identification and utilization.

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