Variant biomarker discovery using mass spectrometry-based proteogenomics

Frontiers in Aging

Aging

Luke Reilly¹  Yue A. Qi¹  Andrew B. Singleton²  Mark R. Cookson³  Sahba Seddighi⁴  Michael E. Ward⁴ 

[1] Center for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States;Center for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States;Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States;Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States;National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States;

关键词: biomarker;    proteogenomics;    aging;    neurodegenerative;    cancers;   

DOI  :  10.3389/fragi.2023.1191993

 received in 2023-03-22, accepted in 2023-04-13,  发布年份 2023

来源: Frontiers

【 摘 要 】

Genomic diversity plays critical roles in risk of disease pathogenesis and diagnosis. While genomic variants—including single nucleotide variants, frameshift variants, and mis-splicing isoforms—are commonly detected at the DNA or RNA level, their translated variant protein or polypeptide products are ultimately the functional units of the associated disease. These products are often released in biofluids and could be leveraged for clinical diagnosis and patient stratification. Recent emergence of integrated analysis of genomics with mass spectrometry-based proteomics for biomarker discovery, also known as proteogenomics, have significantly advanced the understanding disease risk variants, precise medicine, and biomarker discovery. In this review, we discuss variant proteins in the context of cancers and neurodegenerative diseases, outline current and emerging proteogenomic approaches for biomarker discovery, and provide a comprehensive proteogenomic strategy for detection of putative biomarker candidates in human biospecimens. This strategy can be implemented for proteogenomic studies in any field of enquiry. Our review timely addresses the need of biomarkers for aging related diseases.

【 授权许可】

Unknown   
Copyright © 2023 Reilly, Seddighi, Singleton, Cookson, Ward and Qi.