Degradomics in Biomarker Discovery

Abstract

The upregulation of protease expression and proteolytic activity is implicated in numerous pathological conditions such as neurodegeneration, cancer, cardiovascular and autoimmune diseases, and bone degeneration. During disease progression, various proteases form characteristic patterns of cleaved proteins and peptides, which can affect disease severity and course of progression. It has been shown that qualitative and quantitative monitoring of cleaved protease substrates can provide relevant prognostic, diagnostic, and therapeutic information. As proteolytic fragments and peptides generated in the affected tissue are commonly translocated to blood, urine, and other proximal fluids, their possible application as biomarkers is the subject of ongoing research. The field of degradomics has been established to enable the global identification of proteolytic events on the organism level, utilizing proteomic approaches and sample preparation techniques that facilitate the detection of proteolytic processing of protease substrates in complex biological samples. In this review, some of the latest developments in degradomic methodologies used for the identification and validation of biologically relevant proteolytic events and their application in the search for clinically relevant biomarker candidates are presented. The current state of degradomics in clinics is discussed and the future perspectives of the field are outlined.

A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells

“…Ischemia-related stress is known to cause various proteolytic events, and monitoring of cleaved protease substrates can provide information on stress-related molecular mechanisms, which can have a significant prognostic, diagnostic, and therapeutic value [ 20 , 21 ]. The upregulation of protease expression and proteolytic activity is implicated also in numerous pathological conditions, such as cancer, cardiovascular and other diseases [ 22 , 23 ]. During disease progression, proteases produce characteristic patterns of cleaved proteins, which characterize severity and progression.…”

Combinatorial degradomics: Precision tools to unveil proteolytic processes in biological systems

“…J o u r n a l P r e -p r o o f One of the techniques, which has been applied to discovery degradomics is data independent acquisition (DIA) mass spectrometry, allowing discovery and quantification of thousands of peptides and newly generated proteoforms [50,51]. DIA shifts the paradigm of identifying the most abundant ions in a peptide mixture to measuring specified windows of masses and thus turns the stochastic nature of data dependent acquisition (DDA) shotgun proteomics into a more unbiased approach [52].…”

Proteoform Analysis of the Human Olfactory System: A Window into Neurodegenerative Diseases

“…Usually, considering the intricate cellular composition and diversity of proteins within the OB, the application of high-resolution mass spectrometry (MS) for proteome-wide analysis, integrated with the bioinformatic analysis of proteins, has emerged as an appealing technology [ 15 , 16 ].…”