degradomics

Degradomics is the genome- or proteome-wide study of proteolysis, focusing on protease activities, their substrates, and the specific cleavage sites produced in a biological system. The term reflects the aim of mapping the degradome, the complete set of proteolytic events that shape cellular function, signaling, and physiology.

Global degradomics employs terminomics and N-terminomics to capture protein N-termini generated by proteolysis. Techniques such as TAILS (Terminal Amine Isotopic Labeling of Substrates), COFRADIC, PICS, and related approaches enrich and identify neo-N-termini by mass spectrometry, enabling large-scale cleavage-site mapping under various conditions or diseases. Activity-based proteomics (ABPP) complements this by profiling active proteases with active-site-directed probes, providing functional readouts of protease activity. Quantitative strategies using isotopic labeling, such as SILAC, TMT, or iTRAQ, enable comparison of proteolytic events across samples.

Applications of degradomics span basic biology and medicine. It aids in understanding development, tissue remodeling, immune responses, and pathogen-host interactions. In disease contexts, degradomics helps identify protease substrates and cleavage markers associated with cancer progression, neurodegeneration, inflammation, and aging, and can reveal protease networks and cascades that drive pathology. The data generated inform biomarker discovery and the development of protease-targeted therapies.

Challenges include detecting low-abundance substrates and transient cleavages, substrate redundancy, and the influence of post-translational modifications on proteolysis. Technical hurdles involve sample complexity, dynamic range, and the need for standardized workflows and robust bioinformatics pipelines to integrate degradomic data with other omics.