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In contrast to enzymes such as trypsin, where cleavage sites can be predicted with a great deal of certainty (Manea et al., 2007), identifying putative cleavage sites of endogenous tissue ECM proteases (such as members of matrix metalloproteinases [MMPs] and cathepsins) requires the use of machine learning algorithms which can predict cleavage sites in protein sequences (Ozols et al., 2021a