Discovery proteomics refers to the use of proteomics as a hypothesis-free tool to globally profile the proteome of a given sample. In discovery proteomics, bottom-up or shotgun proteomics is based on the analysis of peptides generated after enzymatic digestion of a protein mixture. Digested peptides are separated by LC before MS/MS analysis. In comparison to gene expression analysis ECM proteomics offers certain advantages. First, many diseases manifest over years. Therefore, although transcript levels provide a window into cellular activity at the time of harvest, they merely provide an indirect assessment of protein synthesis at a single time point. When studying dynamic entities such as the ECM, transcript levels become more extraneous, particularly as nascent ECM proteins are incorporated into the existing matrix, and actual ECM protein abundance is determined by the balance of protein synthesis, deposition, and degradation.