Enhancing the biological insight from limited proteolysis-coupled mass spectrometry

Limited proteolysis combined with mass spectrometry (LiP-MS) facilitates probing structural changes on a proteome-wide scale in situ. Distinguishing the different signal contributions, such as changes in protein abundance, from protein abundance changes remains challenging. We propose a two-step approach, first removing unwanted variations from the LiP signal that are not caused by protein structural effects and subsequently inferring the effects of variables of interest on the remaining signal. Using LiP-MS data from three species we demonstrate that our framework provides a uniquely powerful approach for deconvolving LiP-MS signals and inferring protein structural changes.