Depletion-dependent Activity-Based Protein Profiling coupled to SWATH/DIA Mass Spectrometry detects serine hydrolase lipid remodeling in lung adenocarcinoma progression

These raw data correspond to a lipidomic analysis of free fatty acids in tumour biopsies to validate the results of the chemical proteomic method. 

Main point of the study

The results of proteomic profiling of (clinical) sample cohorts are generally assumed to more closely represent the functional state of the samples tested than transcript profiles. Yet, standard proteomic methods display the abundance and not the state of activity of the detected proteins. Systematic profiling of enzyme activities in the context of whole proteome measurements would provide a further significant step towards the description of the functional state of a cell. 

We describe a novel concept in chemoproteomics that concurrently quantifies the active and inactive fraction and the total amount of tested enzymes in the context of the total tissue proteome. The method relies on well tested  activity-based probes  but used advanced mass spectrometric and bespoke software tools to generate mechanistic insights into the regulations of enzyme activity.  

The method was benchmarked against state of the art techniques and applied to classify a cohort of lung adenocarcinoma tissues into aggressive and less aggressive samples based the activity profiles of serine hydrolases and to propose a mechanistic explanation of the disease phenotypes based on environmental and genetic vulnerabilities of patients.