Lipid-centered multi-omics analysis for systems biology

Systems biology provides a systems-level understanding by using a holistic approach to investigate the behavior of complex biological processes and organization in terms of molecular constituents. This is accomplished by selectively combining quantitative measurements, computational modelling and simulation. An essential prerequisite of systems biology is the availability of methods that enable comprehensive quantitative analysis of multiple molecular layers and their constituents. The aim of this study is to tackle this challenge and, to this purpose, it introduces a mass spectrometry-compatible sample preparation strategy that facilitates the SImultaneous Metabolite, Protein and Lipid Extraction from one sample aliquot (SIMPLEX). Furthermore, the versatility of this method was demonstrated in two model systems with different levels of complexity: i) a cell culture model for studying peroxisomal proliferator-activated receptor gamma (PPARG) signaling, and ii) a complex biological system, such as the mice heart, for the exploratory study of caveolinopathy-associated dilative cardiomyopathy together with a more targeted investigation on myoglobin function in lipid metabolism. These multi-omics applications revealed correlations between all three molecular layers as a function of perturbation, demonstrating that SIMPLEX is a suitable strategy to explore cross-talk within and between molecular layers of biological systems with various complexity.