Figure 1

Schematic illustration of the workflows for identification of candidate lipid drug-response markers by MALDI-FTICR MS and their fast measurement by whole cell MALDI-TOF MS biotyping. In concentration-response studies, cells are treated with defined concentrations of an inhibitor and spotted onto a MALDI target plate in 384-well format. The pre-spotted target plate is coated with DHB-matrix using a SunCollect sprayer. MS-spectra are acquired in automated fashion using an ultrafleXtreme MALDI-TOF/TOF MS instrument. Spectra are imported into the R programming environment for automated data preprocessing and evaluation. Fast feature extraction of putative concentration-dependent m/z is performed using m/z feature-wise variance analysis. Based on sigmoidal curve fits, extracted m/z features are evaluated for suitability as concentration-response markers. Structural analysis of candidate marker lipids is performed by ultra-high resolution tandem mass spectrometry using a 7 T Solarix XR FTICR (orange workflow). The identified marker can be used to evaluate drug-potencies of novel pharmaceuticals (black workflow).