The Java application is freely available for non-commercial users at http://genome.tugraz.at/lda. Raw data associated with this manuscript may be downloaded from ProteomeCommons.org Tranche using the following hash: ZBh3nS5bXk6I/Vn32tB5Vh0qnMpVIW71HByFFQqM0RmdF4/4Hcn H3Wggh9kU2teYVOtM1JWwHIeMHqSS/bc2yYNFmyUAAAAAAACl DQ ==

We developed decision rule sets for Lipid Data Analyzer (LDA; http://genome.tugraz.at/lda2), enabling automated and reliable annotation of lipid species and their molecular structures in high-throughput data from chromatography-coupled tandem mass spectrometry. Platform independence was proven in various mass spectrometric experiments, comprising low- and high-resolution instruments and several collision energies. We propose that this independence and the capability to identify novel lipid molecular species render current state-of-the-art lipid libraries now obsolete.

Quantitative determination of lipid species provides insights to lipid homeostasis and its dysregulation in diseased states. Thus, lipidomic approaches by mass spectrometrybased technology are attractive for characterization of specifi c lipids as modulators or disruptors of signaling and metabolic pathways, or as biomarkers in the clinical setting ( 1-5 ). Particularly, mass spectrometry and advanced bioinformatics tools enable such approaches today ( 6, 7 ).Direct infusion shotgun mass spectrometry is established for "global" lipidomic analysis ( 8-13 ). It is fast and simple, but it suffers from inherent ion suppression effects that may be of advantage in some cases ( 14 ). Yet, for certain triacylglycerol-rich samples, a precleaning step is necessary ( 13 ). As an alternative approach, liquid chromatography coupled to mass spectrometry (i.e., LC/ESI-MS) can be used. Here, a variety of different reversed-phase and normal-phase liquid chromatographic separation techniques afford higher detection sensitivity in mass spectrometers (15)(16)(17)(18)(19)(20)(21)(22)(23)