LipidXplorer Preface

Aims and Scope

In shotgun lipidomics lipids are extracted from cells, tissues or organisms and the total extracts are directly infused into a tandem mass spectrometer (reviewed in [1]). Mass spectrometry characterizes lipid molecules in two major ways. First, in MS experiments it determines their intact masses. Second, in MS/MS experiments, lipid precursors are dissociated into structure –specific fragments which determine the individual molecular species. No extra calculation need to be done for quantification, since total lipid extracts are infused.

Top-down lipidomics is a strategy that aims at the rapid quantitative characterization of global changes within the lipidome and is solely reliant on accurate masses of intact lipid precursors [2]. Bottom-up lipidomics quantifies individual molecular species by detecting characteristic structural fragment ions using tandem mass spectrometry [3].

LipidXplorer is a software that supports a variety of shotgun lipidomics experiments [4]. It is designed to support bottom-up and top-down shotgun lipidomics experimenters performed at all type of tandem mass spectrometers. Lipid identification does not rely on a database resource of reference or simulated mass spectra.

Design and Operation Concept

LipidXplorer organizes MS and MS/MS spectra (acquired from all samples of lipidomics experiments, including biological and technical repeats) into a flat-file database termed MasterScan. Scans are averaged and individual spectra aligned considering instrument specific peak attributes, such as mass resolution, mass accuracy, peak occupancy, among others.

The MasterScan is then interrogated by user-defined lipid class –specific and/or lipid species -specific queries written in the Molecular Fragmentation Query Language (MFQL). Identified and annotated lipid species, along with intensities of user-defined fragment or precursor ions, are reported.

Further details on the installation and all aspects of the lipid identification by LipidXplorer are provided in [4] and here:

LipidXplorer is written in Python. The original publication version used Python 2.6. Versions 1.2.7 and up require Python 2.7. For further information on dependencies, please see LipidXplorer_Installation for further details or [4]. Due to the end-of-life of Python 2, we plan to migrate the codebase. New releases of LipidXplorer (Version 1.2.9 and onwards) will require Python 3.

Disclaimer

Despite all efforts that have been put into the development and testing of each release of LipidXplorer, the software might still contain some errors and bugs. Therefore we provide no warranty and assume no responsibility for any consequences caused by the program installation and use. Please use it at your own risk.

License

This program is a free software; you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation. See the file LICENSE.txt for details.

Contact

Please contact us over the LipidXplorer discussion group: [LipidXplorer Google Group]

Everyone can join. It is open for questions and suggestions and other issues related to the software.

References

[1] Han, X. and Gross, R.W. 2005. Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples. Mass Spectrom Rev 24(3): 367-412.

[2] Schwudke, D., Hannich, J.T., Surendranath, V., Grimard, V., Moehring, T., Burton, L., Kurzchalia, T., and Shevchenko, A. 2007. Top-down lipidomic screens by multivariate analysis of high-resolution survey mass spectra. Anal Chem 79: 4083-4093.

[3] Schwudke, D., Oegema, J., Burton, L., Entchev, E., Hannich, J.T., Ejsing, C.S., Kurzchalia, T., and Shevchenko, A. 2006. Lipid profiling by multiple precursor and neutral loss scanning driven by the data-dependent acquisition. Anal Chem 78(2): 585-595.

[4] Herzog, R., Schwudke, D., Schuhmann, K., Sampaio, J.L., Bornstein, S.R., Schroeder, M., and Shevchenko, A. 2011. A novel informatics concept for high-throughput shotgun lipidomics based on the molecular fragmentation query language. Genome Biol 12(1): R8.