Abstract
BackgroundA new lipid class named ‘fatty acid esters of hydroxyl fatty acids’ (FAHFA) was recently discovered in mammalian adipose tissue and in blood plasma and some FAHFAs were found to be associated with type 2 diabetes. To facilitate the automatic annotation of FAHFAs in biological specimens, a tandem mass spectra (MS/MS) library is needed. Due to the limitation of the commercial available standard compounds, we proposed building an in silico MS/MS library to extend the coverage of molecules.ResultsWe developed a computer-generated library with 3267 tandem mass spectra (MS/MS) for 1089 FAHFA species. FAHFA spectra were generated based on authentic standards with negative mode electrospray ionization and 10, 20, and 40 V collision induced dissociation at 4 spectra/s as used in in ultra-high performance liquid chromatography-QTOF mass spectrometry studies. However, positional information of the hydroxyl group is only obtained either at lower QTOF spectra acquisition rates of 1 spectrum/s or at the MS3 level in ion trap instruments. Therefore, an additional set of 4290 fragment-rich MS/MS spectra was created to enable distinguishing positional FAHFA isomers. The library was generated based on ion fragmentations and ion intensities of FAHFA external reference standards, developing a heuristic model for fragmentation rules and extending these rules to large swaths of computer-generated structures of FAHFAs with varying chain lengths, degrees of unsaturation and hydroxyl group positions. Subsequently, we validated the new in silico library by discovering several new FAHFA species in egg yolk, showing that this library enables high-throughput screening of FAHFA lipids in various biological matrices.ConclusionsThe developed library and templates are freely available for commercial or noncommercial use at http://fiehnlab.ucdavis.edu/staff/yanma/fahfa-lipid-library. This in silico MS/MS library allows users to annotate FAHFAs from accurate mass tandem mass spectra in an easy and fast manner with NIST MS Search or PepSearch software. The developing template is provided for advanced users to modify the parameters and export customized libraries according to their instrument features.Graphical abstractExample of experimental and in silico MS/MS spectra for FAHFA lipidsElectronic supplementary materialThe online version of this article (doi:10.1186/s13321-015-0104-4) contains supplementary material, which is available to authorized users.
Highlights
A new lipid class named ‘fatty acid esters of hydroxyl fatty acids’ (FAHFA) was recently discovered in mammalian adipose tissue and in blood plasma and some FAHFAs were found to be associated with type 2 diabetes
In order to enable extensive profiling and automatic annotation of FAHFA species, an MS/MS library with more structural diversity is needed. Today, such mass spectral libraries can be created by applying rules of fragmentation patterns on large in silico structure list, as we have previously shown for over 200,000 mass spectra in LipidBlast [2] for twenty-six common lipid classes such as phosphatidylcholines, Ma et al J Cheminform (2015) 7:53 monogalactosyldiacylglycerols or triacylglycerols
Negative mode electrospray in silico MS/MS spectra were modelled based on the reference spectra of 9-PAHSA under 10, 20, and 40 V collision induced dissociation (CID) voltages acquired with UHPLC-quadrupole time of flight (QTOF) MS/MS profiling methods at 4 spectra/s (Fig. 1a; Additional file 1)
Summary
A new lipid class named ‘fatty acid esters of hydroxyl fatty acids’ (FAHFA) was recently discovered in mammalian adipose tissue and in blood plasma and some FAHFAs were found to be associated with type 2 diabetes. A novel lipid class named ‘fatty acid esters of hydroxyl fatty acids’ (FAHFA) was discovered in mice adipose tissues [1]. In order to enable extensive profiling and automatic annotation of FAHFA species, an MS/MS library with more structural diversity is needed Today, such mass spectral libraries can be created by applying rules of fragmentation patterns on large in silico structure list, as we have previously shown for over 200,000 mass spectra in LipidBlast [2] for twenty-six common lipid classes such as (lyso) phosphatidylcholines, Ma et al J Cheminform (2015) 7:53 monogalactosyldiacylglycerols or triacylglycerols.
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