Top-down lipidomic screens by multivariate analysis of high-resolution survey mass spectra.
Direct profiling of total lipid extracts on a hybrid LTQ Orbitrap mass spectrometer by high-resolution survey spectra clusters species of 11 major lipid classes into 7 groups, which are distinguished by their sum compositions and could be identified by accurately determined masses. Rapid acquisition of survey spectra was employed as a "top-down" screening tool that, together with the computational method of principal component analysis, revealed pronounced perturbations in the abundance of lipid precursors within the entire series of experiments. Altered lipid precursors were subsequently identified either by accurately determined masses or by in-depth MS/MS characterization that was performed on the same instrument. Hence, the sensitivity, throughput and robustness of lipidomics screens were improved without compromising the accuracy and specificity of molecular species identification. The top-down lipidomics strategy lends itself for high-throughput screens complementing ongoing functional genomics efforts.
Schwudke
Dominik
D
MPI of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Hannich
J Thomas
JT
Surendranath
Vineeth
V
Grimard
Vinciane
V
Moehring
Thomas
T
Burton
Lyle
L
Kurzchalia
Teymuras
T
Shevchenko
Andrej
A
D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics / Q000254:growth & development; D008055:Lipids / Q000032:analysis* / Q000737:chemistry*; D015394:Molecular Structure; D034622:RNA Interference; D053719:Tandem Mass Spectrometry / Q000379:methods*
D008055:Lipids