High-coverage lipidomics for functional lipid and pathway analyses.

Rapid advances in front-end separation approaches and analytical technologies have accelerated the development of lipidomics, particularly in terms of increasing analytical coverage to encompass an expanding repertoire of lipids within a single analytical approach. Developments in lipid pathway analysis, however, have somewhat lingered behind, primarily due to (1) the lack of coherent alignment between lipid identifiers in common databases versus that generated from experiments, owing to the differing structural resolution of lipids at molecular level that is specific to the analytical approaches adopted by various laboratories; (2) the immense complexity of lipid metabolic relationships that may entail head group changes, fatty acyls modifications of various forms (e.g. elongation, desaturation, oxidation), as well as active remodeling that demands a multidimensional, panoramic view to take into account all possibilities in lipid pathway analyses. Herein, we discuss current efforts undertaken to address these challenges, as well as alternative form of "pathway analyses" that may be particularly useful for uncovering functional lipid interactions under different biological contexts. Consolidating lipid pathway analyses will be indispensable in facilitating the transition of lipidomics from its prior role of phenotype validation to a hypothesis-generating tool that uncovers novel molecular targets to drive downstream mechanistic pursuits under biomedical settings.