Directed Non-Targeted Mass Spectrometry and Chemical Networking for Discovery of Eicosanoids

TL;DR

This study employs advanced mass spectrometry and chemical networking to identify over 500 eicosanoids in human plasma, including 46 novel molecules, revealing their associations with inflammation, age, and obesity, thus expanding understanding of their biological roles.

Contribution

The paper introduces a combined mass spectrometry and computational approach to discover and characterize a broad spectrum of eicosanoids, including novel molecules, in human plasma.

Findings

Over 500 eicosanoid-like signals identified in plasma.

46 previously undescribed eicosanoids discovered.

Eicosanoid levels correlate with inflammation, age, and obesity.

Abstract

Eicosanoids and related species are critical, small bioactive mediators of human physiology and inflammation. While ~1100 distinct eicosanoids have been predicted to exist, to date, less than 150 of these molecules have been measured in humans, limiting our understanding of eicosanoids and their role in human biology. Using a directed non-targeted mass spectrometry approach in conjunction with computational chemical networking of spectral fragmentation patterns, we find over 500 discrete chemical signals highly consistent with known and putative eicosanoids in human plasma, including 46 putative novel molecules not previously described, thereby greatly expanding the breath of prior analytical strategies. In plasma samples from 1500 individuals, we find members of this expanded eicosanoid library hold close association with markers of inflammation, as well as clinical characteristics linked with inflammation, including advancing age and obesity. These experimental and computational approaches enable discovery of new chemical entities and will shed important insight into the role of bioactive molecules in human disease.