An understanding of how cells respond to perturbation is essential for biological applications; however, most approaches for profiling cellular response are limited in scope to pre-established targets. Global analysis of molecular mechanism will advance our understanding of the complex networks constituting cellular perturbation and lead to advancements in areas, such as infectious disease pathogenesis, developmental biology, pathophysiology, pharmacology, and toxicology. We have developed a high-throughput multiomics platform for comprehensive, de novo characterization of cellular mechanisms of action. Platform validation using cisplatin as a test compound demonstrates quantification of over 10 000 unique, significant molecular changes in less than 30 days. These data provide excellent coverage of known cisplatin-induced molecular changes and previously unrecognized insights into cisplatin resistance. This proof-of-principle study demonstrates the value of this platform as a resource to understand complex cellular responses in a high-throughput manner.
Bile acids (BAs) are a family of hydroxylated steroids secreted by the liver that aid in the breakdown and absorption of dietary fats. BAs also function as nutrient and inflammatory signaling molecules, acting through cognate receptors, to coordinate host metabolism. Commensal bacteria in the gastrointestinal tract are functional modifiers of the BA pool, affecting composition and abundance. Deconjugation of host BAs creates a molecular network that inextricably links gut microtia with their host. In this review we highlight the roles of BAs in mediating this mutualistic relationship with a focus on those events that impact host physiology and metabolism.
Bile acids serve as one of the most important classes of biological molecules in the gastrointestinal system. Due to their structural similarity, bile acids have historically been difficult to accurately annotate in complex biological matrices using mass spectrometry. They often have identical or nominally similar mass-tocharge ratios and similar fragmentation patterns that make identification by mass spectrometry arduous, normally involving chemical derivatization and separation via liquid chromatography. Here, we demonstrate the use of drift tube ion mobility (DTIM) to derive collision cross section (CCS) values in nitrogen drift gas ( DT CCS N2 ) for use as an additional descriptor to facilitate expedited bile acid identification. We also explore trends in DTIM measurements and detail structural characteristics for differences in DT CCS N2 values between subclasses of bile acid molecules.
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