After the feature presentation: technologies bridging untargeted metabolomics and biology

Abstract

Liquid chromatography/mass spectrometry-based untargeted metabolomics is now an established experimental approach that is being broadly applied by many laboratories worldwide. Interpreting untargeted metabolomic data, however, remains a challenge and limits the translation of results into biologically relevant conclusions. Here we review emerging technologies that can be applied after untargeted profiling to extend biological interpretation of metabolomic data. These technologies include advances in bioinformatic software that enable identification of isotopes and adducts, comprehensive pathway mapping, deconvolution of MS(2) data, and tracking of isotopically labeled compounds. There are also opportunities to gain additional biological insight by complementing the metabolomic analysis of homogenized samples with recently developed technologies for metabolite imaging of intact tissues. To maximize the value of these emerging technologies, a unified workflow is discussed that builds on the traditional untargeted metabolomic pipeline. Particularly when integrated together, the combination of the advances highlighted in this review helps transform lists of masses and fold changes characteristic of untargeted profiling results into structures, absolute concentrations, pathway fluxes, and localization patterns that are typically needed to understand biology.