Untargeted Metabolomics Strategies-Challenges and Emerging Directions.
Metabolites are building blocks of cellular function. These species are involved in enzyme-catalyzed chemical reactions and are essential for cellular function. Upstream biological disruptions result in a series of metabolomic changes and, as such, the metabolome holds a wealth of information that is thought to be most predictive of phenotype. Uncovering this knowledge is a work in progress. The field of metabolomics is still maturing; the community has leveraged proteomics experience when applicable and developed a range of sample preparation and instrument methodology along with myriad data processing and analysis approaches. Research focuses have now shifted toward a fundamental understanding of the biology responsible for metabolomic changes. There are several types of metabolomics experiments including both targeted and untargeted analyses. While untargeted, hypothesis generating workflows exhibit many valuable attributes, challenges inherent to the approach remain. This Critical Insight comments on these challenges, focusing on the identification process of LC-MS-based untargeted metabolomics studies-specifically in mammalian systems. Biological interpretation of metabolomics data hinges on the ability to accurately identify metabolites. The range of confidence associated with identifications that is often overlooked is reviewed, and opportunities for advancing the metabolomics field are described. Graphical Abstract ᅟ.
Department of Chemistry, Vanderbilt University, Nashville, TN, 37235, USA.|Center for Innovative Technology, Vanderbilt University, Nashville, TN, 37235, USA.|Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37235, USA.|Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN, 37235, USA.
Alexandra C
AC
Schrimpe-Rutledge
Department of Chemistry, Vanderbilt University, Nashville, TN, 37235, USA.|Center for Innovative Technology, Vanderbilt University, Nashville, TN, 37235, USA.|Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37235, USA.|Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN, 37235, USA.
Simona G
SG
Codreanu
Department of Chemistry, Vanderbilt University, Nashville, TN, 37235, USA.|Center for Innovative Technology, Vanderbilt University, Nashville, TN, 37235, USA.|Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37235, USA.|Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN, 37235, USA.
Stacy D
SD
Sherrod
Department of Chemistry, Vanderbilt University, Nashville, TN, 37235, USA. john.a.mclean@vanderbilt.edu.|Center for Innovative Technology, Vanderbilt University, Nashville, TN, 37235, USA. john.a.mclean@vanderbilt.edu.|Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37235, USA. john.a.mclean@vanderbilt.edu.|Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN, 37235, USA. john.a.mclean@vanderbilt.edu.
John A
JA
McLean
D000818:Animals; D002853:Chromatography, Liquid; D055442:Metabolome; D055432:Metabolomics / Q000639:trends*; D053719:Tandem Mass Spectrometry
Bioinformatics; Discovery; Global; Identification; Metabolomics; Targeted; Untargeted; Validation