TY - JOUR
T1 - Evaluation of non-uniform sampling 2D1H–13C HSQC spectra for semi-quantitative metabolomics
AU - Zhang, Bo
AU - Powers, Robert
AU - O’Day, Elizabeth M.
N1 - Funding Information:
Conflicts of Interest: The authors report this work (design of the study, collection analysis and interpretation of data) was supported by Olaris, Inc. Bo Zhang and Elizabeth O’Day are employees at Olaris, Inc. Robert Powers is a member of the Scientific Advisory Board at Olaris, Inc.
Funding Information:
Funding: This research was funded by Olaris, Inc, and, in part, by funding from the National Science Foundation under Grant Number (1660921) to R.P. and the National Institutes of Health Grant Number (P20 GM113126, NIGMS, Nebraska Center for Integrated Biomolecular Communication) to R.P.
PY - 2020/5
Y1 - 2020/5
N2 - Metabolomics is the comprehensive study of metabolism, the biochemical processes that sustain life. By comparing metabolites between healthy and disease states, new insights into disease mechanisms can be uncovered. NMR is a powerful analytical method to detect and quantify metabolites. Standard one-dimensional (1D)1H-NMR metabolite profiling is informative but challenged by significant chemical shift overlap. Multi-dimensional NMR can increase resolution, but the required long acquisition times lead to limited throughput. Non-uniform sampling (NUS) is a well-accepted mode of acquiring multi-dimensional NMR data, enabling either reduced acquisition times or increased sensitivity in equivalent time. Despite these advantages, the technique is not widely applied to metabolomics. In this study, we evaluated the utility of NUS1H–13C heteronuclear single quantum coherence (HSQC) for semi-quantitative metabolomics. We demonstrated that NUS improved sensitivity compared to uniform sampling (US).We verified that the NUS measurement maintains linearity, making it possible to detect metabolite changes across samples and studies. Furthermore, we calculated the lower limit of detection and quantification (LOD/LOQ) of common metabolites. Finally, we demonstrate that the measurements are repeatable on the same system and across different systems. In conclusion, our results detail the analytical capability of NUS and, in doing so, empower the future use of NUS1H–13C HSQC in metabolomic studies.
AB - Metabolomics is the comprehensive study of metabolism, the biochemical processes that sustain life. By comparing metabolites between healthy and disease states, new insights into disease mechanisms can be uncovered. NMR is a powerful analytical method to detect and quantify metabolites. Standard one-dimensional (1D)1H-NMR metabolite profiling is informative but challenged by significant chemical shift overlap. Multi-dimensional NMR can increase resolution, but the required long acquisition times lead to limited throughput. Non-uniform sampling (NUS) is a well-accepted mode of acquiring multi-dimensional NMR data, enabling either reduced acquisition times or increased sensitivity in equivalent time. Despite these advantages, the technique is not widely applied to metabolomics. In this study, we evaluated the utility of NUS1H–13C heteronuclear single quantum coherence (HSQC) for semi-quantitative metabolomics. We demonstrated that NUS improved sensitivity compared to uniform sampling (US).We verified that the NUS measurement maintains linearity, making it possible to detect metabolite changes across samples and studies. Furthermore, we calculated the lower limit of detection and quantification (LOD/LOQ) of common metabolites. Finally, we demonstrate that the measurements are repeatable on the same system and across different systems. In conclusion, our results detail the analytical capability of NUS and, in doing so, empower the future use of NUS1H–13C HSQC in metabolomic studies.
KW - Metabolomics
KW - NUS NMR
KW - Reproducibility
UR - http://www.scopus.com/inward/record.url?scp=85086166332&partnerID=8YFLogxK
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U2 - 10.3390/metabo10050203
DO - 10.3390/metabo10050203
M3 - Article
C2 - 32429340
AN - SCOPUS:85086166332
VL - 10
JO - Metabolites
JF - Metabolites
SN - 2218-1989
IS - 5
M1 - 203
ER -