1. Accurate, Fully-Automated NMR Spectral Profiling for Metabolomics.
- Author
-
Ravanbakhsh, Siamak, Liu, Philip, Bjordahl, Trent C., Mandal, Rupasri, Grant, Jason R., Wilson, Michael, Eisner, Roman, Sinelnikov, Igor, Hu, Xiaoyu, Luchinat, Claudio, Greiner, Russell, and Wishart, David S.
- Subjects
NUCLEAR magnetic resonance spectroscopy ,METABOLOMICS ,SMALL molecules ,BODY fluids ,APPROXIMATION theory - Abstract
Many diseases cause significant changes to the concentrations of small molecules (a.k.a. metabolites) that appear in a person’s biofluids, which means such diseases can often be readily detected from a person’s “metabolic profile"—i.e., the list of concentrations of those metabolites. This information can be extracted from a biofluids Nuclear Magnetic Resonance () spectrum. However, due to its complexity, spectral profiling has remained manual, resulting in slow, expensive and error-prone procedures that have hindered clinical and industrial adoption of metabolomics via . This paper presents a system, , which can quickly, accurately, and autonomously produce a person’s metabolic profile. Given a 1D
1 spectrum of a complex biofluid (specifically serum or cerebrospinal fluid), can automatically determine the metabolic profile. This requires first performing several spectral processing steps, then matching the resulting spectrum against a reference compound library, which contains the “signatures” of each relevant metabolite. views spectral matching as an inference problem within a probabilistic graphical model that rapidly approximates the most probable metabolic profile. Our extensive studies on a diverse set of complex mixtures including real biological samples (serum and CSF), defined mixtures and realistic computer generated spectra; involving > 50 compounds, show that can autonomously find the concentration of -detectable metabolites accurately (~ 90% correct identification and ~ 10% quantification error), in less than 5 minutes on a single CPU. These results demonstrate that is the first fully-automatic publicly-accessible system that provides quantitative spectral profiling effectively—with an accuracy on these biofluids that meets or exceeds the performance of trained experts. We anticipate this tool will usher in high-throughput metabolomics and enable a wealth of new applications of in clinical settings. is accessible at . [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF