Metabolome Identification by Systematic Stable Isotope Labeling Experiments and False Discovery Analysis with a Target-Decoy Strategy

Jones, D. R.; Wang, X.; Shaw, T.; Cho, J.-H.; Chen, P.-C.; Dey, K. K.; Zhou, S.; Li, Y.; Kim, N. C.; Taylor, J. P.; Kolli, U.; Li, J.; Peng, J.

doi:10.1101/089904

bioRxiv · 10.1101/089904

Metabolome Identification by Systematic Stable Isotope Labeling Experiments and False Discovery Analysis with a Target-Decoy Strategy

Jones, D. R.·Wang, X.·Shaw, T.·Cho, J.-H.·Chen, P.-C.·Dey, K. K.·Zhou, S.·Li, Y.·Kim, N. C.·Taylor, J. P.·Kolli, U.·Li, J.·Peng, J.

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Abstract

We introduce a formula-based strategy and algorithm (JUMPm) for global metabolite identification and false discovery analysis in untargeted mass spectrometry-based metabolomics. JUMPm determines the chemical formulas of metabolites from unlabeled and stable-isotope labeled metabolome data, and derives the most likely metabolite identity by searching structure databases. JUMPm also estimates the false discovery rate (FDR) with a target-decoy strategy based on the octet rule of chemistry. With systematic stable isotope labeling of yeast, we identified 2,085 chemical formulas (10% FDR), 892 of which were assigned with metabolite structures. We evaluated JUMPm with a library of synthetic standards, and found that 96% of the formulas were correctly identified. We extended the method to mammalian cells with direct isotope labeling and by heavy yeast spike-in. This strategy and algorithm provide a powerful a practical solution for global identification of metabolites with a critical measure of confidence.

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Jones, D. R., Wang, X., Shaw, T., Cho, J.-H., Chen, P.-C., Dey, K. K., Zhou, S., Li, Y., Kim, N. C., Taylor, J. P., Kolli, U., Li, J., Peng, J.. 2016-11-26. Metabolome Identification by Systematic Stable Isotope Labeling Experiments and False Discovery Analysis with a Target-Decoy Strategy. https://doi.org/10.1101/089904

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