Correcting for Naturally Occurring Mass Isotopologue Abundances in Stable-Isotope Tracing Experiments with PolyMID

Stable-isotope tracing is a method to measure intracellular metabolic pathway utilization by feeding a cellular system a stable-isotope-labeled tracer nutrient. The power of the method to resolve differential pathway utilization is derived from the enrichment of metabolites in heavy isotopes that are synthesized from the tracer nutrient. However, the readout is complicated by the presence of naturally occurring heavy isotopes that are not derived from the tracer nutrient. Herein we present an algorithm, and a tool that applies it (PolyMID-Correct, part of the PolyMID software package), to computationally remove the influence of naturally occurring heavy isotopes. The algorithm is applicable to stable-isotope tracing data collected on low- and high- mass resolution mass spectrometers. PolyMID-Correct is open source and available under an MIT license.

Automated summary

Stable-isotope tracing is a method used to measure intracellular metabolic pathway utilization by feeding a cell system a stable-isotope-labeled tracer nutrient. An algorithm and tool, PolyMID-Correct, have been developed to computationally remove the influence of naturally occurring heavy isotopes, making the method more accurate and reliable. This algorithm is applicable to data collected on both low- and high-mass resolution mass spectrometers, and PolyMID-Correct is open source under an MIT license.