Tandem Mass Spectrometry for (13)C Metabolic Flux Analysis: Methods and Algorithms Based on EMU Framework

In the past two decades, (13)C metabolic flux analysis ((13)C-MFA) has matured into a powerful and widely used scientific tool in metabolic engineering and systems biology. Traditionally, metabolic fluxes have been determined from measurements of isotopic labeling by means of mass spectrometry (MS) or nuclear magnetic resonance (NMR). In recent years, tandem MS has emerged as a new analytical technique that can provide additional information for high-resolution quantification of metabolic fluxes in complex biological systems. In this paper, we present recent advances in methods and algorithms for incorporating tandem MS measurements into existing (13)C-MFA approaches that are based on the elementary metabolite units (EMU) framework. Specifically, efficient EMU-based algorithms are presented for simulating tandem MS data, tracing isotopic labeling in biochemical network models and for correcting tandem MS data for natural isotope abundances.