Emulator: An elementary metabolite unit (EMU) based isotope simulator enabled by adjacency matrix

Abstract

Stable isotope based metabolic flux analysis is currently the unique methodology that allows the experimental study of the integrated responses of metabolic networks. This method primarily relies on isotope labeling and modeling, which could be a challenge in both experimental and computational biology. In particular, the algorithm implementation for isotope simulation is a critical step, limiting extensive usage of this powerful approach. Here, we introduce EMUlator a Python-based isotope simulator which is developed on Elementary Metabolite Unit (EMU) algorithm, an efficient and powerful algorithm for isotope modeling. We propose a novel adjacency matrix method to implement EMU modeling and exemplify it stepwise. This method is intuitively straightforward and can be conveniently mastered for various customized purposes. We apply this arithmetic pipeline to understand the phosphoketolase flux in the metabolic network of an industrial microbe Clostridium acetobutylicum. The resulting design enables a high-throughput and non-invasive approach for estimating phosphoketolase flux in vivo. Our computational insights allow the systematic design and prediction of isotope-based metabolic models and yield a comprehensive understanding of their limitations and potentials.