Determination of the Active set of Elementary Flux Modes (EFMs) using Metabolic Flux Data

From a metabolic network alone, we can, in principle, compute all independent possible pathways through the cell, referred to as elementary flux modes (EFMs) [1]. Several algorithms have already been used to determine which set of pathways/EFMs is active [2,3]. A shortcoming of all these methods is that they require the entire set of EFMs as an input, which limits their application to relatively small networks. This is because the problem is NP-hard increasing computational complexity such that solution time stalls (becomes impractically large) for mid- to large scale networks. The aim of this project is to compute the active set of EFMs for networks of genome scale size through use of experimental metabolic flux data from various experiments. Conceptually, this reduces the dimensionality of the problem; rather than determining all EFMs we wish to determine the active set, thereby reducing the computational complexity of the problem.
The project hopes to report on insights into the regulation of cellular pathways, whilst considering the possibility of media design improvement and cell engineering. However, most importantly, the project aims to produce an algorithm for the genome scale data to determine the active set of EFMs. Due to the nature of the research it may also be possible to discover pathways to describe the not yet observed behaviour of the flux in the cell.
To undertake this research; computational methods will be learned and trialled on small scale networks. From here it will be possible to increase the size of the network and develop better modelling techniques to cope with the genome scale.


1. Schuster,S; Dandekar,T and Fell,DA (1999), Trends Biotechnology 17(2), 53-60.
2. von Stosch,M; Rodrigues de Azevedo,C; Luis,M; Feyo de Azevedo,S and Oliveira,R (2016), BMC Bioinformatics, 17:200.
3. Folch-Fortuny,A; Marques,R; Isidro,IA; Oliveira,R; Ferrer,A (2016), Molecular Biosystems 12(3), 737-46.