Ranking E. coli’s ammonium transport and assimilation networks

Researchers of AIMMS and their Japanese colleagues published their research about rank competing explanations

05/01/2019 | 9:44 AM

Researchers of the VU University Amsterdam and the Kyushu Institute of Technology (Japan) published (in npj Systems Biology and Applications) a new way to go about science: rank competing explanations.  They illustrated this for the complex networks enabling nitrogen metabolism in Escherichia coli.

E. coli is capable of growing in media with ammonium present in the low µM range, because of the transporter AmtB. The energetics of the transport remains a matter of debate. A quantitative model appeared necessary for a decision on the controversy. Given the heterogeneityof the data sets in terms of quality, relevance, and completeness, how can modelers still develop models that are sufficiently realistic to test hypotheses about the ammonium transport?

Maeda & Kurata (KIT) and Westerhoff & Boogerd (AIMMS) developed a novel constrained optimization-based parameter estimation technique that allows the integration of heterogeneous experimental data sets with existing knowledge of variable robustness. The technique enabled the authors to objectively quantify the plausibility of models. They implemented the technique on a supercomputer with a fast genetic algorithm and developed two kinetic models based on either the active or the passive transporter hypothesis.  As training datasets, they employed diverse experimental data from three different expert laboratories. For both models, solution parameter sets were found, indicating that both models could fit the training data. However, the plausibility of the active transporter model was 130 times greater than that of the passive transporter model. The new modeling technology enables decisions on the relative rather than absolute validity of mechanisms in complex biological networks, which may change when more data come in. This may constitute a new paradigm for science.

Find the open access article here.


schematisch e coli ranking

Fig. 1 Schematic diagram of the E. coli ammonium transport and assimilation network.