MERRIN: MEtabolic regulation rule INference from time series data.

Abstract

Many techniques have been developed to infer Boolean regulations from a prior knowledge network (PKN) and experimental data. Existing methods are able to reverse-engineer Boolean regulations for transcriptional and signaling networks, but they fail to infer regulations that control metabolic networks. We present a novel approach to infer Boolean rules for metabolic regulation from time-series data and a PKN. Our method is based on a combination of answer set programming and linear programming. By solving both combinatorial and linear arithmetic constraints, we generate candidate Boolean regulations that can reproduce the given data when coupled to the metabolic network. We evaluate our approach on a core regulated metabolic network and show how the quality of the predictions depends on the available kinetic, fluxomics or transcriptomics time-series data. Software available at https://github.com/bioasp/merrin. Supplementary data are available at https://doi.org/10.5281/zenodo.6670164.