Combined multivariate analysis and machine learning reveals a predictive module of metabolic stress response in Arabidopsis thaliana

Abiotic stress exposure of plants induces metabolic reprogramming which is tightly regulated by signalling cascades connecting transcriptional with translational and metabolic regulation. Complexity of such interconnected metabolic networks impedes the functional understanding of molecular plant stress response compromising the design of breeding strategies and biotechnological processes. Thus, defining a molecular network to enable the prediction of a plant's stress mode will improve the understanding of stress responsive biochemical regulation and will yield novel molecular targets for technological application. Arabidopsis wild type plants and two mutant lines with deficiency in sucrose or starch metabolism were grown under ambient and combined cold/high light stress conditions. Stress-induced dynamics of the primary metabolome and the proteome were quantified by mass spectrometry. Wild type data were used to train a machine learning algorithm to classify mutant lines under control and stress conditions. Multivariate analysis and classification identified a module consisting of 23 proteins enabling the reliable prediction of combined temperature/high light stress conditions. 18 of these 23 proteins displayed putative protein–protein interactions connecting transcriptional regulation with regulation of primary and secondary metabolism. The identified stress-responsive core module supports prediction of complex biochemical regulation under changing environmental conditions.