Discovering the transcriptional regulatory architecture of the metabolism has been an important topic to understand the implications of transcriptional fluctuations on metabolism. The reporter algorithm (RA) was proposed to determine the hot spots in metabolic networks, around which transcriptional regulation is focused owing to a disease or a genetic perturbation. Using a z-score-based scoring scheme, RA calculates the average statistical change in the expression levels of genes that are neighbors to a target metabolite in the metabolic network. The RA approach has been used in numerous studies to analyze cellular responses to the downstream genetic changes. In this article, we propose a mutual information-based multivariate reporter algorithm (MIRA) with the goal of eliminating the following problems in detecting reporter metabolites: (i) conventional statistical methods suffer from small sample sizes, (ii) as z-score ranges from minus to plus infinity, calculating average scores can lead to canceling out opposite effects and (iii) analyzing genes one by one, then aggregating results can lead to information loss. MIRA is a multivariate and combinatorial algorithm that calculates the aggregate transcriptional response around a metabolite using mutual information. We show that MIRAs results are biologically sound, empirically significant and more reliable than RA.