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TRIMER: Transcription Regulation Integrated with Metabolic Regulation

ABSTRACT: Summary There has been extensive research in predictive modeling of genome-scale metabolic reaction networks. Living systems involve complex stochastic processes arising from interactions among different biomolecules. For more accurate and robust prediction of target metabolic behavior under different conditions, not only metabolic reactions but also the genetic regulatory relationships involving transcription factors (TFs) affecting these metabolic reactions should be modeled. We have developed a modeling and simulation pipeline enabling the analysis of Transcription Regulation Integrated with Metabolic Regulation: TRIMER. TRIMER utilizes a Bayesian network (BN) inferred from transcriptomes to model the transcription factor regulatory network. TRIMER then infers the probabilities of the gene states relevant to the metabolism of interest, and predicts the metabolic fluxes and their changes that result from the deletion of one or more transcription factors at the genome scale. We demonstrate TRIMER’s applicability to both simulated and experimental data and provide performance comparison with other existing approaches. Graphical abstract Highlights • TRIMER models transcription-regulated metabolism using Bayesian network modeling;• TRIMER integrates prior knowledge (regulatory interaction) with data (expression);• TRIMER enables metabolic behavior prediction for general knockout strategies;• TRIMER includes a simulator as an evaluation platform for similar hybrid models;• TRIMER reliably predicts metabolite yields for both simulated and experimental data. Bioinformatics; Metabolomics; Transcriptomics

SUBMITTER: Niu P

PROVIDER: S-EPMC8567008 | biostudies-literature |

REPOSITORIES: biostudies-literature

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