Changes in transcription factor levels, epigenetic status, splicing kinetics and mRNA degradation can each contribute to changes in the mRNA dynamics of a gene. We present a novel method to identify which of these processes is changed in cells in response to external signals or as a result of a diseased state. The method employs a mathematical model, for which the kinetics of gene regulation, splicing, elongation and mRNA degradation were estimated from experimental data of transcriptional dynamics. The time-dependent dynamics of several species of adipose differentiation-related protein (ADRP) mRNA were measured in response to ligand activation of the transcription factor peroxisome proliferator-activated receptor δ (PPARδ). We validated the method by monitoring the mRNA dynamics upon gene activation in the presence of a splicing inhibitor. Our mathematical model correctly identifies splicing as the inhibitor target, despite the noise in the data.
Oxford Open
Nucleic acids research
From Data to Models: New Bioinformatics Methods and Tools for Data-Driven Predictive Dynamic Modelling in Biotechnological Applications
Evolutionary Intelligence

Rybakova, K. N., Tomaszewska, A., van Mourik, S., Blom, J., Westerhoff, H., Carlberg, C., & Bruggeman, F. (2014). Tracing the molecular basis of transcriptional dynamics in noisy data by using an experiment-based mathematical model . Nucleic acids research. doi:10.1093/nar/gku1272