Abstract
BackgroundElucidating the dynamic behaviour of genetic regulatory networks is one of the most significant challenges in systems biology. However, conventional quantitative predictions have been limited to small networks because publicly available transcriptome data has not been extensively applied to dynamic simulation.ResultsWe present a microarray data-based semi-kinetic (MASK) method which facilitates the prediction of regulatory dynamics of genetic networks composed of recurrently appearing network motifs with reasonable accuracy. The MASK method allows the determination of model parameters representing the contribution of regulators to transcription rate from time-series microarray data. Using a virtual regulatory network and a Saccharomyces cerevisiae ribosomal protein gene module, we confirmed that a MASK model can predict expression profiles for various conditions as accurately as a conventional kinetic model.ConclusionWe have demonstrated the MASK method for the construction of dynamic simulation models of genetic networks from time-series microarray data, initial mRNA copy number and first-order degradation constants of mRNA. The quantitative accuracy of the MASK models has been confirmed, and the results indicated that this method enables the prediction of quantitative dynamics in genetic networks composed of commonly used network motifs, which cover considerable fraction of the whole network.
Highlights
Elucidating the dynamic behaviour of genetic regulatory networks is one of the most significant challenges in systems biology
The regulation of gene G by gene C was employed to compare the microarray data-based semi-kinetic (MASK) method and conventional kinetic model. (b) A log-log scatter plot of the R values of gene C and G. (c) The training data used in estimating the MASK model parameters. (d) The test data used for the validation of the MASK model
We present a microarray data-based semi-kinetic (MASK) method for dynamic simulation of genetic regulatory networks composed of common network motifs
Summary
Elucidating the dynamic behaviour of genetic regulatory networks is one of the most significant challenges in systems biology. Conventional quantitative predictions have been limited to small networks because publicly available transcriptome data has not been extensively applied to dynamic simulation. Modelling the behaviour of genetic regulatory networks has been one of the most significant milestones in systems biology [912]. The dynamic behaviours of genetic networks were quantitatively predicted and analyzed in terms of non-linear ordinary differential equations based on reaction kinetics [13,14,15]. The regulation of gene G by gene C was employed to compare the MASK method and conventional kinetic model. (c) The training data used in estimating the MASK model parameters. (d) The test data used for the validation of the MASK model.
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