Detecting sequence dependent transcriptional pauses from RNA and protein number time series
1 Computational Biology and Machine Learning Lab, Center for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK
2 Laboratory of Biosystem Dynamics, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, Tampere, Finland
BMC Bioinformatics 2012, 13:152 doi:10.1186/1471-2105-13-152Published: 28 June 2012
Evidence suggests that in prokaryotes sequence-dependent transcriptional pauses affect the dynamics of transcription and translation, as well as of small genetic circuits. So far, a few pause-prone sequences have been identified from in vitro measurements of transcription elongation kinetics.
Using a stochastic model of gene expression at the nucleotide and codon levels with realistic parameter values, we investigate three different but related questions and present statistical methods for their analysis. First, we show that information from in vivo RNA and protein temporal numbers is sufficient to discriminate between models with and without a pause site in their coding sequence. Second, we demonstrate that it is possible to separate a large variety of models from each other with pauses of various durations and locations in the template by means of a hierarchical clustering and a random forest classifier. Third, we introduce an approximate likelihood function that allows to estimate the location of a pause site.
This method can aid in detecting unknown pause-prone sequences from temporal measurements of RNA and protein numbers at a genome-wide scale and thus elucidate possible roles that these sequences play in the dynamics of genetic networks and phenotype.