title: Detecting sequence dependent transcriptional pauses from RNA and protein number time series.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Computational Biology and Machine Learning Lab, Center for CancerResearch and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK.
authors: Frank
authors: F
authors: Emmert-Streib
authors: Antti
authors: A
authors: Häkkinen
authors: Andre S
authors: AS
authors: Ribeiro
mesh_terms: D003062:Codon / Q000235:genetics; D003627:Data Interpretation, Statistical; D015870:Gene Expression; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D015233:Models, Statistical; D011387:Prokaryotic Cells / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism*; D013269:Stochastic Processes; D014158:Transcription, Genetic
chemical_list: D003062:Codon; D012313:RNA