Natalie Williams Week 10

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Outline of Nonlinear differential equation model for quantification of transcriptional regulation applied to microarray data of Saccharomyces cerevisiae

Introduction

  • Gene regulation makes a working copy of the genetic information of DNA sequences into proteins and/or functional RNAs.
    • Promoting regions must be recognized by transcription regulatory proteins which bind RNA polymerase to the DNA strand.
  • Microarray developments have made it easier to follow the changes of the cell's gene expression over time.
    • Analyzing this microarray data, we could better understand the relationships between genes and their transcription factor regulators.
    • Because these relationships collectively form a network among the genes, it should be possible to construct networks by studying the results of microarray data.
  • Budding yeast, Saccharomyces cerevisiae, has been studied extensively in the lab.
    • There is a lot of knowledge about its genome.
    • Expression data was collected and analyzed to figure out what genes were being used at a specific stage of the cell cycle.
    • Genes were grouped based on where their regulators bound to promoter regions.
  • Methods in which networks were produced previously:
    • A generalized linear model was going to be created to described regulators and guess the pattern of regulators and their target genes.
    • A kinetic model with Bayesian networks was used to predict gene regulatory networks as well as the proteins that regulate genes expression.
    • Including both information from the genome and gene expression data named another method to predicting networks.
      • Another research furthered this method by using promoter regions or the sigma factor.
  • An alternative method used in this paper:
    • A model based on nonlinear differential equation model was used.
      • It called for all potential regulators
      • Genes from a group of potential regulators are picked and the model is applied to try to fit the gene expression results of the target genes.
      • This is done for all potential regulators
  • In this model:
    • There were 40 target genes;
    • 184 possible regulators were identified;
    • The data were analyzed using a linear model; and,
    • Results from the linear model were compared to that of the nonlinear differential equation system to see how well it predicted the target genes' profiles.


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