Nika Vafadari Week 10

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Electronic Lab Notebook Week 10

Purpose

Preparation for jornal Club 2

Biological Terms

Outline

Main Result Presented in Paper
Significance of Work
Introduction

Regulation of gene expression

    • DNA (gene) —> RNA molecules and functional proteins
    • For regulation to occur—> transcriptional regulatory proteins must recognize promotor sequence in order to bind RNA polymerase and start transcription reaction to environmental stress & cell development can lead to modification/change in gene expression

DNA microarrays

    • visualize and record change in gene expression over the time (duration of cell cycle/developmental processes) by looking at the change in mRNA levels
    • to understand relationship between regulators/ target genes and the network interactions that result
    • these networks are what lead to changes in the amount of RNA/ changes in gene expression

Cell cycle control

    • well studied in Saccharomyces cerevisiae leading to the establishment of large transcriptomic databases that include the changes in RNA synthesis throughout the cell cycle
    • Goal: collect microarray gene expression data (genome wide) pertaining to cell cycle in yeast—> analyze through clustering methods —> identify cell cycle controlled genes


Methods

Previous methods

  • grouped genes based on which promoter the transcriptional regulators bind to instead of similarity in pattern of gene expression
  • identified potential networks through the use of differential equations in order to develop a generalized linear model to predict the pattern of transcription of a specific gene
    • Wolf and Wang: used fuzzy logic
    • Nachman et al.: used dynamic Bayesian networks with a kinematic model
    • Bar-Joseph: used gene expression analysis and genomic info alongside one another
    • Wang et al. and Makita et al.: extending the work of Bar-Joseph, incorporated promoter sequence analysis into gene expression analysis

Alternative method presented in paper

  • replaces linear model with model using nonlinear differential equation
    • Procedure applied
      • starts by selecting set of potential regulators —> 184 chosen
      • select set of specific target genes within S. cerevisiae —> 40 genes selected
      • select genes from within the set of potential regulators to apply model to in order to see if it fits the gene expression profile of the specified gene correctly
      • repeat for selected target genes and potential regulators
      • determine true regulators by identifying regulators that model the profile of the target gene correctly
Results

Dynamic model of transcriptional control

  • Model Assumptions
    • the relationship/ interaction between regulators and target genes is repeated over time
    • combinatorial control by regulators exists/causes change in gene expression of a target gene
  • Equation 1
  • Equation 2
  • Equation 3
  • Equation 4
  • Equation 5
  • Equation 6
  • Equation 7

Acknowledgments

  • Various sites referenced linked and referenced next to each term were used to define the biological terms.
  • The equations, figures and key info pertaining to the construction of the model and execution of the experiment were copied and pasted from the article referenced below.
  • Except for what is noted above, this individual journal entry was completed by me and not copied from another source.

References

  • Dahlquist, Kam D. (2017) BIOL398-05/S17:Week 10. Retrieved from http://www.openwetware.org/wiki/BIOL398-05/S17:Week_10 on 27 March 2017.
  • Vu, T. T., & Vohradsky, J. (2007). Nonlinear differential equation model for quantification of transcriptional regulation applied to microarray data of Saccharomyces cerevisiae. Nucleic acids research, 35(1), 279-287. doi: 10.1093/nar/gkl1001


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