QSB: Computational Modeling of Genome-wide Transcriptional Regulation

  • Pugh, Frank (PI)
  • Azmy, Yousry Y. (CoPI)

Project: Research project

Project Details

Description

Pugh

0425662

The primary goal of this research is to construct a computational model that replicates changes in gene expression in response to experimental perturbations of the transcription machinery. Hence, there is a strong coupling between the construction and validation effort for the computational model on the one hand and experimental observations on the other. As elaborated in the body of the proposal, the number of potential experiments that can be attempted to fully test all possible response permutations is beyond exhaustive experimentation or computation, necessitating the following simplifying compromise: (1) Construction and validation mode: The trove of existing experimental results will be employed in this mode. A portion of the data will be used in constructing the model, i.e. computing its parameters, then the remaining data will be used to validate and refine the constructed model, (2) Predictive mode: The model will be executed for new settings not in the experimental database that will then be verified experimentally. Some of the cases will break the model and new parameters will be computed to satisfy previously catalogued experiments. When a new set of parameters cannot be found this will indicate deficiency of the model and a new connection scheme will be sought and verified. The validation sequence is then repeated, and (3) Prospective mode: An important utility of the computational model is to guide future experiments by identifying new experiments to perform that are deemed interesting from the biochemical/ biological viewpoint based on certain criteria. Achievement of these objectives and the computational tools that enable them will establish the framework for a comprehensive model of transcription complex assembly in yeast.

StatusFinished
Effective start/end date9/15/048/31/08

Funding

  • National Science Foundation: $499,526.00

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