Johnson and O'Neil LMU Symposium 2016: Difference between revisions

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==Abstract Draft==
==Abstract Draft==


'''Modeling the dynamics of a 21-gene, 50-edge gene regulatory network controlling the transcriptional response to cold shock in ''Saccharomyces cerevisiae'' using GRNmap'''
'''Evaluating Hap4's Role in the Gene Regulatory Network that Controls the Response to Cold Shock in ''Saccharomyces cerevisiae'' using GRNmap'''


Gene expression is regulated by proteins called transcription factors which can either repress or activate a gene’s transcriptional output. A gene regulatory network (GRN) consists of a set of transcription factors that regulate the level of expression of genes encoding other transcription factors. The dynamics of a GRN show how gene expression in the network changes over time. A MATLAB software package called GRNmap uses ordinary differential equations to model the dynamics of medium-scale GRNs from budding yeast, ''Saccharomyces cerevisiae''. The program estimates production rates, expression thresholds, and regulatory weights for each transcription factor in the network based on DNA microarray data using a penalized least squares function. DNA microarray data for 6189 yeast genes was obtained from the Dahlquist lab where they subjected yeast to cold shock at 13°C and measured gene expression at three time points (after 15, 30, and 60 minutes of cold shock). We performed a modified ANOVA to determine which genes had a log<sub>2</sub> fold change significantly different than zero at any of the timepoints studied. We found that xxx genes were significantly changed at an adjusted p value of < 0.05. These genes were then submitted to the YEASTRACT database to determine which transcription factors reglated themWe generated xxx candidate GRNs that ranged in size from 35 genes and 104 edges to 15 genes and xx edges.  From this analysis we expect to gain insight into potential missing genes in the gene regulatory network that controls the cold shock response in yeast. Our working code is available on the GRNmap page ( http://kdahlquist.github.io/GRNmap/), and visualization of the network is available on GRNsight ( http://dondi.github.io/GRNsight/).
Gene expression is regulated by proteins called transcription factors which either repress or activate a gene’s transcriptional output. A gene regulatory network (GRN) is a set of transcription factors that regulate the level of expression of genes encoding other transcription factors. The dynamics of a GRN show how gene expression in the network changes over time. A MATLAB software package called GRNmap uses ordinary differential equations to model the dynamics of medium-scale GRNs from budding yeast, ''Saccharomyces cerevisiae''. The program estimates production rates, expression thresholds, and regulatory weights for each transcription factor in the network based on DNA microarray data. Data were obtained from a yeast strain deleted for the Hap4 transcription factor subjected to cold shock at 13°C for 15, 30, and 60 minutes. A modified ANOVA showed that 1794 genes had a log<sub>2</sub> fold change significantly different than zero at any of the timepoints. These genes were submitted to the YEASTRACT database to determine their transcription factors regulatorsFrom this we generated 32 candidate GRNs that ranged in size from 35 genes, 102 edges to 15 genes, 28 edges.  We then estimated and compared the parameter values for production rates, expression thresholds, and regulatory weights for each GRN. A comparison of the actual least squares error to the minimum theoretical least squares error allowed us to evaluate which size network best explains gene expression.  From this analysis we have gained insight into Hap4's role in the gene regulatory network that controls the cold shock response in yeast.
 
Word count: 330


Required word count: 250
Required word count: 250
Actual word count: 249

Latest revision as of 20:06, 11 February 2016

Abstract Draft

Evaluating Hap4's Role in the Gene Regulatory Network that Controls the Response to Cold Shock in Saccharomyces cerevisiae using GRNmap

Gene expression is regulated by proteins called transcription factors which either repress or activate a gene’s transcriptional output. A gene regulatory network (GRN) is a set of transcription factors that regulate the level of expression of genes encoding other transcription factors. The dynamics of a GRN show how gene expression in the network changes over time. A MATLAB software package called GRNmap uses ordinary differential equations to model the dynamics of medium-scale GRNs from budding yeast, Saccharomyces cerevisiae. The program estimates production rates, expression thresholds, and regulatory weights for each transcription factor in the network based on DNA microarray data. Data were obtained from a yeast strain deleted for the Hap4 transcription factor subjected to cold shock at 13°C for 15, 30, and 60 minutes. A modified ANOVA showed that 1794 genes had a log2 fold change significantly different than zero at any of the timepoints. These genes were submitted to the YEASTRACT database to determine their transcription factors regulators. From this we generated 32 candidate GRNs that ranged in size from 35 genes, 102 edges to 15 genes, 28 edges. We then estimated and compared the parameter values for production rates, expression thresholds, and regulatory weights for each GRN. A comparison of the actual least squares error to the minimum theoretical least squares error allowed us to evaluate which size network best explains gene expression. From this analysis we have gained insight into Hap4's role in the gene regulatory network that controls the cold shock response in yeast.

Required word count: 250 Actual word count: 249