A Bioinformatic Analysis of Gene Expression Networks in Genetic – and Diet – Manipulated Mice (DSI-SRP)
This DSI-SRP fellowship funded Nilai Vemula to work in the laboratory of Professor Mark Magnuson in the Department of Molecular Physiology and Biophysics during the summer of 2019. Nilai anticipates graduating in 2022 with a major in Physics.
The project funded by this fellowship aimed to better understand the divergent effects of metabolic stress on pancreatic beta-cell gene expression, we performed iterative weighted gene correlation network analysis (iterativeWGCNA) on 31 different RNA-Seq datasets collected from male and female mice that had been metabolically stressed by excitotoxicity (via chronic membrane depolarization due to the absence of Abcc8), overnutrition (via a high fat diet), and the combination of both stresses. IterativeWGCNA grouped the responsive genes into 33 modules of 40 to 561 genes that clustered into four larger meta-modules and 11 independent modules. Inspection of the network revealed the dominant effect of excitotoxicity, with the effects of overnutrition and sex being less impactful. These findings both confirm and extend previous studies that have established the importance of intracellular Ca2+ concentration and Ca2+-signaling for maintaining beta-cell function and identity. They also indicate that the effects of overnutrition and sex are smaller than that of excitotoxicity.
In addition to receiving support through a DSI-SRP fellowship, this project was supported and facilitated by the DSI Data Science Team through their regular summer workshops and demo sessions.