“School of Biological Sciences”

Back to Papers Home
Back to Papers of School of Biological Sciences

Paper   IPM / Biological Sciences / 15739
School of Biological Sciences
  Title:   Three-way interaction model to trace the mechanisms involved in Alzheimer’s disease transgenic mice
1.  Nasibeh Khayer
2.  Sayed-Amir Marashi
3.  Mehdi Mirzaie
4.  Fatemeh Goshadrou
  Status:   Published
  Journal: Plos One
  No.:  9
  Vol.:  12
  Year:  2017
  Pages:   https://doi.org/10.1371/journal.pone.0184697
  Supported by:  IPM
Alzheimer's disease (AD) is the most common cause for dementia in human. Currently, more than 46 million people in the world suffer from AD and it is estimated that by 2050 this number increases to more than 131 million. AD is considered as a complex disease. Therefore, understanding the mechanism of AD is a universal challenge. Nowadays, a huge number of disease-related high-throughput “omics” datasets are freely available. Such datasets contain valuable information about disease-related pathways and their corresponding gene interactions. In the present work, a three-way interaction model is used as a novel approach to understand AD-related mechanisms. This model can trace the dynamic nature of co-expression relationship between two genes by introducing their link to a third gene. Apparently, such relationships cannot be traced by the classical two-way interaction model. Liquid association method was applied to capture the statistically significant triplets which are involved in three-way interaction. Subsequently, gene set enrichment analysis (GSEA) and gene regulatory network (GRN) inference were applied to analyze the biological relevance of the statistically significant triplets. The results of this study suggest that the innate immunity processes are important in AD. Specifically, our results suggest that H2-Ob as the switching gene and the gene pair Csf1r, Milr1 form a statistically significant and biologically relevant triplet, which may play an important role in AD. We propose that the homeostasis-related link between mast cells and microglia is presumably controlled with H2-Ob expression levels as a switching gene.
Received: May 16, 2017; Accepted: August 29, 2017; Published: September 21, 2017

Download TeX format
back to top
scroll left or right