Week 1! We’re starting off the year, and our research, with some literature review to provide ourselves with a little context. Our proposed research plan mainly draws on two papers that laid out the methodological groundwork for us.
The first paper provides pertinent results and insights into the connection between cell motility and schizophrenia. The researchers concluded that cells in patients with schizophrenia are less adhesive and more motile than the cells of healthy control subjects, which was shown to improve with the inhibition of the focal adhesion kinase (FAK) protein. The results of this paper showed that there is a correlation between the altered motility of patient cells and dysregulated gene expression in the FAK signaling pathway within these cells. This paper provided us with the informational basis necessary to choose what kinds of genes we will shine our focus on – schizophrenia and migration association genes.
The second paper essentially laid out the framework for our methodology. In this paper, the researchers used a machine-learning algorithm to predict genes associated with autism spectrum disorder (ASD). They then validated these predicted genes experimentally using an independent-case sequencing study and were further able to demonstrate that this large set of ASD genes played roles in key pathways and brain development.
Pulling from both these papers, we plan to develop a network diffusion algorithm to identify candidate schizophrenia and migration associated genes. We are going to computationally build a list of predicted genes and (hopefully) validate them experimentally. However, before we do that, we need to delve into the nitty gritty of how the autism paper’s machine-learning algorithm was created.
In the paper, it outlines how the approach was based upon a human brain-specific gene functional-interaction network nicknamed GIANT (Genome-scale Integrated Analysis of gene Networks in Tissues). We began with a few initial questions: How is a functional-interaction standard set up? How was GIANT constructed? These questions will no doubt open up a whole new corridor of doors to explore; over the next couple of weeks, our goal is to investigate these questions through literature review and learn more about how we can utilize these tools in the coming year.