nikunj-gupta / gene-regulatory-network-inference-in-autoimmune-diseases

Gene Regulatory Network Inference

Gene Regulatory Network Inference

Defining Gene Regulatory Networks in Autoimmune Disease

Genome-wide association studies (GWAS) have identified hundreds of genetic polymorphisms associated with the risk of autoimmune diseases. Despite these great strides in mapping, we know little about the biology or functions of these risk factors. Many of the variants identified are themselves associated with gene regulatory elements and are near genes of interest in the immune system. However, the evidence to show their causality is largely absent. Since coding-change variants are less frequently associated in autoimmune diseases, the most favored hypothesis is that these disorders arise from genetic perturbations at one or more regulatory elements affecting the biology of human immune cells.

In this project, we wish to address this gap by systematically defining the gene regulatory network in human immune cells and to understand how sequence polymorphisms or other changes in regulatory elements perturb this network. We will define the regulatory networks present in different human immune cells, identifying the enhancers (E) and transcription factor (TF), binding sites (TFBS) and their transcriptional targets. We will specifically study the transcriptional mechanisms by which risk variants alter binding and transcription at these sites and dysregulate the network.

These experiments are the critical next step in understanding how genetic variation impacts the biology of immune cells to result in disease. Using this strategy, we can understand how genetic risk alleles alter binding in regulatory elements, and how that impacts gene expression and cytokine production in immune cells.

Datasets

https://drive.google.com/drive/folders/1rBmVgJBHUaGT35hlJI3zFBgMQN5CuRpV?usp=sharing