A cell line multi-omics AI based approach to screen for the effects of a Qatari RGS4 gene mutation on G protein stabilization in Autism

This project aims to investigate a newly discovered homozygous missense mutation (c.100G>C, p.E34Q) in the RGS4 gene of a Qatari autism patient. This mutation is present in a highly conserved regulatory sequence and is significant because the RGS4 protein plays a crucial role in brain function by regulating G proteins of the Gαo/i class. Mutations in close related genes have also been previously linked to autism. The central objective is to understand how this specific RGS4 mutation alters the function of G proteins and contributes to the patient's condition. The project will encompass obtaining CRISPR-Cas9 engineered cell lines with - and without the RGS4 mutation as well as an RGs4 knockout. These cell lines will then be used to monitor the activity of G proteins and their regulators through a series of targeted biochemical and cellular assays. The project will also measure cell-level proteomics, epigenetics, and transcriptomics. With standard - and AI-driven analyses techniques we will identify significant patterns and differences between the affected and control cell lines. A second research question; if the current large scale omics techniques are also sensitive enough to pick up the specific alterations, which are measured with the targeted G-protein assays, will be a goal as well.

Hamad Bin Khalifa University (HBKU)