Integrated Machine Learning Analysis of Biomarkers for Glaucoma Therapy

This study will analyze hundreds of thousands of concomitant molecular alterations to identify those that reflect physiological processes that end up causing glaucoma. One of the main aims is to highlight which changes of metabolism and methylation modifications of the DNA are associated with glaucoma or intraocular pressure elevations. Because there are such potential changes, finding out which are important to glaucoma, or intraocular pressure control, is an arduous task that can only be completed through newly available machine learning techniques. These techniques can discover patterns hidden among many variables, which would take the human eye an impossibly long time to detect.

The purpose of this project is to identify highly variable and modifiable molecular changes that participate in mechanisms causing primary open-angle glaucoma, as immediate targets of novel treatments.

Glaucoma is caused by a combination of adverse external factors and inherited genetic susceptibility. Genetic association studies have identified hundreds of genes, improving our understanding of glaucoma. But genetics discovers only immutable risk factors, which only indirectly can be targeted by novel therapies.Much of its risk is caused by non-heritable, or “environmental” factors. These factors can switch on and off parts of the genome at different times and in different tissues via chemical modifications of DNA (known as epigenetics), which often result in synchronized metabolic alterations. These factors are in principle preventable and modifiable.

This project will identify modifiable changes of metabolism or chemical modifications of the DNA that lead to glaucoma.This project will use powerful machine learning to stack millions of data points acquired through high-throughput platforms (“omics”) in a very large number of individuals to identify robust signals of epigenetic and metabolic changes that together modulate the glaucoma risk. These factors will be compared against catalogues of chemicals and currently known drugs that are known to cause alterations of their levels in the cell and organism and the off-label use of which may immediately benefit glaucoma patient

This project will be the first large scale mechanism of biological components and factors that are known to fluctuate as a result of external (environmental) factors and potentially more amenable to pharmacological intervention. This project will allow us to better understand what happens to the biological processes that start from the genes, are modified by unknown factors in the cell environment and end up causing glaucoma. Many of these intermediate biological links have been studied and may be modified by chemicals, which if identified, can be of potential use to treat glaucoma.

This project will most likely improve our understanding of the molecular cascades that end up with the development of high intraocular pressure and glaucoma in patients. It will identify molecular mediators that vary during the life course and which are likely to be influenced by chemical compounds. This project will search the pool of known substances to identify those that are known to cause biological changes that would counter the changes that are associated with glaucoma.