Illuminating dark gene targets through coevolution

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2025.

Over five thousand genes in the human genome lack functional information. Bioinformatics, artificial intelligence, and big data analysis can speed up uncovering their biological roles. We propose a project exploiting our advanced coevolutionary analysis method, which has the potential to reveal functions for about 10% of TDark genes. In this project we seek to refine our analysis method for precision and sensitivity, ultimately generating a comprehensive list of TDark genes with potential implications in biological pathways and human diseases. To further enhance the precision of functional predictions, we will incorporate structural insights by integrating protein complex interactions inferred through AI-based predictions. An equally important facet of our project involves experimental validation of the functional predictions derived from our analysis. Our initial coevolutionary analysis identified a candidate gene involved in protein glycosylation, a modification that plays a key role in tissue development. This hypothesis will be tested experimentally. Our project aims to elucidate functions for numerous uncharacterized human genes and contribute to our understanding of protein modification in brain development.