QBI and Rezo Therapeutics present a seminar with Pedro Beltrao, Associate Professor in the Department of Biology at ETH Zurich. Dr. Beltrao has a Biochemistry degree from University of Coimbra and a PhD in Biology from the University of Aveiro for research conducted at EMBL-Heidelberg under the supervision of Luis Serrano. He did his postdoctoral research at the University of California San Francisco under the supervision of Prof. Nevan Krogan. He was a group leader at EMBL-EBI from 2013 to 2021. 

The number of genetic studies of human traits and diseases has grown over the past years with many thousands of traits analysed by genome-wide association studies or clinical studies. However, connecting trait associated genetic variation to mechanisms through individual proteins and cellular mechanisms remains a challenge. Dr. Beltro's group is interested in building computational pipelines that aim to address this challenge. As an example, they have been developing resources that use cutting-edge AI methods to facilitate the interpretation of protein missense variants. To illustrate this, he will present work on the application of AlphaFold2 in predicting structures of human protein complexes in order to study interface disease related mutations.

In parallel, Dr. Beltrao's group has been using interaction network-based methods to expand and prioritize trait associated genes for over 6000 traits influenced by common and rare mutations, showing how this recovers known disease genes and drug targets. The similarity of network expansion scores identifies groups of traits likely to share a common genetic basis as well as the biological processes underlying this. Through this work they can identify protein complexes and pathways linked to specific diseases or those that influence a large number of human traits. His group aims to develop easy to use computational resources that can improve the workflow of clinicians, with a particular focus on rare disorders to facilitate the classification of variants of unknown significance, prioritization of novel disease genes and novel drug target candidates.

Talk Title: The Genetics of Human Trait Variation – From Atoms to Organism

Host: Nevan Krogan