MLFPM Winter Symposium 2021:  Nataša Pržulj
Channel: MLFPM ITN
Date: 22/03/2021

MLFPM Winter Symposium on March 11, 2021

Nataša Pržulj (Catalan Institution for Research and Advanced Studies (ICREA) & Barcelona Supercomputing Center & University College London): Between viral targets and differentially expressed genes in COVID-19: the sweet spot for therapeutic intervention

The COVID-19 pandemic is raging. It revealed the importance of rapid scientific advancement towards understanding and treating new diseases. To address this challenge, we build onto our previous methods for extracting new biomedical knowledge from the wiring patterns of systems-level, heterogeneous biomedical networks. These methods are needed due to the flood of molecular and clinical data, measuring interactions between various bio-molecules in and around a cell that form large, complex systems. These systems-level network data provide heterogeneous, but complementary information about cells, tissues and diseases. The challenge is how to mine them collectively to answer fundamental biological and medical questions. This is nontrivial, because of computational intractability of many underlying problems on networks (also called graphs), necessitating the development of approximate algorithms (heuristic methods) for finding approximate solutions.

We will give an overview of the lab’s work. Also, we will focus on explaining how we adapt an explainable artificial intelligence algorithm for data fusion and utilize it on new omics data on viral-host interactions, human protein interactions, and drugs to better understand SARS-CoV-2 infection mechanisms and predict new drug-target interactions for COVID-19. We discover that in the human interactome, the human proteins targeted by SARS-CoV-2 proteins and the genes that are differentially expressed after the infection have common neighbors central in the interactome that may be key to the disease mechanisms. We uncover 185 new drug-target interactions targeting 49 of these key genes and suggest re-purposing of 149 FDA-approved drugs, including drugs targeting VEGF and nitric oxide signaling, whose pathways coincide with the observed COVID-19 symptoms. Our integrative methodology is universal and can enable insight into this and other serious diseases, as well as personalize treatment.

The MLFPM Winter Symposium 2021 is part of the H2020 Marie Curie Innovative Training Network "Machine Learning Frontiers in Precision Medicine" (https://mlfpm.eu). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 813533.