Networks have proven time and again to be highly versatile tools in modeling biological interactions, finding useful applications in basic and clinical research alike. In the majority of these applications, however, the inherently context-specific nature of these interactions remains largely unaccounted for, despite increasingly granular and
multi-dimensional biomedical data. In this seminar, I will present two network-based methods that we are currently developing to address, in a context-aware manner, present challenges related to computational drug discovery and cellular signaling. I will first talk about our method that uses a large-scale pharmacogenomic database to build over 50 cell type-specific gene-perturbation networks and integrates these networks with diverse disease phenotypes and cheminformatic data for a nested prioritization of cell lines and perturbations. I will demonstrate that our method outperforms currently available techniques in terms of predictive power and offers the potential to be a feasible blueprint for a cell type-specific drug discovery and repositioning platform. I will then switch over to a multilayer network-based statistical framework that we are building that uses high-dimensional edges, or multilinks, to model crosstalk between signaling pathways. I will show that using statistically overrepresented multilinks as proxies of crosstalk results in better identification of signaling crosstalk compared to single layer-based methods, suggesting the utility of the multilayer modeling of signaling crosstalk, with potential future applications to extend our approach to tissue- and disease-specific crosstalk.

Arda Halu is an Instructor in Medicine and Associate Scientist at the Channing Division of Network Medicine, Brigham and Women’s Hospital (BWH) and Harvard Medical School (HMS). His research interests lie at the intersection of network science, computational biology, genomics and systems medicine. Prior to joining the Faculty of Medicine at HMS, he was a Postdoctoral Fellow at BWH/HMS (2015-2020) and a Postdoctoral Associate at the Massachusetts Institute of Technology (2014-2015). He obtained his PhD in Physics at Northeastern University, Boston, in 2014 (supervised by Dr. Ginestra Bianconi), and holds MS and BS degrees in Physics from Bogazici University in Istanbul, Turkey. Dr. Halu is a recipient (2020-2025) of the Mentored Quantitative Research Career Development Award (K25) from the National Heart, Lung, and Blood Institute, National Institutes of Health.