A knowledge graph representation learning approach to predict novel kinase-substrate interactions

The human proteome contains a vast network of interacting kinases and substrates. Even though some kinases have proven to be immensely useful as therapeutic targets, a majority are still understudied. In this work, we present a novel knowledge graph representation learning approach to predict novel interaction partners for understudied kinases. Our approach uses a phosphoproteomic knowledge graph constructed by integrating data from iPTMnet, Protein Ontology, Gene Ontology and BioKG. The representation of kinases and substrates in this knowledge graph are learned by performing directed random walks on triples coupled with a modified SkipGram or CBOW model. These representations are then used as an input to a supervised classification model to predict novel interactions for understudied kinases. We also present a post-predictive analysis of the predicted interactions and an ablation study of the phosphoproteomic knowledge graph to gain an insight into the biology of the understudied kinases.

Understanding the factors driving the opioid epidemic using machine learning

In recent years, the US has experienced an opioid epidemic with an unprecedented number of drugs overdose deaths. Research finds such overdose deaths are linked to neighborhood-level traits, thus providing opportunity to identify effective interventions. Typically, techniques such as Ordinary Least Squares (OLS) or Maximum Likelihood Estimation (MLE) are used to document neighborhood-level factors significant in explaining such adverse outcomes. These techniques are, however, less equipped to ascertain non-linear relationships between confounding factors. Hence, in this study we apply machine learning based techniques to identify opioid risks of neighborhoods in Delaware and explore the correlation of these factors using Shapley Additive explanations (SHAP). We discovered that the factors related to neighborhoods environment, followed by education and then crime, were highly correlated with higher opioid risk. We also explored the change in these correlations over the years to understand the changing dynamics of the epidemic. Furthermore, we discovered that, as the epidemic has shifted from legal (i.e., prescription opioids) to illegal (e.g.,heroin and fentanyl) drugs in recent years, the correlation of environment, crime and health related variables with the opioid risk has increased significantly while the correlation of economic and socio-demographic variables has decreased. The correlation of education related factors has been higher from the start and has increased slightly in recent years suggesting a need for increased awareness about the opioid epidemic.