In Silico Prediction of Blood-Brain Barrier Permeability of Chemical Compounds through Molecular Feature Modeling

Abstract: The introduction of computational techniques to analyze chemical data has given rise to the analytical study of biological systems, known as "bioinformatics". One facet of bioinformatics is using ML technology to detect multivariable trends in various cases. Amongst the most pressing cases is predicting blood-brain barrier (BBB) permeability. The development of new drugs to treat central nervous system disorders presents unique challenges due to poor penetration efficacy across the blood-brain barrier. In this research, we aim to mitigate this problem through an ML model that analyzes chemical features. To do so: (i) An overview into the relevant biological systems and processes as well as the use case is given. (ii) Second, an in-depth literature review of existing computational techniques for detecting BBB permeability is undertaken. From there, an aspect unexplored across current techniques is identified and a solution is proposed. (iii) Lastly, a two-part in silico model to quantify likelihood of permeability of drugs with defined features across the BBB through passive diffusion is developed, tested, and reflected on. Testing and validation with the dataset determined the predictive logBB model's mean squared error to be around 0.112 units and the neuroinflammation model's mean squared error to be approximately 0.3 units, outperforming all relevant studies found.