Genetic Perturbation Modelling for Human Cell Therapy With BRNET.

Abstract

Cellular responses to genetic perturbations are prevalent in wide contexts from the fundamental understandings on pathology to the development of clinical therapies and the discovery of novel drug targets. Nonetheless, the substantial amount of possible perturbation combinations renders wet-lab experiments prohibitively expensive and time-consuming. To address it, the BRNET model is proposed for predicting non-linear transcriptional outcomes where multiple perturbations exist. BRNET integrates prior knowledge with advanced embeddings into a non-stacked neural structure to predict transcriptional responses to both individual and multiple genetic perturbations. For unseen scenarios, BRNET also generalizes well under the corresponding perturbations. Experimental results highlight the capabilities of BRNET, demonstrating promising performance as compared to established deep learning models.