Mining hidden knowledge: Embedding models of cause-effect relationships curated from the biomedical literature

Abstract

We explore the use of literature-curated signed causal gene expression and gene-function relationships to construct un-supervised embeddings of genes, biological functions, and diseases. Our goal is to prioritize and predict activating and inhibiting functional associations of genes, and to discover hidden relationships between functions. As an application, we are particularly interested in the automatic construction of networks that capture relevant biology in a given disease context. We evaluated several unsupervised gene embedding models leveraging literature-curated signed causal gene expression findings. Using linear regression, it is shown that, based on these gene embeddings, gene-function relationships can be predicted with about 95% precision for the highest scoring genes. Function embedding vectors, derived from parameters of the linear regression model, allow to infer relationships between different functions or diseases. We show for several diseases that gene and function embeddings can be used to recover key drivers of pathogenesis, as well as underlying cellular and physiological processes. These results are presented as disease-centric networks of genes and functions. To illustrate the applicability of the computed gene and function embeddings to other machine learning tasks we expanded the embedding approach to drug molecules, and used a simple neural network to predict drug-disease associations.