The Alzheimer's Knowledge Base - A knowledge graph for therapeutic discovery in Alzheimer's Disease research (Preprint)

BACKGROUND As global populations age and become susceptible to neurodegenerative illnesses, new therapies for Alzheimer’s Disease (AD) are urgently needed. Existing data resources for drug discovery and repurposing fail to capture heterogeneous biomedical knowledge that is central to the disease’s etiology and response to drugs. We designed the Alzheimer’s Knowledge Base (AlzKB) to alleviate this need by providing a comprehensive knowledge representation of AD etiology and candidate therapeutics. OBJECTIVE We designed the Alzheimer’s Knowledge Base (AlzKB) to alleviate this need by providing a comprehensive knowledge representation of AD etiology and candidate therapeutics. METHODS We designed AlzKB as a large, heterogeneous graph knowledge base assembled using 22 diverse external data sources describing biological and pharmaceutical entities at different levels of organization (chemicals, genes, anatomy, diseases, etc.). AlzKB uses an OWL 2 ontology to enforce semantic consistency and allow for ontological inference. We provide a public version of AlzKB and allow users to run and modify local versions of the knowledge base. RESULTS AlzKB is freely available at http://alzkb.ai, and currently contains 118,902 entities with 1,309,527 relationships between those entities. To demonstrate its value, we use graph data science and machine learning to (a.) propose new therapeutic targets based on similarities of AD to Parkinson Disease and (b.) repurpose existing drugs that may treat AD. For each use case, AlzKB recovers known therapeutic associations while proposing biologically plausible new ones. CONCLUSIONS AlzKB is a new, publicly available knowledge resource that enables researchers to discover complex translational associations for AD drug discovery. Through two use-cases, we show that it is a valuable tool for proposing novel therapeutic hypotheses based on public biomedical knowledge.