The precision medicine process for treating rare disease using the artificial intelligence tool mediKanren

Abstract

There are over 6,000 different rare diseases estimated to impact 300 million people worldwide. As genetic testing becomes more common practice in the clinical setting, the number of rare disease diagnoses will continue to increase, resulting in the need for novel treatment options. Identifying treatments for these disorders is challenging due to a limited understanding of disease mechanisms, small cohort sizes, interindividual symptom variability, and little commercial incentive to develop new treatments. A promising avenue for treatment is drug repurposing, where FDA-approved drugs are repositioned as novel treatments. However, linking disease mechanisms to drug action can be extraordinarily difficult and requires a depth of knowledge across multiple fields, which is complicated by the rapid pace of biomedical knowledge discovery. To address these challenges, The Hugh Kaul Precision Medicine Institute developed an artificial intelligence tool, mediKanren, that leverages the mechanistic insight of genetic disorders to identify therapeutic options. Using knowledge graphs, mediKanren enables an efficient way to link all relevant literature and databases. This tool has allowed for a scalable process that has been used to help over 500 rare disease families. Here, we provide a description of our process, the advantages of mediKanren, and its impact on rare disease patients.

Functional genomics and small molecules in mitochondrial neurodevelopmental disorders

“…The rich datasets generated for individuals with mitochondrial neurodevelopmental disorders – neuroimaging, clinical phenotyping, genotyping, and potentially multi-omic technologies – may provide an opportunity to use AI to improve precision medicine. Finally, AI may provide opportunities to quickly identify biological pathways and FDA-approved drugs for drug repurposing in mitochondrial neurodevelopmental disorders [ 162 ]. A future in which precision medicine is a reality for all patients with mitochondrial neurodevelopmental disorders is on the horizon.…”

Artificial intelligence for optimizing benefits and minimizing risks of pharmacological therapies: challenges and opportunities

“…This tool has been applied to some pilot studies, facilitating a more rapid identification of new drug candidates and new drug targets by harnessing the potential of Big Data (Chen et al, 2016). Similarly, the Hugh Kaul Institute for Precision Medicine has created mediKanren, an AI-based platform that, using knowledge graphs, allows to efficiently link all relevant literature and databases to identify drugs, genetic targets, and, ultimately, potentially relevant therapeutic options for rare diseases (Foksinska et al, 2022). AI may play a pivotal role in the development and utilization of digital therapeutics (DTx), providing a personalized and data-driven approach to patient care.…”

The Impact of Artificial Intelligence in the Odyssey of Rare Diseases

“…As biomedical discoveries continue to generate big amounts of data, an opportunity emerges for AI to help in translating biomedical knowledge into a format that can be used to identify therapeutic strategies for patients. Recently, The Hugh Kaul Precision Medicine Institute created mediKanren [ 94 ], an AI platform based on knowledge graphs that uses the mechanistic insight of genetic disorders to identify therapeutic strategies, enabling an efficient way to link all relevant literature and databases. The method was tested by analyzing genetic data and publications of two rare disorders related to missense variants in the TMLHE and RHOBTB2 genes, revealing molecular mechanisms and pathways which have provided new therapeutic targets.…”