Comprehensive curation of drug induced mechanistic toxicological processes and adverse outcome pathway in Drug Induced liver Injury (DILI) based on literature review

Drug-induced liver injury (DILI) is one of the most critical concerns and a leading cause of acute liver failure. Over the past decade, predictive toxicology has become a critical aspect in the safety evaluation of drugs as well as playing an important role in both pre-and post-marketing of drugs, including market withdrawal due to predicted as well as reported hepatotoxicity associated with liver failure.

The Adverse Outcome Pathway (AOP) framework is an important tool, which represents the link between molecular initiating events and an adverse outcome, such as hepatotoxicity, steatosis, cholestasis, etc., through a number of intermediate key events, at the tissue, as well as organ level, based on existing knowledge. We have implemented a thorough literature curation process to extensively cover the DILI AOP. The curation approach includes strategically generating keywords to select positive articles from the literature, followed by manual curation. The longitudinal spreadsheet-based curation template we use was designed to cover the flow of mechanistic correlation of information from molecular level to key events (or phenotypes), adverse outcomes and diseases, associated with clinical as well as preclinical studies. This literature-based comprehensive curation and construction of an AOP simplifies and facilitates liver toxicity prediction and the safety evaluation of drugs.

Presenter: Jesintha Maniraja (Curadigm Datalytics)

Jesintha Maniraja, Ph.D. is a senior scientific leader and entrepreneur with a strong scientific and biomedical content management background with solid business insight. Dr. Maniraja is the CEO and Head of Curation Strategy at Curadigm Datalytics, and a well-known curation leader in the life science community, with 18+ years of experience in biomedical content management, data curation, knowledgebase development, data harmonization, and product development. She has worked for international organizations, such as the University of Brussels, Belgium, BIOBASE, Germany, QIAGEN, India, and Excelra, India, as the Head of Curation and Products. She has predominantly worked on the following scientific and therapeutic areas: gene variants, biomarkers, pathways and networks, transcription factors and regulation, pharmacogenomics, oncology, neuronal, CVD, respiratory diseases, autoimmune and rare diseases, metabolic disorders, lung cancer, liver, and pulmonary toxicities, obesity, ILD, primary immunodeficiency diseases, brain tumors, antiemetics, and PGX.