SteatoSITE: an Integrated Gene-to-Outcome Data Commons for Precision Medicine Research in NAFLD

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Modelling predicts that by 2030 over 100 million people will be diagnosed with the progressive inflammatory NAFLD subphenotype, nonalcoholic steatohepatitis (NASH). The pathobiology of NAFLD is complex, disease progression is variable and unpredictable, and there are no qualified prognostic biomarkers or licensed pharmacotherapies. It represents an unmet precision medicine challenge. We established a retrospective multicentre national cohort of 940 patients, across the complete NAFLD disease spectrum, integrating quantitative digital pathology, hepatic RNA-sequencing and 5.67 million days of longitudinal electronic health record follow-up into a secure, searchable platform (SteatoSITE) to accelerate new biomedical discoveries in NAFLD. Here we show that disease stage-specific transcriptional profiles, gene ontology and pathway enrichment analyses, and bulk tissue cell-type deconvolution using single-cell RNA-sequencing data uncover new cell and molecular targets that can be linked to the time-stamped clinical outcomes for rational biomarker and drug development.