A Quantitative Systems Pharmacology Platform Reveals NAFLD Pathophysiological States and Targeting Strategies.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) has a high global prevalence with a heterogeneous and complex pathophysiology that presents barriers to traditional targeted therapeutic approaches. We describe an integrated quantitative systems pharmacology (QSP) platform that comprehensively and unbiasedly defines disease states, in contrast to just individual genes or pathways, that promote NAFLD progression. The QSP platform can be used to predict drugs that normalize these disease states and experimentally test predictions in a human liver acinus microphysiology system (LAMPS) that recapitulates key aspects of NAFLD. Analysis of a 182 patient-derived hepatic RNA-sequencing dataset generated 12 gene signatures mirroring these states. Screening against the LINCS L1000 database led to the identi

SUBMITTER: Lefever DE 

PROVIDER: S-EPMC9227696 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature