A combined AI and cell biology approach surfaces targets and mechanistically distinct Inflammasome inhibitors.

ABSTRACT: Inflammasomes are protein complexes that mediate innate immune responses whose dysregulation has been linked to a spectrum of acute and chronic human conditions, which dictates therapeutic development that is aligned with disease variability. We designed a scalable, physiologic high-content imaging assay in human PBMCs that we analyzed using a combination of machine-learning and cell biology methods. This resulted in a set of biologically interpretable readouts that can resolve a spectrum of cellular states associated with inflammasome activation and inhibition. These methods were applied to a phenotypic screen that surfaced mechanistically distinct inflammasome inhibitors from an annotated 12,000 compound library. A set of over 100 inhibitors, including an array of Raf-pathway inhibitors,

SUBMITTER: Chen D 

PROVIDER: S-EPMC11648265 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature