xNNPCD identifies regulators of programmed cell death by integrating perturbation transcriptomes with cancer dependency profiles (opens in new tab)

Programmed cell death (PCD) encompasses multiple regulated processes whose dysregulation shapes cancer fitness, yet current computational studies largely use known PCD genes for prognosis rather than discovering regulators. We developed xNNPCD, an interpretable neural-network framework that links CRISPR-Cas9 perturbation signatures from CMap to gene dependency profiles from DepMap. The model constrains hidden neurons to five PCD pathways and iteratively refines a prior gene-pathway mask matri...