DECIPHER estimates cell-type proportions from bulk omics via disentangled representation learning and supports prognostic stratification in lung adenocarcinoma
The authors present DECIPHER, an end-to-end representation-learning framework for cell-type deconvolution that learns a domain-constant representation (Zc) for deconvolution and a domain-specific representation (Zs) to model domain-associated variation, estimates cell-type proportions from Zc via differentiable non-negative least-squares optimization, shows robust and competitive deconvolution performance across simulated datasets, experimentally generated bulk-cell mixtures, real-world datasets and multiple molecular modalities, and further shows that the learned Zc supports chronological age prediction across independent cohorts and prognostic stratification in lung adenocarcinoma.