Privacy-preserving federated tensor decomposition of single-cell immune data: recovering multicellular programs across institutions
arXiv:2606.24938v1 Announce Type: cross Abstract: Tensor decomposition of donor $\times$ cell-type $\times$ gene single-cell data recovers multicellular programs: coordinated axes of inter-individual transcriptional variation that span cell types and stratify disease. Yet immune single-cell atlases are increasingly multi-institution, multi-ancestry, and governed, so patient cells often cannot be pooled. We present a federated estimator: each site computes a local program subspace, and a coordinator merges these by stacked SVD under federated global-mean centering, provably equivalent (up to truncation) to the centralised decomposition. This centering makes the merge robust to site-label confounding (program AUC $0.957$ vs.\ $0.861$ for naive per-site centering). Only program subspaces leave a site, and aggregation is compatible with secure aggregation. On a 261-donor systemic lupus erythematosus atlas it recovers the canonical interferon program (ISG enrichment AUC $0.998$; case–control separation $0.958$; bootstrap $\DeltaAUC=-0.000$, 95\% CI $[-0.004,+0.012]$ vs.\ centralised), across institution-scale and multi-ancestry partitions, and across three real COVID-19 sites (subspace correlation $0.989$). It recovers the program when no site observes all cell types (correlation $1.000$, exact by construction), which fixed-feature federated PCA cannot. On an interstitial-lung-disease atlas the recovered program predicts disease better than the best single cell type (AUC $0.96$ vs.\ $0.91$; gap 95\% CI excludes zero) and the advantage survives federation; a liver cohort is consistent ($p=0.005$). Membership-inference shows secure aggregation cuts attack AUC from $0.91$ to $0.61$. The method enables cross-institution, cross-ancestry recovery of multicellular immune programs without sharing cells.