Tensor decomposition of donor
× cell-type
× gene single-cell data recovers \emph{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
ΔAUC=−0.000, 95% CI
[−0.004,+0.012] vs.\ centralised), across institution-scale and multi-ancestry partitions, and across three \emph{real} COVID-19 sites (subspace correlation
0.989). It recovers the program when \emph{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.
Axel Faes, Stephanie M. van den Berg, Maryam Amir Haeri