Stéphanie M. van den Berg

Axel Faes, Stephanie M. van den Berg, Maryam Amir Haeri

Tensor decomposition of donor $\times$ cell-type $\times$ 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 $Δ\text{AUC}=-0.000$, 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.

Stéphanie M. van den Berg, Ulrich Halekoh, Sören Möller et al.

We develop a supervised deep-learning approach to estimate mutual information between two continuous random variables. As labels, we use the Linfoot informational correlation, a transformation of mutual information that has many important properties. Our method is based on ground truth labels for Gaussian and Clayton copulas. We compare our method with estimators based on kernel density, k-nearest neighbours and neural estimators. We show generally lower bias and lower variance. As a proof of principle, future research could look into training the model with a more diverse set of examples from other copulas for which ground truth labels are available.

Jakob Nolte, Maureen M. J. Guichelaar, Donald E. Bouman et al.

Longitudinal MRI analysis is crucial for predicting disease outcomes, particularly in chronic conditions like hepatocellular carcinoma (HCC), where early detection can significantly influence treatment strategies and patient prognosis. Yet, due to challenges like limited data availability, subtle parenchymal changes, and the irregular timing of medical screenings, current approaches have so far focused on cross-sectional imaging data. To address this, we propose HCCNet, a novel model architecture that integrates a 3D adaptation of the ConvNeXt CNN architecture with a Transformer encoder, capturing both the intricate spatial features of 3D MRIs and the complex temporal dependencies across different time points. HCCNet utilizes a two-stage pre-training process tailored for longitudinal MRI data. The CNN backbone is pre-trained using a self-supervised learning framework adapted for 3D MRIs, while the Transformer encoder is pre-trained with a sequence-order-prediction task to enhance its understanding of disease progression over time. We demonstrate the effectiveness of HCCNet by applying it to a cohort of liver cirrhosis patients undergoing regular MRI screenings for HCC surveillance. Our results show that HCCNet significantly improves predictive accuracy and reliability over baseline models, providing a robust tool for personalized HCC surveillance. The methodological approach presented in this paper is versatile and can be adapted to various longitudinal MRI screening applications. Its ability to handle varying patient record lengths and irregular screening intervals establishes it as an invaluable framework for monitoring chronic diseases, where timely and accurate disease prognosis is critical for effective treatment planning.