Nils Mechtel

Jiayuan Ding, Jianhui Lin, Ziyang Miao et al.

Pre-trained foundation models (FMs) have begun transforming single-cell genomics, but scaling them raises privacy concerns. Moreover, unlike text data, single-cell data is unordered and exhibits a unique tabular structure that current single-cell FMs overlook. We introduce Tabula, a privacy-preserving FM designed with federated learning (FL) that explicitly models the tabular structure of single-cell data. To deploy Tabula, we further developed Chiron, a decentralized AI agent-enabled platform for collaborative training across institutions without sharing raw data. Beyond strong performance across downstream benchmarks, Tabula reveals combinatorial regulatory logic across diverse biological systems, including hematopoiesis, pancreatic endogenesis, neurogenesis, and cardiogenesis. Using a new scRNA-seq dataset of paired young and aged human fibroblasts, Tabula nominates rejuvenation factors through age- and identity score-guided in silico prioritization, outperforming conventional approaches. Thus, Tabula represents an important advance in single-cell foundation modeling by integrating tabular learning with FL, paving the way toward privacy-preserving virtual cells for human health.

Alexander Holmberg, Nils Mechtel, Wei Ouyang

We present a domain adaptation of video diffusion models to generate highly realistic time-lapse microscopy videos of cell division in HeLa cells. Although state-of-the-art generative video models have advanced significantly for natural videos, they remain underexplored in microscopy domains. To address this gap, we fine-tune a pretrained video diffusion model on microscopy-specific sequences, exploring three conditioning strategies: (1) text prompts derived from numeric phenotypic measurements (e.g., proliferation rates, migration speeds, cell-death frequencies), (2) direct numeric embeddings of phenotype scores, and (3) image-conditioned generation, where an initial microscopy frame is extended into a complete video sequence. Evaluation using biologically meaningful morphological, proliferation, and migration metrics demonstrates that fine-tuning substantially improves realism and accurately captures critical cellular behaviors such as mitosis and migration. Notably, the fine-tuned model also generalizes beyond the training horizon, generating coherent cell dynamics even in extended sequences. However, precisely controlling specific phenotypic characteristics remains challenging, highlighting opportunities for future work to enhance conditioning methods. Our results demonstrate the potential for domain-specific fine-tuning of generative video models to produce biologically plausible synthetic microscopy data, supporting applications such as in-silico hypothesis testing and data augmentation.