scAnyOmics: Foundation-Model Distillation for Any-to-Any Completion of Multi-omics Virtual Cells

Abstract

Recent advances in single-cell technologies have enabled the profiling of multiple molecular modalities, including transcriptomics, proteomics, and chromatin accessibility, providing a more comprehensive understanding of cellular states. However, integrating heterogeneous modalities and predicting missing molecular information remain challenging, particularly when paired measurements are limited. Here, we introduce scAnyOmics, a generative framework that distills knowledge from a frozen single-cell foundation model into a multimodal student model. scAnyOmics integrates scRNA-seq, protein-marker measurements, and scATAC-seq into a shared representation, enabling cross-modal prediction and reconstruction of missing modalities. We assembled 690,880 cells from six publicly available studies, covering both paired and partially paired multi-omics measurements, to systematically evaluate its predictive performance. We further evaluated scAnyOmics on held-out donor data, where it outperformed baseline methods across multiple evaluation metrics. Beyond cross-modal reconstruction, we explored its applications in cell-type annotation, perturbation-response prediction, and biological age estimation. Overall, scAnyOmics provides a unified framework for integrating incomplete single-cell multi-omics data and transferring pretrained biological knowledge, supporting the development of virtual cell models across diverse cellular contexts and experimental platforms.