Toward Computationally Complete Spatial Omics
Multimodal spatial omics has transformed biology by mapping molecular complexity within intact tissues, yet current technologies remain limited in the number of modalities measured simultaneously and often produce lower-quality data than single-modality assays. We present COSIE, a computational framework that generates high-resolution, multilayered molecular landscapes across tissue sections, individuals, and platforms. COSIE integrates histology, epigenome, transcriptome, proteome, and metabolome into a unified representation. Applied to 12 datasets spanning 10 spatial technologies, eight modalities, and nine tissue types, ranging from thousands of spots to millions of cells, COSIE outperforms existing methods. It resolves tissue structures, enhances noisy measurements, predicts unmeasured modalities, and captures dynamic processes. In human tumors, COSIE identifies invasive subregions linked to clinical outcomes and predicts spatial gene expression in TCGA samples using only histology images. By transforming fragmented data into comprehensive spatial maps, COSIE advances computationally complete spatial omics and the creation of digital tissue twins for biomedicine.
Authors
- Nadja Sachs (ORCID: https://orcid.org/0000-0001-8031-017X)
- Amelia Schroeder
- Fuduan Peng (ORCID: https://orcid.org/0000-0003-4068-530X)
- Xiaokang Yu
- Chia-Yu Chen (ORCID: https://orcid.org/0000-0003-1342-2184)
- Laith Z. Samarah (ORCID: https://orcid.org/0000-0003-1358-2727)
- Stephanie Pei Tung Yiu (ORCID: https://orcid.org/0000-0002-1792-247X)
- Wei Li (ORCID: https://orcid.org/0000-0003-0425-1723)
- Ming Li (ORCID: https://orcid.org/0000-0002-8427-605X)
- Alex K. Shalek
- Niklas Blank
- Xuyu Qian
- Humam Kadara
- Sizun Jiang
- Liran Mao
- Zihao Chen
- Lorena Gomez
- Ye Won Cho
- Joshua Rabinowitz
- Yunhe Liu
- Shunzhou Jiang
- Idania Lubo
- Linghua Wang
- David M Kim
- Kaitian Jin
- Luisa Maren Solis Soto
- Yanxiang Deng
- Lars Maegdefessel
- Anki Basak
- Christoph Thaiss
Institutions
- Beth Israel Deaconess Medical Center (US)
- Children's Hospital of Philadelphia (US)
- The University of Texas MD Anderson Cancer Center (US)
- Harvard University (US)
- Princeton University (US)
- Columbia University Irving Medical Center (US)
- TUM Klinikum (DE)
- Karolinska Institutet (SE)
- Palo Alto Institute (US)
- German Centre for Cardiovascular Research (DE)
- Ludwig Cancer Research (US)
- Massachusetts Institute of Technology (US)
- Columbia University (US)
- University of Pennsylvania (US)
- Philadelphia University (US)
- Stanford University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-03-05
- DOI
- https://doi.org/10.64898/2026.03.03.709303
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00