B. Dai, Y. Yan, Z. Wang, Y. Liang, S. Li, P. Hu, X. Yang, C. Wang, L. Yi, C. Sun, J. Huang, X. Zhou, H. Chen, D. Zhang, Q. Zou, Y. Du, Z. Hu, Y. Xing, G. Cao, Z. Feng, J. Feng, S. Xu, W. Hu, Y. Zuo, B.-Z. Qian, Z. Yuan
Establishing a unified physical and molecular coordinate system from fragmented multi-modal data is a longstanding challenge in biology. Here, we present MAPS, a modality-agnostic platform for spatial biology comprising (1) MAPS-alignment for ultrafast alignment of any modality, (2) MAPS-integration for both anchored and unanchored integration across orthogonal modalities for 3D multi-modal reconstruction, and (3) MAPS-Explorer for large-scale interactive 3D analysis. MAPS outperformed existing methods across extensive benchmarks on 34 datasets spanning 16 technology platforms and 6 modalities, while delineating fine-grained multi-modal tissue architectures across diverse biological systems in mouse and human. At cross-consortium scale, MAPS integrated 434 slices comprising 21 million cells from 18 atlases and 5 modalities to construct the most comprehensive 3D multi-modal mouse brain atlas. At individual laboratory scale, MAPS empowered routine 2D spatial assays to reconstruct continuous 3D multi-modal landscapes of human hepatocellular carcinoma, revealing the limitations of 2D spatial relationships and uncovering depth-dependent immune-state transitions.