A novel multislice framework for precision 3D spatial domain reconstruction and disease pathology analysis.

The development of spatial transcriptomics (ST) technologies has revolutionized the way we map the complex organization and functions of tissues. These technologies offer valuable insights into the organization and function of complex biological systems. However, existing methods often focus too narrowly on single modalities or resolutions, thereby hindering the comprehensive capture of multilayered biological heterogeneity. Here, STMSC is proposed as a multislice joint analysis framework featuring a precorrection mechanism that enables the precise identification of complex spatial domains, advancing disease pathology insights. STMSC assumes that precise three-dimensional (3D) reconstruction is essential for an in-depth investigation of tissue components and mechanisms. Incorporating hematoxylin and eosin (H&E) imaging data, STMSC enhances slice alignment accuracy in 3D reconstruction. By deconstructing microenvironments, it reconstructs fine-grained cellular landscapes and emphasizes collective cellular behavior in defining spatial domains. Its graph attention autoencoder with precorrection balances biological information at different levels, improving the accuracy of ST analyses. By analyzing consecutive tissue slices and pathological data sets, STMSC accurately reconstructs 3D structures and provides deeper insights into complex cancer environments. Specifically, STMSC captures intra- and interstage heterogeneity in cancer development, offering novel insights into the complexity of pathological tissue structures.