FROM SPATIAL MAPS TO MOLECULAR NETWORKS: CONNECTOGENOMICS AS THE NEXT GENERATION OF SPATIAL BIOLOGY

Abstract

Spatial omics has transformed biological research by enabling molecular profiling while preserving the spatial organization of tissues. Unlike conventional omics approaches that often lose spatial context during sample processing, spatial omics integrates molecular information with tissue architecture to investigate cellular heterogeneity, cell–cell communication, and tissue organization. Connectogenomics is an emerging field that combines spatial omics, connectomics, and network biology to characterize molecular and cellular interaction networks within biological systems. By representing biological entities as interconnected nodes and edges, connectogenomics provides a systems-level framework for understanding tissue organization, development, and disease progression. This review examines fundamental concepts of spatial omics, including cellular heterogeneity and cell–cell communication, and discusses limitations of traditional omics that have contributed to the development of spatially resolved approaches. Major sequencing-based technologies, including volumetric DNA microscopy, single-cell Hi-C, and proximity network assays, are discussed alongside computational approaches for dimensionality reduction and network analysis. Applications in cancer research, neuroscience, developmental biology, plant biotechnology, and precision medicine are highlighted. Current challenges include high dimensional data analysis, computational complexity, limited spatial resolution, multi-omics integration, and experimental validation. Finally, emerging opportunities involving artificial intelligence and high-resolution spatial technologies are considered for advancing systems-level understanding of complex biological networks.