Connectogenomics: edges-first spatial biology

Trends Biotechnol. 2025 Nov 6:S0167-7799(25)00419-6. doi: 10.1016/j.tibtech.2025.10.012. Online ahead of print.

Abstract

Spatial omics maps cell types and spatial context together. Current methods fall into two streams: mapping coordinates (where things are) and measuring connections between cells that are in contact or close proximity. We introduce the term connectogenomics as a practical umbrella for sequencing assays that directly record such contacts as a network. Combining coordinates with measured contacts lets us verify whether apparent neighbors truly interact and turn network features - such as contact density or hub centrality - into quantitative readouts. We propose a framework with four complementary tiers and a feedback loop: directly measured molecular contacts can validate coordinate-based analyses, while coordinate maps guide where to prioritize contact measurements. We illustrate this approach in cancer immunotherapy, development, and pooled genetic screens.

Keywords: connectogenomics; graph theory; spatial omics; systems biology; tissue microenvironment.

Publication types

  • Review