Toward a multiomics framework for understanding symbiotic nitrogen fixation

Reducing dependence on synthetic nitrogen fertilizer requires biologically grounded alternatives. Symbiotic nitrogen fixation supplies fixed nitrogen but is restricted to a narrow angiosperm clade, limiting direct deployment in most major nonleguminous crops. We synthesize how telomere-to-telomere genomes and pangenomes expose structural and regulatory variants for nodulation; how single-cell and spatial transcriptomics resolve stage-specific cell states and division of labor; and how epigenomic and 3D genome maps reveal principles of regulatory control for infection, organogenesis, and fixation. Extending to actinorhizal symbioses tests single- versus multiple-origin models. We present an artificial intelligence-guided roadmap that integrates sequence, chromatin accessibility, and expression data to prioritize regulatory elements, propose compact edit sets, and guide cell type-specific deployment in nonleguminous crops, advancing from descriptive catalogs to testable models and iterative validation.