Year: 2026
Type: preprint
Abstract: Complex systems exhibit organization not only through their components but also via their interdependencies. Local nucleotide dependencies underpin regulatory motifs and RNA structures, yet principles governing a higher-order organization across the human genome remain unknown. Here we systematically perturbed every position of the complete telomere-to-telomere human genome using Nucleotide Transformer v3 with an exascale compute cluster, generating nucleotide-resolution dependency maps that reveal a directed, weighted network of position-to-position genomic relationships. This network recapitulates known biological features and uncovers recurrent, directional architectures termed ‘relons’, spanning coding, non-coding, and unannotated regions. These relational modules reflect evolutionary and functional constraints and associate with human genetic variation and pathogenic variants. Our findings suggest a higher-order relational layer of genome organization, providing a framework to interpret DNA as a complex system of dependencies beyond linear and 3D structure, with implications for understanding genetic variation and disease.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7222720957