A relational architecture of the human genome
- 1RWTH Aachen, University Hospital
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 com- plete telomere-to-telomere human genome using Nucleotide Transformer v3 with an ex- ascale 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 architec- tures termed 'relons', spanning coding, non-coding, and unannotated regions. These re- lational modules reflect evolutionary and functional constraints and associate with hu- man genetic variation and pathogenic variants. Our findings suggest a higher-order rela- tional layer of genome organization, providing a framework to interpret DNA as a complex system of dependencies beyond linear and 3D structure, with implications for under- standing genetic variation and disease.
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BibTeX
@misc{kurth2026relational,
title = {{A relational architecture of the human genome}},
author = {I. Kurth and J. Krause and M. Danner and F. Kraft and T. Islam and M. Begemann and Z. Ziad and M. Elbracht and M. Bode},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.15.759350},
url = {https://www.biorxiv.org/content/10.64898/2026.10.15.759350v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A relational architecture of the human genome
AU - I. Kurth
AU - J. Krause
AU - M. Danner
AU - F. Kraft
AU - T. Islam
AU - M. Begemann
AU - Z. Ziad
AU - M. Elbracht
AU - M. Bode
PY - 2026
DA - 2026/10/15
PB - bioRxiv
DO - 10.64898/2026.10.15.759350
UR - https://www.biorxiv.org/content/10.64898/2026.10.15.759350v1
AB - 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 com- plete telomere-to-telomere human genome using Nucleotide Transformer v3 with an ex- ascale 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 architec- tures termed 'relons', spanning coding, non-coding, and unannotated regions. These re- lational modules reflect evolutionary and functional constraints and associate with hu- man genetic variation and pathogenic variants. Our findings suggest a higher-order rela- tional layer of genome organization, providing a framework to interpret DNA as a complex system of dependencies beyond linear and 3D structure, with implications for under- standing genetic variation and disease.
ER -