Paradigm Lost.

🤖 Plain-English Summary

: The 3-dimensional (3D) architecture of the genome in the nucleus of a living cell plays an unexpected yet fundamental regulatory role in cell biology. : A more complete understanding of human biology will require models that account for the flow of information to and from the 3D genomic architecture in living cells, together with its regulation and logic.

🔑 Key Findings

• As an imprint of the cellular genetic, epigenetic and metabolic status, it discriminates pathological conditions through conditional changes to long-range 3D interactions (up to 300 kb) and thus could act as a powerful molecular biomarker linked closely to clinical outcomes.
• : Here an assessment is made of the latest paradigm shift in molecular biology from a supply chain where information flows from DNA to RNA to protein, to the concept of heritable 3D folding of the genome reflecting the epigenetic and metabolic state of the cell, and which serves as a molecular biomarker for complex clinical outcome.
• : While biomarkers based on individual components of the supply chain fail to accurately reflect clinical outcomes, 3D genomics offers highly informative insights, exemplified for immuno-oncology and prostate cancer diagnosis by clinical tests of superior performance, already in practice in the US and UK.

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