Method

Characterization of network hierarchy reflects cell state specificity in genome organization

    • 1Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China;
    • 2Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, 100871, China;
    • 3Changping Laboratory, Beijing, 102206, China
    • 4 These authors contributed equally to this work.
Published February 24, 2023. Vol 33 Issue 2, pp. 247-260. https://doi.org/10.1101/gr.277206.122
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Abstract

Dynamic chromatin structure acts as the regulator of transcription program in crucial processes including cancer and cell development, but a unified framework for characterizing chromatin structural evolution remains to be established. Here, we performed graph inferences on Hi-C data sets and derived the chromatin contact networks. We discovered significant decreases in information transmission efficiencies in chromatin of colorectal cancer (CRC) and T-cell acute lymphoblastic leukemia (T-ALL) compared to corresponding normal controls through graph statistics. Using network embedding in the Poincaré disk, the hierarchy depths of chromatin from CRC and T-ALL patients were found to be significantly shallower compared to their normal controls. A reverse trend of change in chromatin structure was observed during early embryo development. We found tissue-specific conservation of hierarchy order in chromatin contact networks. Our findings reveal the top-down hierarchy of chromatin organization, which is significantly attenuated in cancer.

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