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<p>Single-cell chromosome conformations vary significantly among individual cells. We introduce a two-step dimensionality reduction method for density-based, unsupervised clustering of single-cell 3D chromosome structures from simulations or multiplexed 3D-FISH imaging. Our method clusters up to half of all structures into 5–12 prevalent conformational states per chromosome. These states are distinguished by subdivisions into chromosome territory domains, whose boundary locations influence subnuclear positions and speckle associations of certain genes and establish long-range structural variations of more than 10&#xa0;Mb. Territory domain boundaries are found at few sequence locations, shared among cell types and often situated at syntenic breakpoints.</p>

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Unveiling the role of chromosome structure morphology on gene function through chromosome conformation analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月13日

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  • Yuxiang Zhan,
  • Asli Yildirim,
  • Lorenzo Boninsegna,
  • Frank Alber

摘要

Single-cell chromosome conformations vary significantly among individual cells. We introduce a two-step dimensionality reduction method for density-based, unsupervised clustering of single-cell 3D chromosome structures from simulations or multiplexed 3D-FISH imaging. Our method clusters up to half of all structures into 5–12 prevalent conformational states per chromosome. These states are distinguished by subdivisions into chromosome territory domains, whose boundary locations influence subnuclear positions and speckle associations of certain genes and establish long-range structural variations of more than 10 Mb. Territory domain boundaries are found at few sequence locations, shared among cell types and often situated at syntenic breakpoints.