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PARTAGE:复制时间与基因表达的平行分析

PARTAGE: Parallel analysis of replication timing and gene expression.

作者信息

Murari Lakshana Sruthi Sadu, Dickinson Quinn, Meyer-Nava Silvia, Rivera-Mulia Juan Carlos

机构信息

Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, Minnesota.

Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, Minnesota.

出版信息

bioRxiv. 2025 Sep 6:2025.09.02.673838. doi: 10.1101/2025.09.02.673838.

Abstract

The human genome is partitioned into functional compartments that replicate at specific times during the S-phase. This temporal program, referred to as replication timing (RT), is co-regulated with the 3D genome organization, is cell type-specific, and changes during development in coordination with gene expression. Moreover, RT alterations are linked to abnormal gene expression, genome instability, and structural variation in multiple diseases, including cancer. However, mechanistic links between RT, large-scale 3D genome architecture, and transcriptional regulation remain poorly understood. A major limitation is that current approaches require the separate profiling of RT and transcriptomes from independent batches of samples, obscuring the complex co-regulation between the epigenome and transcriptome. Here, we developed , a multiomics approach that enables joint profiling of copy number variation (CNV), RT, and gene expression from the same sample, providing a more accurate integrative view of the complex relationships between RT and gene regulation.

摘要

人类基因组被划分为在S期特定时间进行复制的功能区室。这种时间程序,称为复制时间(RT),与3D基因组组织共同调控,具有细胞类型特异性,并在发育过程中与基因表达协调变化。此外,RT改变与多种疾病(包括癌症)中的异常基因表达、基因组不稳定和结构变异有关。然而,RT、大规模3D基因组结构和转录调控之间的机制联系仍知之甚少。一个主要限制是,目前的方法需要从独立批次的样本中分别分析RT和转录组,从而掩盖了表观基因组和转录组之间复杂的共同调控。在这里,我们开发了一种多组学方法,能够对同一样本中的拷贝数变异(CNV)、RT和基因表达进行联合分析,从而更准确地综合了解RT与基因调控之间的复杂关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e411/12424761/7d647be48055/nihpp-2025.09.02.673838v1-f0001.jpg

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