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基因间相互作用在妊娠乳腺基因组特征中的作用。

The role of gene to gene interaction in the breast's genomic signature of pregnancy.

机构信息

IMUVA Mathematical Institute, University of Valladolid, Valladolid, Spain.

Faculty of Economics, University of Valladolid, Valladolid, Spain.

出版信息

Sci Rep. 2021 Jan 29;11(1):2643. doi: 10.1038/s41598-021-81704-8.

Abstract

Full-term pregnancy at an early age confers long-term protection against breast cancer. Published data shows a specific transcriptomic profile controlling chromatin remodeling that could play a relevant role in the pregnancy-induced protection. This process of chromatin remodeling, induced by the breast differentiation caused by the first full-term pregnancy, has mainly been measured by the expression level of genes individually considered. However, genes equally expressed during the process of chromatin remodeling may behave differently in their interaction with other genes. These changes at the gene cluster level could constitute an additional dimension of chromatin remodeling and therefore of the pregnancy-induced protection. In this research, we apply Information and Graph Theories, Differential Co-expression Network Analysis, and Multiple Regression Analysis, specially designed to examine structural and informational aspects of data sets, to analyze this question. Our findings demonstrate that, independently of the changes in the gene expression at the individual level, there are significant changes in gene-gene interactions and gene cluster behaviors. These changes indicate that the parous breast, through the process of early full-term pregnancy, generates more modules in the networks, with higher density, and a genomic structure performing additional and more complex functions than those found in the nulliparous breast.

摘要

早期足月妊娠可提供长期乳腺癌保护。已发表的数据显示,一种特定的转录组特征控制着染色质重塑,它可能在妊娠诱导保护中发挥相关作用。这种由首次足月妊娠引起的乳腺分化引起的染色质重塑过程,主要通过单独考虑的基因的表达水平来衡量。然而,在染色质重塑过程中表达水平相同的基因,在与其他基因的相互作用中可能表现出不同的行为。这些基因簇水平的变化可能构成染色质重塑的另一个维度,也是妊娠诱导保护的一个维度。在这项研究中,我们应用信息和图论、差异共表达网络分析和多元回归分析,专门设计用于检查数据集的结构和信息方面,来分析这个问题。我们的研究结果表明,独立于个体水平上基因表达的变化,基因-基因相互作用和基因簇行为发生了显著变化。这些变化表明,经足月妊娠诱导的哺乳期乳腺,通过早期足月妊娠过程,在网络中产生了更多模块,具有更高的密度,以及表现出比未孕乳腺更多样化和更复杂功能的基因组结构。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c707/7846553/e8f51522ab6b/41598_2021_81704_Fig1_HTML.jpg

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