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整合 5hmC 和基因表达数据以推断调控机制。

Integrating 5hmC and gene expression data to infer regulatory mechanisms.

机构信息

Department of Oncology.

Department of Computer Science.

出版信息

Bioinformatics. 2018 May 1;34(9):1441-1447. doi: 10.1093/bioinformatics/btx777.

Abstract

MOTIVATION

Epigenetic mechanisms are known to play a major role in breast cancer. However, the role of 5-hydroxymethylcytosine (5hmC) remains understudied. We hypothesize that 5hmC mediates redox regulation of gene expression in an aggressive subtype known as triple negative breast cancer (TNBC). To address this, our objective was to highlight genes that may be the target of this process by identifying redox-regulated, antioxidant-sensitive, gene-localized 5hmC changes associated with mRNA changes in TNBC cells.

RESULTS

We proceeded to develop an approach to integrate novel Pvu-sequencing and RNA-sequencing data. The result of our approach to merge genome-wide, high-throughput TNBC cell line datasets to identify significant, concordant 5hmC and mRNA changes in response to antioxidant treatment produced a gene set with relevance to cancer stem cell function. Moreover, we have established a method that will be useful for continued research of 5hmC in TNBC cells and tissue samples.

AVAILABILITY AND IMPLEMENTATION

Data are available at Gene Expression Omnibus (GEO) under accession number GSE103850.

CONTACT

bollig@karmanos.org.

摘要

动机

表观遗传机制在乳腺癌中起着重要作用。然而,5-羟甲基胞嘧啶(5hmC)的作用仍研究不足。我们假设 5hmC 介导了一种称为三阴性乳腺癌(TNBC)的侵袭性亚型的基因表达的氧化还原调控。为了解决这个问题,我们的目标是通过确定与 TNBC 细胞中 mRNA 变化相关的、氧化还原调节的、抗氧化敏感的、基因定位的 5hmC 变化,来突出可能是该过程靶点的基因。

结果

我们着手开发一种方法来整合新的 Pvu 测序和 RNA 测序数据。我们的方法将全基因组、高通量 TNBC 细胞系数据集合并,以识别抗氧化剂处理后响应的显著、一致的 5hmC 和 mRNA 变化,产生了一个与癌症干细胞功能相关的基因集。此外,我们已经建立了一种方法,将有助于继续研究 TNBC 细胞和组织样本中的 5hmC。

可用性和实施

数据可在基因表达综合数据库(GEO)中获取, accession number 为 GSE103850。

联系人

bollig@karmanos.org

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