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meGPS:一种整合甲基化组和转录组数据的用于肝细胞癌检测的多组学生物标志物。

meGPS: a multi-omics signature for hepatocellular carcinoma detection integrating methylome and transcriptome data.

机构信息

Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medicine College of Jinan University, Shenzhen 518020, China.

School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.

出版信息

Bioinformatics. 2022 Jul 11;38(14):3513-3522. doi: 10.1093/bioinformatics/btac379.

Abstract

MOTIVATION

Hepatocellular carcinoma (HCC) is a primary malignancy with a poor prognosis. Recently, multi-omics molecular-level measurement enables HCC diagnosis and prognosis prediction, which is crucial for early intervention of personalized therapy to diminish mortality. Here, we introduce a novel strategy utilizing DNA methylation and RNA expression data to achieve a multi-omics gene pair signature (GPS) for HCC discrimination.

RESULTS

The immune genes with negative correlations between expression and promoter methylation are enriched in the highly connected cancer-related pathway network, which are considered as the candidates for HCC detection. After that, we separately construct a methylation GPS (mGPS) and an expression GPS (eGPS), and then assemble them as a meGPS with five gene pairs, in which the significant methylation and expression changes occur between HCC tumor and non-tumor groups. Reliable performance has been validated by independent tissue (age, gender and etiology) and blood datasets. This study proposes a procedure for multi-omics GPS identification and develops a novel HCC signature using both methylome and transcriptome data, suggesting potential molecular targets for the detection and therapy of HCC.

AVAILABILITY AND IMPLEMENTATION

Models are available at https://github.com/bioinformaticStudy/meGPS.git.

SUPPLEMENTARY INFORMATION

Supplementary data are available at Bioinformatics online.

摘要

动机

肝细胞癌(HCC)是一种预后不良的原发性恶性肿瘤。最近,多组学生物分子水平测量可用于 HCC 的诊断和预后预测,这对于实现早期干预和个性化治疗以降低死亡率至关重要。在这里,我们介绍了一种利用 DNA 甲基化和 RNA 表达数据来实现 HCC 区分的多组学生物基因对特征(GPS)的新策略。

结果

表达与启动子甲基化呈负相关的免疫基因在高度关联的癌症相关途径网络中富集,被认为是 HCC 检测的候选基因。之后,我们分别构建了甲基化 GPS(mGPS)和表达 GPS(eGPS),然后将它们组装成一个具有五个基因对的 meGPS,其中 HCC 肿瘤和非肿瘤组之间存在显著的甲基化和表达变化。独立的组织(年龄、性别和病因)和血液数据集验证了可靠的性能。本研究提出了一种多组学生物 GPS 识别程序,并利用甲基化组和转录组数据开发了一种新的 HCC 特征,为 HCC 的检测和治疗提供了潜在的分子靶标。

可用性和实施

模型可在 https://github.com/bioinformaticStudy/meGPS.git 上获得。

补充信息

补充数据可在生物信息学在线获得。

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