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LPRP:一种基因-基因交互网络构建算法及其在乳腺癌数据分析中的应用。

LPRP: A Gene-Gene Interaction Network Construction Algorithm and Its Application in Breast Cancer Data Analysis.

机构信息

College of Computer Science and Technology, Jilin University, Changchun, 130012, China.

Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, Changchun, 130012, China.

出版信息

Interdiscip Sci. 2018 Mar;10(1):131-142. doi: 10.1007/s12539-016-0185-4. Epub 2016 Sep 17.

Abstract

The importance of the construction of gene-gene interaction (GGI) network to better understand breast cancer has previously been highlighted. In this study, we propose a novel GGI network construction method called linear and probabilistic relations prediction (LPRP) and used it for gaining system level insight into breast cancer mechanisms. We construct separate genome-wide GGI networks for tumor and normal breast samples, respectively, by applying LPRP on their gene expression datasets profiled by The Cancer Genome Atlas. According to our analysis, a large loss of gene interactions in the tumor GGI network was observed (7436; 88.7 % reduction), which also contained fewer functional genes (4757; 32 % reduction) than the normal network. Tumor GGI network was characterized by a bigger network diameter and a longer characteristic path length but a smaller clustering coefficient and much sparse network connections. In addition, many known cancer pathways, especially immune response pathways, are enriched by genes in the tumor GGI network. Furthermore, potential cancer genes are filtered in this study, which may act as drugs targeting genes. These findings will allow for a better understanding of breast cancer mechanisms.

摘要

先前已经强调了构建基因-基因相互作用(GGI)网络以更好地理解乳腺癌的重要性。在这项研究中,我们提出了一种新的 GGI 网络构建方法,称为线性和概率关系预测(LPRP),并将其用于深入了解乳腺癌的机制。我们通过将 LPRP 应用于癌症基因组图谱(TCGA)分析的基因表达数据集,分别为肿瘤和正常乳腺样本构建全基因组 GGI 网络。根据我们的分析,在肿瘤 GGI 网络中观察到大量基因相互作用的丧失(7436;88.7%减少),与正常网络相比,肿瘤 GGI 网络中的功能基因也更少(4757;32%减少)。肿瘤 GGI 网络的特征是网络直径更大、特征路径长度更长,但聚类系数更小,网络连接稀疏。此外,许多已知的癌症途径,特别是免疫反应途径,在肿瘤 GGI 网络中被基因富集。此外,本研究还筛选出了潜在的癌症基因,它们可能作为药物靶点基因。这些发现将有助于更好地理解乳腺癌的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/380b/5838217/3045b5001af8/12539_2016_185_Fig1_HTML.jpg

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