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

机译:LPRP:基因-基因相互作用网络构建算法及其在乳腺癌数据分析中的应用

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摘要

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s12539-016-0185-4) contains supplementary material, which is available to authorized users.
机译:先前已经强调了构建基因-基因相互作用(GGI)网络以更好地了解乳腺癌的重要性。在这项研究中,我们提出了一种新颖的GGI网络构建方法,称为线性和概率关系预测(LPRP),并将其用于获得对乳腺癌机制的系统级了解。我们通过在癌症基因组图谱分析的基因表达数据集上应用LPRP,分别为肿瘤和正常乳腺样品构建单独的全基因组GGI网络。根据我们的分析,在肿瘤GGI网络中观察到了大量基因相互作用(7436;减少88.7%),其中功能基因也比正常网络少(4757;减少32%)。肿瘤GGI网络的特点是网络直径较大,特征路径长度较长,但是聚类系数较小,网络连接稀疏。另外,肿瘤GGI网络中的基因丰富了许多已知的癌症途径,尤其是免疫应答途径。此外,在这项研究中,潜在的癌症基因被过滤掉了,它们可能充当靶向基因的药物。这些发现将使您可以更好地了解乳腺癌的发病机理。电子补充材料本文的在线版本(doi:10.1007 / s12539-016-0185-4)包含补充材料,授权用户可以使用。

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