Utilizing Gene Co-expression Network for Identifying Subnetwork Biomarkers for Cancer

Narumol Doungpan, Jonathan H. Chan, A. Meechai
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Abstract

Cancer is one of the major causes of death worldwide. Gene biomarkers identification for diagnosis, prognosis or predictive cancer is challenging work. This work aims to study the applicability of gene co-expression network (GCN) to identify gene subnetwork biomarkers for cancer using a previously developed subnetwork-based method. Four lung cancer expression datasets, gene-set, protein-protein interaction (PPI) and gene-gene interaction (GGI) data from public databases were used. The GCN was constructed using two criteria. The GCN constructed by using whole genes in the expression data with minimum spanning of the interaction within the network termed MST-based Gene Co-expression Network (MST-GCN) and the GCN was constructed by using gene members of a certain gene-set termed a Gene-set-based Gene Co-expression Network (gGCN). The subnetworks that resulted from MST-GCN and gGCN were compared with subnetworks that resulted from PPI and GGI data. The identified subnetworks were evaluated by classification performance and the overlapped gene with cancer related genes retrieved from a public database. The gGCN resulted in subnetworks that improved classification performance when compared with other network data. The identified subnetworks results from GGI contained more lung cancer related genes while the results from GCN and PPI contained more well-known lung cancer related genes.
利用基因共表达网络识别癌症亚网络生物标志物
癌症是世界范围内死亡的主要原因之一。基因生物标记物鉴别诊断、预后或预测癌症是一项具有挑战性的工作。本工作旨在研究基因共表达网络(GCN)的适用性,利用先前开发的基于子网络的方法识别癌症的基因子网络生物标志物。使用来自公共数据库的四种肺癌表达数据集,基因集、蛋白-蛋白相互作用(PPI)和基因-基因相互作用(GGI)数据。GCN是用两个标准构建的。利用网络内相互作用跨越最小的表达数据中的全基因构建的GCN称为基于mst的基因共表达网络(MST-GCN),而利用某一基因集的基因成员构建的GCN称为基于基因集的基因共表达网络(gGCN)。将MST-GCN和gGCN生成的子网与PPI和GGI数据生成的子网进行比较。通过分类性能和从公共数据库中检索到的与癌症相关基因重叠的基因来评估所识别的子网络。与其他网络数据相比,gGCN产生的子网提高了分类性能。GGI确定的子网络结果包含更多的肺癌相关基因,而GCN和PPI的结果包含更多已知的肺癌相关基因。
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