Integrative gene network construction for predicting a set of complementary prostate cancer genes
Integrative gene network construction for predicting a set of complementary prostate cancer genes
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DOI：
10.1093/bioinformatics/btr283
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发表时间：
2011-07-01
期刊：
影响因子：
5.8
通讯作者：
Park, Sanghyun
中科院分区：
文献类型：
--
作者：
Ahn, Jaegyoon;Yoon, Youngmi;Park, Sanghyun
动机：癌症的诊断和预后以及在生物学途径的背景下理解肿瘤发生是生物信息学中最重要的研究领域之一。最近，已经有几次尝试整合相互作用组和转录组数据，以识别提供已知和候选癌症基因的有限解释的子网络，以及提高分类准确性。然而，这些研究提供的信息很少的详细角色确定的癌症genes.Results：为了提供更多的信息的网络，我们构建了网络，将遗传相互作用和人工策划的基因调控蛋白质相互作用网络。为了使我们新构建的网络具有癌症特异性，我们确定了两个基因在癌症和正常表型之间表现出不同表达模式的边缘。我们发现，各种数据集的整合提高了分类准确性，这表明我们的网络比仅基于蛋白质相互作用的网络更完整。我们还表明，我们的网络比其他特征选择算法包含更多的已知癌症相关基因。通过观察一些癌症特异性子网络的例子，我们能够预测癌基因和其他癌症候选基因在前列腺癌细胞中更详细和可解释的作用。
Motivation: Diagnosis and prognosis of cancer and understanding oncogenesis within the context of biological pathways is one of the most important research areas in bioinformatics. Recently, there have been several attempts to integrate interactome and transcriptome data to identify subnetworks that provide limited interpretations of known and candidate cancer genes, as well as increase classification accuracy. However, these studies provide little information about the detailed roles of identified cancer genes.Results: To provide more information to the network, we constructed the network by incorporating genetic interactions and manually curated gene regulations to the protein interaction network. To make our newly constructed network cancer specific, we identified edges where two genes show different expression patterns between cancer and normal phenotypes. We showed that the integration of various datasets increased classification accuracy, which suggests that our network is more complete than a network based solely on protein interactions. We also showed that our network contains significantly more known cancer-related genes than other feature selection algorithms. Through observations of some examples of cancer-specific subnetworks, we were able to predict more detailed and interpretable roles of oncogenes and other cancer candidate genes in the prostate cancer cells.