Prediction of a gene regulatory network linked to prostate cancer from gene expression, microRNA and clinical data.
Prediction of a gene regulatory network linked to prostate cancer from gene expression, microRNA and clinical data.
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DOI：
10.1093/bioinformatics/btq395
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发表时间：
2010-09-15
期刊：
影响因子：
--
通讯作者：
Van de Peer Y
中科院分区：
文献类型：
--
作者：
Bonnet E;Michoel T;Van de Peer Y
动机：癌症是一种复杂的疾病，由多个基因和途径的突变引发。人们越来越感兴趣的是应用系统生物学方法来分析各种类型的癌症相关数据，以了解疾病引起的变化的压倒性复杂性。结果如下：我们使用基因表达、microRNA表达和临床参数重建了一个调控模块网络，所有这些都是在来自具有侵袭性或非侵袭性形式的前列腺癌患者的淋巴母细胞系中测量的。我们的分析确定了几个富含细胞周期相关基因的模块，以及可能与前列腺癌相关的新功能类别。据预测，控制这些模块表达水平的调节因子中，几乎有三分之一是microRNA。其中一些已经被定性为多种疾病（包括癌症）的病因。我们还预测了从未与这种类型的肿瘤相关的新型microRNA。此外，几个模块的条件依赖性表达可以与表征前列腺癌侵袭性的临床参数的值相关联。总之，我们的研究结果有助于阐明前列腺癌侵袭性和非侵袭性形式的后果。可用性：完整的监管网络可通过以下网址作为交互式补充网站提供：http://bioinformatics.psb.ugent.be/webtools/pronet/联系人：yves. psb.vib-ugent.be
Motivation: Cancer is a complex disease, triggered by mutations in multiple genes and pathways. There is a growing interest in the application of systems biology approaches to analyze various types of cancer-related data to understand the overwhelming complexity of changes induced by the disease. Results: We reconstructed a regulatory module network using gene expression, microRNA expression and a clinical parameter, all measured in lymphoblastoid cell lines derived from patients having aggressive or non-aggressive forms of prostate cancer. Our analysis identified several modules enriched in cell cycle-related genes as well as novel functional categories that might be linked to prostate cancer. Almost one-third of the regulators predicted to control the expression levels of the modules are microRNAs. Several of them have already been characterized as causal in various diseases, including cancer. We also predicted novel microRNAs that have never been associated to this type of tumor. Furthermore, the condition-dependent expression of several modules could be linked to the value of a clinical parameter characterizing the aggressiveness of the prostate cancer. Taken together, our results help to shed light on the consequences of aggressive and non-aggressive forms of prostate cancer. Availability: The complete regulatory network is available as an interactive supplementary web site at the following URL: http://bioinformatics.psb.ugent.be/webtools/pronet/ Contact: yves.vandepeer@psb.vib-ugent.be
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3.2
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