利用软计算规则推断癌症特异性基因调控网络。

Xiaosheng Wang, Osamu Gotoh
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引用次数: 16

摘要

基因调控网络的扰动是肿瘤发生的主要原因。因此,推断基因调控网络是攻克癌症的关键一步。在这项工作中,我们提出了一种基于软计算规则推断定向基因调控网络的方法,该方法可以识别基因表达的重要因果调控关系。首先,我们使用监督学习方法识别与特定癌症(结肠癌)相关的重要基因。接下来,我们通过推断已鉴定基因之间的调控关系,以及基因组内其他基因对它们的调控关系,重构基因调控网络。我们得到了两个有意义的发现。一是上调基因比下调基因受更多基因调控,而下调基因比上调基因受更多基因调控。二是肿瘤抑制因子对肿瘤激活因子的抑制作用较强,对其他肿瘤抑制因子的激活作用较强,而肿瘤激活因子对其他肿瘤激活因子的激活作用较弱,说明生物系统具有鲁棒性。这些发现为癌症的发病机制提供了有价值的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Inference of cancer-specific gene regulatory networks using soft computing rules.

Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.

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