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从与疾病相关的基因表达数据构建协同网络。

Construction of synergy networks from gene expression data related to disease.

作者信息

Chatterjee Prantik, Pal Nikhil Ranjan

机构信息

Electronics and Communication Sciences Unit, Indian Statistical Institute, Calcutta, India.

Electronics and Communication Sciences Unit, Indian Statistical Institute, Calcutta, India.

出版信息

Gene. 2016 Sep 30;590(2):250-62. doi: 10.1016/j.gene.2016.05.029. Epub 2016 May 22.

Abstract

A few methods have been developed to determine whether genes collaborate with each other in relation to a particular disease using an information theoretic measure of synergy. Here, we propose an alternative definition of synergy and justify that our definition improves upon the existing measures of synergy in the context of gene interactions. We use this definition on a prostate cancer data set consisting of gene expression levels in both cancerous and non-cancerous samples and identify pairs of genes which are unable to discriminate between cancerous and non-cancerous samples individually but can do so jointly when we take their synergistic property into account. We also propose a very simple yet effective technique for computation of conditional entropy at a very low cost. The worst case complexity of our method is O(n) while the best case complexity of a state-of-the-art method is O(n(2)). Furthermore, our method can also be extended to find synergistic relation among triplets or even among a larger number of genes. Finally, we validate our results by demonstrating that these findings cannot be due to pure chance and provide the relevance of the synergistic pairs in cancer biology.

摘要

已经开发了一些方法,使用协同作用的信息理论度量来确定基因是否在特定疾病方面相互协作。在此,我们提出了协同作用的另一种定义,并证明我们的定义在基因相互作用的背景下改进了现有的协同作用度量。我们将此定义应用于一个前列腺癌数据集,该数据集包含癌组织和非癌组织样本中的基因表达水平,并识别出那些单个基因无法区分癌组织和非癌组织样本,但在考虑它们的协同特性时能够联合区分的基因对。我们还提出了一种非常简单但有效的技术,以非常低的成本计算条件熵。我们方法的最坏情况复杂度为O(n),而一种先进方法的最佳情况复杂度为O(n(2))。此外,我们的方法还可以扩展以找到三联体甚至更多基因之间的协同关系。最后,我们通过证明这些发现并非纯粹出于偶然来验证我们的结果,并提供了协同基因对在癌症生物学中的相关性。

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