A single-shot determination of differential gene network on multiple disease subtypes

Arnab Sadhu, B. Bhattacharyya, T. Mukhopadhyay
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Abstract

                Differential gene expressional network determines the prominent genes under altered phenotypes. Traditional approach requires n(n-2)/2 comparisons for n phenotypes. We present a direct method for determining the differential network under multiple phenotypes.                 We explore the non-discrete nature of gene expression as a pattern in fuzzy rough set. An edge between a pair of genes represents positive region of fuzzy similarity relation upon a phenotypic change. We apply a weight ranking formula and obtain a directed ranked network; we term it as Phenotype Interweaved Network. Nodes with large in-degree connectivity bubble up as significant genes under respective phenotypic changes.                 We test the method on datasets of six diseases and achieve good corroboration with results of previous studies in two-step approach. The subgraphs of isolated genes achieve good significance upon validation through information theoretic approach. Top ranking genes determined in all our case studies have parity with genes reported by wet-lab tests.
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一次测定多种疾病亚型的差异基因网络
差异基因表达网络决定了表型改变下的突出基因。传统方法需要对n个表型进行n(n-2)/2个比较。我们提出了一种确定多种表型下差异网络的直接方法。我们探索基因表达的非离散性质作为一种模式在模糊粗糙集。一对基因之间的边表示表型变化时模糊相似关系的正区域。应用权重排序公式,得到一个有向排序网络;我们称之为表型交织网络。具有大程度连通性的节点在各自的表型变化下成为显著基因。我们在六种疾病的数据集上对方法进行了测试,采用两步法与前人的研究结果得到了很好的印证。分离基因的子图经过信息论方法的验证,具有很好的意义。在我们所有的案例研究中确定的顶级基因与湿实验室测试报告的基因相同。
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