hARACNe: improving the accuracy of regulatory model reverse engineering via higher-order data processing inequality tests.

hARACNe: improving the accuracy of regulatory model reverse engineering via higher-order data processing inequality tests.
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Haracne:通过高阶数据处理不平等测试提高监管模型逆向工程的准确性。

DOI:
10.1098/rsfs.2013.0011
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发表时间:
2013-08-06
期刊:
影响因子:
4.4
通讯作者:
Califano A
Califano A
中科院分区:
生物学2区
文献类型:
--
作者:
Jang IS;Margolin A;Califano A

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A key goal of systems biology is to elucidate molecular mechanisms associated with physiologic and pathologic phenotypes based on the systematic and genome-wide understanding of cell context-specific molecular interaction models. To this end, reverse engineering approaches have been used to systematically dissect regulatory interactions in a specific tissue, based on the availability of large molecular profile datasets, thus improving our mechanistic understanding of complex diseases, such as cancer. In this paper, we introduce high-order Algorithm for the Reconstruction of Accurate Cellular Network (hARACNe), an extension of the ARACNe algorithm for the dissection of transcriptional regulatory networks. ARACNe uses the data processing inequality (DPI), from information theory, to detect and prune indirect interactions that are unlikely to be mediated by an actual physical interaction. Whereas ARACNe considers only first-order indirect interactions, i.e. those mediated by only one extra regulator, hARACNe considers a generalized form of indirect interactions via two, three or more other regulators. We show that use of higher-order DPI resulted in significantly improved performance, based on transcription factor (TF)-specific ChIP-chip data, as well as on gene expression profile following RNAi-mediated TF silencing.
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