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NetAct:一个使用基因活性构建核心转录因子调控网络的计算平台。

NetAct: a computational platform to construct core transcription factor regulatory networks using gene activity.

机构信息

Department of Biomedical Informatics, Emory University, Atlanta, GA, 30322, USA.

Department of Bioengineering|, Northeastern University, Boston, MA, 02115, USA.

出版信息

Genome Biol. 2022 Dec 27;23(1):270. doi: 10.1186/s13059-022-02835-3.

Abstract

A major question in systems biology is how to identify the core gene regulatory circuit that governs the decision-making of a biological process. Here, we develop a computational platform, named NetAct, for constructing core transcription factor regulatory networks using both transcriptomics data and literature-based transcription factor-target databases. NetAct robustly infers regulators' activity using target expression, constructs networks based on transcriptional activity, and integrates mathematical modeling for validation. Our in silico benchmark test shows that NetAct outperforms existing algorithms in inferring transcriptional activity and gene networks. We illustrate the application of NetAct to model networks driving TGF-β-induced epithelial-mesenchymal transition and macrophage polarization.

摘要

系统生物学中的一个主要问题是如何识别控制生物过程决策的核心基因调控回路。在这里,我们开发了一个名为 NetAct 的计算平台,该平台使用转录组学数据和基于文献的转录因子-靶标数据库来构建核心转录因子调控网络。NetAct 使用靶基因表达来稳健地推断调控因子的活性,基于转录活性构建网络,并整合数学模型进行验证。我们的计算机基准测试表明,NetAct 在推断转录活性和基因网络方面优于现有算法。我们说明了 NetAct 在建模 TGF-β诱导的上皮-间充质转化和巨噬细胞极化的网络中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/684c/9793520/950e56717239/13059_2022_2835_Fig1_HTML.jpg

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