Document Type


Publication Date



JGM, JMG, Transcription Factors, Computational Biology, Gene Expression Regulation, Gene Regulatory Networks, Systems Biology, Algorithms

JAX Source

Genome Biol. 2022;23(1):270.







The study is supported by startup funds from The Jackson Laboratory and Northeastern University, by the National Cancer Institute of the National Institutes of Health under Award Number P30CA034196, and by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R35GM128717.


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.


This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the mate- rial. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// The Creative Commons Public Domain Dedication waiver ( cdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.