NetAct: a computational platform to construct core transcription factor regulatory networks using gene activity.
Kenong Su1, Ataur Katebi2,3, Vivek Kohar4
1Department of Biomedical Informatics, Emory University, Atlanta, GA, 30322, USA.
Genome Biology
|December 27, 2022
Summary
We developed NetAct, a computational platform to identify core gene regulatory networks. NetAct accurately infers transcription factor activity and network construction for biological decision-making.
Area of Science:
- Systems biology
- Computational biology
- Gene regulatory networks
Background:
- Identifying core gene regulatory circuits is crucial for understanding biological decision-making.
- Existing methods for network construction have limitations in accuracy and scope.
Purpose of the Study:
- To develop a computational platform, NetAct, for constructing core transcription factor regulatory networks.
- To robustly infer transcription factor activity and validate network models.
Main Methods:
- NetAct integrates transcriptomics data with literature-based transcription factor-target databases.
- It infers regulator activity from target gene expression.
- Network construction is based on transcriptional activity, with mathematical modeling for validation.
Main Results:
- NetAct outperforms existing algorithms in inferring transcriptional activity and gene networks in silico benchmark tests.
- The platform successfully models networks driving key biological processes like epithelial-mesenchymal transition and macrophage polarization.
Conclusions:
- NetAct provides a robust and accurate computational approach for constructing core gene regulatory networks.
- This platform can advance the understanding of biological decision-making processes and disease mechanisms.
Keywords:
Cellular state transitionsEpithelial-mesenchymal transitionGene regulatory circuitsGene regulatory networksMacrophage polarizationMathematical modelingSystems biologyTranscriptional activityMore Related Videos
Related Concept Videos
02:13Cooperative Binding of Transcription Regulators
6.5K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.5K
02:33Combinatorial Gene Control
8.4K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.4K
01:27Constitutive and Regulated Gene Expression
83
Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...
83
01:30General Transcription Factors
5.5K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.5K
02:16Transcription Factors
76.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
76.3K
02:04Co-activators and Co-repressors
7.4K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.4K