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Updated: May 9, 2026

Generating the Transcriptional Regulation View of Transcriptomic Features for Prediction Task and Dark Biomarker Detection on Small Datasets
Published on: March 1, 2024
REACTIN: regulatory activity inference of transcription factors underlying human diseases with application to breast
Mingzhu Zhu1, Chun-Chi Liu, Chao Cheng
1Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755, USA.
Background:
Genetic alterations of transcription factors (TFs) have been implicated in the tumorigenesis of cancers. In many cancers, alteration of TFs results in aberrant activity of them without changing their gene expression level. Gene expression data from microarray or RNA-seq experiments can capture the expression change of genes, however, it is still challenge to reveal the activity change of TFs.
Results:
Here we propose a method, called REACTIN (REgulatory ACTivity INference), which integrates TF binding data with gene expression data to identify TFs with significantly differential activity between disease and normal samples. REACTIN successfully detect differential activity of estrogen receptor (ER) between ER+ and ER- samples in 10 breast cancer datasets. When applied to compare tumor and normal breast samples, it reveals TFs that are critical for carcinogenesis of breast cancer. Moreover, Reaction can be utilized to identify transcriptional programs that are predictive to patient survival time of breast cancer patients.
Conclusions:
REACTIN provides a useful tool to investigate regulatory programs underlying a biological process providing the related case and control gene expression data. Considering the enormous amount of cancer gene expression data and the increasingly accumulating ChIP-seq data, we expect wide application of REACTIN for revealing the regulatory mechanisms of various diseases.
Insights
This study introduces REACTIN, a novel method to infer transcription factor (TF) activity from gene expression and TF binding data. REACTIN identifies key TFs in cancer development and predicts patient survival, offering a new tool for disease research.
Area of Science:
- Genomics
- Cancer Biology
- Bioinformatics
Background:
- Transcription factor (TF) genetic alterations are linked to cancer development.
- TF activity changes in cancer often occur without altered gene expression levels.
- Current gene expression data analysis struggles to reveal TF activity shifts.
Purpose of the Study:
- To develop a method for inferring TF regulatory activity from integrated data.
- To identify TFs with differential activity between disease and normal states.
- To explore the role of TFs in cancer and their predictive value for patient outcomes.
Main Methods:
- Developed REACTIN (REgulatory ACTivity INference) by integrating TF binding and gene expression data.
- Applied REACTIN to identify differentially active TFs in cancer datasets.
- Utilized REACTIN to analyze transcriptional programs associated with patient survival.
Main Results:
- REACTIN successfully detected differential estrogen receptor (ER) activity in breast cancer datasets.
- The method identified critical TFs involved in breast cancer carcinogenesis.
- REACTIN revealed transcriptional programs predictive of patient survival in breast cancer.
Conclusions:
- REACTIN is a valuable tool for investigating biological regulatory programs using gene expression data.
- The method facilitates the study of regulatory mechanisms in various diseases.
- Expected wide application of REACTIN due to abundant cancer and ChIP-seq data.
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