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bioRxiv · 10.64898/2026.01.16.699950

eTRex Reveals Oncogenic Transcriptional Regulatory Programs Across Human Cancers

Lu, Z.·Yang, Y.·Zheng, Q.·Gao, F.·Xu, L.·Wang, X.
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Abstract

Transcriptional regulators (TRs) are essential proteins that regulate gene transcription, and their dysregulation defines the oncogenic transcriptional regulatory programs that drive tumor-specific gene expression. Existing pan-cancer resources summarize these programs by aggregating signals across individual datasets, neglecting the context-specific features that capture the diversity of transcriptional regulation underlying cancer heterogeneity. By developing a variational Bayesian hierarchical model named eTRex (epigenomics-based Transcriptional Regulator explorer) and applying it to 4,819 cancer-related ATAC-seq datasets, we provide a comprehensive pan-cancer atlas of functional TR profiles that preserve the context-specific features of each dataset. This study reveals both common regulators across diverse malignancies and those with highly specific roles. We extensively validated these findings using independent CRISPR/Cas9 screening, mutation, and transcriptomic datasets. Collectively, this pan-cancer atlas of functional TR profiles represents a comprehensive, biologically interpretable resource for uncovering transcriptional regulatory programs, identifying biomarkers, prioritizing therapeutic targets in oncology, and is freely accessible through an interactive web portal.

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Lu, Z., Yang, Y., Zheng, Q., Gao, F., Xu, L., Wang, X.. 2026-01-20. eTRex Reveals Oncogenic Transcriptional Regulatory Programs Across Human Cancers. https://doi.org/10.64898/2026.01.16.699950

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