TENET

TENET identifies key transcription factors and regulatory elements linked to a specific cell type by finding significantly correlated differences in gene expression and regulatory element DNA methylation between case and control input datasets.

Key Features:

• Correlation Analysis: Identifies significantly correlated differences in gene expression and regulatory element DNA methylation between case and control datasets.
• Gene Ranking: Identifies top genes by number of significant regulatory element DNA methylation site links.
• Visualization Tools: Generates plots displaying and comparing methylation and expression data and methylation site link counts.
• Survival Analysis: Performs survival analysis on results.
• TF Motif Searching: Searches for transcription factor motifs in the vicinity of linked regulatory element DNA methylation sites.
• Custom TAD and Peak Overlap Analysis: Performs custom topologically associating domain and peak overlap analysis.
• UCSC Genome Browser Track Generation: Generates UCSC Genome Browser track files.
• TCGA Data Download: Provides a utility function to download methylation, expression, and patient survival data from The Cancer Genome Atlas.

Scientific Applications:

• Cell Type-Specific Regulatory Element Identification: Identifies transcription factors and regulatory elements linked to a specific cell type using histone mark and open chromatin datasets from cell lines, primary cells, and tissues.
• Cancer Type Association: Highlights transcription factors and regulatory elements associated with different cancer types through pan-cancer analysis.
• 3D Epigenome Characterization: Enables characterization of three-dimensional epigenomes of cell types of interest for clinical applications.

Methodology:

TENET compares histone mark and open chromatin features along with matched DNA methylation and gene expression data, and interrogates findings using motifs, clinical information, and other genomic and chromatin conformation capture datasets.