rTRM

rTRM reconstructs transcriptional regulatory modules by integrating transcription factor binding sites, cell type-specific gene expression profiles, and protein-protein interaction networks to capture interactions among TFs and co-factors that regulate gene expression with spatiotemporal specificity.

Key Features:

• Integration of Genomic Data: rTRM combines TF binding data, cell type-specific gene expression, and protein-protein interaction (PPI) networks to provide a comprehensive view of transcriptional regulation.
• Identification of Bridging Proteins: rTRM identifies bridging proteins that lack direct DNA-binding but contribute to TRM formation via protein interactions.
• Precision in Prediction: Application to embryonic stem cells (ESC) and hematopoietic stem cells (HSC) identified 77 and 96 proteins respectively, with a significant proportion independently validated as regulators of these cell types.

Scientific Applications:

• Cell Type-Specific Regulation: rTRM has been used to reconstruct TRMs for ESCs, HSCs, neural progenitor cells, trophoblast stem cells, and differentiated CD4(+) T cells.
• Mechanistic Insights: By predicting co-factors that modulate master regulatory TFs, rTRM provides insights into genomic site selection, epigenetic modulation, and signal integration.
• Disease Research: Mapping abnormal TRMs can reveal disease mechanisms and potential pathways for therapeutic intervention.

Methodology:

rTRM integrates TF binding, cell type-specific gene expression, and PPI data and leverages protein-protein interaction information to identify proteins involved in complex formation, including non–DNA-binding bridging proteins.