RTNduals

RTNduals identifies co-regulatory loops by detecting overlapping targets between pairs of regulons generated with the RTN package to infer dual regulons and assess regulatory agreement between transcription factors.

Key Features:

• Regulon generation: Leverages the RTN package to generate regulons (groups of genes regulated by common transcription factors) for downstream pairwise analysis.
• Pairwise regulon comparison: Performs comparative analysis of shared gene targets between regulon pairs to detect overlap.
• Dual regulon inference: Infers "dual regulons" from shared targets to indicate putative co-regulatory loops and agreement on predicted downstream effects.
• Regulatory coherence assessment: Assesses regulatory coherence or discordance between transcription factors based on overlap patterns of target genes.
• Enrichment testing with eQTL-linked genes: Tests regulon overlaps for enrichment with genes linked to risk loci through expression quantitative trait loci (eQTLs).
• Identification of overlapping regulons: Can identify sets of overlapping regulons, exemplified by the identification of 36 overlapping regulons enriched for risk loci in a breast cancer study.
• Linkage to TF mutation and subtype biology: Relates enriched regulons to transcription factors frequently mutated in cancer and to breast cancer subtype–specific TF subgroups (e.g., ER+ luminal A/B and ER- basal-like).

Scientific Applications:

• Gene regulatory network analysis: Dissects co-regulatory relationships between transcription factors within gene regulatory networks.
• Disease risk locus interpretation: Prioritizes regulons and dual regulons enriched for genes linked to risk loci via eQTLs, as applied to breast cancer (PMID: 26618344).
• Subtype-specific regulatory stratification: Stratifies transcription factors and regulons according to associations with breast cancer subtypes such as ER+ luminal A/B and ER- basal-like.
• Identification of candidate regulatory circuits: Highlights co-regulatory circuits that may underlie disease-associated pathways and potential therapeutic targets.

Methodology:

RTNduals uses regulons generated by the RTN package, performs pairwise comparative analysis of shared gene targets to infer dual regulons and regulatory coherence or discordance, and applies enrichment testing with eQTL-linked genes to identify overlapping regulons (36 overlapping regulons reported in the referenced breast cancer study).