PhyloCTCFLooping

PhyloCTCFLooping analyzes vertebrate genomic sequences to detect CTCF-motif–encoded chromatin looping by computing a 3D ratio (3DR) that quantifies relative distances between convergent and divergent CTCF motif pairs for studying 3D genome and topologically associating domain (TAD) evolution.

Key Features:

• CTCF Motif Analysis: Identifies CTCF motifs, determines motif orientation, and compares distances between convergent and divergent CTCF motif pairs to assess sequence-encoded looping signals.
• 3D Ratio (3DR) Computation: Computes the 3D ratio (3DR), a statistic that quantifies the relative distances between convergent and divergent CTCF motifs as an indicator of chromatin looping.
• Evolutionary Insights: Compares 3DR values across vertebrate genomes to investigate the evolution of chromatin looping and TAD organization and to reveal evolutionary constraints in DNA sequence associated with 3D genome architecture.
• Ancestral Character Reconstruction: Infers ancestral 3DR values via ancestral character reconstruction to explore historical changes in genomic 3D organization.

Scientific Applications:

• Gene expression regulation: Enables investigation of how sequence-encoded chromatin loops correlate with gene regulatory programs across species.
• Replication-timing programs: Facilitates study of relationships between 3D genome organization inferred from sequence and replication-timing schedules.
• Comparative evolutionary genomics: Supports comparative analyses of 3D genome features across vertebrates using only genomic sequences.
• 3D genome and TAD evolution: Provides metrics to study the evolutionary dynamics of topologically associating domains and higher-order chromatin structure.

Methodology:

Identify CTCF motifs and orientations in vertebrate genomes; calculate distances between convergent and divergent motif pairs; compute the 3DR statistic; compare 3DR metrics across species; perform ancestral character reconstruction of 3DR values.