TraFaC

TraFaC identifies and compares compositionally similar transcription factor (TF) binding site clusters within evolutionarily conserved noncoding genomic sequences to locate candidate regulatory regions.

Key Features:

• Conserved sequence analysis (BLASTZ): Uses BLASTZ to detect evolutionarily conserved noncoding genomic sequences for comparative analysis.
• TF-binding site analysis (MatInspector): Uses MatInspector to identify transcription factor binding sites within sequences.
• Integration of BLASTZ and MatInspector results: Merges conserved-sequence and TFBS analyses to focus on phylogenetically conserved regions enriched for cis-elements.
• 200-bp moving average window: Computes the density of co-occurring cis-element TF-binding sites using a 200-bp moving average window.
• Regulogram visualization: Plots hit count, defined as TF-binding site density, as a function of position within aligned orthologous genomic regions.
• Trafacgram visualization: Illustrates the relative arrangement of shared cis-elements within compositionally similar TF-binding site clusters.
• Detection across nonorthologous regulatory regions: Detects similarities in composition and relative arrangement of cis-element clusters across nonorthologous genes, promoters, and enhancers.
• Sensitivity to cis-element shuffling: Remains sensitive to rearrangements of cis-elements within known functional regulatory regions, including less-conserved orthologous genes.

Scientific Applications:

• Regulatory region identification: Locates candidate control regions enriched for TF-binding site clusters within conserved noncoding DNA.
• Comparative cis-element analysis: Compares composition and relative arrangement of cis-element clusters across orthologous and nonorthologous genes.
• Promoter and enhancer characterization: Characterizes compositionally similar TF-binding site clusters in promoters and enhancers with coordinated regulatory properties.
• Evolutionary functional genomics: Assesses phylogenetic conservation of regulatory architecture beyond primary sequence similarity.

Methodology:

Integrates BLASTZ conserved-sequence analysis with MatInspector TF-binding site identification, computes TF-binding site density using a 200-bp moving average window, and visualizes results as Regulograms (hit count versus position in aligned orthologous regions) and Trafacgrams (relative arrangement of shared cis-elements within clusters).