Phyloscan

Phyloscan detects transcription factor binding sites in promoter and intergenic regions and identifies regulons across related bacterial species by integrating evolutionary conservation and motif recurrence across orthologous sequences.

Key Features:

• Evolutionary Conservation: Exploits conservation of functional transcription factor binding sites across species to improve site identification accuracy.
• Repetitive Motifs: Uses multiple occurrences of binding sites within promoter regions to increase confidence in true functional sites.
• Mixed Sequence Data Utilization: Accepts aligned and unaligned sequence data, and combinations thereof, to incorporate orthologous data from related species.
• Phylogenetic Considerations: Statistically accounts for phylogenetic relationships when using aligned data and assumes phylogenetic independence for unaligned data.
• Statistical Significance: Calculates statistical significance of gene predictions directly without relying on training sets.
• Evidence Aggregation: Aggregates evidence by combining matching sites in orthologous sequences with multiple occurrences within intergenic regions.

Scientific Applications:

• Microbial regulon discovery: Identifies transcription factor binding sites and delineates regulons across bacterial species by integrating orthologous sequences and promoter-region motif recurrence.
• Benchmarking and empirical discovery: Demonstrated superior sensitivity and specificity compared to MONKEY on synthetic data modeled on Enterobacteriales, Vibrionales, and Pasteurellales, and identified novel Crp and PurR binding sites in E. coli from Enterobacteriales sequence data.

Methodology:

Combines evidence from matching sites in orthologous sequences with multiple occurrences within intergenic regions, handles aligned and unaligned sequence data (statistically accounting for phylogeny for aligned data and assuming phylogenetic independence for unaligned data), and computes statistical significance of gene predictions without using training sets.