CREME

CREME identifies and visualizes cis-regulatory modules in the human genome by detecting combinations of transcription factor (TF) binding sites in promoter regions of genes that are potentially co-expressed or co-regulated.

Key Features:

• Identification of Cis-Regulatory Modules: Detects clusters of TF binding sites within promoter regions that are likely to co-occur and constitute functional cis-regulatory modules.
• Input and Output: Accepts a list of gene accession numbers and reports statistically significant combinations of TF binding sites shared among the input promoters.
• Database Utilization: Uses a comprehensive annotation of putative TF binding sites across the human genome derived from position weight matrices and evolutionary conservation with mouse and rat genomes.
• Statistical Scoring and Visualization: Evaluates identified cis-regulatory modules for statistical significance and provides graphical visualizations of significant TF combinations in promoters.

Scientific Applications:

• Transcriptional network analysis: Characterizes cooperative TF interactions and regulatory modules underlying gene expression programs.
• Regulatory mechanism discovery in development and disease: Helps elucidate cis-regulatory architectures that drive context-specific or disease-related expression patterns.
• Functional interpretation of noncoding variation: Aids linking genetic variants in promoter regions to potential effects on TF binding combinations and gene regulation.

Methodology:

Scans an annotated database of putative TF binding sites (based on position weight matrices and cross-species conservation with mouse and rat) using a search algorithm to identify combinations of TF sites that frequently occur in close proximity within promoter regions of the input gene set, followed by statistical evaluation of module significance.