oPOSSUM

oPOSSUM identifies over-represented transcription factor binding sites (TFBSs) in gene promoters to infer regulatory mechanisms underlying co-expressed genes by integrating a pre-computed database of conserved TFBSs from human and mouse promoters with statistical methods.

Key Features:

• TFBS over-representation detection: Identifies TFBSs over-represented among co-expressed genes to implicate transcription factors mediating co-regulation.
• Conserved TFBS database: Uses a pre-computed database of conserved TFBSs from human and mouse promoters.
• Statistical analysis with empirical thresholds: Applies statistical methods with empirically defined thresholds to maintain low false positive rates and tolerate up to 50% noise in gene expression data.
• Species-specific versions: Provides versions tailored for Caenorhabditis elegans and Saccharomyces cerevisiae for investigation of conserved binding sites.
• Ortholog mapping and alignment improvements: Incorporates improved ortholog mapping, sequence alignments, and alternative promoter delineation for human and mouse analyses.
• Integration with oPOSSUM2: Integrates with oPOSSUM2 to enable analysis of over-represented motif combinations in human and mouse genes.
• User-defined background gene sets: Supports the use of custom background gene sets for analyses.
• Updated TFBS models including JASPAR: Uses updated transcription factor binding site models that include new profiles from the JASPAR database.

Scientific Applications:

• Transcription factor identification: Identifies candidate transcription factors that may mediate co-regulation in co-expressed gene sets.
• Tissue-specific and transcript profiling studies: Detects mediating TFs within tissue-specific gene sets and across transcript profiling studies.
• Cross-species conserved site analysis: Investigates conserved binding sites in Caenorhabditis elegans and Saccharomyces cerevisiae.
• Motif combination analysis: Analyzes over-represented motif combinations in human and mouse genes via integration with oPOSSUM2.

Methodology:

Integrates a pre-computed database of conserved TFBSs from human and mouse promoters with statistical methods using empirically defined thresholds; employs ortholog mapping, sequence alignments, and alternative promoter delineation; uses updated TFBS models from the JASPAR database; and integrates with oPOSSUM2 for analysis of motif combinations.