SADMAMA

SADMAMA detects significant variations in binding affinity between two sets of sequences by modeling binding sites as matches to a known, possibly gapped, position weight matrix (PWM) to test for enrichment in both the number and quality of PWM matches.

Key Features:

• PWM-based binding site modeling: Models binding sites as matches to a known, possibly gapped, position weight matrix (PWM).
• Comparative enrichment testing: Evaluates whether one set of sequences is significantly enriched relative to another in both number and quality of PWM matches.
• Simplified statistical models: Provides simplified models for straightforward assessment of sequence enrichment.
• Bootstrapping with site-protected resampling: Implements bootstrapping including a site-protected resampling procedure to address deficiencies of naive resampling techniques.

Scientific Applications:

• Differential ARS activity analysis: Applied to assess differential ARS activity observed in mcm1-1 mutant experiments.
• Replication origin function investigation: Used to demonstrate the importance of multiple weak ACS matches for efficient replication origin function in Saccharomyces cerevisiae.
• Chromatin silencing studies: Used to provide explanations for the negative effects of FKH2 on chromatin silencing.

Methodology:

Models binding sites as PWM matches (including gapped PWMs) and implements two statistical approaches: simplified models and bootstrapping with a site-protected resampling procedure.