XXmotif

XXmotif identifies regulatory motifs enriched in sets of nucleotide sequences (DNA or RNA) and represents them as position weight matrices (PWMs) to characterize binding sites of proteins and non-coding RNAs.

Key Features:

• Direct optimization of statistical significance: Minimizes enrichment P-values for PWM optimization rather than maximizing likelihood.
• High-throughput P-value computation: Efficiently computes millions of enrichment P-values across thousands of candidate PWMs.
• Order-statistics evaluation of placements: Uses order statistics to evaluate all possible motif placements within input sequences.
• Multifaceted scoring: Scores motifs for conservation and positional clustering to assess biological relevance.
• PWM representation: Produces motifs as position weight matrices (PWMs) for downstream analysis.

Scientific Applications:

• Analysis of binding specificity: Characterizes sequence-dependent DNA and RNA binding affinities of proteins and non-coding RNAs to investigate gene regulatory mechanisms.
• Functional genomics datasets: Applied to ChIP-chip, ChIP-seq, miRNA knock-down, and coexpression datasets for motif discovery.
• Benchmarking: Demonstrated superior sensitivity and reliability on yeast and metazoan sequence benchmarks compared to state-of-the-art tools.
• Regulatory element discovery: Identified known regulators and novel motifs in Drosophila melanogaster segmentation modules and human core promoters, including an Initiator motif similar to those in fly and yeast.

Methodology:

Direct minimization of enrichment P-values for PWM optimization; computation of enrichment P-values for millions of candidate PWMs across sequences; evaluation of motif placements using order statistics; scoring of motifs for conservation and positional clustering; representation of motifs as PWMs.