GREAT

GREAT assigns biological meaning to cis-regulatory genomic regions identified from DNA binding events by associating non-coding loci with nearby genes and testing for ontology term enrichment.

Key Features:

• Region-to-gene assignment: Leverages genomic annotations to assign non-coding cis-regulatory regions to nearby genes based on proximity and association.
• Proximal and distal binding integration: Incorporates both proximal and distal binding sites to capture regulatory elements that are not immediately adjacent to genes.
• Statistical testing: Employs a binomial test to control for false positives among the input genomic regions.
• Ontology coverage: Utilizes annotations from 20 diverse ontologies to map regions to functional terms.
• Region-centric enrichment: Performs region-centric functional enrichment as an alternative to traditional gene-based approaches.

Scientific Applications:

• ChIP-seq analysis: Interprets ChIP-seq peaks and other DNA binding event datasets to infer regulatory functions.
• Transcription factor studies: Has been applied to datasets for SRF, NRSF, GABP, Stat3, and p300 to reveal regulatory roles across developmental contexts.
• Open chromatin and epigenomics: Applies to open chromatin regions and localized epigenomic markers to assign putative functions.
• Comparative genomics: Can be used with comparative genomics datasets to relate conserved non-coding regions to functional annotations.
• Functional discovery: Facilitates uncovering functions overlooked by existing methods and generating testable hypotheses.

Methodology:

Assigns regions to genes using genomic annotations and proximity/association, incorporates proximal and distal binding sites, applies a binomial test for enrichment/false-positive control, and maps results to terms from 20 ontologies.