g:Profiler

g:Profiler performs functional enrichment analysis and gene list interpretation to identify enriched Gene Ontology (GO) terms, pathways, and related annotations from flat and ranked gene lists.

Key Features:

• Functional Enrichment Analysis: Analyzes flat and ranked gene lists to identify statistically significant Gene Ontology (GO) terms, pathways, and other gene-function annotations.
• Gene Identifier Translation: Translates hundreds of gene identifiers across various databases via g:Convert to enable consistent identifier mapping.
• Data Synchronization with Ensembl: Synchronizes underlying data sources with Ensembl on a quarterly basis to update genome and pathway annotations.
• Species Support: Supports 467 species and strains, including mammals, plants, insects, fungi, and parasites, enabling cross-species analyses.
• Novel Functional Datasets: Incorporates transcription factor binding site predictions, Mendelian disease annotations, protein expression data, protein complex information, and mappings of human genetic polymorphisms.
• Programmatic Interfaces: Provides programmatic access via the R package gprofiler2, a Python interface, and a BioJS component for integration into computational workflows.
• Analysis Modules: Includes g:Convert for identifier mapping, g:Orth for orthologous gene searches, and g:Sorter for co-expression analysis.
• Multiple Testing Correction over Ontologies: Implements statistical methods to estimate the true effect of multiple testing over complex structures like GO to improve enrichment accuracy.
• Network and Disease Analysis: Performs network analysis to identify enriched protein-protein interaction modules and supports functional analysis of human disease genes.
• Reproducibility and Release Archival: Maintains past releases to support reproducibility and transparency of analyses.

Scientific Applications:

• High-throughput Data Interpretation: Interprets gene lists from high-throughput experiments by identifying enriched biological processes and pathways.
• Cross-species Functional Analysis: Enables orthology-based and comparative analyses across 467 supported species and strains.
• Disease Gene Annotation: Supports functional annotation and analysis of human disease genes, including Mendelian disease annotations and human genetic polymorphism mappings.
• Protein Interaction Module Discovery: Identifies enriched protein-protein interaction modules through network analysis.
• Regulatory and Co-expression Analysis: Investigates transcription factor binding site predictions and co-expression patterns using TF datasets and g:Sorter.

Methodology:

Analyzes flat and ranked gene lists; translates identifiers; performs orthologous gene searches and co-expression analysis; applies statistical estimation for multiple testing over complex ontologies like GO; conducts network analysis for enriched protein-protein interaction modules; and updates data quarterly from Ensembl.