GOReverseLookup: A gene ontology reverse lookup tool

Area of Science:

• Bioinformatics
• Computational Biology
• Genomics

Background:

• The Gene Ontology (GO) project provides a structured framework for gene characterization and annotation.
• Traditional gene annotation focuses on mapping genes to GO terms, but lacks robust reverse querying capabilities.
• There is a growing need for tools that facilitate identifying genes associated with researcher-defined phenotypes.

Purpose of the Study:

• Introduce GOReverseLookup, a novel tool for identifying over- or underrepresented genes in user-defined phenotypes.
• Enable reverse querying of genes based on sets of GO terms.
• Facilitate orthologous gene querying across multiple databases (Ensembl, UniProtKB) for cross-species research.

Main Methods:

• GOReverseLookup queries genes linked to user-input GO terms, grouped into 'bundles' representing states of interest.
• The tool retrieves all GO terms associated with each queried gene.
• Statistical relevance is computed to determine gene involvement in the defined states of interest.

Main Results:

• Demonstrated utility in identifying genes related to rheumatoid arthritis.
• Successfully discovered genes associated with chronic inflammation and tumorigenesis.
• Identified a substantial number of significantly associated genes in both use cases.

Conclusions:

• GOReverseLookup is a valuable resource for understanding the genetic basis of phenotypes.
• The tool has diverse applications in functional genomics, systems biology, and drug discovery.
• GOReverseLookup can significantly aid in identifying potential gene targets during early research phases.