GeneAutomate: A Browser-Based, Integer-Indexed Platform for Dual-Gene-List Functional Annotation and Interactive Network Visualization

Abstract

Comparative interpretation of two gene lists, for example, two treatment arms, two tissues, or a discovery and a validation cohort, is a routine task in functional genomics. While several tools offer dual-list comparison (e.g., EnrichmentMap, RRHO packages), they typically require local software installation, R/Bioconductor, or manual reconciliation of separate single-list outputs. Most widely used web-based enrichment tools (DAVID, g:Profiler, Enrichr, ShinyGO, WebGestalt) are built around the analysis of a single gene list at a time, and those that support comparison often lack interactive, publication-ready visualization or depend on server-side query latency. Here we present GeneAutomate, a browser-based tool purpose-built for side-by-side comparison of two gene lists. GeneAutomate performs Over-Representation Analysis (ORA) against Gene Ontology (GO) and Reactome using an exact hypergeometric test with Benjamini-Hochberg false discovery rate correction, and Gene Set Enrichment Analysis (GSEA) when ranked (log2 fold-change) input is supplied, alongside Protein-Protein Interaction (PPI) subgraph extraction from BioGRID physical interactions. All reference data (Gene Ontology, Reactome, BioGRID, and NCBI/Ensembl identifier cross-references) are pre-compiled offline into a single integer-indexed database of approximately 32 MB for Homo sapiens, in which every gene identifier Ensembl ID, Entrez ID, official symbol, or alias is resolved to one canonical integer prior to any user query. This design removes live database round-trips from the runtime path, enabling fast, at-your-desk enrichment without installation or a server-side per-query bottleneck. The tool renders thirteen interactive, D3.js- and Cytoscape.js-based comparative visualizations, including a Rank-Rank Hypergeometric Overlap (RRHO) heatmap, a GO-slim "Radar/Spider" functional fingerprint, and chord/edge-bundled cross-talk diagrams that are, to our knowledge, not offered as an integrated set by any existing academic or commercial ORA/GSEA platform. GeneAutomate is an unfunded, individual student project developed with feedback from a professor, and is in its final stage of development. It requires no installation or login. We describe the tools architecture, statistical methods, and comparative feature set relative to established academic tools (DAVID, ShinyGO, g:Profiler, Enrichr, WebGestalt, STRING, PANTHER, GeneMANIA, Cytoscape, clusterProfiler, GSEA, Metascape) and commercial platforms (IPA, MetaCore, Pathway Studio, iPathwayGuide, Partek Pathway), and we state candidly the current versions limitations, which are planned to be the added in next version: single-species (human-only) coverage, no upstream regulator analysis, and comparison currently limited to two (occasionally three) concurrent lists. GeneAutomate is available at https://geneautomate.tech/.