OrthoGuide: A Database for Rooting Inference of Orthologous Genes

Abstract

Orthology provides a powerful framework for investigating the evolutionary history of biological systems, as genes within the same orthologous group typically share a common ancestry. By tracing their distribution across species, it is possible to infer the evolutionary origin of genes and reconstruct the stepwise assembly of molecular pathways and regulatory networks. However, performing such analyses at scale often requires specialized computational tools and expertise, limiting their accessibility to a broader community. Here, we introduce OrthoGuide, a database and web application that provides precomputed evolutionary rooting information for orthologous groups across 360 eukaryotic species. The platform enables users to query gene sets and rapidly explore their evolutionary origins through an intuitive interface, without the need for local computational workflows. In addition to tabular outputs, OrthoGuide offers interactive visualizations that facilitate the interpretation of evolutionary patterns and the identification of key events in the emergence of biological systems. By removing technical barriers and standardizing large-scale evolutionary inferences, OrthoGuide enables researchers to translate gene lists into biologically meaningful hypotheses. This resource democratizes access to orthology-based evolutionary analyses and supports the investigation of system-level evolutionary processes across a wide range of organisms. The web application and the database are hosted at https://dalmolingroup.imd.ufrn.br/orthoguide/.