Genes-to-Pathways Species Conservation ANalysis (G2P-SCAN): enabling the exploration of conservation of biological pathways and processes across species.

The last two decades has witnessed a strong momentum towards integration of cell-based and computational approaches in safety assessments. This is fuelling a global regulatory paradigm shift towards reduction and replacement of the use of animals in toxicity tests while promoting the use of new approach methodologies. The understanding of conservation of molecular targets and pathways provides an opportunity to extrapolate effects across species and ultimately to determine the taxonomic applicability domain of assays and biological effects. Despite the wealth of genome-linked data available, there is a compelling need for improved accessibility, while ensuring it reflects the underpinning biology. Here, we present the novel pipeline Genes-to-Pathways Species Conservation ANalysis (G2P-SCAN) to further support understanding on cross-species extrapolation of biological processes. This R package extracts, synthetizes and structures the data available from different databases i.e. gene orthologues, protein families, entities and reactions, linked to human genes and respective pathways across six relevant model species. The use of G2P-SCAN enables the overall analysis of orthology and functional families to substantiate the identification of conservation and susceptibility at pathway level. In this manuscript we discuss five case studies, demonstrating the validity of the developed pipeline and its potential use as species extrapolation support. We foresee this pipeline will provide valuable biological insights and create space for the use of mechanistic-based data to inform potential species susceptibility for research and safety decisions purposes. This article is protected by copyright. All rights reserved. Environ Toxicol Chem 2023;00:0-0. © 2023 SETAC.