Abstract Summary The conservation of pathways and genes across species has allowed scientists to use non-human model organisms to gain a deeper understanding of human biology. However, the use of traditional model systems such as mice, rats, and zebrafish is costly, time-consuming and increasingly raises ethical concerns, which highlights the need to search for less complex model organisms. Existing tools only focus on the few well-studied model systems, most of which are complex animals. To address these issues, we have developed O rthologous Ma trix and M odel O rganisms, a software and a website that provide the user with the best simple organism for research into a biological process of interest based on orthologous relationships between the human and the species. The outputs provided by the database were supported by a systematic literature review. Availability and implementation https://omabrowser.org/omamo/ , https://github.com/DessimozLab/omamo Contact christophe.dessimoz@unil.ch and sina.majidian@unil.ch

OMAMO: orthology-based model organism selection