biostudies-literatureSchoenstein MAgence Nationale de la Recherche806-819https://www.ebi.ac.uk/biostudies/studies/S-EPMC12756282biostudies-literatureUnknown93(6)Phylogenetic profiling, involving the analysis of presence-absence of orthologs in a set of species, is a way to infer functional association between genes through co-evolutionary patterns. Since its inception, numerous methods have been described to construct phylogenetic profiles, evaluate their similarity, or identify clusters of co-evolving genes. However, few of these methods are available as downloadable software. We present Profylo, a phylogenetic profiling toolkit made available as an open-source Python 3.0 package. Profylo implements seven methods for comparing phylogenetic profiling, four algorithms for identification of co-evolving clusters, as well as tools to help with their analysis, including visualization features. We take advantage of the variety of methods implemented in Journal of molecular evolutionProfylo: A Python Package for Phylogenetic Profile Comparison and Analysis.PMC12756282ANR-24-CPJ1-0082-01Nevers YMermillod PSchoenstein MKress ALecompte OfalseProfylo: A Python Package for Phylogenetic Profile Comparison and Analysis.Phylogenetic profiling, involving the analysis of presence-absence of orthologs in a set of species, is a way to infer functional association between genes through co-evolutionary patterns. Since its inception, numerous methods have been described to construct phylogenetic profiles, evaluate their similarity, or identify clusters of co-evolving genes. However, few of these methods are available as downloadable software. We present Profylo, a phylogenetic profiling toolkit made available as an open-source Python 3.0 package. Profylo implements seven methods for comparing phylogenetic profiling, four algorithms for identification of co-evolving clusters, as well as tools to help with their analysis, including visualization features. We take advantage of the variety of methods implemented in 2025-01-01T00:00:00Z2025 Dec2026-05-29T03:23:19.679Z2026-05-29T03:13:08.933ZS-EPMC127562824116013110.1007/s00239-025-10280-6