HyPhy

HyPhy, short for Hypothesis Testing using Phylogenies, is a cross-platform open-source software package for evolutionary biology. It provides a flexible platform for testing evolutionary hypotheses using phylogenetic trees and sequence data, with a focus on detecting natural selection at sites and across lineages.

The software features a dedicated scripting language (the HyPhy batch language) and an optional graphical user interface. It runs on Windows, macOS, and Linux, and supports nucleotide, amino acid, and codon alignments, with input in standard formats and accompanying phylogenetic trees. It also offers built-in simulation capabilities for power analysis and model checking.

Built-in methods include site-wise approaches such as FEL, SLAC, and FUBAR; episodic methods such as MEME; and branch-site tests such as aBSREL and BUSTED, as well as RELAX for testing changes in selection pressure intensity. Users can compose custom analyses by writing HyPhy batch scripts or extending the platform via its API.

HyPhy is widely used in molecular evolution research to study natural selection, functional constraint, and diversification across genomes. It is maintained by a community of researchers and developers with extensive online documentation, tutorials, and example datasets. The project is open-source, with source code and documentation available publicly on platforms like GitHub, enabling reproducible analyses.