HyPhy.org is home to the HyPhy¹⁾ molecular evolution and statistical sequence analysis software package developed by members of the Viral Evolution Group at the School of Medicine at UCSD and collaborators at other institutions.

HyPhy is a feature rich and mature (in development since 1997), feature rich, scriptable and fast maximum likelihood sequence analysis software platform with over 4000 registered users and over 300 citations in peer reviewed literature.

HyPhy is a scriptable package that can fit statistical evolutionary models to alignment of homologous sequences using Maximum likelihood ²⁾, estimate various parameters that have biological meaning, for example branch lengths, substitution rates, dN/dS ratios, recombination breakpoints, and test hypotheses about how sequences in the alignment have evolved. HyPhy focuses on inference about the evolutionary process. Even though it can do limited alignment and phylogenetic reconstruction, much better specialized programs exist for these purposes.

Here are some of the applications that HyPhy is often used for:

• Positive and negative selection detection
• Recombination analysis
• Detecting co-evolving residues
• Genomic and multiple-gene evolutionary inference
• Molecular clock and relative rate tests
• Nucleotide, protein and codon model selection
• As a likelihood analysis engine for other software and web services
• One-off analyses: tasks that no other package does out of the box and are not worth writing a specialized program for

HyPhy is an actively developed package, that is updated almost daily. If you are comfortable with building software packages from source, you may want to take a look at the HyPhy SVN repository and bug tracking system

Regrettably, HyPhy does not have a proper user manual (unlike a commercial package), but there are various documentation resources available for different user levels.

• Some of the most popular HyPhy functions (recombination, positive selection detection, etc) are implemented in a web-server hosted at http://www.datamonkey.org
• HyPhy tutorial that introduces program concepts, graphical user interface, some concepts of statistical sequence analysis by example and basic HyPhy batch language usage. This document appeared as a book chapter in ''Statistical Methods in Molecular Evolution''. Download PDF
• Theory and practice of detecting positive selection from sequence alignments – a book chapter that appears in the second edition of The Phylogenetic Handbook. Download PDF
• HyPhy has an active developer and user community, members of which interact in our forums