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HyPhy: Hypothesis testing using Phylogenies HyPhy is an open-source software package for the analysis of genetic sequences (in particular the inference of natural selection) using techniques in phylogenetics, molecular evolution, and machine learning. It features a rich scripting language for limitless customization of analyses. Additionally, HyPhy features support for parallel computing environments (via message passing interface). HyPhy was designed to allow the specification and fitting of a broad class of continuous-time discrete-space Markov models of sequence evolution. To implement these models, HyPhy provides its own scripting language - HBL, or HyPhy Batch Language, which can be used to develop custom analyses or modify existing ones. Importantly, it is not necessary to learn (or even be aware of) HBL in order to use HyPhy, as most common models and analyses have been implemented for user convenience. Once a model is defined, it can be fitted to data (using a fixed topology tree), its parameters can be constrained in user-defined ways to test various hypotheses (e.g. is rate1 > rate2), and simulate data from. HyPhy primarily implements maximum likelihood methods, but it can also be used to perform some forms of Bayesian inference (e.g. FUBAR), fit Bayesian graphical models to data, run genetic algorithms to perform complex model selection. Features - Support for arbitrary sequence data, including nucleotide, amino-acid, codon, binary, count (microsattelite) data, including multiple partitions mixing differen data types. - Complex models of rate variation, including site-to-site, branch-to- branch, hidden markov model (autocorrelated rates), between/within partitions, and co-varion type models. - Fast numerical fitting routines, supporting parallel and distributed execution. - A broad collection of pre-defined evolutionary models. - The ability to specify flexible constraints on model parameters and estimate confidence intervals on MLEs. - Ancestral sequence reconstruction and sampling. - Simulate data from any model that can be defined and fitted in the language. - Apply unique (for this domain) machine learning methods to discover patterns in the data, e.g. genetic algorithms, stochastic context free grammars, Bayesian graphical models. - Script analyses completely in HBL including flow control, I/O, parallelization, etc. Registration you are highly advised to fill the registration form found at: https://veg.github.io/hyphy-site/register/ Citing Sergei L. Kosakovsky Pond, Simon D. W. Frost and Spencer V. Muse (2005) HyPhy: hypothesis testing using phylogenies. Bioinformatics 21(5): 676-679