Standard, Stand-alone, & Ecosystem Analyses#
HyPhy is designed as a modular, extensible evolutionary analysis engine. While selection analyses are its most famous application, the platform supports a wide array of built-in CLI standard analyses, community batch files (hyphy-analyses), and direct integration with web platforms like Galaxy.
1. Built-in CLI Standard Analyses#
When running HyPhy from the command line, you can execute a wide variety of standard analyses directly. Running hyphy -i launches an interactive prompt, or you can run any analysis headlessly by passing its command name (viewable via hyphy --help).
Below is an overview of the core built-in analyses:
| Command | Analysis Name | Description |
|---|---|---|
| busted | BUSTED | Test for episodic gene-wide selection. |
| busted-ph | BUSTED-Phenotype | Test if episodic selection is associated with phenotype/foreground branches. |
| absrel | aBSREL | Test for lineage-specific episodic positive selection using an adaptive branch-site model. |
| fel | FEL | Identify individual sites subject to pervasive selection using a maximum likelihood approach. |
| fubar | FUBAR | High-power Bayesian method for detecting site-level pervasive selection on large alignments. |
| meme | MEME | Mixed Effects Model of Evolution to find site-level episodic and pervasive positive selection. |
| slac | SLAC | Counting-based site-level selection test using joint maximum likelihood ancestral reconstruction. |
| relax | RELAX | Test for selection relaxation or intensification along a designated set of branches. |
| prime | PRIME | Property-Informed Models of Evolution to test if selection preserves or alters amino acid properties. |
| gard | GARD | Heuristic search for recombination breakpoints and partitioned tree reconstruction. |
| contrast-fel | Contrast-FEL | Test for site-level differences in selective pressures between predefined clades. |
| contrast-meme | Contrast-MEME | Mixed-effects test for site-level selective differences between clades. |
| bgm | BGM | Apply Bayesian Graphical Models to detect coevolutionary interactions between codon positions. |
| fmm | FitMultiModel | Fit models permitting double or triple instantaneous nucleotide substitutions. |
| fst | F_ST | Compute population genetic differentiation measures with permutation testing. |
| sm | Slatkin-Maddison | Test for gene flow and estimate migration events across populations. |
| leisr | LEISR | Infer relative evolutionary rates on nucleotide/protein alignments (similar to Rate4Site). |
| sw / spl | Sliding Window / SimPlot | Map genetic similarity/distance along alignments using a sliding window. |
| cln | Clean Names | Sanitize sequence headers and replace stop codons with gaps. |
| conv | Convert Codons | Translate an in-frame codon multiple sequence alignment to proteins. |
| label-tree | Label Branches | Annotate branches in a Newick tree for downstream partition analyses. |
2. Galaxy Ecosystem Integration#
The Galaxy Project is a web-based platform for accessible, reproducible, and transparent computational biomedical research. Galaxy is a primary partner in the HyPhy ecosystem, providing a user-friendly graphical interface for high-performance clusters without requiring command-line usage.
The Galaxy Intergalactic Utilities Commission (IUC) maintains official, robust wrapper XMLs for HyPhy tools under the tools-iuc repository. The local equivalents are stored in galaxy-tools/tools-iuc/tools/hyphy.
Supported Galaxy XML Wrappers:#
- Selection Tests:
hyphy_busted.xml,hyphy_absrel.xml,hyphy_fel.xml,hyphy_fubar.xml,hyphy_meme.xml,hyphy_slac.xml - Clade-Specific & Property Tests:
hyphy_cfel.xml(Contrast-FEL),hyphy_prime.xml(PRIME) - Recombination & Relaxation:
hyphy_gard.xml,hyphy_relax.xml - Utility & Networks:
hyphy_bgm.xml(Coevolution),hyphy_cln.xml(Data prep),hyphy_conv.xml(Translation)
By packaging parameter validations, automatic test suites (in /test-data), and detailed biological guidelines directly inside these wrappers, Galaxy enables seamless integration of HyPhy into multi-tool automated workflows.
3. Community Stand-alone Analyses (hyphy-analyses)#
For advanced pipelines, custom models, and experimental methods, the HyPhy team maintains the hyphy-analyses repository. These analyses can be run locally using the HyPhy command-line engine by passing the path to their corresponding batch file.
Selection & Modeling Extensions#
- BUSTED-PH: Test if episodic diversifying selection is associated with a specific phenotype/trait on foreground branches.
- BUSTED-MH: BUSTED variant supporting multiple instantaneous nucleotide substitutions.
- BUSTED-SR: BUSTED variant incorporating synonymous rate variation.
- RELAX-joint: Joint RELAX analysis across multiple gene alignments to boost statistical power.
- RELAX-scan: Perform sliding-window scans of selection relaxation along a gene.
- MulticlassSynonymousSubstitutions: Model codon evolution with multiple distinct classes of synonymous codons.
Model Fitting & Emulation#
- FitMG94: Maximum likelihood fit of a standard Muse-Gaut 94 codon model.
- FitMultiModel: Fit and compare models with single, double, and triple instantaneous mutations.
- PAML-emulator: Emulate standard PAML models (such as M0, M1a, M2a, M7, M8) directly within the HyPhy framework.
- NucleotideNonREV: Fit non-reversible nucleotide models of sequence evolution.
Simulation & Synthetic Data#
- SimulateMG94: Simulate synthetic codon alignments along a tree under MG94 models.
- SimulateProtein: Simulate amino acid sequence evolution under standard matrices.
Sequence Preparation & Utilities#
- codon-msa: A helper workflow for generating codon-aware multiple sequence alignments.
- LabelTrees: Automatically annotate phylogenetic trees for downstream branch-partition analyses.
- clean-names / remove-duplicates: Sanitization scripts to clean sequence headers and prune identical taxa from trees and alignments.
- extract-partitions: Extract multi-partition alignments into individual files.