BEAST phylonco

This is a BEAST2 package for Bayesian inference of molecular data for cancer evolution. This package implements error models and substitution models for inference of timed trees in a Bayesian MCMC framework.

Paper: Chen, K., Moravec, J. C., Gavryushkin, A., Welch, D., & Drummond, A. J. (2022). Accounting for errors in data improves divergence time estimates in single-cell cancer evolution. Molecular biology and evolution, 39(8), msac143.

See bioDS/beast-phylonco-paper for datasets and analyses in the paper.

If you have any questions, please use the beast-users google group https://groups.google.com/u/0/g/beast-users

Software requirements

This package requires Java 17 and at least BEAST v2.7

For version requirements and lphy / lphybeast setup instructions see the latest release notes

Features

The current release has the following features.

Error Models

• GT16 diploid nucleotide error model (16 states)
• Binary error model
• Nucleotide error model (4 states - A, G, C, T)
• General error model (n states)

Substitution Models

• GT16 diploid nucleotide model (16 states)
• Binary substitution model
• SiFit2 substitution model (2 states)
• SiFit3 substitution model (3 states)

User guide

How to install

You can install the Phylonco package using the Package Manager, or by command line.

Package manager:

1. Start BEAUti, open the Package Manager by selecting File -> Manage packages from the Menu.
2. From the Package Manager, select phylonco and click Install/Upgrade to install.
3. This may take a few minutes to install the package and dependencies.
4. Restart BEAUti after installation is complete, and the phylonco package should now appear as Installed.

Command line:

~/beast/bin/packagemanager -add phylonco

Input format

All models accept input genotypes in Nexus format. See here for the genotype codes.

For the GT16 model, VCF files can be converted to Nexus or FASTA format using www.github.com/bioDS/vcf2fasta

Running BEAST

Start the BEAST software

Set the input file to one of the examples e.g., examples/test_GT16_error.xml

Running BEAST on command line

These models can be run using the Java implementation (slower), or the Beagle implementation (faster). We recommend using Beagle with the GPU option for large datasets.

Java option

To run the Java implementation, use the commands:

Windows
java -jar c:\Users\BEASTUser\Desktop\BEAST\lib\launcher.jar -java beast.xml

Mac
/Applications/BEAST\ 2.6.6/bin/beast -java beast.xml

Linux
~/beast/bin/beast -java beast.xml

Beagle option

To run datasets using Beagle, we need to install Beagle, and modify a single line in our XML. Open your XML in a text editor, find the element with id='treeLikelihood' and replace the spec field with spec='phylonco.beast.evolution.likelihood.BeagleTreeLikelihoodWithError'.

For example, replace this

<input id='treeLikelihood' spec='phylonco.beast.evolution.likelihood.TreeLikelihoodWithErrorFast' useAmbiguities='true' useTipLikelihoods='true'>
    ...
</input>

with the following

<input id='treeLikelihood' spec='phylonco.beast.evolution.likelihood.BeagleTreeLikelihoodWithError' useAmbiguities='true' useTipLikelihoods='true'>
    ...
</input>

To run Beagle with GPU use:

~/beast/bin/beast -beagle_GPU beast.xml

How to setup model via BEAUti

BEAUti currently supports the GT16 Substitution model and Binary Substitution model. Support for error models in Beauti will be added soon.

Setting up a basic analysis:

1. Convert your data from VCF to Nexus format using the full diploid genotype option https://github.com/bioDS/vcf2fasta#converting-vcf-to-nexus
2. Open Beauti, from the menu go to File -> Import Alignment and select your Nexus file. Select the Ambiguities checkbox next to your alignment.
3. Go to the Site Model panel, and select GT16SubstitutionModel.
4. To adjust tree model and priors, use the Priors panel.
5. Go to the MCMC panel and input your required chain length.
6. From the menu go to File -> Save to save your XML. This XML can now be run using BEAST 2.

Adding error models to the analysis:

This requires editing the XML generated from Beauti, see examples in the examples directory.

For developers

Project now uses Maven, for details see dev notes

For manual beast package installation instructions, see here

Citations

• BEAST v2.5: Bouckaert at al. (2019)

• BEAST2 Error models: Chen et al. (2022)

• GT16 model: Kozlov et al. (2022)

• SiFit2, SiFit3 models: Zafar et al. (2017)

• Hou 2012 dataset: Hou et al. (2012)