MTKSimulations

This directory contains multiple folders to run simulations for assessing the performance and accuracy of the new MultiTreeKnit module in TreeKnit.

To read more about how TreeKnit works please refer to the paper:

TreeKnit: Inferring Ancestral Reassortment Graphs of influenza viruses Pierre Barrat-Charlaix, Timothy G. Vaughan, Richard A. Neher bioRxiv 2021.12.20.473456; doi: https://doi.org/10.1101/2021.12.20.473456.

Installation

I use multiple julia packages which are not registered and additionally use a non-master branch of TreeKnit. Thus, to avoid installation issues I always install julia packages using the following commands:

using Pkg
Pkg.add("PackageCompiler")
Pkg.add("TreeTools")
Pkg.add("ArgParse")
Pkg.add("CSV")
Pkg.add("DataFrames")
Pkg.add("Combinatorics")
Pkg.add("StatsBase")
Pkg.add("Distributions")
Pkg.add("Dagger")
Pkg.add("Clustering")
## branch of TreeKnit with MultiTreeKnit module
Pkg.add(url="https://github.com/PierreBarrat/TreeKnit.jl", rev="MTK_no_consistency")
## modules needed for TestRecombTools - package with MCC metrics designed by Pierre
Pkg.add(url="https://github.com/diegozea/ROC.jl", rev="master")
## needed for sequence simulations
Pkg.add(url="https://github.com/anna-parker/TreeAlgs-Fork")
Pkg.add(url="https://github.com/PierreBarrat/TestRecombTools")
## modules needed to simulate ARGs 
Pkg.add(url="https://github.com/PierreBarrat/ARGTools")
Pkg.add(url="https://github.com/anna-parker/MTKTools", rev="main")
## package to plot results
Pkg.add("Plots")

I use Snakemake for coordinating my simulations and running treetime in the divergence time simulation pipeline. To reconstruct my mamba environment run the command:

mamba env create -f environment.yml

Incase an error occurs the feat/multiTK_arg branch of treetime should be used and needs to installed via the command:

pip install https://github.com/neherlab/treetime/archive/feat/multiTK_arg.zip

Simulations

As I performed most simulations on a cluster I have included a bash script for launching simulations in SLURM- note that I use parallel TreeKnit which requires all computatiosn to be performed on one node. Simulations are managed by the Snakemake file in each simulation folder - with parameters in the config.json file. The general set up is:

• Simulate 8 segment ARGs with ARGTools with these parameters. ARGs map to true MCCs and true trees of each segment.
• Take arbitrary $k \leq 8$ subsamples of these 8 segment trees as input for TreeKnit. Typically internal branches of input trees are additionally removed at random to create unresolved trees.
• Assess the accuracy of TreeKnit's inference - write a summary of accuracy to a txt file
• Plot results of simulations
• remove unnecessary files, zip output files

1. Accuracy of MCCs

Assessment of MCC accuracy with VI and rand index.

2. Accuracy of Resolved Polytomies

Using RF - distance improvement of tree and percentage of missing splits that are corrected or incorrectly added back to the tree.

3. Accuracy of Shared Branches

Using percentage of branches that are correctly and incorrectly inferred to be shared amongst tree pairs.

4. Accuracy of Divergence Time Estimations

Improvement of divergence time inference with TreeTime when TreeKnit is used to infer shared branches and this information is used in ancestral sequence reconstruction and branch length/ divergence time inference.

5. Consistency of MCCs

Make sure that the Maximally Compatible Clades found by TreeKnit fulfill all necessary conditions, e.g. they are topologically compatible and are consistent.