PaReBrick 0.1.5

A bioinf tool for finding genome rearrangements in bacterial genomes

PaReBrick (Parallel Rearrangement and Breakpoints)

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Project goals

Bacterial genomes are remarkably plastic on the evolutionary time scale, and genomic rearrangements such as inversions, deletions, insertions, and duplications independently occur in the genomes of different strains, which may serve a mechanism of the adaptation to changing environmental conditions. Identification of these events requires laborious manual inspection and verification of the phyletic pattern consistency. Thus, the main goal of this project is identification and description of parallel rearrangements occurring in bacterial genomes.

More strictly, our goal is to find characters which are non-convex on a phylogenetic tree, or in other words characters with homoplasy. Homoplasy is when a character state has been gained independently in separate lineages over the course of evolution. You can see an example of convex and non-convex characters below:

Non-convex character (character with homoplasy)	Convex character (homoplasy-free character)

Methods

This method takes synteny blocks and phylogenetic tree for some strains as input and Method consist of two main parts:

1. Constructing characters and them states (~colors of leaves) with synteny blocks:
   • Balanced rearrangements (focused in inversions) — search pattern in multiple breakpoint graph;
   • Unbalanced rearrangements — considered as copy number variation.
2. Checking convexity of constructed characters on a phylogenetic tree. Also counting "measure" of non-convexity for all non-convex characters and sort by its value.

For output size reduction and detection of phyletic patterns of blocks in unbalanced rearrangements case, character clustering is performed.

Installation

PaReBrick can be installed with pip:

pip install PaReBrick

Script parameters

Main script of project including all modules together can be run with python and console arguments.

Input

Here is input parameters of that script:

PYTHONPATH=. python3 src/main.py --help
usage: main.py [-h] --tree TREE --blocks_folder BLOCKS_FOLDER
               [--labels LABELS] --output OUTPUT

Based on synteny blocks and phylogenetic tree this tool calls parallel
rearrangements.

optional arguments:
  -h, --help            show this help message and exit
  --tree TREE, -t TREE  Tree in newick format, must be parsable by ete3
                        library.You can read more about formats supported by
                        ete3 at http://etetoolkit.org/docs/latest/tutorial/tut
                        orial_trees.html#reading-and-writing-newick-trees
  --blocks_folder BLOCKS_FOLDER, -b BLOCKS_FOLDER
                        Path to folder with blocks resulted as output of
                        original Sibelia or maf2synteny tool.
  --labels LABELS, -l LABELS
                        Path to csv file with tree labels, must contain two
                        columns: `strain` and `label`.
  --output OUTPUT, -o OUTPUT
                        Path to output folder.

Output

Output consist of tree folders.

1. preprocessed_data — here you can find blocks_coords.infercars for better blocks representation and region annotation. And genomes_permutations_unique.txt file used for calling balanced characters.
2. balanced_rearrangements_output — this folder contains stats.csv file with all non-convex characters statistics of balanced rearrangements. And folders characters, trees with character representation in rendered .pdf tree and .csv formats.
3. unbalanced_rearrangements_output — this folder contains stats.csv file with all non-convex characters statistics of unbalanced rearrangements. And folders characters, trees with character in rendered .pdf tree and .csv formats in subfolders according to their clustering representation.

Example

Code must be with PYTHONPATH in root of the project. Running on example input:

PYTHONPATH=. python3 src/main.py -t example-data/e_coli/input/tree.nwk -b example-data/e_coli/input/maf2synteny-output -o example-data/e_coli/output -l example-data/e_coli/input/labels.csv

Example output

<Running module: Preprocess Data>
-------------------------------------------------------------------------------- 
Converting block coords to infercars format
-------------------------------------------------------------------------------- 
<Module finished: Preprocess Data>, elapsed 6.938694953918457 seconds


<Running module: Parsers and check strains>
-------------------------------------------------------------------------------- 
Blocks count: 409
Unique one-copy blocks count: 49
Mean block coverage: 17.835936180054084 %
Mean unique one-copy blocks coverage: 7.925360661469914 %

Strains in blocks file count: 414
Strains in tree leafs count: 414
Intersected strains count: 414
-------------------------------------------------------------------------------- 
<Module finished: Parsers and check strains>, elapsed 1.1283211708068848 seconds


<Running module: Balanced rearrangements characters>
-------------------------------------------------------------------------------- 
Breakpoint graph parsed
Edges in breakpoint graph: 185
Getting characters from breakpoint graph component, size=66
-------------------------------------------------------------------------------- 
<Module finished: Balanced rearrangements characters>, elapsed 11.117300987243652 seconds


<Running module: Balanced rearrangements stats>
-------------------------------------------------------------------------------- 
Counting distances between unique one-copy blocks, may take a while
Got characters after breakpoint graph consideration: 33
Left non-convex characters after filtering: 26
-------------------------------------------------------------------------------- 
<Module finished: Balanced rearrangements stats>, elapsed 7.587311029434204 seconds


<Running module: Balanced rearrangements output>
-------------------------------------------------------------------------------- 
-------------------------------------------------------------------------------- 
<Module finished: Balanced rearrangements output>, elapsed 20.30529260635376 seconds


<Running module: Unbalanced rearrangements characters>
-------------------------------------------------------------------------------- 
-------------------------------------------------------------------------------- 
<Module finished: Unbalanced rearrangements characters>, elapsed 0.05289006233215332 seconds


<Running module: Unbalanced rearrangements stats and clustering>
-------------------------------------------------------------------------------- 
Got characters after copy number variation consideration: 409
Left non-convex characters after filtering: 261
Counting distances between non-convex character blocks, may take a while
Jaccard index matrix constructed
Proximity matrix constructed
Clustring is done
Clusters: 86
-------------------------------------------------------------------------------- 
<Module finished: Unbalanced rearrangements stats and clustering>, elapsed 13.429708242416382 seconds


<Running module: Unbalanced rearrangements output>
-------------------------------------------------------------------------------- 
-------------------------------------------------------------------------------- 
<Module finished: Unbalanced rearrangements output>, elapsed 178.54327082633972 seconds


Total elapsed time: 239.10328888893127