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OR IF there are genes you wish to be excluded from deletion (kicking in from the second stage), create a text file "exclusionlist.txt". IF you would like to create a custom file of genes to attempt to knockout from the Mycoplasma genitalium in-silico genome:
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Install time: download time of Minesweeper.
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The command line software we used included: P圜harm (IDE software) for an inbuilt desktop terminal and python debugging.FileZilla (ftp software) to move files in bulk to and from the supercomputer.Putty (ssh software)/ the terminal to access the supercomputer.We used the following GUI software on Windows/Linux Cent OS: We used a standard office desktop computer, with 8GB of ram, to write new code, interact with the supercomputer, and run single whole-cell model simulations. The use of no external libraries means that the code is longer than it could be, but it (hopefully) has greater clarity / is easier to understand. To check whether you have python3 installed, type into your terminal / IDE: python -version It has been tested on Windows 7 and Ubuntu 14.04. It uses no external libraries, so it should be able to be run on any modern operating system (most come with Python preinstalled) via a terminal / IDE (integrated development environment). Minesweeper is written in Python3 and consists of four scripts (one for each stage). Progress is recorded in the deletion log in /OUTPUT_final. Stages one to three are sequential, with stage four repeating until Minesweeper stops. These are run on a supercomputer and the automatically produced summary file is used as input for the next stage. Minesweeper (Installation)Įach Minesweeper script requires a text file(s) as input and produces simulation files as output. To visualise the steps of our algorithms see our figures, available on FigShare. įor more information, see a copy of the Methods section of the manuscript, at the bottom of this document. The algorithms and the background theory are explained in our paper, available on bioRxiv. The Minesweeper algorithm can be manually run on a non-dedicated desktop, with its output determining what simulations to be run on the supercomputer.
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The GAMA algorithm also needs a dedicated PC to split and monitor the simulations across the cluster(s) automatically. This code, in combination with the Mycoplasma genitalium whole-cell model produces in-silico genome designs by knocking out modelled genes at scale.īoth algorithms require supercomputer(s) to run the simulations. GAMA Version: 0.1 (Chalkley et al 2019, )
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GAMA License: GNU General Public License v3.0, gpl-3.0 (gpl-3)
Minesweeper License: GNU General Public License v3.0, gpl-3.0 (gpl-3) Protocol Book Chapter: (update post publication)Īffiliation: Genome Design Group, Life Sciences, University of Bristol BS8TQ UK
“Designing Minimal Genomes Using Whole-Cell Models.” Nature Communications 11 (1): 836. Paper: Rees-Garbutt, Joshua, Oliver Chalkley, Sophie Landon, Oliver Purcell, Lucia Marucci, and Claire Grierson. GAMA and Minesweeper: genome design algorithms for whole-cell models I could find no examples in the previous Minesweeper run results of dividing cells that did not produce protein or RNA during the cell cycle, but these functions will now ensure that won't happen. produce both protein and RNA during the cell cyle). The cell now has to divide and have two UP scores (i.e. This is in line with changes to runGraphs.m (Analysis_Code_for_Mycoplasma_genitalium_whole-cell_model repository) that added Protein and RNA starting and ending values, and assigned a score to both (UP or DOWN) to the output (endtimes.txt). Introduced a new function (dividedAndProducedProteinRNA) to check that simulations both produced a dividing cell and produced protein and RNA during the cell cycle. September 2020 - Published Minesweeper_1.0.Īdded a new function to Scripts 2 - 4X, based on suggestions from Viva Examiners. Genome Design Algorithm for Minimal Genomes using Whole Cell Models