misosoup 1.0.0

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MiSoS(oup)

Minimal Supplying Community Search (misosoup) is a command line tool that searches for minimal microbial communities. These are communities in which every member is required for the community to persist. misosoup can be used for two major objectives: (1) Find minimal communities in a given medium or (2) Find minimal supplying communities in a medium; these are the minimal communities required for growth of a strain (or species) of interest, that we refer to as the focal strain.

As input misosoup takes a set of genome-scale metabolic models; one for each strain (species) that will be considered as potential community members. The tool will then execute a series of constraint-based optimizations to find minimal communities. For the computation of the solutions metabolic steady-state is assumed (as in Flux Balance Analysis). Once computed, community members, their respective growth rates and there metabolic consumption and secretion will be reported in a human-readable and parsable format.

Details

To find minimal microbial communities misosoup solves a repeated sequence of optimization problems using MILP formulations:

1. Minimize the number of community member (see Zelezniak, et al. PNAS doi:10.1073/pnas.1421834112)
2. Fix the active community members and optimize growth of the total community biomass. If this fails, exclude the community from the possible solutions and repeat.
3. Optionally: Execute a third optimization to reflect parsimonious enzyme usage (see Lewis, et al. Mol Syst Bio doi:10.1038/msb.2010.47)

Install MiSoS(soup)

pip install misosoup

If you are unable to install gurobipy, it may need to be installed manually e.g. on a hpc cluster, to make use of the local gurobi installation. In such a case please refer to the instructions on the cluster support page.

Usage

After installation, you can easily use misosoup with:

misosoup MODEL_PATH/*.xml --output OUTPUT_FILE --media MEDIA_FILE --strain STRAIN

Arguments

• MODEL_PATH: indicates the path to the directory where the metabolic models are described. Strains with metabolic models included in this directory will be considered as potential members in the minimal communities. The models should be in sbml format and follow the same naming conventions (e.g. if glucose's id in one model is 'glc__D', the same id should be used in the other models).
• --output
  • Use OUTPUT_FILE for output in yaml format. If it is not given, the results will be printed to stdout.
• --media
  • Load media from MEDIA_FILE. The file should contain the description of the growth media that shall be tested. The file should contain a dictionary with all media that the community should be evaluated on. Each of the media needs to contain a dictionary of exchange reactions and there lower bound, (i.e. R_EX_ac_e: -10 provides acetate to the communities). The medium with id base_medium will be added to all media.
• --strain
  • Indicates the focal STRAIN model id. If no strain is provided, misosoup computes minimal communities.

Additional arguments

misosoup can be used with the additional arguments:

misosoup MODEL_PATH/*.xml --output OUTPUT_FILE --media MEDIA_FILE --strain STRAIN --parsimony --community-size COMMUNITY_SIZE --minimal-growth MINIMAL_GROWTH --exchange-format EXCHANGE_FORMAT --validate --log LOG

• --parsimony
  • If this flag is used the algorithm will return the solution that minimizes the total flux. This does not affect the community members but can alter what each member consumes and secretes.
• --community-size
  • Look for communities up to size COMMUNITY_SIZE, then stop.
• --minimal-growth
  • Set the MINIMAL_GROWTH rate of strains. Every strain that makes up a community needs to satisfy this minimal growth constraint. The default growth rate used is 0.01 (1/h).

For further description:

misosoup --help

Output file

The .yaml output file will give:

• The community members: y_<STRAIN_NAME>: 1.0.
• The growth of each community member Growth_<STRAIN_NAME>.
• The total community growth community_growth.
• The flux at which metabolites are taken up or secreted to the medium. Negative and positive fluxes indicate consumption and secretion, respectively. This consumption/secretion pattern is given for:
  • The community as a whole: (R_EX_<ID>_e)
  • Each community member separately (R_EX_<ID>_<STRAIN_NAME>_i).

Example

cd example

The following code will run misosoup to find minimal supplying communities for A1R12 in a medium that contains acetate as carbon source:

misosoup ./strains/*.xml --output ./example_output.yaml --media medium_MBM_no_co2_hco3.yaml --strain A1R12 --parsimony 

In the example, we run misosoup to find minimal supplying communities that would allow growth of A1R12 in MBM with acetate (ac) as the sole source of carbon. Looking at the output of the simulation (example_output.yaml) you'll see that misosoup found two alternative supplying communities:

• Solution 1: A1R12 can grow when in the presence of I3M07. If we inspect this solution in more detail we can see (for example):
  • Each strain produces carbon dioxide. We note this by looking at the strain-specific carbon dioxide fluxes: R_EX_co2_e_A1R12_i: 0.742 and R_EX_co2_e_I3M07_i: 0.957.
  • The community as a whole also produces carbon dioxide, which can be seen looking at the community-level carbon dioxide flux R_EX_co2_e: 1.699.
• Solution 2: A1R12 can grow when in the presence of I2R16. A similar analysis to the one conducted for solution 1 could be followed.

Citation

If you use misosoup, please cite X.

Workflows

snakemake is a useful tool to execute many experiments and gather results. See misosoup Workflow Template on how to use it.

Development

Add here some information for developers on how the repo is structured or a basic description of the main scripts.

MIT License

Copyright (c) 2021 Nicolas Ochsner

Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the "Software"), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions:

The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software.

THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE.