[!] NOTICE TO USERS: POPPY now (v0.1.3-alpha) uses the offline Equilibrator-API to obtain thermodynamic data. Please refrain from using older versions to access Equilibrator due to capacity constraints of that server.

Prospecting Optimal Pathways with PYthon

Tools for creating and exploring metabolic reaction networks.

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1. Construct reaction network

poppy_create.py constructs a network of potential metabolic reactions using resources supplied by KEGG (http://www.kegg.jp/) and MINE (http://minedatabase.mcs.anl.gov/).

Example: Create a combined KEGG and MINE reaction network

./poppy_create.py --kegg --enhance --equilibrator_filter --infile examples/E_coli.origins.txt network.pkl

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2. Enumerate and evaluate pathways

poppy_path.py performs path-finding, sub-network extraction and enumeration of putative biosynthetic pathways. Can write HTML reports for pathway enumeration.

Example: Enumerate pathways to 4-hydroxybutanoic acid in E. coli and Synechocystis

./poppy_path.py -p 4 -d 3 -r 5 --model examples/E_coli.model.tab --bounds examples/E_coli.concentrations.tab --ratios examples/E_coli.ratios.tab --pH 7.6 --c_min 0.0000001 --c_max 0.1 --pathway_html E_coli_pathways network.pkl C00989

./poppy_path.py -p 4 -d 3 -r 5 -S examples/Synechocystis.origins.txt --model examples/Synechocystis.model.tab --bounds examples/Synechocystis.concentrations.tab --ratios examples/Synechocystis.ratios.tab --pH 8.4 --c_min 0.0000001 --c_max 0.1 --pathway_html Synechocystis_pathways network.pkl C00989

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3. Calculate model network reaction Gibbs free energy changes

poppy_rank.py ranks identified pathways in terms of thermodynamic driving forces. Also used for calculating transformed standard reaction Gibbs free energy changes.

Example: Calculate reaction delta G:s for the E. coli and Synechocystis models

./poppy_rank.py --write_gibbs --pH 7.6 examples/E_coli.model.tab E_coli.model_drgs.tab

./poppy_rank.py --write_gibbs --pH 8.4 examples/Synechocystis.model.tab Synechocystis.model_drgs.tab

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4. Standalone MDF and NEM analysis

mdf.py performs Max-min Driving Force (MDF; Noor et al., 2014) and Network-Embedded MDF (NEM) analysis.

Example: Perform NEM analysis on lysine biosynthesis in E. coli and Synechocystis

./mdf.py --min_conc 0.0000001 --max_conc 0.1 --constraints examples/E_coli.concentrations.tab --ratios examples/E_coli.Lys_opt_ratios.tab --pathway examples/E_coli.Lys_pathway.txt examples/E_coli.model.tab E_coli.model_drgs.tab E_coli_Lys_nem.csv

./mdf.py --min_conc 0.0000001 --max_conc 0.1 --constraints examples/Synechocystis.concentrations.tab --ratios examples/Synechocystis.Lys_opt_ratios.tab --pathway examples/Synechocystis.Lys_pathway.txt examples/Synechocystis.model.tab Synechocystis.model_drgs.tab Synechocystis_Lys_nem.csv

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Dependencies

Python ≥ 3.5.1 with:

• SciPy and NumPy (https://www.scipy.org/)
• NetworkX (https://github.com/networkx/networkx)
• RDKit (https://github.com/rdkit/rdkit)
• MINE-API (https://github.com/JamesJeffryes/MINE-API; included as mineclient3.py)
• tablib
• PuLP
• eQuilibrator-API (https://gitlab.com/elad.noor/equilibrator-api)

R ≥ 3.0 with:

• ggplot2
• RColorBrewer

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Author

Johannes Asplund-Samuelsson ([email protected])