Extraction of context-specific models via XomicsToModel

Author: German Preciat, Analytical BioSciences, Leiden University

INTRODUCTION

The XomicsToModel pipeline of the COBRA Toolbox v3.4, facilitates the generation a thermodynamic-flux-consistent, context-specific, genome-scale metabolic model in a single command by combining a generic model with bibliomic, transcriptomic, proteomic, and metabolomic data. To ensure the network's quality, several thermodynamic consistency checks are implemented within the function. To generate a thermodynamic-flux-consistent, context-specific, genome-scale metabolic model, the function requires three inputs: a generic COBRA model and two variables containing the context-specific data and technical information defined by the user.
This tutorial shows how to extract a context-specific genome-scale model of a dopaminergic neuron (iDopaNeuroC) from the human generic model Recon3D . The iDopaNeuroC model is extracted using data from manual curation of a dopaminergic neuron to identify active and inactive genes, reactions, and metabolites, as well as information from in vitro experiments such as exometabolomic quantification and transcriptomic sequencing of a cell culture of pluripotent stem cell-derived dopaminergic neurons.

PROCEDURE

Install MATLAB and then the COBRA Toolbox as described here: https://opencobra.github.io/cobratoolbox/stable/installation.html
Select a solver suitable for solving linear (LP) and quadratic (QP) optimisation problems, e.g., mosek, gurobi, ibm_cplex, etc.
[~, ~] = changeCobraSolver('mosek', 'all', 0);

Generic model

The COBRA model Recon3D, representing human metabolic reconstruction, a can be found in a file with the extension ".mat". Recon3D , which is found in the VMH database, can be used as a generic model for human metabolism. The thermodynamic consistent human metabolic reconstruction Recon3D.
inputFolder = ['~' filesep 'work' filesep 'sbgCloud' filesep 'programExperimental' ...
filesep 'projects' filesep 'xomics' filesep 'data' filesep 'Recon3D_301'];
genericModelName = 'Recon3DModel_301_xomics_input.mat';
load([inputFolder filesep genericModelName])

Context-specific data

This type of information represents the biological system's phenotype and can be obtained through a review of the literature or experimental data derived from the biological system. The context-specific data can be loaded from a spreadsheet or added manually.

Automated data integration

Tables or multiple data sets can be inserted in an external worksheet document so that the preprocessingOmicsModel function can include them in the options variable. The name of the sheet corresponding to the options field must be the same as those specified above and in the manuscript, or they will be omitted.
Bibliomic data. It is derived from manual reconstruction following a review of the literature. This includes data on the activation or inactivation of genes, reactions, or metabolites. Another example is the addition of coupled reactions or the constraints of different reactions based on phenotypic observations.
Manually curated data. To read the table and prepare the variable specificData it is used the function preprocessingOmicsModel. In this tutorial the bibliomic data is contained in the file 'bibliomicData.xlsx'.
dataFolder = [fileparts(which('tutorial_XomicsToModel.mlx')) filesep 'iDopaNeuro' filesep 'data' filesep];
bibliomicData = 'bibliomicData.xlsx';
specificData = preprocessingOmicsModel([dataFolder bibliomicData], 1, 1);
Reading inputData from : /home/rfleming/work/sbgCloud/programExperimental/projects/xomics/code/tutorials/iDopaNeuro/data/bibliomicData.xlsx Reading sheet: activeGenes Reading sheet: activeReactions Reading sheet: cellCultureData Reading sheet: coupledRxns Reading sheet: essentialAA Reading sheet: inactiveGenes Reading sheet: mediaData Reading sheet: presentMetabolites Reading sheet: rxns2add Reading sheet: rxns2constrain Reading sheet: rxnsHypothesis Reading sheet: rxns2remove Reading sheet: sinkDemand
Metabolomic data. Differences in measured concentrations of metabolites within cells, biofluids, tissues, or organisms are translated into flux units of flux ().
In this tutorial the exometabolomic data is saved in the table 'exoMet'.
specificData.exoMet = readtable([dataFolder 'exometabolomicData.txt']);
Proteomic data. This information indicates the level of expression of the proteome.
For this tutorial no proteomic data was used.
Transcriptomic data. Indicates the level of transcriptome expression and can also be used to calculate reaction expression. Transcriptomic data can be analysed in FPKM.
In this tutorial the transcriptomic analysis is saved in the table 'transcriptomicData'.
specificData.transcriptomicData = readtable([dataFolder 'transcriptomicData.txt']);
specificData.transcriptomicData.genes = string(specificData.transcriptomicData.genes);

Technical parameters

With these options, technical constraints can be added to the model, as well as setting the parameters for model extraction or debugging.
Bounds. They are the instructions that will be set in the boundaries.
param.TolMinBoundary = -1e4;
param.TolMaxBoundary = 1e4;
feasTol = getCobraSolverParams('LP', 'feasTol');
param.boundPrecisionLimit = feasTol * 10;
Exchange reactions. They are the instructions for the exchange, demand, and sink reactions.
param.closeIons = true;
param.closeUptakes = true;
param.nonCoreSinksDemands = 'closeAll';
param.sinkDMinactive = true;
Extraction options. The solver and parameters for extracting the context-specific model.
param.activeGenesApproach = 'oneRxnPerActiveGene';
param.tissueSpecificSolver = 'thermoKernel';
param.fluxEpsilon = feasTol * 10;
param.fluxCCmethod = 'fastcc';
Data-specific parameters. Parameters that define the minimum level of transcript/protein to be considered as present in the network (treshold) and weather the transcripts below the set treshold should be removed from the model.
param.addCoupledRxns = 1;
param.curationOverOmics = false;
param.inactiveGenesTranscriptomics = true;
param.metabolomicWeights='mean';
param.transcriptomicThreshold = 2;
param.weightsFromOmics = true;
Debugging options. The user can specify the function's verbosity level as well as save the results of the various blocks of the function for debugging.
param.printLevel = 1;
param.debug = true;
if isunix()
name = getenv('USER');
else
name = getenv('username');
end
param.diaryFilename = [pwd filesep datestr(now,30) '_' name '_diary.txt'];

XomicsToModel function

[iDopaNeuro1, modelGenerationReport] = XomicsToModel(model, specificData, param);
XomicsToModel run, beginning at:16-Dec-2022 08:56:14 -------------------------------------------------------------- XomicsToModel input specificData: inputData: '/home/rfleming/work/sbgCloud/programExperimental/projects/xomics/code/tutorials/iDopaNeuro/data/bibliomicData.xlsx' activeGenes: {239×1 cell} activeReactions: {334×1 cell} cellCultureData: [1×6 table] coupledRxns: [11×5 table] essentialAA: [9×1 table] inactiveGenes: {61×1 cell} mediaData: [56×3 table] presentMetabolites: [45×4 table] rxns2add: [21×9 table] rxns2constrain: [48×5 table] rxnsHypothesis: [33×5 table] rxns2remove: [233×5 table] sinkDemand: [49×8 table] exoMet: [49×13 table] transcriptomicData: [18530×2 table] XomicsToModel input param: TolMinBoundary: -10000 TolMaxBoundary: 10000 boundPrecisionLimit: 1e-05 closeIons: 1 closeUptakes: 1 nonCoreSinksDemands: 'closeAll' sinkDMinactive: 1 activeGenesApproach: 'oneRxnPerActiveGene' tissueSpecificSolver: 'thermoKernel' fluxEpsilon: 1e-05 fluxCCmethod: 'fastcc' addCoupledRxns: 1 curationOverOmics: 0 inactiveGenesTranscriptomics: 1 metabolomicWeights: 'mean' transcriptomicThreshold: 2 weightsFromOmics: 1 printLevel: 1 debug: 1 diaryFilename: '/home/rfleming/20221216T085613_rfleming_diary.txt' inactiveReactions: [] thresholdP: 0 uptakeSign: -1 thermoFluxEpsilon: 1e-05 growthMediaBeforeReactionRemoval: 1 metabolomicsBeforeExtraction: 1 workingDirectory: '/home/rfleming' findThermoConsistentFluxSubset: 1 plotThermoKernelStats: 0 plotThermoKernelWeights: 0 finalFluxConsistency: 0 relaxOptions: [1×1 struct] boundsToRelaxExoMet: 'both' Replacing reaction name DM_atp_c_ with ATPM, because it is not strictly a demand reaction. Old reaction formulas ATPS4mi adp[m] + pi[m] + 4 h[i] -> h2o[m] + 3 h[m] + atp[m] CYOOm2i o2[m] + 8 h[m] + 4 focytC[m] -> 2 h2o[m] + 4 ficytC[m] + 4 h[i] CYOOm3i o2[m] + 7.92 h[m] + 4 focytC[m] -> 1.96 h2o[m] + 4 ficytC[m] + 0.02 o2s[m] + 4 h[i] CYOR_u10mi 2 h[m] + 2 ficytC[m] + q10h2[m] -> q10[m] + 2 focytC[m] + 4 h[i] NADH2_u10mi 5 h[m] + nadh[m] + q10[m] -> nad[m] + q10h2[m] + 4 h[i] 0×0 empty char array New reaction formulas ATPS4minew 4 h[c] + adp[m] + pi[m] -> h2o[m] + 3 h[m] + atp[m] CYOOm2inew o2[m] + 8 h[m] + 4 focytC[m] -> 2 h2o[m] + 4 h[c] + 4 ficytC[m] CYOOm3inew o2[m] + 7.92 h[m] + 4 focytC[m] -> 1.96 h2o[m] + 4 h[c] + 4 ficytC[m] + 0.02 o2s[m] CYOR_u10minew 2 h[m] + 2 ficytC[m] + q10h2[m] -> 4 h[c] + q10[m] + 2 focytC[m] NADH2_u10minew 5 h[m] + nadh[m] + q10[m] -> 4 h[c] + nad[m] + q10h2[m] Feasible generic input model. -------------------------------------------------------------- Generating model without an objective function. -------------------------------------------------------------- Adding 21 reactions ... Reaction boundaries not provided. Default (min and max) values will be used based on the reaction formula. acleua h2o[c] + acleu_L[c] -> ac[c] + leu_L[c] acthra h2o[c] + acthr_L[c] -> ac[c] + thr_L[c] acileua h2o[c] + acile_L[c] -> ac[c] + ile_L[c] acglua h2o[c] + acglu[c] -> glu_L[c] + ac[c] CE1554tm CE1554[c] <=> CE1554[m] RE2031M accoa[m] + ala_L[m] <=> h[m] + coa[m] + CE1554[m] RE2642C h2o[c] + CE1554[c] <=> ac[c] + ala_L[c] CE1554t CE1554[c] <=> CE1554[e] EX_CE1554[e] CE1554[e] <=> DM_ps_hs[c] ps_hs[c] <=> CYSTS_H2S cys_L[c] + hcys_L[c] <=> HC00250[c] + cyst_L[c] DHBOX h2o2[c] + quinonemethide[c] -> 3,4-dihydroxybenzaldehyde[c] + methanimine[c] DM_clpn_hs[c] clpn_hs[c] -> EX_adocbl[e] adocbl[e] <=> EX_ca2[e] ca2[e] <=> EX_cl[e] cl[e] <=> EX_mg2[e] mg2[e] <=> EX_selni[c] selni[c] <=> EX_zn2[e] zn2[e] <=> NORCON dopa[c] + fald[c] + 3,4-dihydroxybenzaldehyde[c] -> CE2172[c] Q-METHRED fe2[c] + CE5276[c] -> quinonemethide[c] 0 deleted non-core metabolites, corresponding to generic model. 0 deleted core metabolites, corresponding to generic model. Old model does not contain these core reactions (now removed from core reaction set): {'DM_ca2[c]' } {'EX_HC01944[e]'} {'EX_adpcbl[e]' } {'Htmi' } {'RE1917C' } 0 deleted non-core reactions, corresponding to generic model. 0 deleted core reactions, corresponding to generic model. -------------------------------------------------------------- Identifying the stoichiometrically consistent subset... --- findStoichConsistentSubset START ---- --- Summary of stoichiometric consistency ---- 5843 10620 totals. 3 1818 heuristically external. 5840 8802 heuristically internal: 5840 8800 ... of which are stoichiometrically consistent. 0 2 ... of which are stoichiometrically inconsistent. 0 0 ... of which are of unknown consistency. 5840 8800 Confirmed stoichiometrically consistent by leak/siphon testing. --- findStoichConsistentSubset END ---- 3 deleted non-core metabolites, corresponding to stoichiometric inconsistency. 0 deleted core metabolites, corresponding to stoichiometric inconsistency. Old model does not contain these core reactions (now removed from core reaction set): {'DM_ca2[c]' } {'EX_HC01944[e]'} {'EX_adpcbl[e]' } {'Htmi' } {'RE1917C' } 0 deleted non-core reactions, corresponding to stoichiometric inconsistency. 5 deleted core reactions, corresponding to stoichiometric inconsistency. Reversible_Reaction Name lb ub equation ___________________ _________________________________________________ ______ _____ _____________________________________________________ {'RE2130C' } {'RE2130C' } -1000 1000 {'dopa[c] + fald[c] <=> h2o[c] + CE2172[c] ' } {'CYSTS_H2S' } {'Cystathionine Beta-Synthase (sulfide-forming)'} -10000 10000 {'cys_L[c] + hcys_L[c] <=> HC00250[c] + cyst_L[c] '} {'EX_adocbl[e]'} {'Exchange of adenosylcobalamin' } -10000 10000 {'adocbl[e] <=> ' } {'EX_mg2[e]' } {'Exchange of magnesium' } -10000 10000 {'mg2[e] <=> ' } {'EX_selni[c]' } {'Exchange of selenite' } -10000 10000 {'selni[c] <=> ' } 3 stoichiometrically inconsistent metabolites removed. 5 stoichiometrically inconsistent reactions removed. Feasible stoichiometrically consistent model with new reactions. Feasible model with default bounds. -------------------------------------------------------------- Assuming gene expression is NaN for 160 genes where no transcriptomic data is provided. Model statistics: 5840 x 10615 stoichiometric matrix. 1566 exchange reactions. 109 exchange reactions in the core reaction set. 7 exchange reactions in the rxns2Constrain set. 1456 exchange reactions with uptake closed 239 closed non-core sink/demand reactions via param.nonCoreSinksDemands = closeAll 10 core sink/demand reactions. 10 open core sink/demand reactions. Feasible after closing non-core sink/demand reactions. -------------------------------------------------------------- Adding growth media information... The following reactions could not be constrained since they are not present in the model: {'EX_HC01944[e]'} {'EX_adpcbl[e]' } {'EX_mg2[e]' } {'EX_selni[c]' } Adding constraints on 52 reactions These reactions have bounds larger than the recommended value = abs(10000) The bounds for the following reactions have been adjusted: Number of corrected bounds (to min/max boundary): 2 Reverse_Reaction, 0 bound Name lb_before lb_after ub_before ub_after equation _________________________ ____________________________ _________________ ________ _________ ________ ________________ {'EX_na1[e]'} {'Exchange of Sodium' } -17903.1402873266 -10000 0 0 {'na1[e] <=> '} {'EX_cl[e]' } {'Exchange of chloride ion'} -14916.2499880923 -10000 0 0 {'cl[e] <=> ' } Feasible after application of media constraints. -------------------------------------------------------------- Adding quantitative metabolomics constraints ... -0.621631949021564 Feasible after application of metabolomic constraints -------------------------------------------------------------- Checking for mismatches ... -------------------------------------------------------------- Adding custom constraints ... tissueSpecificSolver = thermoKernel. Ignoring specificData.rxns2constrain for demand reactions, i.e. with prefix DM_ Adding constraints on 38 reactions Feasible after application of custom constraints. -------------------------------------------------------------- Adding 11 sets of coupled reactions ... coupledRxnId constraints ___________________________ __________________________________________________________________________________ {'Phosphatidylcholine' } {'PCHOLP_hs + PLA2_2 + SMS >= 2.025' } {'Adenosine Monophosphate'} {'AMPDA + NTD7 >= 0.2265' } {'Glutamate' } {'- ALATA_L + GLUCYS + GLUDxm + GLUDym - ASPTA - ILETA - LEUTA - VALTA >= 1.2225'} {'Aspartate' } {'ARGSS + ASPTA >= 1.1925' } {'Serine' } {'GHMT2r + r0060 >= 0.8625' } {'Arginine' } {'GLYAMDTRc + r0145 + ARGN >= 0.7245' } {'Tyrosine' } {'TYR3MO2 + TYRTA + HMR_6728 + HMR_6874 >= 0.55875' } {'Histidine' } {'HISDC + HISD >= 1.095' } {'Leucine + Isoleucine' } {'ILETA + LEUTA >= 1.305' } {'Valine + Methionine' } {'METAT + VALTA >= 0.705' } {'Glycine' } {'GTHS - GHMT2r >= 0.7725' } coupledRxnId constraints ___________________________ __________________________________________________________________________________ {'Phosphatidylcholine' } {'PCHOLP_hs + PLA2_2 + SMS >= 2.025' } {'Adenosine Monophosphate'} {'AMPDA + NTD7 >= 0.2265' } {'Glutamate' } {'- ALATA_L + GLUCYS + GLUDxm + GLUDym - ASPTA - ILETA - LEUTA - VALTA >= 1.2225'} {'Aspartate' } {'ARGSS + ASPTA >= 1.1925' } {'Serine' } {'GHMT2r + r0060 >= 0.8625' } {'Arginine' } {'GLYAMDTRc + r0145 + ARGN >= 0.7245' } {'Tyrosine' } {'TYR3MO2 + TYRTA + HMR_6728 + HMR_6874 >= 0.55875' } {'Histidine' } {'HISDC + HISD >= 1.095' } {'Leucine + Isoleucine' } {'ILETA + LEUTA >= 1.305' } {'Valine + Methionine' } {'METAT + VALTA >= 0.705' } {'Glycine' } {'GTHS - GHMT2r >= 0.7725' } Feasible model after adding coupling constraints. -------------------------------------------------------------- Removing 233 reactions ... The following reaction(s) to be removed is(are) not in the model: {'HMR_biomass_Renalcancer' } {'DM_HMR_biomass_renalcancer'} {'biomass_components' } {'EX_ser_D[e]' } {'EX_pro_D[e]' } {'HMR_1708' } {'HMR_1934' } {'r0947' } {'r1431' } {'r1432' } {'RE1096R' } {'RE1134R' } {'RE2117M' } {'RE2768R' } {'RE2782C' } {'RE3111M' } {'RE3338C' } {'RE3340C' } {'RE3448C' } {'RE3564C' } {'RE3627C' } {'DM_adchac[c]' } {'DM_alchac[c]' } Feasible model after removing inactive reactions. 2 deleted non-core metabolites, corresponding to bibliomic inactive reactions. 0 deleted core metabolites, corresponding to bibliomic inactive reactions. 210 deleted non-core reactions, corresponding to bibliomic inactive reactions. 0 deleted core reactions, corresponding to bibliomic inactive reactions. -------------------------------------------------------------- Removing 973 inactive genes... 57 manually selected inactive genes have been marked as active by omics data and will be discarded: {'5834' } {'10165' } {'246213' } {'2571' } {'26227' } {'100137049'} {'100526794'} {'2752' } {'26227' } {'10060' } {'10858' } {'10873' } {'1160' } {'125965' } {'130752' } {'1346' } {'1468' } {'1583' } {'1588' } {'1607' } {'170712' } {'206358' } {'2110' } {'240' } {'2645' } {'27165' } {'2747' } {'2820' } {'3099' } {'3101' } {'341947' } {'349565' } {'366' } {'374291' } {'3767' } {'412' } {'43' } {'5053' } {'5106' } {'548596' } {'57084' } {'622' } {'64802' } {'6505' } {'6529' } {'6531' } {'6538' } {'6571' } {'6581' } {'6582' } {'6818' } {'6833' } {'7054' } {'79751' } {'83733' } {'84889' } {'8659' } 11 inactive genes are not in the model to be removed. Infeasible model after temporarily closing reactions corresponding to inactive genes, relaxing... itn obj obj_old err(obj) err(x) card(v) card(r) card(p) card(q) 0 8.4066 1332.5 1324.1 2.8021e+05 1272 0 1 4 1 8.2951 8.4066 0.11146 5.1996e+05 1242 0 1 4 2 8.4569 8.2951 0.16175 5.362e+05 1283 0 1 4 3 8.4867 8.4569 0.029796 5.3872e+05 1281 0 1 4 4 8.6194 8.4867 0.13272 5.3926e+05 1384 0 1 4 5 8.285 8.6194 0.33442 5.3742e+05 1246 0 1 4 6 8.7531 8.285 0.46819 5.398e+05 1322 0 1 4 7 8.264 8.7531 0.48915 5.4022e+05 1295 0 1 4 8 8.6802 8.264 0.4162 5.3896e+05 1326 0 1 4 9 8.4196 8.6802 0.26057 5.4105e+05 1277 0 1 4 10 8.5304 8.4196 0.11073 5.3927e+05 1277 0 1 4 11 8.3826 8.5304 0.14776 5.397e+05 1263 0 1 4 12 8.6824 8.3826 0.29983 5.4096e+05 1335 0 1 4 13 8.4864 8.6824 0.19599 5.4213e+05 1273 0 1 4 14 8.4448 8.4864 0.041662 5.4075e+05 1273 0 1 4 15 8.3701 8.4448 0.074667 5.4132e+05 1282 0 1 4 16 8.7422 8.3701 0.37209 5.4318e+05 1311 0 1 4 17 8.5835 8.7422 0.1587 5.4349e+05 1293 0 1 4 18 8.6017 8.5835 0.018147 5.4035e+05 1310 0 1 4 19 8.4429 8.6017 0.15872 5.3978e+05 1300 0 1 4 itn obj obj_old err(obj) err(x) card(v) card(r) card(p) card(q) Relaxed model is feasible. Statistics: 1 lower bound relaxation(s) 4 upper bound relaxation(s) 0 steady state relaxation(s) The lower bound of these reactions had to be relaxed: Closed_Reaction Name lb_before lb_after ub_before ub_after equation _______________ _____________________________________________ _________ ____________________ _________ ________ ______________________ {'URAt'} {'Uracil Transport via Faciliated Diffusion'} 0 -0.00701902520631847 0 0 {'ura[e] -> ura[c] '} The upper bound of these reactions had to be relaxed: Closed_Reaction Name lb_before lb_after ub_before ub_after equation _______________ _______________________________________________ _________ ________ _________ ____________________ _________________________________________________________________ {'KHK' } {'Ketohexokinase' } 0 0 0 0.287664725528884 {'atp[c] + fru[c] -> h[c] + adp[c] + f1p[c] ' } {'MMEm' } {'Methylmalonyl Coenzyme A Epimerase/Racemase'} 0 0 0 0.116051401069853 {'mmcoa_R[m] -> mmcoa_S[m] ' } {'OIVD1m'} {'2-Oxoisovalerate Dehydrogenase (Acylating' } 0 0 0 0.922557070436596 {'nad[m] + coa[m] + 4mop[m] -> nadh[m] + co2[m] + ivcoa[m] ' } {'SERPT' } {'Serine C-Palmitoyltransferase' } 0 0 0 0.000100000001111766 {'h[c] + ser_L[c] + pmtcoa[c] -> co2[c] + 3dsphgn[c] + coa[c] '} ... done. 5 reaction(s) were not deleted based on inactive genes as their removal would cause the model to be infeasible.) 480 genes were specified as inactive but not removed as they are involved in reactions that may be catalysed by other gene products, or are essential. 123 deleted non-core metabolites, corresponding to inactive genes. 0 deleted core metabolites, corresponding to inactive genes. 1747 deleted non-core reactions, corresponding to inactive genes. 0 deleted core reactions, corresponding to inactive genes. Feasible model after removing inactive genes (that do not affect core reactions). -------------------------------------------------------------- Identifying flux consistent reactions ... 5715 x 8658 stoichiometric matrix, before flux consistency. --- findFluxConsistentSubset START ---- 2965 flux consistent metabolites 2750 flux inconsistent metabolites 4983 flux consistent reactions 3675 flux inconsistent reactions --- findFluxConsistentSubset END ---- 2739 deleted non-core metabolites, corresponding to flux inconsistency. 11 deleted core metabolites, corresponding to flux inconsistency. mets metNames _________________ _____________________________________________________________________ {'Tyr_ggn[c]' } {'Tyr-194 Of Apo-Glycogenin Protein (Primer For Glycogen Synthesis)'} {'pre_prot[r]' } {'Glycophosphatidylinositol (Gpi)-Anchored Protein Precursor' } {'retfa[c]' } {'Fatty Acid Retinol' } {'thm[m]' } {'Thiamin' } {'no2[c]' } {'Nitrite' } {'CE1273[c]' } {'5Beta-Cholestane-3Alpha,7Alpha,12Alpha,24S,25-Pentol' } {'pail35p_hs[n]'} {'1-Phosphatidyl-1D-Myo-Inositol 3,5-Bisphosphate' } {'c101coa[c]' } {'Decenoyl Coenzyme A' } {'fe3[c]' } {'Iron (Fe3+)' } {'6hddopaqn[c]' } {'6-Hydroxydopamine-Quinone' } {'gm1_hs[n]' } {'Ganglioside Gm1' } 3630 deleted non-core reactions, corresponding to flux inconsistency. 45 deleted core reactions, corresponding to flux inconsistency. Forward_Reaction, 0 bound Name lb ub equation _________________________ ________________________________________________________________ __ _____ _____________________________________________________________________________________________ {'ACHEe' } {'Acetylcholinesterase' } 0 10000 {'h2o[e] + ach[e] -> h[e] + ac[e] + chol[e] ' } {'APOC_LYS_BTNPm'} {'Proteolysis of ApoC-Lys-Biotin, Mitochondrial' } 0 10000 {'h2o[m] + apoC_Lys_btn[m] -> apoC[m] + biocyt[m] ' } {'ARGNm' } {'Arginase, Mitochondrial' } 0 10000 {'h2o[m] + arg_L[m] -> urea[m] + orn[m] ' } {'CLS_hs' } {'Cardiolipin Synthase (Homo Sapiens)' } 0 10000 {'cdpdag_hs[c] + pglyc_hs[c] -> h[c] + cmp[c] + clpn_hs[c] ' } {'DURIK1m' } {'Deoxyuridine Kinase (ATP:Deoxyuridine), Mitochondrial' } 0 10000 {'atp[m] + duri[m] -> h[m] + adp[m] + dump[m] ' } {'EX_co[e]' } {'Exchange of Carbon Monoxide ' } 0 10000 {'co[e] -> ' } {'G3PD2m' } {'Glycerol-3-Phosphate Dehydrogenase (FAD), Mitochondrial' } 0 10000 {'fad[m] + glyc3p[c] -> fadh2[m] + dhap[c] ' } {'GLYKm' } {'Glycerol Kinase' } 0 10000 {'atp[m] + glyc[m] -> h[m] + adp[m] + glyc3p[m] ' } {'OCOAT1m' } {'3-Oxoacid Coa-Transferase' } 0 10000 {'acac[m] + succoa[m] -> aacoa[m] + succ[m] ' } {'P45011A1m' } {'Cytochrome P450 11A1, Mitochondrial [Precursor]' } 0 10000 {'2 o2[m] + h[m] + nadph[m] + chsterol[m] -> 2 h2o[m] + nadp[m] + 4mptnl[m] + prgnlone[m] '} {'P45027A11m' } {'5-Beta-Cholestane-3-Alpha, 7-Alpha, 12-Alpha-Triol 27-Hydrox'} 0 10000 {'o2[m] + h[m] + nadph[m] + xoltriol[m] -> h2o[m] + nadp[m] + xoltetrol[m] ' } {'P45027A14m' } {'5-Beta-Cytochrome P450, Family 27, Subfamily A, Polypeptide '} 0 10000 {'o2[m] + h[m] + nadph[m] + xol7ah2[m] -> h2o[m] + nadp[m] + xol7ah3[m] ' } {'RBK_D' } {'D-Ribulokinase' } 0 10000 {'atp[c] + rbl_D[c] -> h[c] + adp[c] + ru5p_D[c] ' } {'SARDHm' } {'Sarcosine Dehydrogenase, Mitochondrial' } 0 10000 {'fad[m] + sarcs[m] + thf[m] -> fadh2[m] + gly[m] + mlthf[m] ' } {'STS1' } {'Steryl-Sulfatase' } 0 10000 {'h2o[c] + dheas[c] -> h[c] + dhea[c] + so4[c] ' } {'r0321' } {'Acetoacetate:Coa Ligase (AMP-Forming)' } 0 10000 {'coa[m] + acac[m] + atp[m] -> aacoa[m] + amp[m] + ppi[m] ' } {'FE2DMT1' } {'Uptake of Food Iron by Dmt1 Transporter' } 0 10000 {'h[e] + fe2[e] -> h[c] + fe2[c] ' } {'ARGN' } {'Arginase' } 0 10000 {'h2o[c] + arg_L[c] -> orn[c] + urea[c] ' } {'RBK' } {'Ribokinase' } 0 10000 {'atp[c] + rib_D[c] -> h[c] + adp[c] + r5p[c] ' } {'DOPAOQNOX' } {'Dopamine-O-Quinone Oxidase' } 0 10000 {'h2o2[c] + CE5276[c] -> h2o[c] + 6hddopaqn[c] ' } {'HMR_9726' } {'5-Formyltetrahydrofolate:L-Glutamate N-Formiminotransferase' } 0 10000 {'glu_L[c] + 5fthf[c] -> thf[c] + forglu[c] ' } {'DHBOX' } {'3,4-dihydroxybenzaldehyde oxidase' } 0 10000 {'h2o2[c] + quinonemethide[c] -> 3,4-dihydroxybenzaldehyde[c] + methanimine[c] ' } {'DM_clpn_hs[c]' } {'Demand of cardiolipin' } 0 10000 {'clpn_hs[c] -> ' } {'NORCON' } {'Norsalsolinol consendation' } 0 10000 {'dopa[c] + fald[c] + 3,4-dihydroxybenzaldehyde[c] -> CE2172[c] ' } {'Q-METHRED' } {'Quinonemethide reductase' } 0 10000 {'fe2[c] + CE5276[c] -> quinonemethide[c] ' } Reverse_Reaction, 0 bound Name lb ub equation _________________________ _________________________________ __________________ __ _______________________________________________________ {'r0245' } {'Glycerol:NADP+ Oxidoreductase'} -10000 0 {'nadp[c] + glyc[c] <=> h[c] + nadph[c] + glyald[c] '} {'EX_fe3[e]'} {'Exchange of Iron (Fe3+) ' } -1.63928248314438 0 {'fe3[e] <=> ' } {'EX_k[e]' } {'Exchange of Kalium' } -733.702544787044 0 {'k[e] <=> ' } {'EX_na1[e]'} {'Exchange of Sodium' } -10000 0 {'na1[e] <=> ' } {'EX_ca2[e]'} {'Exchange of calcium' } -220.501332473743 0 {'ca2[e] <=> ' } {'EX_cl[e]' } {'Exchange of chloride ion' } -10000 0 {'cl[e] <=> ' } {'EX_zn2[e]'} {'Exchange of zinc (II) ion' } -0.283998779119298 0 {'zn2[e] <=> ' } Reversible_Reaction Name lb ub equation ___________________ ________________________________________________________________ ____________________ _____ ____________________________________________________ {'EX_i[e]' } {'Exchange of Iodide ' } -10000 10000 {'i[e] <=> ' } {'RE1530M' } {'Thymidine Kinase' } -10000 10000 {'dgtp[m] + duri[m] <=> h[m] + dgdp[m] + dump[m] '} {'C02712tm' } {'Transport of N-Acetylmethionine, Intracellular' } -10000 10000 {'C02712[c] <=> C02712[m] ' } {'ACGLUtm' } {'Transport of N-Acetyl-L-Glutamate, Mitochondrial' } -10000 10000 {'acglu[c] <=> acglu[m] ' } {'r2535m' } {'Transport of L-Homoserine, Mitochondrial' } -10000 10000 {'hom_L[m] <=> hom_L[c] ' } {'EX_fe2[e]' } {'Exchange of Iron (Fe2+)' } -10000 10000 {'fe2[e] <=> ' } {'EX_pnto_R[e]'} {'Exchange of (R)-Pantothenate ' } -1.01132209327515 10000 {'pnto_R[e] <=> ' } {'EX_hxan[e]' } {'Exchange of Hypoxanthine ' } -1.16204812218561 10000 {'hxan[e] <=> ' } {'EX_thm[e]' } {'Exchange of Thiamin' } -1.41539793936734 10000 {'thm[e] <=> ' } {'EX_pydxn[e]' } {'Exchange of Pyridoxine' } -2.26640035357874 10000 {'pydxn[e] <=> ' } {'EX_btn[e]' } {'Exchange of Biotin ' } -0.00110892336408884 10000 {'btn[e] <=> ' } {'CE2172t' } {'Transport of 6, 7-Dihydroxy-1, 2, 3, 4-Tetrahydroisoquinolin'} -10000 10000 {'CE2172[c] <=> CE2172[e] ' } {'EX_CE2172[e]'} {'Exchange of 6, 7-Dihydroxy-1, 2, 3, 4-Tetrahydroisoquinoline'} -10000 10000 {'CE2172[e] <=> ' } 2965 x 4983 stoichiometric matrix, after flux consistency. -------------------------------------------------------------- Identifying thermodynamically flux consistent subset ... 1 model.C constraints removed solver: 'mosek' algorithm: 'default' stat: 0 origStat: 'PRIMAL_INFEASIBLE_CER' origStatText: [] time: 0.00464499999999646 basis: [] f: NaN v: [] y: [] w: [] s: [] ctrs_y: [] ctrs_s: [] x: []
Warning: findThermoConsistentFluxSubset: thermoConsistModel is not feasible.
0 deleted non-core metabolites, corresponding to thermodynamic flux inconsistency. 0 deleted core metabolites, corresponding to thermodynamic flux inconsistency. 1 deleted non-core reactions, corresponding to thermodynamic flux inconsistency. 12 deleted core reactions, corresponding to thermodynamic flux inconsistency. Forward_Reaction, 0 bound Name lb ub equation _________________________ __________________ __ _________________ _______________________________________________ {'KHK'} {'Ketohexokinase'} 0 0.287664725528884 {'atp[c] + fru[c] -> h[c] + adp[c] + f1p[c] '} Forward_Reaction, non-0 bound Name lb ub equation _____________________________ ________________________________________________________________ ______ _____ _________________________________________________________________ {'ALATA_L' } {'L-Alanine Transaminase' } 1.1475 10000 {'akg[c] + ala_L[c] -> pyr[c] + glu_L[c] ' } {'LYSOXp' } {'Transport of L-Lysine Oxidase, Peroxisomal' } 1.095 10000 {'o2[x] + h2o[x] + lys_L[x] -> h2o2[x] + nh4[x] + 6a2ohxnt[x] '} {'PIK4' } {'Phosphatidylinositol 4-Kinase' } 4.125 10000 {'atp[c] + pail_hs[c] -> h[c] + adp[c] + pail4p_hs[c] ' } {'ATPM' } {'Demand for ATP, Cytosolic' } 186 10000 {'h2o[c] + atp[c] -> h[c] + adp[c] + pi[c] ' } {'GHMT2r' } {'Glycine Hydroxymethyltransferase, Reversible' } 0.7725 10000 {'ser_L[c] + thf[c] -> h2o[c] + gly[c] + mlthf[c] ' } {'ILETA' } {'Isoleucine Transaminase' } 1.305 10000 {'akg[c] + ile_L[c] -> glu_L[c] + 3mop[c] ' } {'LEUTA' } {'Leucine Transaminase' } 1.305 10000 {'akg[c] + leu_L[c] -> glu_L[c] + 4mop[c] ' } {'PROD2' } {'Proline Dehydrogenase' } 0.9675 10000 {'fad[c] + pro_L[c] -> h[c] + fadh2[c] + 1pyr5c[c] ' } {'NTD2' } {'5'-Nucleotidase (UMP)' } 0.2415 10000 {'h2o[c] + ump[c] -> pi[c] + uri[c] ' } {'THRD_L' } {'L-Threonine Deaminase' } 0.885 10000 {'thr_L[c] -> nh4[c] + 2obut[c] ' } {'HMR_0653'} {'S-Adenosyl-L-Methionine:Phosphatidylethanolamine N-Methyltra'} 2.025 10000 {'amet[c] + pe_hs[c] -> 2 h[c] + ahcys[c] + M02686[c] ' } 2965 x 4970 stoichiometric matrix, after thermodynamic flux consistency. Infeasible after extraction of thermodynamically feasible subset, relaxing... itn obj obj_old err(obj) err(x) card(v) card(r) card(p) card(q) 0 8.5431 651.14 642.59 2.8354e+05 1252 0 3 0 1 7.9475 8.5431 0.59563 5.2136e+05 1172 0 3 0 2 8.4058 7.9475 0.45835 5.3075e+05 1279 0 3 0 3 8.5054 8.4058 0.099608 5.3921e+05 1213 0 3 0 4 8.3797 8.5054 0.12571 5.3952e+05 1284 0 3 0 5 8.6121 8.3797 0.23242 5.3995e+05 1276 0 3 0 6 8.5337 8.6121 0.078416 5.4113e+05 1299 0 3 0 7 8.5236 8.5337 0.010169 5.411e+05 1241 0 3 0 8 8.5332 8.5236 0.0096319 5.4235e+05 1293 0 3 0 9 8.5411 8.5332 0.0079158 5.4318e+05 1242 0 3 0 10 8.6421 8.5411 0.10104 5.4241e+05 1243 0 3 0 11 8.4761 8.6421 0.16606 5.4348e+05 1225 0 3 0 12 8.7017 8.4761 0.22564 5.4381e+05 1295 0 3 0 13 8.6743 8.7017 0.027477 5.4587e+05 1272 0 3 0 14 8.6722 8.6743 0.0020358 5.4543e+05 1269 0 3 0 15 8.4168 8.6722 0.25544 5.4252e+05 1224 0 3 0 16 8.8788 8.4168 0.46204 5.4502e+05 1283 0 3 0 17 8.3864 8.8788 0.49246 5.4402e+05 1240 0 3 0 18 8.8933 8.3864 0.50697 5.4341e+05 1301 0 3 0 19 8.5211 8.8933 0.37227 5.4603e+05 1221 0 3 0 itn obj obj_old err(obj) err(x) card(v) card(r) card(p) card(q) Relaxed model is feasible. Statistics: 3 lower bound relaxation(s) 0 upper bound relaxation(s) 0 steady state relaxation(s) The lower bound of these reactions had to be relaxed: Forward_Reaction, non-0 bound Name lb_before lb_after ub_before ub_after equation _____________________________ _____________________________________ __________________ _____________________ _________ ________ __________________ {'EX_2hb[e]' } {'Exchange of 2-Hydroxybutyrate ' } 0.0327019285314542 -8.78928874126217e-13 10000 10000 {'2hb[e] -> ' } {'EX_glyc_R[e]'} {'Exchange of D-Glycerate' } 0.287664725528066 -8.18511924904897e-13 10000 10000 {'glyc_R[e] -> '} {'EX_3hivac[e]'} {'Exchange of 3-Hydroxy-Isovalerate'} 0.922557070436904 0 10000 10000 {'3hivac[e] -> '} ... done. 184 active genes not present in model.genes, so they are ignored. -------------------------------------------------------------- Extracting tissue specific model ... Using real valued weights on metabolites and reactions as input to thermoKernel. Using real valued weights from omics on dummy reactions as input to thermoKernel. 13 forced internal reactions and relaxation of bounds so cycleFreeFlux only determines thermodynamic feasibility of these reactions with relaxed not forced bounds. [mosek] reports OPTIMAL but Primal optimality condition in solveCobraQP not satisfied, residual = 0.00080352, while feasTol = 1e-06 [mosek] reports OPTIMAL but Primal optimality condition in solveCobraQP not satisfied, residual = 0.0002657, while feasTol = 1e-06 [mosek] reports OPTIMAL but Primal optimality condition in solveCobraQP not satisfied, residual = 0.00037936, while feasTol = 1e-06 [mosek] reports OPTIMAL but Primal optimality condition in solveCobraQP not satisfied, residual = 0.00021663, while feasTol = 1e-06 [mosek] reports OPTIMAL but Primal optimality condition in solveCobraQP not satisfied, residual = 0.00043043, while feasTol = 1e-06 [mosek] reports OPTIMAL but Primal optimality condition in solveCobraQP not satisfied, residual = 0.00039624, while feasTol = 1e-06 [mosek] reports OPTIMAL but Primal optimality condition in solveCobraQP not satisfied, residual = 0.00035905, while feasTol = 1e-06 [mosek] reports OPTIMAL but Primal optimality condition in solveCobraQP not satisfied, residual = 0.0015834, while feasTol = 1e-06 [mosek] reports OPTIMAL but Primal optimality condition in solveCobraQP not satisfied, residual = 0.0004235, while feasTol = 1e-06 All incentivised metabolites are produced.
2335 deleted non-core metabolites, corresponding to removal by createTissueSpecificModel. 0 deleted core metabolites, corresponding to removal by createTissueSpecificModel. 3520 deleted non-core reactions, corresponding to removal by createTissueSpecificModel. 9 deleted core reactions, corresponding to removal by createTissueSpecificModel. Forward_Reaction, 0 bound Name lb ub equation _________________________ _____________________________________________ __ _________________ _______________________________________________________________________________________________ {'OIVD1m' } {'2-Oxoisovalerate Dehydrogenase (Acylating'} 0 0.922557070436596 {'nad[m] + coa[m] + 4mop[m] -> nadh[m] + co2[m] + ivcoa[m] + dummy_Met_1738 + dummy_Met_594 '} {'EX_3hivac[e]'} {'Exchange of 3-Hydroxy-Isovalerate' } 0 10000 {'3hivac[e] -> ' } Reverse_Reaction, 0 bound Name lb ub equation _________________________ _____________________________________________ ____________________ __ _______________________ {'URAt'} {'Uracil Transport via Faciliated Diffusion'} -0.00701902520631847 0 {'ura[e] <=> ura[c] '} Reversible_Reaction Name lb ub equation ___________________ ________________________________________________ _____________________ _____ ____________________ {'EX_2hb[e]' } {'Exchange of 2-Hydroxybutyrate ' } -8.78928874126217e-13 10000 {'2hb[e] <=> ' } {'EX_lipoate[e]'} {'Exchange of Lipoate ' } -0.0394044564234044 10000 {'lipoate[e] <=> '} {'EX_ncam[e]' } {'Exchange of Nicotinamide ' } -3.81469600757283 10000 {'ncam[e] <=> ' } {'EX_prgstrn[e]'} {'Exchange of Progesterone ' } -0.00161329356250689 10000 {'prgstrn[e] <=> '} {'EX_CE2028[e]' } {'Exchange of Beta-Hydroxy-Beta-Methylbutyrate'} -10000 10000 {'CE2028[e] <=> ' } {'EX_glyc_R[e]' } {'Exchange of D-Glycerate' } -8.18511924904897e-13 10000 {'glyc_R[e] <=> ' } Infeasible tissue specific model. Trying relaxation... itn obj obj_old err(obj) err(x) card(v) card(r) card(p) card(q) 0 5.3659 276.96 271.6 2.2509e+05 888 0 1 0 1 5.5265 5.3659 0.16051 4.1938e+05 901 0 1 0 2 5.764 5.5265 0.23751 4.3585e+05 959 0 1 0 3 5.5763 5.764 0.18767 4.3948e+05 928 0 1 0 4 5.8715 5.5763 0.29517 4.4035e+05 932 0 1 0 5 5.7167 5.8715 0.15471 4.426e+05 944 0 1 0 6 5.8007 5.7167 0.083906 4.4116e+05 940 0 1 0 7 5.6403 5.8007 0.1604 4.4086e+05 927 0 1 0 8 5.8213 5.6403 0.18102 4.4043e+05 957 0 1 0 9 5.5644 5.8213 0.25686 4.3868e+05 929 0 1 0 10 5.7181 5.5644 0.15373 4.3992e+05 938 0 1 0 11 5.6189 5.7181 0.099209 4.408e+05 929 0 1 0 12 5.6687 5.6189 0.049738 4.3927e+05 931 0 1 0 13 5.6075 5.6687 0.061117 4.3911e+05 947 0 1 0 14 5.7732 5.6075 0.16563 4.3951e+05 957 0 1 0 15 5.7726 5.7732 0.00057859 4.4213e+05 939 0 1 0 16 5.8206 5.7726 0.048032 4.4014e+05 954 0 1 0 17 5.7132 5.8206 0.10742 4.3954e+05 939 0 1 0 18 5.6906 5.7132 0.022593 4.4018e+05 951 0 1 0 19 5.7724 5.6906 0.081751 4.4154e+05 933 0 1 0 itn obj obj_old err(obj) err(x) card(v) card(r) card(p) card(q) Relaxed model is feasible. Statistics: 1 lower bound relaxation(s) 0 upper bound relaxation(s) 0 steady state relaxation(s) The lower bound of these reactions had to be relaxed: Forward_Reaction, non-0 bound Name lb_before lb_after ub_before ub_after equation _____________________________ _______________________ ___________________ _____________________ _________ ________ _______________ {'EX_ura[e]'} {'Exchange of Uracil '} 0.00701902520608372 -2.34757525918727e-13 10000 10000 {'ura[e] -> '} ... done. ... relaxation worked. 1299 x 2110 stoichiometric matrix after model extraction. Feasible at end of XomicsToModel. -------------------------------------------------------------- debugXomicsToModel: #Active_genes #Active_rxns #Active_mets Stage 909 432 45 Active list #Active_genes #Model_genes #Active_rxns #Model_rxns #Active_mets #Model_mets lb_obj Obj Message Stage 885 2248 401 10600 45 5835 0 755.003 Feasible Generic model 882 1892 422 10615 45 5840 NaN 0 Feasible 4.debug_prior_to_setting_default_min_and_max_bounds.mat 882 1892 422 10615 45 5840 NaN 0 Feasible 7.debug_prior_to_exchange_constraints.mat 882 1892 422 10615 45 5840 NaN 0 Feasible 10.a.debug_prior_to_media_constraints.mat 882 1892 422 10615 45 5840 NaN 0 Feasible 10.a.debug_prior_to_metabolomicsBeforeExtraction.mat 882 1892 422 10615 45 5840 NaN 0 Feasible 10.b.debug_prior_to_metabolomic_constraints.mat 882 1892 422 10615 45 5840 NaN 0 Feasible 10.c.debug_prior_to_test_exchange_mismatch.mat 882 1892 422 10615 45 5840 NaN 0 Feasible 10.debug_prior_to_custom_constraints.mat 882 1892 422 10615 45 5840 NaN 0 Feasible 11.debug_prior_to_setting_coupled_reactions.mat 882 1892 422 10615 45 5840 NaN 0 Feasible 12.debug_prior_to_removing_inactive_reactions.mat 882 1892 422 10405 45 5838 NaN 0 Feasible 13.debug_prior_to_removing_inactive_genes.mat 873 1620 422 8658 45 5715 NaN 0 Feasible 16.debug_prior_to_flux_consistency_check.mat 719 1307 377 4983 34 2965 NaN 0 Feasible 17.debug_prior_to_thermo_flux_consistency_check.mat 719 1305 366 4970 34 2965 NaN 0 Feasible 18.debug_prior_to_create_dummy_model.mat 719 1305 366 5639 34 3634 NaN 0 Feasible 19.debug_prior_to_create_tissue_specific_model.mat 715 1224 359 2110 34 1299 NaN 0 Feasible 22.debug_prior_to_debugXomicsToModel.mat -------------------------------------------------------------- Diary written to: /home/rfleming/20221216T085613_rfleming_diary.txt XomicsToModel run is complete at:16-Dec-2022 09:09:37

Examining when active metabolites, reactions and genes were added or removed during the model generation process

debugXomicsToModel(model, pwd, modelGenerationReport)
#Active_genes #Active_rxns #Active_mets Stage 909 432 43 Active list #Active_genes #Model_genes #Active_rxns #Model_rxns #Active_mets #Model_mets lb_obj Obj Message Stage 885 2248 401 10600 43 5835 0 755.003 Feasible Generic model 882 1892 422 10615 43 5840 NaN 0 Feasible 4.debug_prior_to_setting_default_min_and_max_bounds.mat 882 1892 422 10615 43 5840 NaN 0 Feasible 7.debug_prior_to_exchange_constraints.mat 882 1892 422 10615 43 5840 NaN 0 Feasible 10.a.debug_prior_to_media_constraints.mat 882 1892 422 10615 43 5840 NaN 0 Feasible 10.a.debug_prior_to_metabolomicsBeforeExtraction.mat 882 1892 422 10615 43 5840 NaN 0 Feasible 10.b.debug_prior_to_metabolomic_constraints.mat 882 1892 422 10615 43 5840 NaN 0 Feasible 10.c.debug_prior_to_test_exchange_mismatch.mat 882 1892 422 10615 43 5840 NaN 0 Feasible 10.debug_prior_to_custom_constraints.mat 882 1892 422 10615 43 5840 NaN 0 Feasible 11.debug_prior_to_setting_coupled_reactions.mat 882 1892 422 10615 43 5840 NaN 0 Feasible 12.debug_prior_to_removing_inactive_reactions.mat 882 1892 422 10405 43 5838 NaN 0 Feasible 13.debug_prior_to_removing_inactive_genes.mat 873 1620 422 8658 43 5715 NaN 0 Feasible 16.debug_prior_to_flux_consistency_check.mat 719 1307 377 4983 32 2965 NaN 0 Feasible 17.debug_prior_to_thermo_flux_consistency_check.mat 719 1305 366 4970 32 2965 NaN 0 Feasible 18.debug_prior_to_create_dummy_model.mat 719 1305 366 5639 32 3634 NaN 0 Feasible 19.debug_prior_to_create_tissue_specific_model.mat 715 1224 359 2110 32 1299 NaN 0 Feasible 22.debug_prior_to_debugXomicsToModel.mat

TIMING

TIMING: 15 minutes to hours (computation) - days (interpretation)

Bibliography

  1. German Preciat, Agnieszka B. Wegrzyn, Ines Thiele, et al., "XomicsToModel: a COBRA Toolbox extension for generation of thermodynamic-flux-consistent, context-specific, genome-scale metabolic models", bioRxiv (2021)
  2. Laurent Heirendt, Sylvain Arreckx, Thomas Pfau, et al., "Creation and analysis of biochemical constraint-based models using the COBRA Toolbox v. 3.0", Nature protocols (2019).
  3. German Preciat, Edinson Lucumi Moreno, Agnieszka B. Wegrzyn, et al., "Mechanistic model-driven exometabolomic characterisation of human dopaminergic neuronal metabolism", bioRxiv (2021)
  4. Elizabeth Brunk, Swagatika Sahoo, Daniel C. Zielinski, et al., "Recon3D enables a three-dimensional view of gene variation in human metabolism", Nature biotechnology (2018)