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RamanLab / minRerouting

Package to understand the compensatory mechanisms performing similar metabolic functions through analysis of Synthetic Lethals
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minRerouting

Package to understand the compensatory mechanisms performing similar metabolic functions through analysis of Synthetic Lethals

Alternate Routes in Networks

The rerouting of the reaction fluxes upon deletion of genes/reactions in the metabolic network is non-trivial and involves complex structrues. This package helps to identify minimal rerouting corresponding to synthetic lethal pairs using constraint based tools.

Workflow for analysis of synthetic lethals

Steps in analysis

  1. Get FastSL toolbox from https://github.com/RamanLab/FastSL

  2. Run FastSL on COBRA model/s object to identify synthetic lethal pairs for given models. Here we explain the example of some of the models of pathogenic organims downloaded from BIGG database. Exchange reactions are exluded from the analysis to focus on intracellular properties of metabolic networks

    addpath('core')

% Recommneded to rename model.mat file to modelNames.mat file
model_names = {'iIT341', 'iML1515', 'iNJ661', 'iPC815', 'iYL1228', 'STM_v1_0', 'e_coli_core', 'iJO1366', 'iSSON_1240'};
% model_names = {'iML1515'};
% path_to_models = {'examples/iIT341/', 'examples/iML1515/', 'examples/iNJ661/','examples/iPC815/', 'examples/iYL1228/', 'examples/STM_v1_0/', 'examples/e_coli_core/', 'examples/iJO1366', 'examples/iSSON_1240'};
path_to_models = {'examples/iML1515/'};

% 2 for double lethals and 3 for triple lethals
Castle = getFastSL(model_names, path_to_models, 2);

    Castle.data has models, SLs, modelNames
    To Do: modify for without fastSL run in cases where SL are identified

  3. Run minRerouting

    % Run multiMinRerouting for 1 norm solution
Castle = multiMinRerouting(Castle, 'one')

  4. Comparitive analysis synthetic lethals Use Castle input Struct to run compareLethals

    Castle = compareLethals(Castle, 2);

    Castle.data with new fields:

    • lethStatus
    • lethCount
    • all_rxns
    • core (Single, Double, Nonessential, Single_to_double)
    • simTable (SingleCnt, Single.rxns)

    To Do: modify for TL compare

    [Castle, lethPair] = compareModelsPairwise(Castle, model1, model2)

    To Do : Need to finish

  5. Save the output data in xls Use Castle structure to save output data in xls format

    get_output_castle(Castle_l1, 'examples/L1_minimal')
get_output_castle(Castle_l2, 'examples/L2_minimal')

  6. pFBA Analysis

    pfba_analysis(model_names, path_to_models)

  7. PSL/RSL Analysis

    psl_rsl_analysis(model_names, path_to_models)