APAP_toxicity_liver

Code availability for the manuscript titled "Metabolic network-based predictions of toxicant-induced metabolite changes in the laboratory rat" by Pannala et al.

Following scripts were used to generate Figures in the main text and Supplementary Fig. S1.

Figure 2: Plot_Fig_2.m

Inputs: processed gene expression fold changes stored in the folder Weights_apap

Outputs: volcano plot for gene expression changes

Figure 4: Plot_Fig_4.m

Inputs: processed metabolic flux analysis data

Outputs: bar charts for absolute flux changes

Figure 5: Plot_Fig_5.m

Inputs: processed metabolite fold changes reported in Suppplementary TableS3

Outputs: volcano plots for metabolite changes

Figure 7: Plot_Fig_7.m

Inputs: processed table of TIMBR predcitions for the metabolite changes given in the folders MFA_10h and NoMFA_10h and observed metabolite changes Mets_increased/decreased_10h_data

Outputs: heatmap showing the observed metabolite changes in the data vs. model predictions at 10 h post APAP treatment Helper functions: Timbr_10h_MFA.m and Timbr_10h_NoMFA.m are used to generate the Tables in the MFA_10h folders

Figure S1: Plot_Fig_S1.m

Inputs: processed table of TIMBR predcitions for the metabolite changes given in the folders MFA_5h and NoMFA_5h and observed metabolite changes Mets_increased/decreased_10h_data

Outputs: heatmap showing the observed metabolite changes in the data vs. model predictions at 5 h post APAP treatment Helper functions: Timbr_5h_MFA.m and Timbr_5h_NoMFA.m are used to generate the Tables in the MFA_5h folders

Predicting biomarkers based on gene expression changes with TIMBR

Generate_timbr_weights.R

Inputs: gene expression changes from the folder Weights_apap, Sleuth_table_liver_.tsv files, Supplementary_iRno_v2.xlsx and gene annotation tables from the file, Biomart_rno_ids.txt.gz

Outputs: TIMBR reaction weights

Helper functions: ncomm_helper.R

Timbr_h_.m

Inputs: TIMBR reaction weights, rat metabolic network in the cobra format iRno_v2.mat

Outputs: TIMBR predictions for metabolite changes

Helper functions: timbr.m and ncomm_blais_model2irrev.m

iRno_v2.mat

Rat genome scale metabolic model version 2 in cobra format

iRno_v2_SBML.xml

Rat genome scale metabolic model version 2 in SBML

Helper function files:

ncomm_helper.R

R source file that defines several helper functions used in the R scripts above.

timbr.m

MATLAB implementation of the TIMBR (transcriptionally-inferred metabolic biomarker response) algorithm

ncomm_blais_model2irrev.m

Modified version of convertToIrreversible from the COBRA toolbox (www.github.com/opencobra/cobratoolbox) that facilitates the mapping of TIMBR reaction weights to irreversible reactions