HepatoNet1 was subjected to additional consistency checks which resulted in the identification of a system of reactions which are not complete and, thus, the respective reactions could not carry a flux. As the reactions described a protein modification in the nucleus, the have been considered beyond the scope of metabolic network and removed. As in liver fibrosis also the hepatocyte excrete collagens, a comprehensive list of collagens have been added as additional macromolecular synthesis functions. This network, caled Hepatonet1b has been used in several projects.
The gene associations to all reactions have been curated in a multi-step process. In the first attempt, the well-known annotations, stored in KEGG database, have automatically been assigned. Then, the remaining reactions have been analyzed with the help of UniProt, BRENDA and Ensemble databases, and further annotations are semi-automatically annotated. Then, homologous enzymes from other mammals (mouse, rat, rabbit, cow) haven been studied to obtain further annotations. Finally, the remaining reactions have been searched for in the scientific literature to assign further genes, or, in most cases confirm, that no gene is associated to the reaction.
HepatoNet1b_human HepatoNet1b with human GPR.
This process has also been performed for mouse genes. In fact, no reaction in HepatoNet1 was found, which is not present in human, and vice versa. The network including mouse annotations, called HepatoNet1b_mouse, is deposited in Biomodels database under the identifier MODEL1208060000 .
HepatoNet1b_mouse HepatoNet1b with mouse GPR.
HepatoNet1 -- Supplementary information
Supplementary files, differently organized than published by MSB
The modelHepatoNet1 as SBML model: Supplementary_Data_1.xml
HepatoNet1 in straight text format: Supplementary_Data_2.zip
Description of pooled metabolites: Supplementary_Notes_1.pdf
Compounds table: Supplementary_Table_1.1.tsv
Reactions table: Supplementary_Table_1.2.tsv
The simulationsDefinition of simulations, main set: Supplementary_Table_2.1a.tsv
Definition of simulations, additional set: Supplementary_Table_2.1b.tsv
Exchange set definition for the main set of simulations: Supplementary_Table_2.2a.tsv
Exchange set definition for the additional set of simulations: Supplementary_Table_2.2b.tsv
Solutions to simulations: Supplementary_Data_3.zip
Details of the computational protocolConcentration ranges: Supplementary_Table_2.3.tsv
Weights for the FBA computations: Supplementary_Table_2.4.tsv
Annotation tablesExchange function annotation: Supplementary_Table_2.5.tsv
Gene annotation (ENSG): Supplementary_Table_3.tsv
Few selected examples of discrepancies referred to in the manuscript: Supplementary_Table_4.pdf