Check and refine the direction of reactions

Most databases (e.g. KEGG) that are used to generate and curate metabolic models automatically, do not save the directionality of reactions. This can become a problem in downstream analyses as the direction of reactions is important for the correctness of the model. Since the direction of a reaction is often missing from databases, the default is to set the reaction to reversible. However, in the worst case, wrongly set reaction directions can be the cause of energy generating cycles (EGCs), which are thermodynamically infeasible.

One of the few databases to reliably store information about a large number of reactions is MetaCyc / BioCyc . The check_direction() function enables the user to check the directions of reactions in a metabolic model against a given either species-specific BioCyc or general MetaCyc database table containing the information about the direction of reactions.

The table should contain all reactions (of interest) and it MUST contain the following columns:

  • Reaction: contains the MetaCyc ID

  • EC-Number: contains the EC number associated with the reactions (EC-X.X.X.X) or nan

  • KEGG reaction: contains the href link to the associated KEGG reaction or nan

  • METANETX: contains the href link to the associated MetaNetX reaction or nan

  • Reaction-Direction: contains a string describing the directionality of the reaction

How to get the table from BioCyc

  1. If you have no BioCyc account you will need to create one. See BioCyc Create Free Account to create an account.

  2. Then you need to search for your specific organism, i.e. the exact strain, and change to the corresponding organism database. In case you want to use MetaCyc, you have to switch to the MetaCyc database.

  3. Within the chosen database you need to click on Tools in the menu bar and select Special SmartTables under SmartTables. (There you need to make an adjustable copy of the table “All reactions of <organism>/MetaCyc”.)

  4. Then follow these steps to obtain the table:

    1. Select the column ‘Reaction’,

    2. then select

      1. ‘Database Links’

      2. and ‘Reaction-Direction’

      under ADD COLUMN and click submit.

    3. From the popup select KEGG reaction and METANETX under Database Links and click Go.

    4. [Optional] If you want the specified order you can click on the ‘Reaction-Direction’ column, then select Move and then Move Column Full Right.

    5. Finally, click Export to Spreadsheet File in the box on the right side and choose frame IDs.

The resulting table should look like this (start of the downloaded file):

Reaction    EC-Number       KEGG reaction   METANETX        Reaction-Direction
RXN-22670   EC-6.3.2                        PHYSIOL-LEFT-TO-RIGHT
RXN-9464    EC-3.3.2.8              <a href='https://www.metanetx.org/equa_info/~A'>MNXR122834</a>  PHYSIOL-LEFT-TO-RIGHT

Note

The requested format is automatically generated by BioCyc by choosing all reactions for a smart table and adding the properties described above as columns and finally exporting it as a txt-file.