About the Pathway Prediction System
The pathway prediction system can be accessed at the EAWAG-BBD Pathway Prediction
page, which can be reached from the "Pathway Prediction" link on the EAWAG-BBD home page,
or by using the following URL: http://umbbd.ethz.ch/predict/.
EAWAG-BBD Pathway Prediction Page.
When the initial prediction on the query compound is finished, the system will bring a user to the Pathway Prediction Results page.
Change Default Options" below.
From the Pathway Prediction Results page, a user is able to see the more likely aerobic transformations of Benzyl Alcohol based
on the biotransformation rules found in the EAWAG-BBD.
The Navigation Bar "BBD Home > PPS Home > 1" permits quick navigation back to previous prediction steps and the PPS and BBD home pages.
The Zoom feature to the right of the Navigation Bar allows the user to resize the prediction results as described on the Viewing and Printing page. The prediction run-time is shown in the "Elapsed time" at the bottom of the results page.
The user can click on any grey compound square in the predicted pathway.
The compound can be rotated in this window. The window can also be increased in size, to better view larger compounds. Double clicking in this new window will produce a MarvinView window. The MarvinView window can provide much additional information on the compound. Information on how to use it is available at http://www.chemaxon.com/marvin/help/view/view-index.html.
By default, the PPS will show "Aerobic" biotransformations, show up to 6 levels, display compounds containing 3 or more carbon atoms, and stop before any level where there are more than 10 compounds. These default options are changeable throughout the prediction process, as described below.
More information is available.
The aerobic likelihood of a transformation is indicated by a color of an arrow that starts from one substrate to one or two products. Users are able to choose, before or after a compound undergoes transformation, if they will view all or only the aerobic likely transformations of a compound by selecting the appropriate button.
If the aerobic setting is chosen, and no very likely, likely, or neutral transformations, but some unlikely and/or very unlikely transformations, are found, the setting is automatically changed to "All" and these transformations are shown.
Some predictions are too complex to be displayed. When this occurs, the prediction is rerun with a decreased number of levels, and a message is displayed under the last compound row as shown below.
The first three levels of the prediction for malathion are shown below using default prediction options.
By default, the system will only display compounds containing 3 or more carbon atoms. A user can change this minimum number of carbon atoms to view more or fewer compounds. In the malathion prediction shown above, the ethanols cleaved by bt0024, the ester cleavage rule, are not displayed using the default settings. The 1-level prediction for malathion with an option to show 2 or more carbon atoms, which shows the missing ethanol, is shown below.
Cleavage compounds (Compounds 2 and 3, Compounds 2 and 4, Compounds 6 and 7) are indicated by two tailed arrows. Duplicate compounds are removed and only one (Compound 2) is left, pointed to by multiple arrows.
An exception to "Show compounds containing above a threshold number of carbon atoms" occurs when the parent compound is one carbon or less above the threshold. In those cases, compounds with one or more carbons are shown.
A user can decrease or increase the threshold value.
Shown below is the prediction for malathion, limited to no more than 5 compounds.
Clicking the "Rule" button will open a new browser window containing the rule page of the biotransformation rule associated with the specific reaction. The Biotransformation rule page provides a user with links to the PPS, a list of All BTrules, and the EAWAG-BBD Main Menu. It also provides one or more descriptions of the type(s) of reactions handled by the rule, the likelihood the reaction will occur under aerobic conditions, a list of EAWAG-BBD reactions that exemplify the rule, staff comments, similar biotransformation rules (if any), and a way for the user to provide comments. A list of all rules the system uses is available. More information about BTrules is available in About the BBD.
Clicking the "Cpd" button will open a new browser window containing the compound page of a biotransformation. The compound page provides a user with a graphic image of the compound, its chemical formula, molecular weight, SMILES string, and links to reaction pages in the EAWAG-BBD where the compound is either the substrate or product. More information about compound pages is available in About the BBD.
To continue the pathway, select the "Next" button on another transformation. The Navigation Bar will then expand to "BBD Home > PPS Home > 1 > 2" for easy navigation to previous PPS prediction pages or BBD or PPS Home pages. The biotransformed compound selected will appear as an intermediate compound in the new predicted pathway starting from the original compound. The colored arrow indicates the aerobic likelihood of the biotransformation that connects two compounds.
This indicates that this compound is readily degraded. If you click on a "Green Next" button, your predicted pathway is completed by ending at the chosen compound. At the same time, all branches ending at other compounds are removed. In the example below, compound 6 and 8, not on the path between compound 1 and compound 9, the chosen compound, are removed.
The "Green Cpd" button indicates that this compound is found in a KEGG pathway. Clicking the "Green Cpd" button brings a user to a KEGG pathway web page. Alternatively, a user may choose to continue prediction by clicking on a non-green "Next" button, if one is present.
Compounds are removed by entering their numbers (the small number shown in the upper left of each grey compound square), separated by commas, in the "Remove Products:" box, and then clicking on the "Go!" button below the box. The starting compound (compound 1) cannot be removed. The (More) link will open this section of the EAWAG-PPS help webpage in a separate window.
For example, above is the 3-level prediction for benzenesulfinate. If it is desired to remove the compound benzene (product 3) in level 1, and phenol in level 2 (product 5), these compounds, and all compound boxes and rule arrows following them, are removed by entering "3,5" (or "5,3") in the "Remove Products:" box, and clicking the "Go!" button.
The partial prediction is shown below:
To return to the original prediction, click on the "Show Original" button, to the right of the "Go!" button after a partial prediction has been made.
Once back at the original, you can return to the partial prediction by clicking on the "Show Partial" button, in the same position as the "Show Original" button. Compounds in a partial prediction retain the same numbers as in the original prediction. Since some compounds were removed, there are gaps in the number sequence.
Removing compounds can be done in multiple steps, without returning to the original prediction. In the above example, you can get to the same result by first choosing to remove compound 3 (or 5), and, after reviewing the result, choosing to remove compound 5 (or 3). If you return to the original prediction, you can remove different compounds to create a new partial prediction. If a previous partial prediction exists, the new one overwrites it.
Zoom In, Zoom Out, and PDF buttons all work in a partial prediction the same as in the original.
Clicking the Clear button in a partial prediction returns to the original.
Compound, Rule and Next buttons work in a partial prediction as in the original.
If the Next button is clicked in a partial prediction, the Next step in the prediction will be that of the original, not the partial, prediction.
Compare the previous predicted pathway for benzyl alcohol, with the pathway below for p-chlorobenzyl alcohol. The aerobic likelihood for the first three transformations are likely, as above. However when the ring is oxygenated and cleaved, the aerobic likelihoods are neutral for the chlorinated compound, rather than the likely value found for the non-halogenated compound.
A second use of variable aerobic likelihood is for nitro groups. Aerobically likely or neutral rules for oxidation of aliphatic carbons have been changed to unlikely when the chain contains one or more nitro groups.
Variable Aerobic Likelihood" section above.
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