Open PHACTS Explorer: Pharmacology by Enzyme Family

Transcription

1 Open PHACTS Explorer: Pharmacology by Enzyme Family

2 This document is a tutorial for using Open PHACTS Explorer (explorer.openphacts.org) to obtain pharmacological information for families of enzymes classified by Enzyme Commission or EC codes. Features: Access ChEMBL pharmacology data based on target hierarchy - Enzyme classification Provenance, in the form of links to the original data Easy export of pharmacology to TSV file, including SMILES/InChI structures Index: 1. Retrieving pharmacological information 2. What information is retrieved in Pharmacology by Enzyme family? 3. Provenance 4. Additional options 5. Filtering records 6. Sorting/displaying records 7. Downloading data

3 1. Retrieving pharmacological information: In the navigation tree on the left-hand side, expand the Pharmacology folder and then select the application Pharmacology by Enzyme family. This opens a new tab in the Open PHACTS Explorer window: In order to select an enzyme family for a pharmacology query, click on the Browse EC codes button. The following widget will appear; showing 6 families of enzymes based on top level EC codes:

4 Here you can select the enzyme family of interest at the highest level or expand the library by successively clicking on the small triangle in front of each folder to reach the desired sub-category: 1. - Click on Use selection to choose an Enzyme family Select an Enzyme family name by clicking on Use selection button. Finally, click on Start search button to complete the query: 2. - Click on Start search to perform the query Your input is now translated into a SPARQL-query that searches pharmacology data for your enzyme family in the OPS triple store. Once your query has been processed, the results will be presented as a table:

5 2. What information is retrieved in Pharmacology by Enzyme family? Below is a brief description of the information displayed, arranged by Column headers: Structure: 2D Image of the compound Compound Name: Name of the compound Target Name: Name of the molecular target, in this case, the selected enzyme family, including all subunits and isozymes in all species Target Organism: Origin of the target Assay Organism: The organism from which the protein/cell-line was derived for an in vitro assay. May differ from the target organism (e.g., for a human protein expressed in nonhuman cells, or pathogen-infected human cells) Assay Description: Description of the bioassay Activity Type: Type of end-point measurement: e.g. IC50, LD50, %inhibition, etc Relation: Symbol constraining the activity value (e.g. >, <, =) Value: Activity data point Units: Units of measurement

6 InChI: An InChI (IUPAC International Chemical Identifier) is a string of characters capable of uniquely representing a chemical substance. It is derived from a structural representation of that substance in a way designed to be independent of the way that the structure was drawn therefore ensuring that a compound will always produce the same identifier (+ info) InChIKey: The InChIKey is a short, fixed-length character signature based on a hash code of the InChI string (+ info) 3. Where does the information come from? (Provenance) You can see the provenance information by setting the Provenance button to On :

7 Note that the color coding scheme used for provenance is visible by placing the cursor over the question mark icon The information displayed in Pharmacology by Compound comes from ChemSpider, ChEMBL, DrugBank and ConceptWiki. There is a small icon next to the information that links out to the origin of the information. Icon DataBase ConceptWiki ChemSpider ( ChEMBL ( DrugBank ( e.g. Clicking on ChEMBL icon compound: opens a new ChEMBL window with information for your

8 4. Additional options: Once your results are displayed in the interface, you can access additional information by using the right mouse button: Search for compound by name: Clicking this option opens a new tab showing further information about the compound (see Compound by Name tutorial): Search for compound by SMILES: Clicking this option opens a new tab showing Compound by Structure exact search (see Compound by Structure tutorial):

9 Search for target by name: Clicking this option opens a new tab showing information about the target selected (see Target by Name tutorial). Copy Data: Placing your mouse over this option opens a new window, with the option to copy the Compound Name, Target Name and SMILES:

10 Compound Name Target Name SMILES Information from ChemSpider: Double clicking on any record opens a Chemspider widget where you can access further compound related information from other public databases.

11 5. Filtering records: Pharmacology by Enzyme family allows you apply filters, to narrow down your search results. Alternatively, you can add the filters prior to the search to only display results of interest. In this version you can use two types of filters: Filtering by activity type and Filtering by Assay Organism. In order to access the filter tool, click on Filter button: Add Activity Type filter: In order to display compounds with desired activity: 1. Choose the activity type that you want to filter: Activity, IC50, Percentage Inhibition or Potency 2. Choose conditions: >, <, =, <=, >= 3. Manually enter a value 4. Choose units 5. Click on the icon Add this activity filter 6. Finally, click on Search Click again on Start search button to perform the search.

12 Add organism filter: In order to display compounds active in desired Assay Organism/s: 1. Enter the Assay Organism that you want to filter: Homo Sapiens, Rattus norvegicus, etc 2. Select it from the drop-down menu 3. Click on the icon Add this organism filter 4. Finally, click on search Click on this to remove added filter/s. Click again on Start search button to perform the search. You can remove these filters to view all records by clicking on the close button in the filter status bar and clicking on Start search again.

13 6. Column Sorting and Display: You can view the data sorted by a selected column (eg. ascending or descending activity values) and also select the columns you wish to be displayed. TIP: Click directly on the header to sort ascending. Click again to sort descending. (a) Sorting values: Click on Sort Ascending or Sort Descending to sort data accordingly. (b) Displayed columns: Place your mouse on Columns and a new window will appear where you can check/uncheck columns to display. By checking columns, you can choose which information you would like to display.

14 Column order: Alternatively, you can arrange the columns in the order you prefer by clicking on the column header and dragging it to the desired location. 7. Downloading data: The results can be downloaded in a standard format, for further off-line analysis. Click on Download tsv file button. This will convert your results into a Tab Separated Values File (tsv-file) that can be saved to your computer.