Open PHACTS Explorer: Compound by Name

Transcription

1 Open PHACTS Explorer: Compound by Name

2 This document is a tutorial for obtaining compound information in Open PHACTS Explorer (explorer.openphacts.org). Features: One-click access to integrated compound information from ChEMBL, ChemSpider and DrugBank: 2-D structures, calculated molecular properties (logp, molecular weight, Lipinski Rule of Five parameters) and bioactivity data (binding constants, pharmacology) Search by name and jump straight to pharmacology data Information on absorption, distribution, metabolism, excretion and toxicity (ADMET) Provenance, in the form of links to the original data Access to more compound-centric information via inbuilt ChemSpider "widget" Index: 1. Searching by compound name 2. ConceptWiki 3. What information is retrieved? 4. Provenance 5. Pharmacology Data 6. ChemSpider Data

3 1. Searching by Compound name: In the navigation tree on the left-hand side, expand the Compound folder and then select the application Compound by Name. A tab will open with an input field for the compound name. As you start typing, for example, Aspirin, the system starts to match your text input with the content in ConceptWiki and returns a list of auto-completed target names in a drop-down menu: Select your compound of interest by clicking on it, in this case: Aspirin and complete your query by clicking on the Search button:

4 Your input is now translated into a SPARQL-query that searches compound data in the Open PHACTS triple store. Once your query has been processed your results will be presented as below: 2. ConceptWiki: ConceptWiki is a community annotation system containing over one million biomedical concepts, derived from authorities such as the Unified Medical Language System (UMLS), SwissProt, Gene Ontology (GO), and the chemical terminology necessary for Open PHACTS from ChemSpider. To access the ConceptWiki page, click on (definition) which appears during the search process.

5 Clicking this link opens a window in ConceptWiki: The ConceptWiki interface consists of a table with 2 columns. The first column lists synonymous terms for the searched concept. The second column lists the contributing authority for each term: UMLS, SwissProt, ChemSpider, ConceptWiki, or Community. Given that all authorities are part of the biomedical community, all contributed terms are assumed to also be part of the Community ; unless, it is specifically removed by a community editor and then would only be retained by the authority. Each authority has a preferred term, which is highlighted in bold font in the authority column. In this case the preferred term for the authority ChemSpider is Aspirin while that of UMLS is Dispril.

6 3. What information is retrieved in Compound by Name? (a) Physical-Chemistry information: This information is retrieved from ChemSpider, ChEMBL and DrugBank (see provenance). ALogP: Calculated value for the lipophilicity of a molecule expressed as log (octanol/water partition coefficient (+ info) H-Bond Acceptors: Number of Hydrogen Bond Acceptors in the compound (+ info) H-Bond Donors: Number of Hydrogen Bond Donors in the compound (+ info) Molecular Weight: The molecular weight (Mw) of a substance is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12) MW Freebase: Molecular Weight Freebase Polar Surface Area: (PSA) is defined as the surface sum over all polar atoms, primarily oxygen and nitrogen, also including their attached hydrogens (+ info) Rotatable Bonds: Number of rotatable bonds, i.e. single bonds between heavy atoms

7 SMILES: (Simplified Molecular Input Line Entry System) is a line notation for entering and representing chemical structures and reactions (+ info) Standard 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) Standard InChIKey: The InChIKey is a short, fixed-length character signature based on a hash code of the InChI string (+ info) For further information, please see: (b) Biological properties (when available): This information is retrieved from DrugBank as Aspirin is an approved drug (see provenance). Description: General properties, composition and/or preparation Metabolism: Mechanism by which or organ location where the drug is neutralized Protein Binding: Percentage of the drug that is bound in plasma proteins

8 Toxicity: Lethal dose (LD50) values from test animals, description of side effects and toxic effects seen in humans For further information please see: 4. Where does the information come from? (Provenance) You can see the provenance information by setting the Provenance button to On : The information displayed in Compound by Name comes from ChemSpider, ChEMBL and DrugBank. Note that there is a small icon next to the information that links out to the origin of the information. Icon DataBase Concept Wiki page ChemSpider ( ChEMBL ( DrugBank ( e.g. Clicking on ChEMBL icon opens a new ChEMBL window with information for Aspirin.

9 5. Retrieving Pharmacology Data from compound search result: Clicking on the Pharmacology Data button allows direct access to all pharmacological data for the compound.

10 A new tab is opened with pharmacological information about your compound. Note that the same result can be obtained by performing the compound name search directly in the Pharmacology by Compound tool. For further information please go to Pharmacology by Compound tutorial. 6. Retrieving ChemSpider information from Compound by Name : You can also access compound information from ChemSpider information by clicking on ChemSpider Info button:

11 This opens a widget within OPS Explorer with compound details retrieved from ChemSpider: Further compound related information can be obtained by following the links under the various Data Sources.