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GUEST POST by Emma Schymanski: Suspect Screening with MetFrag and the CompTox Chemistry Dashboard

08 Dec

Identifying “known unknowns” via suspect and non-target screening of environmental samples with the in silico fragmenter MetFrag (http://msbi.ipb-halle.de/MetFragBeta/) typically relies on the large compound databases ChemSpider and PubChem (see e.g. Ruttkies et al 2016). The size of these databases (over 50 and 90 million structures, respectively), yield many false positive hits of structures that were never produced in sufficient amounts to be realistically found in the environment (e.g. McEachran et al 2016). One motivation behind the US EPA’s CompTox Chemistry Dashboard is to provide access to compounds of environmental relevance – currently approx. 760,000 chemicals. While the web services are not yet available to incorporate the Dashboard in MetFrag as a database like ChemSpider and PubChem, there are a number of features in MetFragBeta that enables users to use the CompTox Chemistry Dashboard to perform “known unknown” identification with MetFrag. This post highlights the Suspect Screening Functionality.

First we have our (charged) mass. Take m/z = 256.0153. This was measured in positive mode and we assume (correctly) that it’s [M+H]+. Make sure you set this correctly in MetFrag.

 

Then retrieve your candidates, e.g. using ChemSpider or PubChem and a 5 ppm error margin:

Take the peak list from MassBank here: https://massbank.eu/MassBank/jsp/RecordDisplay.jsp?id=EA267612&dsn=Eawag and copy into the Fragmentation settings:

You could now process the candidates … but we have not done anything with the Dashboard! This is hidden in the middle in the “Candidate Filter & Score Settings” tab:

You can use the Candidate Filter to process ONLY candidates that are in the CompTox Chemistry Dashboard, excluding all other candidates, by clicking on “Suspect Inclusion Lists” and selecting the “DSSTox” box (see screenshot), which retains (currently) 11 of the 156 ChemSpider candidates:

Once finished the processing, the plot in the “Statistics” tab should look something like this – depending on what additional scores you selected:

It is also possible to use one (or more!) suspect lists to SCORE the different candidates without excluding any matches from ChemSpider or PubChem, by selecting the same box under the “MetFrag Scoring Terms” part instead (see screenshot). Additional lists like the Swiss Pharma list shown below can be downloaded from the NORMAN Suspect Exchange (http://www.norman-network.com/?q=node/236) and also viewed under the lists tab in the CompTox Chemistry Dashboard (https://comptox.epa.gov/dashboard/chemical_lists). MetFrag only needs a text file containing InChIKeys of the substances for the upload – which can be obtained from the Dashboard or Suspect Exchange downloads.

Using the Suspect Lists as a “Scoring term”, along with some other criteria and restrictions, will give you a results plot looking more like this:

Curious to find out more? MetFrag comes with a built-in example and you can try this exact example yourself by visiting http://msbi.ipb-halle.de/MetFragBeta/ and using the peak list copied from the bottom of the spectrum available at https://massbank.eu/MassBank/jsp/RecordDisplay.jsp?id=EA267612&dsn=Eawag

There are many more features to discover: try the website, read the paper (Ruttkies et al 2016) and if you have any questions, please comment below!

Author: Emma Schymanski, 21/11/2017

 

About tony

Antony (Tony) J. Williams received his BSc in 1985 from the University of Liverpool (UK) and PhD in 1988 from the University of London (UK). His PhD research interests were in studying the effects of high pressure on molecular motions within lubricant related systems using Nuclear Magnetic Resonance. He moved to Ottawa, Canada to work for the National Research Council performing fundamental research on the electron paramagnetic resonance of radicals trapped in single crystals. Following his postdoctoral position he became the NMR Facility Manager for Ottawa University. Tony joined the Eastman Kodak Company in Rochester, New York as their NMR Technology Leader. He led the laboratory to develop quality control across multiple spectroscopy labs and helped establish walk-up laboratories providing NMR, LC-MS and other forms of spectroscopy to hundreds of chemists across multiple sites. This included the delivery of spectroscopic data to the desktop, automated processing and his initial interests in computer-assisted structure elucidation (CASE) systems. He also worked with a team to develop the worlds’ first web-based LIMS system, WIMS, capable of allowing chemical structure searching and spectral display. With his developing cheminformatic skills and passion for data management he left corporate America to join a small start-up company working out of Toronto, Canada. He joined ACD/Labs as their NMR Product Manager and various roles, including Chief Science Officer, during his 10 years with the company. His responsibilities included managing over 50 products at one time prior to developing a product management team, managing sales, marketing, technical support and technical services. ACD/Labs was one of Canada’s Fast 50 Tech Companies, and Forbes Fast 500 companies in 2001. His primary passions during his tenure with ACD/Labs was the continued adoption of web-based technologies and developing automated structure verification and elucidation platforms. While at ACD/Labs he suggested the possibility of developing a public resource for chemists attempting to integrate internet available chemical data. He finally pursued this vision with some close friends as a hobby project in the evenings and the result was the ChemSpider database (www.chemspider.com). Even while running out of a basement on hand built servers the website developed a large community following that eventually culminated in the acquisition of the website by the Royal Society of Chemistry (RSC) based in Cambridge, United Kingdom. Tony joined the organization, together with some of the other ChemSpider team, and became their Vice President of Strategic Development. At RSC he continued to develop cheminformatics tools, specifically ChemSpider, and was the technical lead for the chemistry aspects of the Open PHACTS project (http://www.openphacts.org), a project focused on the delivery of open data, open source and open systems to support the pharmaceutical sciences. He was also the technical lead for the UK National Chemical Database Service (http://cds.rsc.org/) and the RSC lead for the PharmaSea project (http://www.pharma-sea.eu/) attempting to identify novel natural products from the ocean. He left RSC in 2015 to become a Computational Chemist in the National Center of Computational Toxicology at the Environmental Protection Agency where he is bringing his skills to bear working with a team on the delivery of a new software architecture for the management and delivery of data, algorithms and visualization tools. The “Chemistry Dashboard” was released on April 1st, no fooling, at https://comptox.epa.gov, and provides access to over 700,000 chemicals, experimental and predicted properties and a developing link network to support the environmental sciences. Tony remains passionate about computer-assisted structure elucidation and verification approaches and continues to publish in this area. He is also passionate about teaching scientists to benefit from the developing array of social networking tools for scientists and is known as the ChemConnector on the networks. Over the years he has had adjunct roles at a number of institutions and presently enjoys working with scientists at both UNC Chapel Hill and NC State University. He is widely published with over 200 papers and book chapters and was the recipient of the Jim Gray Award for eScience in 2012. In 2016 he was awarded the North Carolina ACS Distinguished Speaker Award.
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Posted by on December 8, 2017 in MS Structure Identification

 

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