MetaboLights: Creating the missing Metabolomics community resource

Lead Research Organisation: EMBL - European Bioinformatics Institute
Department Name: Chemoinformatics and Metabolism

Abstract

Metabolomics studies the occurrence and change of concentrations of small molecular weight chemical compounds (metabolites) in organisms, organs, tissues, cells and ultimately cell compartments in the context of environmental changes, disease or other boundary conditions. It does this by means of spectroscopic and chromatographic techniques and by observing at once not only a few but all compounds visible to the particular technique used. To understand what a change in concentration of one or more of the signals in a spectrum or chromatogram ultimately means, the identity and role of the chemical compounds underlying the respective signal needs to be revealed. This requires curated databases with reference data of chemical structures of biological metabolites assigned to their spectra data. It also requires the knowledge about reference concentrations of metabolites in the biological system of interest under given conditions. In genome and protein science large resources exist to document which genes or proteins are found or expressed under certain conditions in the system of interest. In metabolomics, however, a general system with such information has not yet been instantiated. Instead, a number of resources exist which specialize on certain 'kingdoms of life', species or diseases, or analytical devices. Here, we therefore propose to establish a general metabolomics database resource at the European Binformatics Institute in Hinxton, Cambridge, UK, which serves this crucial information to the biological community in the UK and worldwide. This resource, with the working title 'MetaboLights', will serve information about metabolites and their reference spectra and chromatographic data, their occurrence and concentrations in organisms, tissues, cells, etc, under well-defined conditions, and last but not least documentation about how metabolomics experiments were conducted. Like all other EBI resources, the MetaboLights databases will be completely open to the public, including open access to the data. Data will be made available in publicly accepted open standards. The software will be open source. MetaboLights is not meant to replace specialist resources for Metabolomics. Rather, it will build on prior art and collaborate. We are dedicated to close collaboration with all major parties involved in the creation of this prior art, such as the Metabolomics Society, Metabomeeting and the Metabolomics Standards Initiative. In the molecular biology universe as it exists today, none of the large database efforts, neither in genomics nor any other area, lives an isolated life. Rather, there is a regulated ecosystem of resources, such as GenBank, Ensemble and DDBJ for the genome sciences, which interchange data freely and compete on how to present this data and on its analysis. We aim to come to similar data sharing agreements with major resources such as the Human Metabolome Database, the Golm Metabolome Database or the Rikken Metabolomics Platform. However, MetaboLights will be the first comprehensive, cross-species, cross-technique database which combines curated reference data of pure metabolites, curated information about their occurrence and concentration in species, organs, tissues and cell types under various condition with data characterizing the experiment which lead to these findings.

Technical Summary

This project will instantiate, at the European Bioinformatics Institute (EBI) in Hinxton, Cambridge, UK, the MetaboloLights Metabolomics database with various different components focussed on both data standards and primary experimental data. The resource will be cross-species, cross-application and will cover all relevant analytical methods. To date metabolomic databases have either focused on spectra and metadata associated with the analysis of standards or data associated with a small number of species or one analytical tool. MetaboLights will characterize the metabolites in various aspects: 1.through their chemical structure, names and related information, 2.through their spectral (NMR, MS) and chromatographic information (retention times) and 3.through their occurrence, concentration or absence in a particular species, organ, tissue or cell type. All of this information will further be linked to other resources of interest at either the EBI or elsewhere, including the Reactome database for pathway analysis, to our chemo-genomics database ChEMBL to account for drug interactions, or to UniProt and PDB to linked to their respective processing enzymes or to other biomacromolecules with which the metabolite is known to interact. There will further be d) a database for metabolomics experiment management. This is a vital resource still needed by the metabolomic community to encourage multi-lab collaborative projects, and aid peer review and software development. For the success of MetaboLights it will also be essential to work on a data input pipeline supporting the user to the greatest possible extent. The types of data used in metablomics are an order of magnitude more diverse than those in proteomics and the task of creating such a pipeline will be complex. Here we plan to again closely cooperate with the community in creating open standards and encourage the vendors to implement the production of open formats in their instrument software.

Planned Impact

The MetaboLights resource, designed to become the third missing pillar of large Omics resources, to compliment the EBI's proteomics and genomics resources, will benefit a number of significant communities performing biological research and development in metabolomics and functional genomics. This is in congruence with a number of strategic research priorities of the BBSRC. In systems approaches to biological research, metabolomics allows us to study how the metabolic system reacts to changes in the environments, to stress, to disease and other boundary conditions with high time resolution. These data can then be mapped to biological pathway models and impose a dynamic view of the system. For ageing research, metabolomics is used to study and characterize states and dynamics of the ageing organism with no (urine) or low (blood) invasiveness, or through tissue analysis. Both in bioenergy research as well as in crop science, metabolomics is used to study how plants or microbes used for energy harvesting react to environmental changes (robustness) or how their energy metabolism react to genetic manipulation or other perturbations (flexibility). Generally, the field is of major importance for our understanding of how biological systems, most notably metabolic networks behave under various conditions and for developing a personalized medicine because metabolites, as end products of cellular regulatory processes, provide insights into the response of biological systems to genetic or environmental changes as well as diseases. Metabolomics is also widely used in UK industry including the drug safety assessment process in the pharmaceutical industry, pesticide toxicology in agrochemicals, biomarker discovery for medical diagnostics and plant fitness for crop development. Metabolic profiles are therefore ideal a) as a diagnostic technique and b) for classifying organisms (including humans) by their phenotype. According to Goodacre and coauthors, in order to deal with the torrent of data from metabolomics, it 'is clear [...] that we shall need good databases, very good data and even better algorithms [... and that ] curation of these databases is essential if they are to be useful to the wider community'. To government agencies and ministries, this resource could become a portal of information about small molecule biomarkers and their significance for a particular diagnostic tool or method, thereby aiding in decision making and setting new strategic priorities in medical diagnostics, an area of great interest to the NHS. This work will also provide bioinformatic resources for a number of major companies in the UK such as GlaxoSmithKline, Syngenta, AstraZeneca and Unilever. The work of all of the beneficiaries listed above will benefit because the MetaboLights resource will be the first comprehensive, cross-species, cross-technique database which combines curated reference data of pure metabolites, curated information about their occurrence and concentration in organs, tissues and cell types under various conditions with data characterizing the experiment which lead to these findings. Considerable synergy for the understanding of metabolism can be leveraged by cross-species analogy when metabolomics information is put into its genomic and transcriptomic context. Since we aim at creating a unique and general metabolomics resource, based in the UK, which will interact with all relevant international databases in the field. The biological community will immediately benefit from MetaboLights because like all other EBI resources, the MetaboLights databases will be completely open to the public, including open access to the data. Data will be made available in publicly accepted open standards. As for all EBI resources, we will provide training material and courses about MetaboLights which will be open and accessible for everyone.

Publications

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Beisken S (2015) SpeckTackle: JavaScript charts for spectroscopy. in Journal of cheminformatics

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Haug K (2017) Global open data management in metabolomics. in Current opinion in chemical biology

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Kale NS (2016) MetaboLights: An Open-Access Database Repository for Metabolomics Data. in Current protocols in bioinformatics

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Rocca-Serra P (2016) Data standards can boost metabolomics research, and if there is a will, there is a way. in Metabolomics : Official journal of the Metabolomic Society

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Salek RM (2013) The MetaboLights repository: curation challenges in metabolomics. in Database : the journal of biological databases and curation

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Salek RM (2015) COordination of Standards in MetabOlomicS (COSMOS): facilitating integrated metabolomics data access. in Metabolomics : Official journal of the Metabolomic Society

 
Description Metabolomics is still an emerging field. Genomics and Proteomics has well established methods & channels for disseminating findings, research and primary data. Since our public release in summer 2012 we are seeing a lot more focus on sharing metabolomics data inline with Genomics and Proteomics. This has been driven by the establishment of public repositories like MetaboLights, but also in great degree by publishers and funding agencies (more common in the US). MetaboLights has moved from a relatively unknown offering where we actively had to approach practitioners for data submissions, to now getting studies submitted on a regular basis. MetaboLights has established a metabolite knowledge base/reference tier to present a more unified view of the common knowledge. This is of course an ongoing task and will continue to have very high priority.
Exploitation Route Annotated primary research data is actively downloaded and reused for additional research and training. This data exchange is proving invaluable for establishing new data exchange methods & tools and encouraging open data access.
Sectors Agriculture, Food and Drink,Education,Environment,Healthcare

URL http://www.ebi.ac.uk/metabolights/
 
Description MetaboLights has firmly been established as an important resource for metabolomics practitioners around the world. MetaboLights offers sharing of pre- and post publication metabolomics primary research data, with associated annotations. These studies are frequently downloaded for additional analysis or training purposes. MetaboLights is the main repository recommended for metabolomics data in Nature Scientific Data, the Metabolomics journal and others. MetaboLights is also the primary repository for the EC founded COSMOS (Coordination of Standards in Metabolomics, http://www.cosmos-fp7.eu) project, and is key in enabling standards like mzML and nmrML (http://nmrml.org) for metabolomics. MetaboLights is one of the inaugural partners and drivers of the MetabolomeXchange (http://metabolomexchange.org) for metadata exchange in metabolmics
First Year Of Impact 2011
Sector Agriculture, Food and Drink,Education,Environment,Healthcare,Government, Democracy and Justice,Pharmaceuticals and Medical Biotechnology,Other
 
Title MetaboLights study archive and reference layer 
Description MetaboLights is a database for Metabolomics experiments and derived information. The database is cross-species, cross-technique and covers metabolite structures and their reference spectra as well as their biological roles, locations and concentrations, and experimental data from metabolic experiments. 
Type Of Material Database/Collection of data 
Year Produced 2012 
Provided To Others? Yes  
Impact MetaboLights is currently hosting: - 106 studies - 713 protocols - 37508 samples - 56 organisms from submitted studies - 1593 organisms from compounds - 11168 Reference compounds - 390 registered submitters 
URL http://www.ebi.ac.uk/metabolights/statistics
 
Title Metabolite Identification plugin for ISAcreator 
Description We have developed an ISAcreator plugin to simplify the reporting of metabolites identified in an experiment. We have based the reporting format on the suggested mzTAB (small molecule section) standard (https://code.google.com/p/mztab). 
Type Of Technology Software 
Year Produced 2011 
Open Source License? Yes  
Impact Simplified metabolite annotations due to PubChem search integration. 
URL https://github.com/EBI-Metabolights/ISAcreatorPlugins
 
Title NMR & MS spectral viewer (SpeckTackle) 
Description SpeckTackle, a custom-tailored JavaScript charting library for spectroscopy in life sciences. SpeckTackle is freely available and targeted at life science communities that deal with spectroscopic data such as coming from mass spectroscopy, infrared spectroscopy, or NMR. It contains several default chart types, supports common functionality, e.g. for spectra overlays or tooltips, and is designed to be portable. 
Type Of Technology Webtool/Application 
Year Produced 2014 
Impact MetaboLights is using this component. This has given MetaboLights a more feature rich NMR & MS special viewer, which runs on top of the existing reference spectra. Example: http://www.ebi.ac.uk/metabolights/MTBLC27570#nmrspectra 
URL https://bitbucket.org/sbeisken/specktackle/wiki/Home
 
Description Beta-Release of the MetaboLights repository layer website 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact MetaboLights will consist of a repository layer of published metabolomics experiments and a reference layer about the roles and properties of individual metabolites. We have released a beta-version of the repository layer in February 2012.

Establishment of international data and knowledge exchange in metabolomics
Year(s) Of Engagement Activity 2012
URL http://www.ebi.ac.uk/metabolights
 
Description MetaboLights 2.0 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact On the 4th March 2013 we launched the next major version of the website, MetaboLights 2.0


Changed & New features:
- New design. All pages have a new visual layout and some pages are completely redesigned.
- Study submission queue system. Studies are now queued after initial upload and you are kept up to date on the progress via email
- You can now directly download the whole study archive from the study details page and we also give you direct ftp folder access from the same page
Year(s) Of Engagement Activity 2013
URL http://www.ebi.ac.uk/metabolights/
 
Description MetaboLights Reference Layer official launch presentation 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact MetaboLights presentation, where we officially launched the MetaboLights reference layer (Metabolite centric view collating scientific knowledge for each compound)

Sparked more interest in MetaboLights and discussions of which spectral datasets we should include
Year(s) Of Engagement Activity 2013
URL http://www.metabolomics2013.org/
 
Description MetaboLights and COSMOS training (University of Birmingham) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact Half day practical training course on MetaboLights, the role of COSMOS (Coordination of Standards in Metabolomics).



- We also planned further joint training course(s) with Birmingham and committed to a close collaboration on datasets originating from Birmingham.
- Agreement of data sharing
- Agreement to try to arrange yearly, two per year, practical training courses between UBH and EBI (Lab work in Birmingham, data deposition and analysis at the EBI)
Year(s) Of Engagement Activity 2013
 
Description MetaboLights production website launched 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact We officially launched the MetaboLights production website on the 2012 International conference of the Metabolomics Society. Following this an EMBL-EBI press release was released.

This was the first main step in establishing MetaboLights as the primary publicly open repository for metabolomics data and associated metadata.
Year(s) Of Engagement Activity 2012
URL http://www.ebi.ac.uk/metabolights
 
Description MetaboLights training for the French Metabolomic and Fluxomic Network (#1) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact After the 2n part (Hands on training) we had a discussion about some new features, some of which we now have implemented.

As a result of this presentation and hands-on training course, members of the French Metabolomic and Fluxomic Network are now submitting data to MetaboLights
Year(s) Of Engagement Activity 2013
URL https://colloque6.inra.fr/7_js_reseau_francais_metabolomique_fluxomique
 
Description Metabolomics Data Standards and Data Processing Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact International workshop at the Metabolomics Innovation Centre at University of Alberta, broadcasted live on YouTube with international observers.

Closer collaborations with the Wishart lab in Canada, Pubchem and MetaboLights. MetaboLights will now include MetaboAnalyst as part of our offering
Year(s) Of Engagement Activity 2014
URL http://www.metabolomicscentre.ca/workshops/metabolomic-data-july-2014
 
Description Metabolomics and MetaboLights training 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Knowledge transfer to Cambridge University PhD students.

MetaboLights getting known to future practitioners, general increase in requests.
Year(s) Of Engagement Activity 2012
URL http://ruddles.bio.cam.ac.uk/%7Edpjudge/Course_List
 
Description Metabolomics and MetaboLights training (#2) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact Half a day training at University of Cambridge (Department of Genetics) in metabolomics and MetaboLights in general This is part of the EBI Roadshows and we will provide training at Cambridge University every quarter Online training material, hands-on exercises etc

no actual impacts realised to date
Year(s) Of Engagement Activity 2013
 
Description Metabolomics and MetaboLights training (#3) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Supporters
Results and Impact EMBO Practical Course on Metabolomics Bioinformatics for Life Scientists was a 5 day hands-on training course at the EBI. Focusing on metabolomics. We also gave a training session on MetaboLights.

This was a highly interactive course and has resulted in us getting a better understanding of the global metabolomics community and we educated the delegates in advanced methods & techniques used in metabolomics. We see rather a lot of international collaborations after these training courses.
Year(s) Of Engagement Activity 2013
URL http://www.ebi.ac.uk/training/course/embo-practical-course-metabolomics-bioinformatics-life-scientis...
 
Description Metabolomics and MetaboLights training (#4) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact EMBO Practical Course on Metabolomics Bioinformatics for Life Scientists. This is the 2nd EMBO funded training course, held in 2014.
This is a very popular course and is oversubscribed to a rate of 5:1. 5 day hands-on training course at the EBI. Focusing on metabolomics.

We also gave a training session on MetaboLights The course covers optimal study design for metabolomics experiments, various data analysis methods, usage of online databases and resource as well theoretical a practical approaches on data fusion. Other topics will include: visualization of metabolomics data on metabolic pathways, methods of identification of unknown compounds, differential expression, data quality and reproducibility assessment using statistical analysis and optimal experimental study design.

Training a group of metabolomics practitioners from around the world. Metabolomics communications network between all trainers and participants established.
Year(s) Of Engagement Activity 2014
URL http://www.ebi.ac.uk/training/course/metabolomics-2014
 
Description NIH - The Common Funds Metabolomics infrastructure meeting, workshop and new international consortium (MetabolomeXchange) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a joint meeting between MetaboLights (representing Europe) and members of the 6 NIH funded Metabolomics core centres in the US. (The Common Funds Metabolomics infrastructure)

Agreed on international data and metadata exchange. This resulted in an official meeting at EMBL-EBI in April, which launched the MetabolomeXhange consortium. MetabolomeXchange comprises of leading practitioners from around the world, including Japan, Australia, US, Canada and several European countries.
Year(s) Of Engagement Activity 2014
URL http://metabolomexchange.org
 
Description Official launch presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We officially launched MetaboLights produciton in Washington on the 28th June 2012 This was the official public launch of the MetaboLights repository. There was about 500 conference delegates at the launch. We also had a booth/stand all days at the conference centre.

This was instrumental in putting MetaboLights on the map.
Year(s) Of Engagement Activity 2012
URL http://www.metabolomics2012.org
 
Description Poster and presentation at the MetaboMeeting on Cambridge 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact At the MetaboMeeting we presented posters for ChEBI and MetaboLights. We also had a presentation on metabolomics that covered both these resources.
We get quite a lot of interest as a result of these activities, and study submission frequency normally increase as a result
Year(s) Of Engagement Activity 2015
URL http://thempf.org/mpf_cms3/conferences/forthcoming-meetings/metabomeeting-2015
 
Description SpeckTackle is cross-browser compatible and easy to integrate into existing resources, used in MetaboLights and PRIDE repositories. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Presentation to show the flexibility and scalability of the JavaScript component.

EMBL-EBI PRIDE (PRoteomics IDEntifications database) is currently using this component to dynamically display MS spectra.
Year(s) Of Engagement Activity 2014
URL http://wwwdev.ebi.ac.uk/pride/archive/viewer#protein=29261__P02768-1&peptide=29261__P02768-1__AAFTEC...