Standardising the fluxomics workflows

This Metabolomics Community-led project on the standardization of fluxomics workflows aims at:

  • establishing standards for isotopic labeling data deposition, a major fluxomics input, and accordingly extending MetaboLights (EMBL-EBI), the reference database for quantitative metabolomic datasets;
  • establishing interoperability among largely-used fluxomic tools, building upon the PhenoMeNal fluxomic tool inventory,
  • extending BioSchemas to metabolic reactions and their dynamics, using the metabolic reaction database Rhea (SIB) for metabolic model reconstruction,
  • containerizing the fluxomic workflow for use in cloud-based environment, and
  • standardizing the fluxomics training. The study is aligned with the Human Data and Plant Science Use Cases and the existing Proteomics, Galaxy and the suggested Toxicology, Nutrition and Microbial Biotechnology Communities.

Background

Metabolic reaction rates (fluxes) provide a measure of the in vivo enzymatic activities that cannot be directly available from the transcriptomic, proteomic or metabolomic data alone, even extended with isotopic labeling measurements.

However, flux distribution maps and through them, metabolic network dynamics, can be revealed when analyzing these data integrated with regulatory information using multi-level and multi-scale models. In this context, fluxomics is an integral part of the bioinformatics and systems biology toolbox. It has significant applications in industrial biotechnology, metabolic or protein engineering, nutritional systems biology, toxicology, precision agriculture and crop improvement and network and systems medicine for the investigation of (patho)physiological mechanisms of complex diseases.

A successful fluxomic analysis is based on the accuracy of quantitative metabolomic data (extra- and intra-cellular) and isotopic labeling measurements and the reconstruction of metabolic networks that describe the stoichiometry - and when available the regulation- of metabolic reactions. To date, the community lacks standardized isotopic labeling data repositories, interoperability among the fluxomic tools and harmonized fluxomic training workflows. In this context, the Metabolomics Community decided to focus its second implementation study on the standardization of fluxomic workflows.

Goals

Standardization of the fluxomic workflow requires (a) standardization and FAIRification of the quantitative metabolomic and isotopic labeling data input, (b) standardized reconstruction of metabolic models, based on metabolic reaction databases and ontologies, extended with regulatory information, and (c) interoperability of the various fluxomics tools and the metabolomic and ontology databases. The standardized workflow could be containerized to work in a cloud-based environment. In this implementation study, these objectives will be pursued through the following specific aims:

  1. To establish standard rules for the deposition of isotopic labeling data and accordingly extend the MetaboLights database (EMBL-EBI), established as the reference repository for quantitative metabolomic data. This work will build upon ongoing efforts at EBI and ES node in collaboration with the Data, Tools and Interoperability Platforms.
  2. To identify largely used fluxomic tools and establish their interoperability, building upon the PhenoMeNal fluxomic tool inventory, in collaboration with the ELIXIR Tools and Interoperability platforms. This implementation study will focus exclusively on open source software, in alignment with the general recommendations of ELIXIR.
  3. To establish interoperability between the databases (quantitative metabolomic and isotopic labeling, metabolic reaction, ontologies, protein, signaling networks) and the fluxomic tools for the accurate reconstruction of relevant metabolic models, and to extend BioSchemas to metabolic reactions and their dynamics, in collaboration with the Interoperability platform. Rhea (SIB), to be linked to UniProt by the end of 2018, will be used as the reference metabolic reaction information resource.
  4. To containerize the standardized fluxomic workflow for use in cloud-based environment in interaction with the Compute platform.
  5. To standardize the fluxomic training workflow and organize webinars and a summer school based on the guidelines and best practices as described in the ELIXIR Training Toolkit, in close collaboration with the Training platform.

Platform/Community: 

People involved: 

Maria Klapa
Martin Reczko
Aristotelis Chatziioannou
Marta Cascante Serratosa
seliv55
Hankemeier
Merlijn van Rijswijk
Gianluigi Zanetti
Oliver Kohlbacher
lgalke
Fabien Jourdan
Reza Salek
Philippe Rocca-Serra
Claire O'Donovan
Vidya Velagapudi
Kim Kultima
Ola Spjuth
ruth.shimmo
Kairi Koort
Alan Bridge
Jiri Vondrasek
Chris Evelo
Alasdair J G Gray
Nicholas Moschonas
Ronan Fleming
Luca Pireddu
Jean-Charles Portais
Bart Ghesquiere