METASTAVA

OHEJP Metastava project logo

The Project #METASTAVA

Start: 1 January 2018
Duration: 2 Years
Domain: Foodborne Zoonoses
Keywords: Next generation sequencing (NGS), metagenomics, method validation, diagnostics, quality assurance
Contact: Steven Van Borm (Sciensano)

METASTAVA: Standardisation and validation of metagenomics methods for the detection of foodborne zoonoses, antimicrobial resistance and emerging threats

The objectives of METASTAVA were to evaluate the potential use of metagenomic analysis to the public health reference laboratory by (i) targeted collection of reference data and reference materials, (ii) generating focused validation data, and (iii) proposing criteria and tools for a robust quality assurance (QA) of metagenomic workflows from sample selection for interpretation of results.

Metagenomic analysis is increasingly used to identify possible causes of unexplained disease outbreaks, to complement routine diagnostic evaluation, and to study the role of the microbiome and virome in health and disease. Standardisation of metagenomics data generation and analysis tools is being sufficiently covered by other ongoing initiatives (including COMPARE). However, translating these promising technological developments into diagnostic tools for veterinary and public health laboratories requires careful validation, which was the focus of this project.

METASTAVA focused on using metagenomic analysis for robust diagnostics. The project identified several important gaps in our knowledge of NGS and metagenomics that needed to be filled by the:

  1. Development of a set of reference data for the model pathogens, representing most common sample types.
  2. Development of harmonized workflows for the generation and analysis of metagenomic data fitting to a defined diagnostic scope for the model pathogens.
  3. Development of a validation protocol for metagenomic diagnostics (including quality assurance and robustness testing).

Project Outputs and Outcomes

The METASTAVA project addressed the identified gaps and used hepatitis E virus (HEV), norovirus (NoV), zoonotic pox viruses, antibiotic resistant bacteria and Shigatoxigenic Escherichia coli (STEC), as model pathogens in developing the methods and reference datasets.

Overall, METASTAVA standardised and validated metagenomics methods/guidelines for the detection of foodborne zoonoses, antimicrobial resistance and emerging threats in diagnostic laboratories. This project has helped to ensure that the diagnostic use of metagenomic methods for pathogen detection are made more accessible to public health, veterinary health and food sector laboratories.

Please read the project impact brochure, for more information on METASTAVA’s outputs and outcomes.

It is also available on Zenodo.

Project Assets

Chi-Wai Chan, M,. Roy, S., Bonifacio, J., Zhang, YY., Chhabra, P., Chan, JCM., Celma, C., Igoy, MA., Lau SL., Mohammad, KN., Vinjé, J., Vennema, H., Breuer, J., Koopmans, M., de Graaf, M. (2021). Detection of Norovirus Variant GII.4 Hong Kong in Asia and Europe, 2017-2019. Emerging Infectious Diseases. 27(1), pp 283- 293. DOI: https://doi.org/10.3201/eid2701.203351

Sikkema, RS., Pas, SD., Nieuwenhuijse, DF., O’Toole, A., Verweij, JJ., van der Linden, A., Chestakova, I., Schapendonk, C., Pronk, M., Lexmond, P., Bestebroer, T., Overmars, RJ., van Nieuwkoop, S., van den Bijllaardt, W., Bentvelsen RG., van Rijen, MML., Buiting, AGM., van Oudheusden, AJG., Diederen, BM., Bergmans, AMC., van der Eijk, A., Molenkamp, R., Rambaut, A., Timen, A., Kluytmans, JAJW., Oude Munnink, BB., Kluytmans van den Bergh, MFQ., Koopmans, MPG. (2021). COVID-19 in health-care workers in three hospitals in the south of the Netherlands: a cross-sectional study. The Lancet: Infectious Disease. 20(11), p1273-1280. DOI: https://doi.org/10.1016/S1473-3099(20)30527-2

Izquierdo-Lara, R,, Elsinga, G., Heijnen, L., et al. (2021). Monitoring SARS-CoV-2 Circulation and Diversity through Community Wastewater Sequencing, the Netherlands and Belgium. Emerging Infectious Diseases. 27(5), 1405-1415. DOI: https://doi.org/10.3201/eid2705.204410

Van Borm, S., Vanneste, K., Fu, Q. et al. (2020). Increased viral read counts and metagenomic full genome characterization of porcine astrovirus 4 and Posavirus 1 in sows in a swine farm with unexplained neonatal piglet diarrhea. Virus Genes 56, 696–704. DOI: https://doi.org/10.1007/s11262-020-01791-z

Oude Munnink, BB., Nieuwenhuijse, DF., Stein, M., O’Toole, A., Haverkate, M., Mollers, M., Kamga, SK., Schapendonk, C., Pronk, M., Lexmond, P., van der Linden, A., Bestebroer, T., Chestakova, I., Overmars, RJ., van Nieuwkoop, S., Molenkamp, R., van der Eijk, AA,. Geurtsvan Kessel, C., Vennema, H., Meijer, A., Rambaut, A., van Dissel, J., Sikkema, RS., Timen, A., Koopmans, M. (2020). Rapid SARS-CoV-2 whole-genome sequencing and analysis for informed public health decision-making in the Netherlands. Nature Medicine. 26, p 1405–1410. DOI: https://doi.org/10.1038/s41591-020-0997-y

Van Borm, S., Fu, Q., Winand, R., Vanneste, K., Hakhverdyan, M., Höper, D., Vandenbussche, F. Evaluation of a commercial exogenous internal process control for diagnostic RNA virus metagenomics from different animal clinical samples. (2020). Journal of Virological Methods, 283. DOI: https://doi.org/10.1016/j.jviromet.2020.113916

METASTAVA DMP

D1.1- Dataset reference data metagenomics data generation-Annex1

D1.1- Dataset reference data metagenomics data generation-Annex2

D1.2- Dataset: reference data metagenomics analysis (confidential)

D1.3- List of sequence datasets (confidential)

D1.6- Review document with guidelines on diagnostic applications of metagenomics: Metastava guidelines for informed mNGS implementation

D2.2- Report and guidelines for the use of exogenous process controls in metagenomics (confidential)

D2.3- Report on batch and contamination effects in metagenomics (confidential)

D2.5- Report on proficiency test (confidential)

D3.1- Spiked sample panels ready for analysis (confidential)

D3.2- Procedure for analysing analytical sensitivity and robustness datasets (confidential)

D3.3- Report: analytical sensitivity and robustness, hepE (confidential)

D3.4- Report: analytical sensitivity and robustness, NoV (confidential)

D3.5- Report: analytical sensitivity and robustness, pox (confidential)

D3.6- Report: analytical sensitivity and robustness, STEC (confidential)

D3.7- Report: analytical sensitivity and robustness, ABR genes detection (confidential)

D4.1- Metastava integration with other research initiatives (confidential)

D4.2- Overview of Metastava output (confidential)

D5.2- Progress and final meeting minutes

Project

Project Updates

METSTAVA project gave presentations at the following external events:

Workshop- ESCV Next Generations Sequencing in Clinical Virology (European Society for Clinical Virology), 20-21 November 2018

Joint 11th International Congress for Veterinary Virology and 12th Annual meeting EPIZONE, 27-30th August 2019

SVA science day, 12th November 2019

International Association for Biological Standardization(IABS) conference on “Next generation sequencing for adventitious virus detection in biologics for humans and animals” 13-14th November 2019

Belgian branch of the World Veterinary Poultry Association (WVPA),  27th February 2020

Project Events

METASTAVA Annual Meeting 18th February 2019

Presentations on METASTAVA project at OHEJP Programme Management Committee- 9th May 2019 & OHEJP Programme Owner’s Committee Meeting- 19th June 2019

Presentations on METASTAVA project at OHEJP Annual Scientific Meetings in 2019 and 2020

JRP METASTAVA project outcomes and expected impact – presentation at POC PMC meeting 24th November 2021

Project Impact Brochure

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