METAMORPHOSE - Development of shotgun METAgenoMics apprOaches in suppoRt of Public Health fOr the next Sequencing Era

Open approaches to identify all biological material in a given sample without a priori knowing what to look for could transform the way specific key public health questions are addressed. Metagenomics is defined as the study of all genetic material within a given sample. Shotgun metagenomics is a potential universal test, capable of detecting the presence of a wide range of microorganisms and their composing genes, incl. viruses, bacteria, parasites and fungi from a sample, without requiring an a priori hypothesis about what is present, and without the need to isolate and/or cultivate. It is based on sequencing. Sciensano invested substantially in the implementation of 2nd-generation sequencing technologies such as offered by the MiSeq instrument (Illumina) for routine surveillance and outbreak investigation. However, these technologies do not allow extracting all possible information from a sample through shotgun metagenomics. Instead, they only produce short reads resulting in a fragmented representation of the genomic content of a metagenomic sample containing multiple microbial species. 3rd-generation sequencing technologies have had a breakthrough with the launch of the MinION instrument (Oxford Nanopore Technologies), which through its production of much longer reads (up to several thousands of bases), portability, real-time data generation, and lower cost, represents a disruptive innovation for microbiology. This technology allows to unambiguously detect and scaffold microbial genes to their host chromosomes, even for complex metagenomics samples, allowing taxonomic classification up to an unprecedented sensitivity, incl. the identification of linked specific genes, such as antimicrobial resistance genes. 

It is clear that developing and implementing shotgun metagenomics approaches within Sciensano opens up opportunities to address specific public health questions, by offering a solution to limitations faced by conventional methods. Metagenomics is commonly being explored by several leading research institutes for pathogen detection and identification, as an essential future analysis tool. However, metagenomics also has the potential to transform the current practice in non-pathogen fields, although yet less explored. The METAMORPHOSE project has 2 main objectives: 

• to develop the shotgun metagenomics approach generically both at the wet and dry lab levels
• to deliver a proof-of-concept of the potential of the approach to answer public health questions using three case studies:
  • Metagenomics to deal with the detection and characterization of genetically modified microorganisms (GMM) used in fermentation products or as a bioweapon
  • Metagenomics to support quality control of vaccines and medicinal products
  • Metagenomics to characterize microbiomes.

METAMORPHOSE aims to develop shotgun metagenomics approaches and to deliver the proof-of-concept using carefully selected case studies, each allowing to create a unique niche for Sciensano. It is clear that all three case studies allow capacity building for new research projects, new or improved expertise and new routine analyses to be performed in the future within Sciensano.