Next generation metagenomics: methodological challenges and opportunities

Metagenomics is one of the newest omics system science technologies but also one that has arguably the broadest set of applications and impacts globally. Metagenomics has found vast utility not only in environmental sciences, ecology and public health but also in clinical medicine and looking into the future, in planetary health. In line with the One Health concept, metagenomics solicits collaboration between molecular biologists, geneticists, microbiologists, clinicians, computational biologists, plant biologists, veterinarians and other healthcare professionals. Almost every ecological niche of our planet hosts an extremely diverse community of organisms that are still poorly characterized. Detailed characterization of the features of such communities is instrumental to our comprehension of ecological, biological and clinical complexity. This expert review article evaluates how metagenomics is improving our knowledge of microbiota composition from environmental to human samples. Furthermore, we offer an analysis of the common technical and methodological challenges and potential pitfalls arising from metagenomics approaches, such as metagenomics study design, data processing and interpretation. All in all, at this critical juncture of further growth of the metagenomics field, it is time to critically reflect on the lessons learned and the future prospects of next generation metagenomics science, technology and conceivable applications, particularly from the standpoint of a metagenomics methodology perspective.