On 24 August at 13:15 Kateryna Pantiukh will defend her doctoral her thesis “From sequences to knowledge: challenges and opportunities of genome-resolved metagenomics”.
Supervisor:
Professor Elin Org, University of Tartu
Oponent:
Professor Rob Knight, California San Diego University
Summary
The human gut contains a large community of bacteria and other microorganisms that help digest food, support the immune system, produce important chemical compounds and can protect us from pathogens. At the same time, certain microbial activities may also contribute to disease. Although the gut microbiome is clearly connected with human health, we still do not fully understand what microbes do and why microbes belonging to the same species may have different effects. This thesis addresses this question using genome-resolved metagenomics, which makes it possible to reconstruct microbial genomes from metagenomic sequencing data.
The thesis is based on data from the Estonian Microbiome Cohort and focuses on what genome-level resolution adds to microbiome research. First, it showed that metagenomic data generated on two short-read sequencing platforms produced highly similar results for taxonomic composition. This supports the combined use of data generated on different platforms, while also showing that functional analysis is more sensitive to technical differences. Second, deeply sequenced cohort samples were used to reconstruct a population-specific collection of microbial genomes. This work produced 84,762 metagenome-assembled genomes representing 2,257 bacterial and archaeal species, including 353 previously uncharacterized species. In addition, the reference collection of human gut archaea was expanded based on the Estonian population.
Using this genome collection, the thesis developed a framework for studying microbiome-health associations at a finer level that takes within-species variation into account. The results showed that some health-related associations become visible only when looking inside a microbial species. This is important because members of the same microbial species may carry different genes, have different functional potential and therefore affect the human body in different ways. Overall, the thesis shows that population-specific microbial genome databases and more precise analytical methods help move microbiome research from asking which microbes are present toward asking which genomic variants of microbes may influence human health.
