The High-resolution Microbiomics group focusses on both theoretical and experimental methods for microbial community analysis. Combining statistical bioinformatics with technological developments in sequencing and ‘omics data generation to resolve both the microbes present in a community and their functional roles and interactions. Current areas of focus include strain resolution from metagenomes, integration of metabolomics and metagenomics, and mathematical models of community assembly. These methods are applied to both simple bench-top experiments with microbial communities and large scale 'omics studies. These studies span a range of environments from host-associated to biotechnology applications.
Methods development
Algorithms developed by our group have been incorporated into a number of bioinformatics pipelines for metagenomics maintained by ourselves and others. These include CONCOCT for metagenome binning - https://github.com/BinPro/CONCOCT, STRONG for strain resolution on assembly graphs - https://github.com/chrisquince/STRONG, and MetaHood - https://github.com/Sebastien-Raguideau/Metahood, which is an integrated metagenome analysis pipeline. We are currently working on the following novel methods:
- Strain genomes from metagenome time series: we have developed algorithms for strain resolved metagenomics from short-read assembly graphs, we will utilise these methods in the future to incorporate long-reads and allow complete genome-resolved metagenomics
- Experimental methods development: we are researching better extraction protocols for long reads and novel library strategies that can link plasmids to genomes such as Meta-HiC
- Novel methods for multi-omics analysis: additional sources of ‘omics data can provide insights on the functional roles of community members. We are working on novel algorithms that integrate metagenomics with metabolomics to enable metabolome changes to be assigned to either the host or microbiome
- Mathematical models for microbial community assembly: modelling of microbial communities has lagged behind data generation. We are developing a synthesis of statistical and dynamical models of microbial community assembly incorporating both niche-and neutral effects
Applications
Our existing pipelines and these novel methods will be applied to a wide range of systems including:
- Bench-top experiments: we use simple mesocosms to explore changes in microbial communities in a controlled fashion, for instance subjecting sediments to sub-lethal levels of antibiotics (collaboration with Prof Wellington - U. of Warwick), or perturbing synthetic human microbiomes in artificial colons (collaboration with the QIB)
- Treatments for pediatric Crohn’s disease: through a long-standing collaboration with Dr Gerasimidis at the University of Glasgow we are involved in the analysis of clinical trials of both therapeutic and ordinary food diets for the treatment of Crohn’s disease. Through integrated analysis of the metagenome and metabolome we aim to gain a mechanistic understanding of dietary action through modulation of the microbiome
- AMR in the environment and human gut: we have developed a complete AMR metagenome analysis pipeline that has been applied to a large-scale analyses of antimicrobial resistance genes both in the River Thames and human gut microbiomes
- Anaerobic digesters: this biotechnology converts organic waste to methane containing biogas that can then be used for heat and power. This conversion is performed by a complex microbial community, we have resolved thousands of microbial genomes from UK industrial AD reactors that we are now using to better understand the waste conversion process
- Gastroenteritic pathogens: we head a large-scale GCRF-funded international consortium to determine the principle reservoirs of non-viral gastroenteritis in Pakistan
