Departments of Medicine and Genetics
Divisions of Hematology and BMT
There are more than 1,000 species of bacteria, viruses and fungi that live in the human gut. Far from being passive passengers, these organisms strongly interact with host metabolism, the immune system, and more. For all of this interaction, the dynamics between human hosts and bacteria (microbiome) has only been explored in earnest for the last fifteen to twenty years. Compelling early experiments have shown that intestinal microbiome composition is associated with obesity, cardiovascular diseases, and the effectiveness of certain cancer chemotherapies. Therefore, understanding the impact of microbiomes speciation on noncommunicable diseases such as cancer, hematological and cardiometabolic disorders (Manzo and Bhatt, Blood, 2015) is fundamental to our health care. But how does one begin to model the dynamics of >1,000, mostly un-sequenced species and strains of bacteria, viruses and fungi? In this presentation, I will discuss approaches that our translational laboratory has developed and applied - these novel molecular and computational tools allow us to study strain level dynamics of the microbiome, to understand how microbial genomes change over time, and predict the functional output of microbiomes. In particular, I will introduce MetaRiboSeq - a method that (i) allows for the indirect measurement of protein abundances by quantification of translated transcripts by adapting ribosomal profiling to metagenomic mixtures and (ii) improves the accurate prediction of small open reading frames from metagenomic sequencing information using a bioinformatics-driven comparative metagenomics approach.
Reader in Genomics and Bioinformatics
King's College London
School of Biosciences
University of Birmingham
A Sequencing Singularity of Infectious Disease?
Sequencing may be the ultimate clinical assay, providing rich information for
both diagnosis, genotyping and surveillance of pathogens in a single assay. In this talk I will detail how our work with portable in-field nanopore sequencing led to new insights into Ebola evolution that were fed in real-time into outbreak response efforts. Further work on Zika demonstrated huge gaps in our knowledge of circulating pathogens in human populations, but reinforced technical difficulties in recovering whole genomes directly from clinical samples with untargeted approacesh. Ultimately, however, metagenomics approaches should be viable for the diagnosis and recovery of whole pathogen genomes from clinical samples. I will also discuss the role ultra long read single molecule sequencing may have on this on ascribing phenotypes like antimicrobial resistance to specific species, as well as the new opportunities offered by direct RNA sequencing which may also allow us to monitor host response to infection. Taken together, recent technological advances make the prospect of a ‘sequencing singularity’ a tantalising prospect
Bioinformatics and Computational Biology Laboratory
The Francis Crick Institute