85 Breaking the dogma with bioinformatics

We are joined again by Prof Mark Pallen who takes us through his early experiences in high-throughput microbial genomics. Mark was pleased that he persuaded Nick Loman to join him in Birmingham. Mark tells us how they worked with George Weinstock to perform the first genome sequence analyses of Gram-negatives for genomic epidemiology—in this case of multi-drug resistant Acinetobacter baumannii. After winning an Ion Torrent sequencer in a competition, Mark and Nick then contributed some pioneering genomic analyses of the German STEC outbreak. One of their studies involved crowd sourced approaches, primed by Twitter and was published in the New England Journal of Medicine; the other provided a performance comparison of newly launched bench top sequencing platforms. Mark, Lee and Nabil discuss how this outbreak overturned dogmas concerning the archetypal status of pathotypes of E. coli. The conversation then moves on to the need for evidence trails and challenging assumptions, whether annotating proteins or quoting Darwin (see https://colinpurrington.com/2012/02/darwin-on-the-floor-lhao/). Nabil recalls the excitement of realtime analysis of an epidemic and acknowledges the legacy of Mark and Nick's work in 2011 to current approaches to the Covid pandemic. Mark describes his exciting experiences exploiting metagenomics in clinical and ancient DNA contexts, including analysis of disease-associated stool samples and of 200-year TB genomes in Hungarian mummies. Yet again this led to overturning of assumptions--in this case that people only get infected with a single strain of M. tuberculosis. It turns out that multiple infections were the norm 200 years ago. Shortly afterwards, Pallen helped assemble a team that analysed undersea sediments shedding light on the Neolithic transition in England and culminating in a Science paper. Mark then takes us through his recent metagenomics analyses of critically ill patients and of the chicken gut, emphasising the excitement of finding hundreds of new species in such a commonplace setting. Mark finishes off by sharing his excitement that there is still so much of the microbial world left for us to discover using sequencing and bioinformatics analyses. We are just 2% of the way there!