Episode 85: Breaking the dogma with bioinformatics

The microbinfie podcast features Professor Mark Pallen's pioneering journey through high-throughput microbial genomics, exploring transformative moments in genomic sequencing and epidemiology during the early 2010s.

We are joined again by Prof. Mark Pallen as he discusses his early experiences in high-throughput microbial genomics. Mark was delighted to have persuaded Nick Loman to join him in Birmingham. Together, they collaborated with George Weinstock to perform the first genome sequence analyses of Gram-negatives for genomic epidemiology, focusing on multi-drug resistant Acinetobacter baumannii.

After winning an Ion Torrent sequencer in a competition, Mark and Nick contributed pioneering genomic analyses of the German STEC outbreak. One of their studies involved crowdsourced approaches, facilitated by Twitter, and was published in the New England Journal of Medicine. The other study provided a performance comparison of newly launched benchtop sequencing platforms. Mark, Lee, and Nabil discuss how this outbreak challenged existing dogmas concerning the archetypal status of pathotypes of E. coli.

The conversation then shifts to the importance of evidence trails and challenging assumptions, whether in annotating proteins or quoting Darwin (see Darwin on the Floor). Nabil recalls the excitement of real-time analysis during an epidemic and acknowledges the legacy of Mark and Nick's work in 2011 to current approaches in the COVID-19 pandemic.

Mark describes his exciting ventures in exploiting metagenomics in clinical and ancient DNA contexts, including analysis of disease-associated stool samples and 200-year-old TB genomes in Hungarian mummies. This research overturned assumptions, showing that multiple infections with M. tuberculosis were common 200 years ago.

Shortly afterward, Pallen helped assemble a team to analyze undersea sediments, shedding light on the Neolithic transition in England, culminating in a paper in Science. Mark then discusses his recent metagenomics analyses of critically ill patients and the chicken gut, emphasizing the discovery of hundreds of new species in such commonplace settings.

Mark concludes by sharing his excitement about the vast expanse of the microbial world yet to be discovered through sequencing and bioinformatics analyses, suggesting that we are only 2% of the way there!

Key Points

1. Emerging Genomic Technologies

• Transition to next-generation sequencing platforms like Ion Torrent
• Collaboration with Nick Loman to explore new sequencing technologies
• Winning an Ion Torrent sequencer that enabled groundbreaking research

2. German E. coli Outbreak Analysis

• Crowdsourced genomic analysis using Twitter during 2011 outbreak
• Published landmark paper in New England Journal of Medicine
• Challenged existing dogmas about E. coli pathotype classifications

3. Metagenomics and Genomic Exploration

• Analyzed diverse sample types including clinical, ancient DNA, and environmental samples
• Discovered hundreds of new microbial species
• Demonstrated the vast unexplored potential of microbial genomics

Take-Home Messages

• Technological innovation enables rapid scientific discovery
• Always question existing scientific assumptions and dogmas
• Collaborative and open-source approaches accelerate research