A list of some of the papers directly from our group, with some short explanations.

2022

Mandrake: visualizing microbial population structure by embedding millions of genomes into a low-dimensional representation

John A Lees, Gerry Tonkin-Hill, Zhirong Yang and Jukka Corander (2022). Mandrake: visualizing microbial population structure by embedding millions of genomes into a low-dimensional representation. Philosophical Transactions of the Royal Society B 377:20210237

https://doi.org/10.1098/rstb.2021.0237

Dimension reduction methods are a popular way to work with large amounts of genetic data: PCA, t-SNE and UMAP have all been used to analyse and visualise lots of samples in two-dimensions. These techniques are often used to cluster data, but have not been explicitly designed to do so. Some of these methods also stuggle to work with the millions of genomes now available.

Here we re-implement and extend the stochastic cluster embedding (SCE) method to work with genetic data, which is optimised to find visually identifiable clusters. Stochastic gradient descent is used to optimise, which we port to GPUs, and can run through datasets with millions of samples in a couple of hours.

We show good clustering of all bacterial data in the ENA as of 2018 (661k samples) and SARS-CoV-2 as of Nov 2021 (about 1M samples). We also make some fun videos and audio of the optimisation process.

See the code on the software page too.

Pneumococcal genetic variability in age-dependent bacterial carriage

Philip HC Kremer, Bart Ferwerda, Hester J Bootsma, Nienke Y Rots, Alienke J Wijmenga-Monsuur, Elisabeth AM Sanders, Krzysztof Trzciński, Anne L Wyllie, Paul Turner, Arie van der Ende, Matthijs C Brouwer, Stephen D Bentley, Diederik van de Beek, John A Lees (2022). Pneumococcal genetic variability in age-dependent bacterial carriage. eLife 11:e69244

https://doi.org/10.7554/eLife.69244

Previous studies have suggested that piliated S. pneumoniae strains are more commonly carried by infants, and there is a lot of evidence showing that infant immune response is different from adult immune response to carriage. Vaccine modelling studies have also suggested that to more effectively immunise against pneumococcal disease, the presently circulating population and distribution in adults and children should be accounted for.

We use genome-wide association studies (GWAS) to search for genetic factors associated with S. pneumoniae carriage in infants versus adults, in a meta-analysis over two populations. Overall we find wide between-cohort differences in strain composition, and between ages, but no clear independent genetic signals associated with infants or adults. This supports proposals future vaccination strategies which are primarily targeted at dominant circulating serotypes in specific pathogen populations.

Here’s our tree and metadata (view on microreact.org):