Visualizing variation within Global Pneumococcal Sequence Clusters (GPSCs) and country population snapshots to contextualize pneumococcal isolates
Authors: Gladstone Rebecca A. , Lo Stephanie W. , Goater Richard , Yeats Corin , Taylor Ben , Hadfield James , Lees John A. , Croucher Nicholas J. , van Tonder Andries J. , Bentley Leon J. , Quah Fu Xiang , Blaschke Anne J. , Pershing Nicole L. , Byington Carrie L. , Balaji Veeraraghavan , Hryniewicz Waleria , Sigauque Betuel , Ravikumar K.L. , Almeida Samanta Cristine Grassi , Ochoa Theresa J. , Ho Pak Leung , du Plessis Mignon , Ndlangisa Kedibone M. , Cornick Jennifer E. , Kwambana-Adams Brenda , Benisty Rachel , Nzenze Susan A. , Madhi Shabir A. , Hawkins Paulina A. , Pollard Andrew J. , Everett Dean B. , Antonio Martin , Dagan Ron , Klugman Keith P. , von Gottberg Anne , Metcalf Benjamin J. , Li Yuan , Beall Bernard W. , McGee Lesley , Breiman Robert F. , Aanensen David M. , Bentley Stephen D. ,   The Global Pneumococcal Sequencing Consortium
Published: May 2020

Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact. Gene presence and absence defined using Roary, and recombination profiles derived from Gubbins are presented in Phandango for each GPSC. Temporal phylogenetic signal was assessed for each GPSC using BactDating. We provide examples of how such resources can be used. In our example use of a country-specific phylogenetic snapshot we determined that serotype 14 was observed in nine unrelated genetic backgrounds in South Africa. The international phylogenetic snapshot of GPSC9, in which most serotype 14 isolates from South Africa were observed, highlights that there were three independent sub-clusters represented by South African serotype 14 isolates. We estimated from the GPSC9-dated tree that the sub-clusters were each established in South Africa during the 1980s. We show how recombination plots allowed the identification of a 20 kb recombination spanning the capsular polysaccharide locus within GPSC97. This was consistent with a switch from serotype 6A to 19A estimated to have occured in the 1990s from the GPSC97-dated tree. Plots of gene presence/absence of resistance genes (tet, erm, cat) across the GPSC23 phylogeny were consistent with acquisition of a composite transposon. We estimated from the GPSC23-dated tree that the acquisition occurred between 1953 and 1975. Finally, we demonstrate the assignment of GPSC31 to 17 externally generated pneumococcal serotype 1 assemblies from Utah via Pathogenwatch. Most of the Utah isolates clustered within GPSC31 in a USA-specific clade with the most recent common ancestor estimated between 1958 and 1981. The resources we have provided can be used to explore to data, test hypothesis and generate new hypotheses. The accessible assignment of GPSCs allows others to contextualize their own collections beyond the data presented here.