How Birmingham is helping with SARS-CoV-2 Genomics

Nick Loman, Professor of Microbial Genomics and Bioinformatics in the Institute of Microbiology and Infection, is leading the team at the University of Birmingham who are part of the COVID-19 Genomics UK Consortium.

Nick explains how the team are working in the lab to help us understand the spread of COVID-19.

“The COVID-19 Genomics UK (COG-UK) consortium was conceived at a meeting in March 2020 with the aim of putting the UK at the front of the genomics effort for SARS-CoV-2. Soon afterwards, the consortium was awarded a £20M grant from UKRI and the Wellcome Trust to set up a network of regional sequencing centres, and distributed analysis capacity. The University of Birmingham are contributing in a number of ways to this effort which has so far resulted in over 40,000 SARS-CoV-2 genomes being sequenced in the UK, well over 50% of the entire effort.

“One reason we were so quick off the blocks in the UK was because of the rapid design of a sequencing protocol for SARS-CoV-2 by Dr Josh Quick (UKRI Future Leaders Fellow), which was posted online in late January 2020 as part of the ARTIC Wellcome Trust Collaborative Award project. Compatible with both nanopore and Illumina sequencing, this is by far the most popular sequencing protocol for SARS-CoV-2 and has been used across four continents. Josh has spent the past months optimising this protocol to reduce the costs and increase the performance, as well as sending out primers. Dr Will Rowe (PDRA) has helped develop a bioinformatics pipeline for the reliable processing of these datasets into consensus sequences.

“In Birmingham, we have settled into a routine for sequencing local samples: we regularly receive inactivated samples from Dr Anna Casey at the Queen Elizabeth Hospital, from Dr Husam Osman and Dr Andrew Bosworth at Heartlands Hospital, and from Dr Fenella Halstead in Hereford. These samples are passed to Dr Claire McMurray (PDRA) who extracts them and performs the sequencing PCR.

“The amplicons are passed to Dr Jo Stockton (PDRA) who prepares nanopore libraries and puts them on the GridION for rapid sequencing. We are able to perform this process in under 24 hours if we need to investigate an outbreak rapidly: apart from hospitals and care homes, we are now receiving samples from factories.

“The GridION data goes straight into CLIMB (the Cloud Infrastructure for Microbial Bioinformatics), along with all the other COG-UK data, thanks to Radoslaw Poplawski (CLIMB Cloud Manager) who keeps this all running. Over this time, he has provided a new rack of hundreds of terabytes of fast SSD storage specifically for the COG-UK project working over the lock-down. The data is managed by a bespoke metadata system called Majora, written by Dr Sam Nicholls (PDRA), which tracks all the sequence data and uploads it to public databases on a weekly basis. Sam created “metadata Friday” - a crunch point in the week where the entire consortium data is processed according to a strict deadline. The trees and analysis can be seen on our website (www.cogconsortium.uk) and we feedback real-time phylogenetics information to the diagnostic labs and public health agencies to identify new clusters for investigation.

“It’s been a great deal of work but it is highly satisfying to see the data being used to help better understand the spread of the virus.”