Genome sequencing information is valuable for researchers and epidemiologists during an epidemic. Yet, generating such information is a laborious process typically performed in well-equipped laboratories using large, delicate and expensive hardware.

Research in the Loman group has developed a novel process for the generation of pathogen sequence data in real-time during public health emergencies of international concern. A new DNA sequencing device, which is capable of real time sequencing, and small enough to fit in a suitcase, was developed by the group in 2016. The device weighs less than 100g and is powered via USB. It is currently being used by more than 1,000 researchers worldwide.

Having a portable DNA sequencing system opens up the possibility to do outbreak genome sequencing in real-time, which can directly impact on the response on the ground, as well as providing a wealth of information about pathogen evolution. Crucially data is shared immediately after it is generated, increasing its use immensely.

Research in the Loman group, which has developed new methods for rapidly and accurately generating whole-genome sequences of microbial genomes in austere, ‘field’ environments, has underpinned its impact throughout. 

Rapid technical advances in ‘next-generation sequencing’ approaches have increased sequencing output whilst reducing the size of sequencing instruments.  In the past 10 years this has increased access to genome sequencing for academic and clinical researchers.  This has resulted in the development of the MinION sequencer by UK spin-out Oxford Nanopore Technologies Ltd. This “pocket sequencer” weighs <100 grams, costs $1000 and is powered by the USB port of a standard laptop. The MinION was released to the first early access users in May 2014.

Nick Loman (Independent Research Fellow 2014-2017 at University of Birmingham and subsequently Professor of Microbial Genomics and Bioinformatics) rapidly recognised the potential of this technology. However, when released, the technology was extremely hard to operate, documentation was limited and it had virtually no software support.

The Loman group were the first to generate and publish usable data of any type from this technology in June 2014 (demonstrating recognition of the serotype-determining region of Pseudomonas aeruginosa - also the first demonstration of the translational potential for this device, in June 2014). The group then tested the device on a large hospital outbreak of Salmonella enterica confirming its use to rapidly assign molecular types. Loman thus recognised that portable nanopore sequencing could have profound effects on wider access to genome sequencing technology and thus be vital for management of outbreaks of infectious diseases.

At release there were no bioinformatics approaches available for handling the long, “noisy” (error-prone) reads generated by this platform. To address this need, Loman developed (with Aaron Quinlan, University of Utah) a package for initial handling of nanopore data, an open-source software tool called Poretools (Loman and Quinlan 2014) which became heavily used. 

The direct impact of this novel process for the generation of pathogen sequence data in real-time was observed during public health emergencies of international concern (PHEICs).

Our process was instrumental in the response to PHEICs during the Ebola epidemic in West Africa from 2014 to 2016 and the Zika virus epidemic in the Americas during 2016. Our process has also been used to investigate serious outbreaks that have not been declared PHEICs, including a severe Yellow Fever outbreak in Brazil in 2017-2018, a surge of Lassa fever cases in Nigeria in 2017 and the Ebola outbreak in DRC in 2018-present.

The successful demonstration of this new model, including the rapid release of data to outbreak responders, and availability of the technical constituents of this process has resulted in impact on policy and practice of epidemiological investigation of infectious diseases.

The main beneficiaries of the impact are governments and public sector bodies (e.g. public health bodies, Ministries of Health) and NGOs (such as WHO and MSF) involved in the response to outbreaks. 

Our process of real-time genome epidemiology has changed standard practice of epidemiology in serious outbreaks. This process (laboratory and bioinformatics protocols) approach was used in 2017 to investigate a large outbreak of Yellow Fever in Brazil, and in 2018 was used to investigate a surge of Lassa cases.