New tools for reproducible hydrogen-deuterium exchange mass spectrometry

Hydrogen-Deuterium exchange mass-spectrometry (HDX-MS) is a key tool in the drug development pipeline, particularly in the antibody, small molecule and vaccine industries, where it is used to determine the binding locations of antibodies on target proteins. However, processing of raw data on HDX-MS is manual, laborious and subject to user bias, and the statistical methodology used for analysis is often flawed.

In 2021, a team at the Department of Statistics developed new software tools which allowed better, faster processing of HDX-MS data. However, the new tools required knowledge of coding and experimental design, lacked the robustness required for industry use, and had only been tested in an academic context.

In January 2022, funding from the EPSRC IAA Technology Fund enabled the team to develop their relationship with existing industrial partner, pharmaceutical company GSK, to develop the tool into commercially appropriate software.

An initial consultation and a week-long learning exchange allowed the team to demonstrate the software to GSK, who provided initial feedback. The software was then installed on GSK’s internal systems and tested on various datasets, with feedback influencing ongoing development and the addition of a ‘control’ package to check the quality of generated data. Testing was very successful and showed that the software reduced the time needed for analysis and processing of large datasets by up to 80%.

A representative from GSK commented: ‘The tool helps scientists to leverage more of their HDX data in less time by directing data curation to those peptides requiring manual inspection. This is especially important for large datasets, where time savings of up to five-fold can be achieved, without any artificial constraint to limit the size of the dataset.’ GSK is now routinely using the software in its operations and, indeed, is expanding the scope of their HDX-MS platform and hiring additional scientists to exploit these capabilities.

The testing process firmly validated the benefits of the new software and demonstrated its potential for wider industrial application. Since GSK scientists are now able to spend more time on other experiments and interpreting the data, the tools have enabled more biotherapeutics to be evaluated. These experiments feed into the downstream pharmaceutical pipelines – ultimately allowing the development of better therapeutics with fewer resources.

Dr Crook comments: ‘This project involved taking already developed academic research into commercialisation, so it was very suitable for IAA funding. The IAA grant allowed us to strengthen ties with an important industrial partner, GSK, and develop the software to the point where we could seek future investment.’

Crook continues: ‘And the potential impact of the software is huge. GSK have estimated a 25% performance gain on their current portfolio. But as well as benefitting GSK directly, their involvement has helped improve the robustness and usability of the software and enable take-up in the broader field. Most large and many small pharmaceutical companies employ HDX in their drug development pipelines, so there is a huge potential market out there. Therapeutics take a long time to develop but in time these tools are likely to identify new targets and therapeutics for a wide range of diseases and have a huge societal impact.’

Since the end of the project, GSK have extended their partnership with Oxford University for another three years, to further expand these tools and integrate them into other areas of the business, including vaccines. The development team have been working with Oxford Mass-spectrometry Therapeutics to integrate the tools into their own pipelines.

Project team

Dr Oliver Crook is Florence Nightingale Bicentenary Research Fellow at New College Oxford

Charlotte Deane is Professor of Structural Bioinformatics in the Department of Statistics

Dr Chun-wa Chung Executive director of Structural & Biophysical Sciences at GlaxoSmithKline

Dr Broncio Aguilar Sanjuan is a software engineer in the Department of Statistics

New tools for reproducible hydrogen-deuterium exchange mass spectrometry was funded by the EPSRC IAA Technology Fund from Jan to June 2022