• AREA OF RESEARCH Metabolic phenotyping, Precision medicine, Phenoconversion, Biomarker discovery
  • TECHNOLOGY UTILISED Nuclear Magnetic Resonance Spectroscopy, Mass Spectrometry
  • LEAD RESEARCHER Professor Jeremy Nicholson

ANPC-led international collaborations on COVID-19

Historical Perspective: One of the driving aims in the creation of the ANPC was to build high technology based laboratory technologies that could undertake biomedical discovery and study human disease at both individual and population scale. In particular there is a focus on gene-environment interactions and how they shape disease risks and responses to therapy at the personal level that can be coupled to precision medicine approaches. The history of the ANPC and the computational and systems medicine center in the HFI is embedded in its international collaborations and outreach which was built over decades by leading members of our group which have pioneered the use of spectroscopic techniques in metabolic phenotyping. The HFI is also the cultural core of the International Phenome Center Network (IPCN) which was transferred from Imperial College London to MU in 2018. The IPCN is focussed on standardisation of metabolic science and harmonisation of technologies applied to major global unmet medical needs. Early in 2020, COVID-19 emerged as the world’s most important unmet medical need and a global health challenge unseen in a century. Consequently, the ANPC and the IPCN put COVID-19 research at the top of their biomedical priority list and we have been working together to understand the biochemical consequences of SARS CoV-2 infection and the detection and prediction of clinical outcomes both acute and chronic.

Analytical Platforms for COVID-19 Phenotyping: The high field NMR and multiplatform MS technologies at the ANPC (Figure 1) offer a multi-window framework for interrogating the biochemical effects of any type disease. This is of quintessential importance in the discovery process on emergent diseases such as COVID-19. The multiplatform capability allows individual patient samples to be processed and interrogated for multiple biochemical windows at the same time in a way that allows deeper biochemical connections between instrumental modalities and biochemical pathway outputs to be analysed statistically in a way that is not possible between laboratories operating remotely on different samples with different technologies. The IPCN connection allows not only access to diverse sample sources, but also the ability to perform interlaboratory comparisons and geographical comparisons of disease properties from patients round the world. This the ANPC-IPCN interaction is unique in the world in its ability to perform harmonised biomarker discovery for COVID-19.

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COVID-19 Biomarker and Stratification Discovery Strategy: We have obtained multiple samples from WA and international sources and have applied the technologies shown in Figure 1 to create deep metabolic databases on the biochemical effects of the disease and their variation with severity and time. Our purpose is to understand the full natural history of the disease from the general “healthy” population through the disease trajectory and into recovery with long term follow up to assess the systemic effects of the disease process and to understand long-term changes in population disease risk incurred by COVID-19. To effect this strategy, we are also integrating research profiling studies on the general population such as the “Busselton study” as reference metrics for gender and age biochemistry in the WA population. This strategy is summarised in Figure 2 and has been generously funded by the Spinnaker Health Research Foundation (weblink) and the McCusker Foundations (weblink)

The combination of integrated multi-technology platforms, integrated informatics and longitudinal population to personal journey profiling is unique and is already giving new insights into the COVID-19 disease process that are clinically actionable.