NCI supercomputing resources and bioinformatics expertise have improved our understanding of the differences between mild/moderate and severe COVID-19, helping to unravel how severe disease develops. These insights from recent research are an important first step towards identifying ‘biomarkers’ that would help doctors identify patients who are at higher risk of developing severe COVID-19 and enable targeted early interventions and treatments.
Using blood samples from hundreds of participants, researchers from the international PREDICT-19 consortium assessed whether different immune response pathways were associated with mild, moderate and severe COVID-19. They analysed the gene expression levels in the whole blood cells of each individual by ribonucleic acid (RNA) sequencing to determine which genes were being ‘switched on or off’ at different disease severity levels. This type of comprehensive analysis had not been undertaken before in a study of this scale.
Processing and analysing this amount of information is a data and compute-heavy job. “I knew immediately that NCI would be a good solution and fit for our research,” said Dr Tracy Chew, Bioinformatics Group Lead at the Sydney Informatics Hub and contributor to the study. “I had previously worked with NCI and appreciate the deep technical expertise NCI staff bring to help optimise workflows on the Gadi supercomputer. Doing the initial processing of the gene expression data at NCI meant this step could be completed in one workflow over a few days, rather than potentially months on smaller high-performance computing systems.”
The workflows used for processing genomic data of this type were developed to work efficiently and powerfully on the Gadi supercomputer. As genomic analyses of big patient cohorts become more common in research, close collaboration between researchers and the computing and data infrastructures they use will be crucial to getting the best science outcomes.
In these studies, researchers found that there were clear differences in gene expression levels between patients with mild/moderate COVID-19 and severe COVID-19. Those with severe COVID-19 showed greater activity in growth factor and cell cycle signalling pathways, and down-regulation of interferon signalling pathways, compared to those with mild/moderate COVID-19. Interferons are important signalling proteins that are critical for the body’s immune response to viral infections.
Significantly, these exciting findings are just the beginning, with the study laying the foundation for future work in this area. “This analysis and clinical data is a valuable resource that other researchers can use to investigate many research questions, including those related to potential therapeutic targets and COVID-19 disease progression,” Dr Chew says. “Furthermore, the scalable workflows for the processing of data that we developed with the Australian BioCommons are freely available for other researchers to use, with possible broad research applications.”
A number of research papers have been published in relation to this study including in Frontiers in Immunology (here and here), the International Journal of Molecular Sciences and Science Advances.
