Berlin Institute of Health: Putting HPC to Work for the World

Researchers from the Center for Digital Health at the Berlin Institute of Health (BIH) are using science to understand the pathophysiology of COVID-19, which can help to inform the development of targeted treatments.

With the world facing the COVID-19 pandemic, scientists around the globe are ramping up research efforts to “crack the code” about how the SARS‐CoV‐2 virus works: What types of cells does it attack? Can we use this information to identify high-risk patients? Can we “confuse” the virus using this knowledge, so that it cannot successfully infect cells? How does the cellular and transcriptional landscape change upon SARS-CoV-2 infection? How does the host immune system react?

Two research facilities that are working together to find the answers to these questions are the Berlin Institute of Health (BIH) and the Charité – Universitätsmedizin Berlin. BIH is working in concert with Intel to optimize its computing resources and make its analytics workloads run faster.

Single-Cell RNA Sequencing Reveals Cells Vulnerable to Be Targeted by the Virus

Previous research had revealed the following:

  • The SARS-CoV-2 virus attaches to a specific receptor (ACE2) on the host cell surface.
  • At least one other cofactor (TMPRSS2) must be present for the virus to be able to penetrate the cell.

“We wanted to find out which specific cells the corona virus attacks,” explains Dr. Christian Conrad, who works at the BIH – Center for Digital Health.

BIH is investigating the infection mechanism of the novel corona virus. (Image courtesy of Markus Hoffmann/Deutsches Primatenzentrum)

Building on these insights, BIH, Charité and collaboration partners in Heidelberg set out to examine samples from the lower respiratory tract of 16 non-virus infected patients. Their goal was to determine which cell types in the lungs and bronchia are vulnerable to infection. BIH’s work includes RNA sequencing on the single-cell level of nearly 60,000 cells. All known cell types in the human lungs and bronchial tubes were identified. Based on their findings, the researchers predicted the main type of epithelial cells likely to be targeted by the virus. Knowing which cells are attacked by the virus can help other researchers develop strategies for counteracting the virus. The findings of this study were published in the EMBO Journal.

Single-Cell Rna Sequencing of COVID-19 Patients

Having concluded their initial study of non-infected lung and bronchial cells, the BIH – Center for Digital Health, in collaboration with the Charité and University Hospital Leipzig, investigated samples from the upper and lower airways of 19 COVID-19-infected patients to better understand the disease. The researchers also explored differences on the single-cell level in patients with moderate symptoms compared to those suffering from severe symptoms, or even those who had died. Multiple samples taken from the same patient at different times further enabled the researchers to investigate cellular and transcriptional changes during disease progression. In total, 36 samples of the respiratory tract from 24 individuals and roughly 160,000 single cells were studied and revealed remarkable insights into the immune response at the primary infection site and mechanisms that are associated with the severity of the disease. The findings of this study were published in Nature Biotechnology.

Accelerating Research

Aiming to investigate the transcriptional profiles of thousands of cells from the respiratory tract of 40 patients was a daunting task, and BIH turned to Intel and Dell for support. Intel provided funding through its Pandemic Response Technology Initiative and helped design a highly optimized HPC architecture tuned for BIH’s sequencing workloads.

Using the hardware configuration from the Intel® Select Solution for Genomics Analytics as a starting point, Intel, Dell, and system integrator System Vertrieb Alexander GmbH (SVA) helped bring the solution to production quickly. BIH initially conducted a proof of concept using eight HPC nodes. Subsequently, BIH was able cost-effectively increase the node count of its HPC cluster from 40 nodes to 68 nodes (a 70 percent increase). According to BIH, the number of cells that can be analyzed in a certain period of time scales linearly with node count. By sequencing the RNA of more cells, BIH researchers can accelerate their exploration of the cellular host response upon infection. Then they can provide additional insights into how the virus might be stopped or at least slowed down.

By sequencing the RNA of more cells, BIH researchers can accelerate their exploration of the cellular host response upon infection. Then they can provide additional insights into how the virus might be stopped or at least slowed down.

Next Steps

The BIH – Center for Digital Health continues investigating samples from COVID-19-infected patients to better understand the host response and pathophysiology of COVID-19. Further research will focus on single-cell RNA profiling as well as genomics analysis. Together, these data may ultimately lead to additional strategies for the treatment of SARS‐CoV‐2 infections. Intel is committed to assisting these efforts as the IT and health and life sciences industries work together to truly make an impact.

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