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CCGA: first port of call for genome analyses

Demand for gene sequencing in research is high. With one of four national sequencing centres, Kiel University is playing in the premier league here. COVID-19 brought quite a few night shifts and much publicity for the researchers.

Scientist in laboratory
© Oliver Franke / IKMB

Regardless of whether the DNA in the sample comes from humans, sea eagles or fruit flies – the modern sequencing equipment at the CCGA often decodes the genetic information within a few hours.

Professor Andre Franke has never before experienced such media hype about his research as he did in June 2020. Even before his work on risk genes for severe disease progression of COVID-19 was published in the top-ranked New England Journal of Medicine, media from all around the world, from the New York Times to CNN, contacted him to have the Genomewide Association Study, which had been published online in advance, explained. The study revealed for example that people with blood type A have a roughly 50 percent higher risk of a severe course of COVID-19 than people with other blood types, and that blood type 0 is associated with a lower risk. While these findings have no immediate therapeutic consequence, they are of great value for further research into the disease.

The genetics professor from Kiel, who is also the director of the Institute of Clinical Molecular Biology (IKMB) and board member of the Cluster of Excellence Precision Medicine in Chronic Inflammation (PMI), attributes the enormous interest in this work to the fact that "we were the first to conduct such a comprehensive genetic study and to identify genetic causes for severe COVID-19 progression". Within just three weeks, the researchers isolated the DNA from more than 4,000 blood samples and measured it using so-called biochips (SNP arrays).

The working group at Kiel University was able to assume such a pioneering role in the genotyping study thanks to the performance and expertise of the Competence Centre for Genomic Analysis (CCGA) at the IKMB at Kiel University and the UKSH with partners from Borstel, Lübeck and Plön. The German Research Foundation (DFG) has been funding the CCGA since 2018 as one of four centres for high-throughput sequencing in Germany in the Next Generation Sequencing (NGS) competence network. And the DFG recently committed to three more years of funding. "The DFG funding allows us to realise projects on a scale that had not been possible before," emphasised Dr Sören Franzenburg, who heads the sequencing research group at the IKMB. "But even before the CCGA was founded, the IKMB was already one of the largest academic sequencing sites in Germany." Its infrastructure had been built up and constantly expanded, in particular by the current Cluster of Excellence’s predecessor. The NGS platform has been successfully anchored in national and international collaborations for more than ten years.

For CCGA spokesperson Professor Philip Rosenstiel, the renewal of funding means "another step on the way to making this important infrastructure permanent. This is especially crucial for the work of the Cluster of Excellence." The CCGA supports genome research at the university and in the Cluster of Excellence PMI. In addition, the centre also uses the DFG funding to provide services to external research groups. Its strength lies in the wide variety of methods. "We are in a position to cover the entire spectrum from small sequencing projects to sequencing of the entire human genome," IKMB director and PMI board member Rosenstiel explained. The expertise of the CCGA was also used for the successful establishment of coronavirus diagnostics at the research site. The researchers started to perform surveillance viral sequencing in February in concert with routine diagnostics and research to detect the spread of mutant variants at an early stage.

There is currently great demand for the very new method of single cell analysis. This method can determine activation states of tens of thousands of cells, while characterising them at the same time by means of sequencing. The activation states provide information on the activity and function of individual immune cells in chronic inflammatory processes, for example. "This method bears great potential for research, as disease processes can now be broken down to the level of the individual cell, which provides completely new starting points for targeted therapies," Rosenstiel explained. A team from his research group has used single-cell genomics to identify specific immature cell types in the blood that are indicative of severe disease progression in COVID-19. In the study, the cells in the blood of a group of COVID-19 patients were analysed in a time series, i.e. at different times during the course of the disease. "And it was ultimately these serial images of the disease that led us to previously unnoticed cell types that are characteristic of severe COVID-19," Rosenstiel explained. Based on these findings, diagnostic testing procedures could be developed that can detect severe disease progression at an early stage based on blood samples.

Author: Kerstin Nees


Gene sequencing and NGS

Gene sequencing is the molecular biological analysis used to decipher the genetic information of organisms. It determines the exact sequence of the DNA building blocks. Since the DNA contains the entire blueprint for the organism and its functions, sequencing is the key to solving countless biomedical questions. For example, it can be used to help identify genes which cause or promote certain diseases.

The first techniques were developed at the end of the 1970s. The procedures used today are significantly more powerful than even a few years ago, and are known collectively as "Next Generation Sequencing" (NGS). With the increasingly powerful technology, a hidden world has become accessible. Today, using this technology, the entire genetic code of a person, i.e. their genome, or the functional status of tens of thousands of individual cells, can be fully decoded within a few hours. (ne)