An industrial building in Glostrup, Denmark, is the site of hectic activity. Behind its walls, luminous figures flash across digital screens, eager hands shoot into the air, while numerous languages blend with the repeated sound of the falling hammer. It is auction day at Kopenhagen Fur—the world’s largest auction house for mink pelts. The large auction house is full of international fur buyers, mainly hailing from China.
They come to Glostrup because Danish mink is renowned for being the finest in the world.
One of the reasons for the high quality of the pelts is the fact that Denmark is one of the only countries in the world to have kept the majority of mink farms free of the disease plasmacytosis—commonly known as Aleutian mink disease. Plasmacytosis is a virus particularly affecting mink and—among other things—results in increased cub mortality, smaller litters, and inferior pelt quality due to fur discoloration. Over the past few decades the Danish Fur Breeders’ Association—also known as Kopenhagen Fur— has therefore invested considerable resources in controlling the disease with routine blood samples of the animals and consistent clearing of infected farms. And these efforts have paid off.
“Denmark’s status as virtually the only country in the world without plasmacytosis has played a major role in the success of our industry,” explains Leif Bruun, Director of Kopenhagen Fur’s technical departments—including Kopenhagen Diagnostics.
Outbreak in Holstebro
However, last summer, Denmark experienced a sudden outbreak of the disease, which Leif Bruun calls a disaster for the Danish mink breeders. More than 200 mink farms in an area surrounding Holstebro were diagnosed with plasmacytosis in the course of a few months, begging the question: where did the infection come from?
During the outbreak, Emma Hagberg, PhD student at DTU Bioinfomatics, found herself working on an industrial PhD project to determine whether it is possible to use so-called full genome sequencing to trace the source of the infection.
“The method is already used by the Danish Veterinary and Food Administration in respect of bacteria or viral infections, for example, enabling inspectors to trace back to the source of infection by means of gene analyses. But I’m one of the first to try it with Aleutian mink disease. What I have done is to extract DNA from samples from infected animals and then perform full genome sequencing. This leaves me with the entire DNA sequence for the specific virus that has infected the animal,” explains Emma Hagberg.
Virus family tree
The next step is to compare the different sequences in order to map the link between viruses from the many samples. This is done by establishing a kind of family tree—a phylogenetic tree. The project is based on research at DTU Bioinformatics. The method can be used in virus traceability, as viruses mutate over time. When you know about a specific virus in a given population, you can create models for how much the virus mutates within a certain time frame, and use this as a parameter in its data analysis.
“You begin by entering your DNA sequences and the associated data about where the sample was taken etc. into a model. You then tell the model what type of virus it is, and how often this type of virus mutates. Finally, you ask the model to figure out how far you need to go back in time to find a common ancestor. If, for example, you need to go back ten years, you can deduce that it is probably not A that has infected B, but rather a relative closer to home,” explains Emma Hagberg.
Routine genome analysis
“I have now performed a proof of concept study showing that full genome analysis can be used to trace the spread of Aleutian mink disease, and that such analysis provides new and important knowledge,” explains Emma Hagberg, who adds: “I studied a case, for example, where two neighbours—B and C—suddenly contracted Aleutian mink disease. It was thought that the infection originated from a third neighbour—A—but A rejected this. My analysis showed that mink farm A had an older version of the virus, which infected both B and C. This suggests that the infection most likely came from A. Using current methods, it would have been impossible to determine this. In fact, there’s still a great deal we don’t know about how infection is spread. Hopefully, my method will shed new light on this.”
Kopenhagen Fur is extremely satisfied with the results:
“The disaster in Holstebro has meant that Emma Hagberg’s PhD project has received a great deal of political attention. Everyone has suddenly realized that if we are to solve these problems, we have to further qualify analysis—for example by going from superficial typing to full genome analysis. In the fight against Aleutian mink disease, there is no tradition for routinely employing molecular biology technologies. Thanks to Emma Hagberg’s results, however, our ambition is now to use her method as a key tool in virus traceability,” says Leif Bruun.
There’s still a great deal we don’t know about how infection is spread. Hopefully, my method will shed new light on this
Supercomputer saves the project
As sequencing becomes ever more cost-effective, the biggest challenge of using full genome sequencing is the huge data volumes to be analysed. The new technologies—next generation sequencing—generate a lot of small pieces DNA sequence—sequence reads—which must be assembled into whole genomes for subsequent analysis by the phylogenetic model, which analyses several hundred genomes at a time. Such a task cannot be handled by a normal computer. However, Emma Hagberg was offered the chance to become a pilot project for a newly established national supercomputer—Computerome. Housed at DTU Risø Campus, the supercomputer can be accessed from a laptop thanks to a state-of-the-art cloud solution. Above all, access to the supercomputer meant that the analyses could suddenly be implemented within a realistic time frame.
“I can’t wait forever for the results to become a product I can offer Danish mink farmers. Access to Computerome has therefore been instrumental, otherwise Emma Hagberg could have continued working on her calculations until she was 80,” says Leif Bruun.
Head of Computerome, Peter Løngreen, is also pleased with the project:
“The project with Kopenhagen Fur is an example of how public research and commercial interests can jointly solve some of the challenges associated with the use of the new supercomputing facilities. Computerome is designed to process life science data. This means that this supercomputer is designed not only for large volumes of data and highly complex calculations, but also to meet exacting data security requirements. Thanks to our cloud solution, we can offer research institutions and companies a level of security and operational stability normally restricted to internal systems.”