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Evolutionary dynamics of viruses and other microbes affect human health

Ville Pimenoff, associate professor in evolutionary medicine at the University of Oulu, makes extensive use of the supercomputing environment and sensitive data services of the CSC – IT Center for Science to study the population genetics of viruses and other biological exposures to humans. Pimenoff specialises in environmental exposures and the human exposome based on biobank data. The concept of an exposome refers to the totality of exposures an individual is subjected to throughout their lifetime in their living environment. The aim of exposome research is to understand the impact of different exposome components in human health.

One of Pimenoff’s recent studies showed that human papillomavirus (HPV) vaccination provides effective immune protection against the most cancer-causing papillomaviruses, while significantly altering the ecological dynamics of the remaining less oncogenic papillomaviruses.

Pimenoff conducted his doctoral dissertation on the genetic history of Finns and Finno-Ugric peoples. Currently he has ten research projects underway, focusing on the short and long-term evolution of microbes that infect humans.

“My work stems from computational metagenomics, using DNA sequence data to analyse genomes of different organisms and microbes in a biological sample. This means that research datasets often amount to tens, sometimes even hundreds of terabytes of sequence data.”

Pimenoff’s study of genetic variation in viruses and other microbes in general requires a large amount of computation and data processing.

Researchers have identified over 200 types of human papillomaviruses (HPVs) that can infect humans. Some dozen of these are among the most common sexually transmitted viruses, and can cause cervical cancer. Basically, most of us will be infected with oncogenic HPV at some point in our lives, usually at a young age. If the oncogenic HPV infection becomes persistent, it can progress to a precancerous lesion and eventually may develop into cancer. Cervical cancer is almost always associated with a long-term HPV infection.

This has led to the development of the HPV vaccines. They all provide protection against cervical cancer in particular, but are also effective against HPV-related cancers in other parts of the genital area and the mouth and throat. According to Pimenoff, the evolutionary ecology study of HPVs indicated that the immune protection including herd immunity provided by the HPV vaccine is an effective way to protect the population from HPV-related cancers, especially when both girls and boys are vaccinated. In addition, adequate vaccination of the whole population changes the ecological dynamics of the remaining papillomaviruses.

“This leads to the conclusion that in the near future, cervical cancer screening for oncogenic HPV infections should be eased or completely stopped for those who have been vaccinated.”

Pimenoff’s research interests range from population genetics of humans to evolution of pathogens affecting human health.

“Clinician looks at the papillomavirus as a viral infection that may indicate the patient will develop cancer. An epidemiologist can investigate whether there are factors in the lifestyle of the population that may increase the risk of HPV infection leading to cancer.”

Pimenoff looks at infections from the pathogen population perspective.

“My point of view is that there is always a large number of viral populations circulating among humans. What I am trying to understand is the transmission dynamics by which these millions of viruses spread in the human population in time and space and affect our health, and how these dynamics may change if, for example, a reasonable number of individuals are vaccinated against some of these viruses. I explore these ecological and evolutionary dynamics at the short (ie. human lifetime) and long (ie. millenia) evolutionary timescales.”

In studying cancer-causing papillomaviruses at population scale, Pimenoff used a large cervical HPV infections cohort data collected from 33 Finnish cities and towns, where a total of 22,000 young individuals were monitored for 16 years since most of them had received the HPV vaccine. The research dataset is the world’s largest community randomized vaccination cohort, providing an excellent setup to examine the evolutionary dynamics of cancer-causing papillomaviruses in the population that has been HPV vaccinated using different vaccination strategies and compared to the non-vaccinated fraction of the population.

“From this cohort data, I used computer-assisted methods to simulate HPV infections prevalence dataset among half a million young Finnish women. I used the computing power of CSC and the sensitive data virtual cloud for the original data derived simulations, and for editing and reviewing the resulting synthetic and original data.”

Synthetic data can be analysed across all of CSC’s services. CSC has a dedicated service for sensitive data

Research on environmental contaminants requires CSC’s services

 

In addition to projects related to viral genomics, Pimenoff makes extensive use of CSC’s services, especially for research on environmental contaminants.

“For a pilot project, we have recruited 100 women in Finland for an exposome study on environmental exposures. Of the women in the pilot, some are also pregnant. For four months the women carry a small air pump, which we call an exposometer. It has a filter that collects small particles such as bacteria, fungi and chemical particles in the air. The filters are changed every two weeks, providing a long sample series of environmental contaminants. DNA is isolated from the microbes in the filters and sequenced. This provides what is known as the metagenomic exposome data.”

The filter extracts also enable a mass spectrometry analysis to detect the different chemical compounds to which the women have been exposed during the monitoring period. This is important particularly because the participants were recruited from different locations, allowing us to assess the similarities and differences in environmental exposures in Finland during different seasons, both in urban and rural areas.

“The processing of such data can only be done in a secure supercomputing environment, and CSC’s sensitive data services enable this.”

Storing, processing and sharing sensitive data requires further development

 

In collaboration with CSC, Pimenoff has built a system where access of the sensitive data can be shared internationally as well. The data is used within the same project in collaboration with partners, and if needed it can be shared with specific research groups through the SD Connect service. Another service, SD Apply, is designed to grant licences for data.

 

“We can grant permission for access to anonymous data to be shared with our international collaborators, but the data sets are processed only within the CSC environment and cannot be physically transferred abroad. CSC’s tools for analysing sensitive genomic data are now better than before. CSC has made a good improvement,” Pimenoff says.

However, some obstacles remain in terms of data processing and the user-friendliness of CSC’s system. How is possible to handle large datasets as smoothly as possible and distribute access rights to different data sets? And how can access rights be managed agilely if a CSC customer is involved in several projects? According to Pimenoff, the user interface of sensitive data services should be developed so as to allow more flexible analysis of large data sets with research collaboration outside Finland.

Ari Turunen

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More information:

 

FIRI  

Article was supported by the Research council of Finland grant No: 345591 for ELIXIR European Life-Sciences Infrastructure for Biological Information (FIRI 2021)

 

University of Oulu

https://www.oulu.fi/en

 

CSC – IT Center for Science

is a non-profit, state-owned company administered by the Ministry of Education and Culture. CSC maintains and develops the state-owned, centralised IT infrastructure.

https://www.csc.fi/en/

https://research.csc.fi/cloud-computing

 

ELIXIR

builds infrastructure in support of the biological sector. It brings together the leading organisations of 21 European countries and the EMBL European Molecular Biology Laboratory to form a common infrastructure for biological information. CSC – IT Center for Science is the Finnish centre within this infrastructure.

https://www.elixir-finland.org

http://www.elixir-europe.org