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Banking on the British Exome

The vast UK Biobank is a treasure trove of genetic data. Scientists are mining it now for potential therapeutic gems. 

Genetic discoveries that could help treat diseases require a large number of human subjects. That’s why the UK Biobank is such a boon to science: From 2006 to 2010, the Biobank, established by the Wellcome Trust medical charity along with other foundations and government agencies, managed a feat that is a biomedical researcher’s dream: It recruited 500,000 people between the ages of 40 and 69 who were willing to undergo a three-hour clinical medical exam. 

Participants gave blood, urine and saliva samples for widespread research use, including genetic analyses and measurement of 20+ circulating biomarkers, and filled out an elaborate questionnaire about their habits and conditions. What’s more is that subjects agreed to have their health data collected both retrospectively and updated on an ongoing basis, approximately once each year. The retrospective data allows researchers to look at history of disease while the prospective data will allow researchers to understand what might contribute to the development of new cases of disease.  The data that is shared with researchers is stripped of any information that could be used to identify individual patients.

Melissa Miller, a geneticist at Pfizer's Kendall Square, Mass, site. 

The best part of this massive medical endeavor? The collected data is open to any researcher who submits a short proposal approved by a committee, says Melissa R. Miller, Applied Human Geneticist at in Pfizer’s Target Sciences and Technologies group in Cambridge, MA. “The only stipulation is that the results that are generated have to be released back to the Biobank administrators. That’s because the idea of the resource is to improve the health of the UK population.” 

Targeting the Exome

Along with teams from five other companies, Pfizer is taking advantage of this novel data set by funding sequencing of the exomes of the UK Biobank participants. “The exome is the part of your genome that codes for proteins,” says Morten Sogaard, VP of Target Sciences & Technologies. Though it only makes up 1 to 2 percent of your DNA, it packs a punch because of its direct effects on the bodies’ processes and traits. When comparing exomes, “you’re more likely to find higher-impact variants that are associated with diseases and that help generate therapeutic hypotheses.” 

Once the exome sequencing project is completed, one plan Miller’s team has is to look at “human knockouts,” or instances in which people who are completely lacking a gene seem to be otherwise healthy. If it’s a gene that researchers are interested in “knocking out” for therapeutic reasons, for instance, Pfizer’s Target Sciences and Technologies team will be able to identify people who are already missing it to assess what the possible consequences might be for others.  

The UK Biobank is also likely to spur developments in the area of data infrastructure as well — the way data from large databases is accessed, stored and managed; it’s also a potential analytical application for artificial intelligence.

Miller is confident that her team will be able to gather insights that will be relevant across disease research areas by comparing exomes and cross-referencing the variants with the phenotypic, clinical and biomarker data on the participants. Understanding how variants on the exome are associated with a biomarker or a disease can help us validate targets of interest for drug discovery.  “We’re excited to start mining this data and linking it with the diseases and other clinical information,” says Miller. “We hope to gather a lot of clues that could eventually help us identify possible new therapeutic targets.”

We hope to gather a lot of clues that could eventually help us identify possible new therapeutic targets.

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