The terms “personalized medicine,” “precision medicine,” and “targeted therapy” make frequent appearances these days. While sometimes vaguely understood, they now are manifest in bricks, mortar and test tubes at UCHealth and the University of Colorado School of Medicine.
The Center for Biomedical Informatics and Personalized Medicine (BIPM), launched about a year and a half ago, is poised to open its DNA Biorepository this week in the recently constructed Bioscience 2 building near the Anschutz Medical Campus. The biorepository was scheduled to open this week, with large equipment to be moved in starting the middle of the month, said Nate Kahn, PhD, manager of the facility.
The bank will not want for deposits. The BIPM this year received approval to purchase a system that extracts DNA from blood samples from patients who give their consent to do so. The program is being piloted at the Cardiac and Vascular Center (CVC) at UCHealth Metro Denver (University of Colorado Hospital) with plans eventually to roll it out across the UCHealth system, said Jessica Mestas, director of system integration for UCHealth.
So far, about 1,000 patients have consented and the blood-sample collection process is underway, Mestas said.
The DNA Biorepository, a three-laboratory suite in Bioscience 2, will be responsible for extracting and purifying DNA from the blood samples and studying tens of thousands of genetic biomarkers. The DNA will be amplified on special chips, enabling high-speed sequencing of each individual’s genome, Kahn said. These genetic twists and turns – the nucleic acid sequences of an individual’s DNA – are the clues that could yield the targeted molecular therapies of tomorrow.
“The goal is to assess variations in the population and the gene pool that are attributable to both disease and to normal health,” Kahn said.
Set for samples
For now, the pilot is limited to the collection of donated blood samples, but the ultimate aim is much broader, said Matthew Taylor, MD, PhD, director of Adult Clinical Genetics at University of Colorado Hospital and associate director of the BIPM.
“We’re not just after DNA,” he said. “We eventually may collect tissue, saliva, urine, and amniotic fluid, as well as cheek swabs and fecal samples,” he said. The biorepository will be “disease agnostic,” he added: open to the curiosity and imagination of researchers of all disciplines. The plan is also to collect patient samples from hospitals that are part of UCHealth North and UCHealth Colorado Springs.
“Our vision is that potentially all our participating patients have something valuable to offer,” Taylor said.
The BIPM effectively changes the paradigm that drove clinical research for decades, Taylor added. In that approach, a researcher interested in a given condition found patients who had it and invited them to join a study. “Enrollment was haphazard and there were limited opportunities for patients,” he said. “Now the idea is for researchers to think of a question and use data from a biorepository to answer it instead of spending two years collecting data.”
Kahn said the DNA Biorepository is a “scalable operation” ultimately capable of handling a half-million genomes. But it is only one part of a vast infrastructure needed to support the aims of the BIPM. The center also has a partnership with the CU Department of Pathology’s Colorado Molecular Correlates Laboratory (CMOCO), which pursues cancer-associated genes with high-speed genetic sequencing. Work on a new space for CMOCO and a Germ Line Testing lab in Biosciences 2 is now underway and should wrap up in the spring, Mestas said.
Crunching the numbers
In addition to physical space, the BIPM is building the technological muscle to handle mountains of information that will be generated by beefed-up sample collection and sequencing. As Kahn noted, a single genome contains enough data to fill a small personal computer. Analyzing information from thousands of genomes requires “a vast amount of computing power,” he said.
That capability is to come from something called TICR (Translational Informatics and Computational Resource), which is scheduled to be fully operational by April 2016, said Kathleen Barnes, PhD, head of the Division of Bioinformatics and Personalized Medicine at CU. TICR’s job is to sift through the raw data produced by genetic sequencing and identify patterns that suggest an increased risk of a condition, say renal disease. That information ultimately feeds back to Health Data Compass, a large data warehouse that in turn shares the data back to the Epic electronic health record.
All samples stored in the DNA Biorepository will be stripped of patient identifying information before being shared with researchers, Barnes said, but the ultimate goal of the BIPM is to bridge pure research and clinical care. Genetic information from individual patients is protected, but will be available to clinicians to review and incorporate in their treatment recommendations.
“We’re building the capacity and tools we need to develop a better system and process for diagnosing and predicting disease,” Barnes said. “We want to be able to say to patients, ‘If you have this disease, this is the therapy that will work best for you.’” Or, as Mestas pointed out, the genetic information for an individual patient could indicate that a particular drug is unlikely to be effective.
“We want to turn predictive analytics into meaningful data for each patient,” Mestas said.
More than meds
Discussions of personalized medicine frequently focus on drugs that target specific genetic mutations (EGFR, KRAS, and ALK in lung cancer, for example), but that view is only part of the picture, Barnes said. Social, environmental, and racial factors may also come into play. Asthma, for example, might arise from an allergy but be most effectively treated for individual patients by covering mattresses to reduce dust or avoiding cats. Genetic evidence might show that an African-American is less likely to respond well to a long-term beta agonist as another drug – key information in making the most effective treatment choice.
“The idea is to harness all the possible genes and environmental factors and figure out how to collect big enough samples to predict [individual risk],” Barnes said. She believes the BIPM could reach that goal in the next couple of years.
The BIPM is “ahead of the curve,” Barnes added, in developing a center that matches the capabilities of current personalized medicine leaders – a list that includes Vanderbilt University Medical Center, Partners HealthCare, Cedars-Sinai, and the University of Cincinnati.
“We have an established data warehouse in Compass that contains millions of patient entries,” she said. “Most personalized medicine programs started with a DNA bank, then had to go back to create an electronic medical record to match the samples with the individuals. We have a jump start.”
Mapping the future
Taylor said he hopes a June 2016 “Understand Your Genome” symposium on the Anschutz Medical Campus will provide another boost for the BIPM. The event, organized by Illumina, whose machines will handle the high-speed genetic sequencing, offers an opportunity for registrants to have their genome sequenced. The $2,900 symposium tab includes education, test preparation and explanation of the results. It’s pricey, concedes Taylor, who has already signed up, but he believes the symposium could raise the profile of the BIPM and help to shed light on the ways genetics is shaping the future of medicine.
“Clinicians will gain a unique insight into the strengths of personalized medicine, and we hope that they will help to spread that throughout the UCHealth system,” Taylor said.
Economics, as well as scientific discovery, back up that contention. The original Human Genome Project, which concluded a dozen years ago, cost an estimated $3 billion. By 2013, the cost of sequencing an entire human genome had dropped to an average of $5,000. Today, high-throughput sequencing instrumentation has dropped the per-genome price to $1,000.
Whatever the future costs, personalized medicine is changing the landscape of health care. The idea has gained not only the attention, but also the financial backing of the Obama administration. The BIPM is part of the shift, Taylor said.
“We are pushing forward to a time when genomic sequencing will be widely available and embraced,” he said.
To register for the “Understand Your Genome” symposium, visit the website. Blood samples must be received by March 11, 2016.