Monday, September 19, 2011

All in a day’s work at the Sheikh Zayed Institute

Over the summer, the Institute had its biggest equipment delivery, both in terms of size and excitement, since opening the doors to the Institute in April. Joseph Devaney, PhD, led the team that installed the state-of-the-art PacBioRS, and offered his insight.

Last month the Sheikh Zayed Institute for Pediatric Surgical Innovation purchased the PacBioRS, an instrument that when running at its full capacity can sequence large portions of the human genome in under one hour. The technology is considered third generation DNA sequencing and there are currently only 25 of these instruments in the world. At the Institute, we hope to be able to generate entire human sequences in a single day using this system. Just to contrast, prior to this 3rd generation technology, the current technology takes anywhere from 24 to 72 DAYS to generate whole genome data.

Someone might ask, Why is it important to be able to sequence a person’s entire genome? It’s important for many reasons. First, knowing a person’s entire genetic sequence is critical for a lot of the research we do at Children’s National Medical Center. In addition, seeing large portions of someone’s genome could be used to guide patient care, and has been used in a handful of extraordinary cases already. In one such example, Bainbridge and colleagues report on fraternal twins with the movement disorder dopa-responsive dystonia, who were not experiencing much relief from the drug that is commonly used to treat this disorder, a synthetic form of dopamine. The children had their genomes sequenced and the scientists were surprised to find mutations in a novel gene that has control over dopamine and serotonin. The children were given a new medication in addition to their previous regiment. Within the first two weeks, their symptoms improved markedly. This technique is not appropriate for all cases, and is still prohibitively expensive for standard medical practice. However, it holds tremendous promise for cases where seeing the entire genetic sequence can provide insight into disease that it not otherwise available.

(Photo, right: Dr. Devaney with the PacBio during set up.)

There are more than 3.1 billion base pairs (bp), of the molecules A, C, T, and G, in a person’s genome. It would take about 9.5 years to read out loud (without stopping) the 3 billion bases in a person's genome sequence and if the 3 billion base pairs were spread out 1 mm apart, they would extend 3000 km (1864 miles) or about 7000 times the height of the Empire State Building. The PacBioRS can decipher the order of a person’s genetic code at a rate of 17,000 bases per hour per well and there are over 150,000 wells. The system uses fluorescence and an extremely fast camera that captures the data in a real time movie format. The massive amounts of data produced by this system require some hefty computing: this system can hold 12 terabytes of sequence data and has over 192 Gigs of RAM.

This powerful new instrument did not come without a struggle. It was delivered on a Saturday when the loading dock was clear, as it required the full effort of six people and a forklift. The system weighs close to 1900 lbs, but luckily our freight elevator can handle more than double that weight! The delivery from start to finish took four hours, which was just the beginning. Once in its new home, the set-up of the instrument took nine days and two service engineers.

The Sheikh Zayed Institute is fortunate to be one of the early adopters of this cutting edge technology. This means that our researchers can test the promise of this instrument within the context of real clinical research projects. We can now begin to integrate a whole host of research approaches for a global view of human health, what we refer to as systems biology, including genomics, transcriptomics, pharmacogenomics, microbiomics, and epigenomics. This technology could revolutionize clinical care and make the Sheikh Zayed Institute and Children’s National Medical Center, a leader in personalized medicine.

--Joseph Devaney, PhD, Assistant Research Professor, Center for Genetic Medicine Research at Children’s National and the Department of Integrated Systems Biology at the George Washington University School of Medicine and Health Sciences.

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