An interview with
Dr. Sean Grimmond, Dr. Ryan Taft, and Dr. David Miller
Institute for Molecular Bioscience
The University of Queensland in Australia
Could you tell us about your work with cancer and genetics?
(Dr. Sean Grimmond) We're carrying out large-scale studies on cancers, such as pancreatic and ovarian. By screening hundreds of patients, we're able to gain a deeper understanding of the mutations at work.
For pancreatic cancer, we've been making preclinical models. We remove and sequence a cancer tumor taken from a patient and insert that tumor into an immune-compromised mouse. Then we search for the cancer's vulnerability, matching the mutation
profile we sequenced to various drugs on the market. The end goal is to eliminate the cancer in the patient before it recurs.
Is it true that your team actually discovered a new genetic condition?
(Dr. Ryan Taft) In our work on rare genetic diseases we're primarily looking at children who have central nervous system disorders. Using whole-genome, whole-exome, and targeted sequencing we look for the genetic origin of disease. We determined that a three-year-old boy is suffering from a congenital disease previously unknown to medicine.
He has a central nervous system disease called leukodystrophy. It's just a fancy word for the fact that a component of some cells in his brain were no longer functioning correctly. He was seen by many of the world's preeminent neurologists.
They knew he was sick, but they couldn't figure out why. In collaboration with Illumina, we sequenced him and his parents, and identified a mutation in a gene that no one had previously associated with a human disease.
Later, we identified nine other children with mutations in that same gene. Now there are at least four research teams around the world looking to develop therapies for this illness.
We're working on rare pediatric genetic disorders. The cases that give us the most pride are the ones that no other sequencing technology could solve—but we did using Illumina technology.
What influenced your decision to participate in the MiSeq trade-in program?
(Dr. David Miller) We were very keen to move to a machine that had higher accuracy, especially because we're working with cancer cells. MiSeq delivers the data quality we need, and the workflow is far more robust.
We're also having great success integrating the MiSeq with the Illumina HiSeq. We use the HiSeq for high-throughput screening, and then rely on the MiSeq for validation.
(Dr. Ryan Taft) We actually did a test using the MiSeq and our previous sequencer, the Ion Torrent™. A young girl had Leigh Syndrome and needed to be sequenced before she could participate in an experimental test. We found the mutation inthe mitochondria, amplified it, and sequenced it on the MiSeq and our old sequencer. The Ion Torrent couldn't find the mutation—but the MiSeq did.
An interview with
Dr. Graham Taylor
The University of Melbourne
Could you tell us about your work bringing next-generation sequencing into clinical diagnostics?
We want to help propel diagnostics into personalized treatment. Currently, we're evaluating exome resequencing and targeted resequencing for quick-turnaround screening of tumors. The goal is to be able to select focused therapies based on genomic information. To make this happen, we need accurate data and the MiSeq delivers. There's so much more you can do with the longer reads. In fact, we're starting to take the sequences we read as being literally true and not an approximation that we deal with by statistical means.
What other areas of research are you pursuing?
We're developing large panels for various neurological conditions that look at single mutations associated with specific disease.
Where do you think this work will lead?
The first step in treatment is to get an accurate diagnosis. Only then can you understand which treatment areas are going to work.
We want to be able to run tests in a one-stop setting where we can identify mutations at the onset and screen those thoroughly all in one go. Currently, multiple labs and tests are involved and that takes too much time and costs huge amounts of money. By doing the tests faster and at a lower cost, we'll be able to improve healthcare for many, many more people.
What led you to rely on the Illumina MiSeq benchtop sequencer?
We took a hard look at the accuracy of sequencers. The Illumina MiSeq was the only available desktop sequencer that met our QC specifications in terms of sensitivity and specificity. The system gives us the accuracy we need to capture all the genes of interest in a single test. What's more, MiSeq has the capacity to easily examine hundred of genes in a single assay.
The workflow is also very simple. Because cluster generation is integrated into the system, we save time—and turnaround time is critical. Plus, with the TruSeq® Custom Amplicon kit, we're getting better results because the outcome is so well defined.
An interview with
Dr. Stephan Schuster
You’re involved with protecting endangered species. How does MiSeq fit into that?
We’re helping to create successful breedings of various animals, from California condors to polar bears. These animals often have a limited breeding season and it’s extremely important to find the best breeding pairs quickly. The MiSeq is the workhorse of everything we do. Through sequencing, we can assess the relationship of two animals and determine genetic compatibility. We’ve had many urgent requests from zoos and conservationists asking if we can help with the characterization of certain animals. Turnaround times are extremely fast with MiSeq. When you’re working to protect endangered species, this is essential. After all, the clock is ticking for these animals.
What do you see in the future for your conservation efforts?
MiSeq provides the longest read lengths available from any benchtop sequencer—and at a cost-effective price. We also avoid spending a lot of time searching for errors since MiSeq has one of the lowest, if not the lowest, error rates. Because of this, it is now practical to do de novo sequencing. This is especially important when it comes to plants. Many plants warrant de novo sequencing because they are so unrelated to everything else in the database. I think the MiSeq is in a unique position to generate this data—data that will help us protect endangered species. By understanding the genome of plant species, we can locate specimens with the best chance of survival based on traits such as blight resistance.
This approach can also be applied to crops as an exciting new approach to protecting our food supply.
Besides conservation, how is next-generation sequencing impacting your environmental work?
One of the areas we’re involved in is environmental surveillance. For example, here in Singapore, we have monitored the contents of a sewage plant for extended periods of time, almost on a daily basis, to see how the content of the sewage plant changes. With MiSeq, we can determine what organisms we’re dealing with quickly and efficiently—running the MiSeq overnight so we have results the next day.
It’s important to know what’s going on with our air and water. If there is an outbreak somewhere, you need to find out what pathogens are in the environment and where they are. We have worked with the National Environmental Agency to make this approach a reality. With this information, health officials can act swiftly and save human lives.
Can you tell us why you took advantage of the MiSeq trade-in program?
Our work requires speed, ease of use, and accuracy. No other benchtop sequencer comes close to matching the MiSeq in these areas. I like how quickly high-quality results can be obtained. As far as workflow, the effort to set up a run was minimal and the instrument interface has set a standard for the entire industry.