Applied Biosystems and Donna Muzny
A partnership for the advancement of science
The Human Genome Sequencing Center (HGSC) at Baylor College of Medicine was founded in 1996, and played a central role in the Human Genome Project. Currently, the Center is hard at work on the 1000 Genomes project, an international research consortium that is creating a new map of the human genome that will provide a view of biomedically relevant DNA variations at a resolution unmatched by current resources.
As Director of Operations, Donna Muzny is helping to lead the Center's efforts by spearheading its transition from first-generation to second-generation sequencers, including the SOLiD™ System from Applied Biosystems. We recently spoke with Ms. Muzny about her work at the HGSC, and how Applied Biosystems is helping the lab accelerate its research capabilities and make significant strides in deciphering the human genome.
Tell us a little about your area of expertise, and what inspired you to pursue this line of research.
I've been working in the field of sequencing technology development since 1986 when I completed my Master's in Genetics. I decided to pursue this particular line of work because I had a keen interest in human genetic diseases and the contributions that I could make towards solving their mysteries. For example, the Center's work on the 1000 Genomes project will help lead to discoveries in diseases such as cancers, coronary artery disease, and mental illness, and then hopefully to personalizing individual genomes that will improve treatments and eventually provide cures.
You're using the Applied Biosystems SOLiD System in your work on the 1000 Genomes project. What does that entail?
All in all, we will be sequencing 25 genomes in our work on the 1000 Genomes project. We are using the SOLiD System to generate about 200 gigabases of sequence data for the pilot 1 and pilot 2 components. Pilot 1 involves sequencing 180 people at low, two-fold coverage and pilot 2 involves sequencing two trio sets with high-density coverage of 20X.
We're also using the SOLiD System to provide data for comparison across different sequencing platforms, which will help our lab and others determine the best way to move forward in the area of sequencing whole genomes.
What are the research implications and the ultimate goals of the project?
From a research perspective, this project will have great implications for determining genetic variation at the 1% level across the genome. Previous to the 1000 Genomes project, the HapMap had only determined variation across the genome at the 5% level.
The end goal is to provide a catalog of genetic variation across 1,000 people from different populations around the world. The catalog will allow the scientific and medical communities to better understand and treat genetic diseases like diabetes, cancer, schizophrenia, and many others.
Why did you choose to use the SOLiD system for this work and what are its biggest advantages?
We chose the SOLiD platform primarily for its high throughput in generating sequences. Currently we're routinely generating 8 gigabases per slide, or 16 gigabases per run. That's equivalent to 5X coverage of the human genome, so within two runs we can have a completed human genome.
We're also able to generate mate-pair reads from 1 to 3 kilobases in length, which provides very good placement of the reads and allows us to determine genetic structural variation in different genomes such as indels, repeats, translocations, insertions, and deletions. Another aspect that is working out very well for us is the ability to compare sequencing across bacterial and mammalian genomes to provide an estimate of accuracy.
You have already generated over 200 gigabases of sequence using the SOLiD system. How did that go, and what will the data contribute to your research?
It went extremely well. The SOLiD System has improved efficiency and increased the amount of data that we can generate, so the cost of sequencing is basically dropping every day. The 200 gigabases of data is currently under analysis and will ultimately have a huge impact in determining how we will sequence human genomes moving forward. By combining the reads and analyzing the genomes, we'll be able to determine the SNPs and what the structure looks like for various genomes.
What excites you the most about the direction your research at the HGSC will take in the future?
I have the privilege of using next-generation technologies like SOLiD to expand applications such as the sequencing of whole genomes, which is so important because its direct application will be making discoveries about, and finding ways to solve, human genetic diseases. These technologies are really revolutionary because they allow us to tackle things that we hadn't imagined we would be able to do just a few years ago. It's very exciting work to be participating in.
How would you describe your collaboration with Applied Biosystems on the 1000 Genomes project?
Collaborating with Applied Biosystems has been a really great growing experience and we've learned a tremendous amount about new technologies along the way. The data generation and analysis is still ongoing, and we're working together to find out how to best go forward with that. We are always bouncing ideas back and forth, and we've received fantastic support from Applied Biosystems in terms of improvements that allowed us to keep the project on schedule. Some of these were the IKA and emulsion PCR advances, a number were upgrades to the instruments that allowed more data to be generated and captured, and others were upgrades to the analysis software.
Looking ahead, there's definitely a commitment on both of our parts to following up on this project and pursuing new ones in the future as we move closer to sequencing whole genomes.