The Genome Institute of Singapore (GIS) is a renowned center for genomic discovery whose mission is to pursue the integration of technology, genetics, and biology towards the goal of individualized medicine. As a senior investigator focusing on cancer research at the GIS, Dr. Yijun Ruan leads a team using the Applied Biosystems SOLiD™ System to expand the Institute's study of the genetic underpinnings of cancer and other complex human diseases.
We recently spoke with Dr. Ruan about his current work at the GIS, and how Applied Biosystems is helping scientists there as they undertake a comprehensive analysis of the genetic changes that characterize cancer in humans.
Tell us a little about your area of expertise, and what you're working on now.
My primary area of expertise is the development of technologies that can be applied to address fundamental questions in genome biology. Here at the GIS, we have been developing paired-end di-tag (PET) sequencing technologies for the last several years. We started with the concatenation method using the Applied Biosystems capillary sequencing approach to PET sequences, and now we are using next-generation sequencing platforms like the SOLiD System from AB.
What type of research are you conducting with the SOLiD system?
We're using the SOLiD System to study the cancer genome. Our goal is to identify all of the genetic variants present in cancer genomes so we can understand what genetic changes lead to the disease. This is leading-edge research that will evolve in two major stages. The first stage will happen pretty quickly, and involves 'picking the low-hanging fruit' by categorizing, or karotyping, the structure variations in cancer samples in order to understand how it develops into genome levels. The second phase will expand on this approach to move toward complete individual genome sequencing.
Why did you choose to team with AB for this work?
AB products have a very good reputation for reliability and accuracy, and we've been using them for several years with excellent results. For our latest research, we evaluated several technologies and concluded that the ultra-high throughput SOLiD System in conjunction with our PET sequencing method is a winning combination for the complicated process of cancer genome sequencing.
On top of the SOLiD technology itself (we joke in our lab that 'SOLiD is really solid'), another deciding factor was the excellent technical support we have received from AB in the past. The SOLiD application team is no exception—they're great to work with and always open to exchanging ideas and helping us to improve our processes and technologies. Of course it also helped that the cost of sequencing using SOLiD is much lower compared to the capillary system.
What is the ultimate goal of this research, and what are its real-world applications?
We're shooting for personalized genomics within the next few years. The genomes of any two people are 99% the same; it's the last 1% and the structural organization of each genome that holds the answers to important questions about an individual's risk of disease and response to therapies. By understanding the cancer genome structure variations across individuals, scientists will be able to give physicians an idea of what kind of cancer genome type a particular patient has, which will help them to personalize the chemotherapy or radiotherapy process to achieve the best results for each patient.
What results have you achieved to date? Have there been any upside surprises?
The SOLiD System combined with our PET sequencing has allowed us to generate personalized digital coverage of genomics profiles much faster than we expected. We still have a long way to go to get from karyogenomics (the architecture of the genome) to the full-blown personalized genome, but this can be considered an early version of personalized genomics and a significant step toward personalizing medicine at the genome level.
Would you say that faster sequencing is the biggest impact the SOLiD System has made on your research?
Definitely. The desire to understand structure variations across individual genomes is not new, but until recently the ability to make much progress on any kind of large scale was limited by the speed of available technologies. The SOLiD system has opened new opportunities to our structural variation studies.
Compared to the old methods of sequencing BAC clones and Fosmid clones using the capillary or standard sequencing methods, it's just unbelievable what we can do with SOLiD now. Using one slide and one rung, we can get a comprehensive coverage of the structural variations in each individual genome in just a few weeks, as opposed to the several months it took before. So, for the first time, it really is feasible to conduct very large-scale studies across many, many individuals.
Does this work have implications for other fields beyond cancer research?
Yes. We will gain a lot of insight about the cancer genome operations using our current format of SOLiD and PET sequencing, but the same application can also be applied to other genetic diseases, diagnostics, population genetics, sequencing genes of healthy individuals to study the evolution of genetic diseases like cancer, and many other areas.
This is important because, through large numbers of genome re-combinations, each new generation of people contributes a certain level of structural variations. My hope is that this research will not only demonstrate the unique applications of our PET-based sequencing, but that it will also serve as a building block for the industry to move forward with the development of more efficient systems that can generate whole genome sequences. If we can generate the entire genome sequence of every newborn child almost instantly, imagine the powerful implications that would have in terms of how we study, predict, diagnose, treat, and ideally prevent genetic diseases.
On a personal level, what is the most rewarding aspect of your current research? What are you most proud of?
I see this as the beginning of an extremely exciting era in the field of biological research, particularly in human genome research. We haven't seen this kind of opportunity to advance the science in the last 10 or 20 years, and I think the impact will be extraordinary and historic. I always feel that I can do better, and the pressure is always on, but maybe that's part of what makes it so exciting. The challenge is to put new technologies like next-generation SOLiD sequencing to work in ways that will significantly benefit people. I'm just very proud to be a part of that.
