By Ming Guo
October 5, 2012 | PHILADELPHIA—BGI is leading a widespread call in the genomics research community for collaborations to extract medically useful information.
At the inaugural International Conference on Genomics in the Americas (ICGA)*, held last week, BGI and Children’s Hospital of Philadelphia (CHOP) cohosted an exciting event with a host of dynamic presentations.
Chairman and founder of BGI, Yang Huanming, opened the event by calling for widespread collaboration. His central theme was that we are all weathering the same global environment of political, ethical, economic, and scientific challenges in the genomics era.
We are “on the same boat, with the same dreams, in the same direction, with the same responsibility to the world, sharing the opportunities and challenges, for the same bright future,” said Yang. He elaborated on four trends he sees in the genomics community: sequence all species, sequence all individuals, humanity above all and the culture of collaboration. As he ended his speech, one person from the audience shouted: “Let’s collaborate!”
BGI Executive Director Wang Jun gave examples of the groundbreaking scientific research that BGI has been engaged in. Perhaps the most interesting is the discovery of gut bacteria as biomarkers for type 2 diabetes, a study recently published in Nature. The sensitivity and specificity of the bacteria group biomarker reached an ROC (receiver operating characteristic) of 0.87, while the host human genetic biomarkers reach only 0.60. “You are what you eat. You can get diabetes from what you eat, and you can get rid of type 2 diabetes because of what you eat,” he said. BGI’s 50-gene panel is likely to be the “perfect biomarker for diabetes,” he said.
Wearing a BGI T-shirt, Wang Jun blends into the crowd of researchers and eager collaborators. Speaking to Bio-IT World after his talk, Wang Jun explained BGI’s perspective in plain language. “Genomics is useful.”
When asked about the potential competitiveness of popular open source genomic analysis solutions such as Galaxy, Wang Jun said, “These types of service platforms are actually good channels for us to get in touch with scientists. BGI does not want to grow as a service company. Our goal is to develop something useful for ordinary people to have a better life. We don’t really see anybody as our competitor.”
Wang Jun declined to comment about BGI’s recent bid for Complete Genomics.
The Future of Genomic Medicine
Hakon Hakonarson (CHOP) laid out the future of genomic medicine in patient care with some simple goals: build a big biobank and genotype 100,000 children for developing diagnostics for more than 50 diseases. So far, CHOP has collected a total of 200,000 genotypes.
Hakonarson then described his team’s work on neurodevelopmental genomics, including the finding of a network of genes in the mGluR pathway that directly contributes to attention deficit disorder. The information is then used to optimize clinical trials with genetics-based patient stratification. It can also help reposition the existing drugs and bypassing the pre-clinical stages of drug discovery.
Eric Green (Director of National Human Genome Research Institute) took a step back by looking at the big picture of our progress towards genomic medicine. Green laid out five steps or domains for applying genomics to clinical care: understanding the structure of genomes, understanding the biology of genomes, understanding the biology of disease, advancing the science of medicine, and improving the effective of health care.
The immediate developments in this field, Green indicated, include pharmacogenomics, newborn sequencing/screening, integration of clinical genomics information system with electronic medical records, and advancing human health through genomics research.
Applying pharmacogenomics in drug discovery is helpful with patient stratification, but it comes with some practical concerns. Rupert Vessey (Merck) said it is time-consuming for patient recruitment due to the additional testing and finer-level of patient stratification. Other obstacles include sample management, FDA approval for new genetic tests, and resistance from IRB, regulators as well as patients. One lesson learned at Merck is to include the development of a genetic test early on in the drug discovery process, or in parallel with drug development. A success case of pharmacogenetics at work is warfarindosing.org.
George Church (Harvard Medical School) pointed out the latest technological advancement in genomics: the quality of haplotyping is increasing, he said, as the resolution improves. Church also discussed advances in epigenomics, 4D imaging, as well as nanopore sequencing technology.
Challenging the Fundamentals
Several presentations challenged conventional wisdom with provocative theories.
For example, Douglas Wallace (CHOP) gave a talk entitled “Next Generation Genomics: the Mitochondrion and the Epigenome”. Wallace challenged two fundamental assumptions of Western medicine. One is the anatomical paradigm of disease, in that we treat symptoms at the location where they occur. He argued that disease is a systemic energy defect occurring at the mitochondrion level.
Another incorrect assumption is that it is nuclear genes that explain Mendelian diseases. In fact, there are 1,000 to 2,000 mitochondrion genes, which impact the nuclear genome. The interaction between mitochondrial DNA and nuclear DNA is very important, he said. He gave evidence showing that the evolution of mitochondrion genes is correlated with human geographic migration.
Gholson Lyon (Cold Spring Harbor Laboratory) described canalization, challenging the gene deterministic view. “We have not systematically sequenced or captured the characterization of any generic alternation in thousands of randomly selected people,” he said. “There are many factors—genetic background and environmental fact, in a canalization way—that seem to be compensating on the genetic effects in a major way, which makes it impossible to predict genetically. Every human body can tolerate multiple mutations... It’s so complex, that I think the only way forward is to work on the ‘network of science’, genotyping and phenotyping thousands of people...” More collaboration is needed to break out the silos of thinking based on single gene or genes.
The conference reception dinner was held in the Penn Museum, under the largest column-less dome in the world, among statues of Buddha and Egyptian mummies. BGI leaders are proudly displaying their Chinese origin, but believe in running a tight ship, navigating wisely in a “flat” world.
“We have the confidence to develop something useful and pay back our investors,” reflected Wang Jun.
*ICG-Americas (International Conference on Genomics in the Americas), Philadelphia, September 27-28, 2012. (www.icgamericas.org)