By Monica Heger
This story was originally published Nov. 20.
HONG KONG — BGI is looking to develop a clinical center within its Hong Kong facilities that will offer sequencing-based diagnostics for monogenic disorders, cancer, other complex disorders, and trisomies.
While the center is still in the planning stages, and the Hong Kong branch needs final approval from its Shenzhen headquarters, Alex Wong, executive director of BGI-Hong Kong, told Clinical Sequencing News that a lab could be built and fully certified to offer diagnostic tests to the international community in the next two years.
The development of the center is just one signal that BGI increasingly sees the future of sequencing in the clinical space.
At this week's International Conference on Genomics in Shenzhen, the institute highlighted several collaborations it has forged in the clinical space, including the recently announced BGI@CHOP center (CSN 9/9/2011) and the Sino-Danish breast cancer consortium, which is using sequencing to find biomarkers that predict drug resistance in breast cancer patients (IS 8/31/2011). BGI is also working with Sweden's Karolinska Institute University Hospital to develop an immunogenetics center in Shenzhen (CSN 11/16/2011) and is planning to kick off a project next year that will sequence 50,000 individuals from Denmark.
Details on the instrumentation the clinical center at BGI-Hong Kong would be equipped with are still being worked out, but would likely include mass spectrometer and a handful of next-gen sequencing machines, including the HiSeq 2000, a MiSeq, and an Ion Torrent PGM, said Wong.
The Hong Kong facility performs the lion's share of BGI's sequencing. The branch is equipped with nearly 100 machines. The HiSeq makes up the vast majority of the facility's instruments, but it also has Life Technologies' SOLiD. It recently acquired, but has not yet purchased, a MiSeq that it is demo-ing, and an Ion Torrent PGM is located at the Shenzhen facility.
The sequencing machines currently take up an entire floor of the Hong Kong branch's five-story building. Wong said that the clinical center would be built on its own floor so it would be completely separate from the research-oriented sequencing floor.
Additionally, BGI will seek all the certification required to offer diagnostic tests globally. To secure accreditation, Wong said that all personnel working in the lab would have to receive training, as well as have the appropriate accreditation. For instance, all the medical and lab technicians will receive training at Prince of Wales hospital in Hong Kong. The center will also have at least one certified pathologist, and the lab manager and director will both be medical doctors. In addition to becoming certified in Hong Kong, Wong said the center would abide by US clinical guidelines such as the Clinical Laboratory Improvement Amendments and the College of American Pathologists.
BGI has already begun offering next-gen sequencing tests in China for deafness, some trisomies, human leukocyte antigen typing, and human papillomavirus. It has approval from the Chinese State Food and Drug Administration for those tests.
In addition, it has used a non-invasive method to sequence maternal plasma from pregnant women to test more than 10,000 women in China for trisomy 21. The approach is similar to the method developed by Dennis Lo's lab at the Chinese University of Hong Kong and which is now being used by Sequenom in its recently launched MaterniT21 test (CSN 10/19/2011).
Wong anticipates an incremental roll-out of the tests, beginning in Hong Kong. Aside from making sure the tests adhere to the various accreditation standards in different countries, another potential hurdle will be navigating the intellectual property space. The Chinese government does not issue patents for things deemed to be necessary for an individual's health, said Wong, but that is not the case in other countries.
For instance, Lo holds a broad patent for using next-gen sequencing of maternal plasma to diagnose trisomy 21. While he licensed the patent to Sequenom to cover the US and European markets, he still holds the rights to develop the test in Hong Kong.
Wong said that BGI would likely have to negotiate the rights from Lo, possible through a licensing deal, to launch a sequencing-based trisomy 21 test in Hong Kong.
While BGI has already begun offering next-gen sequencing-based diagnostics in China, it is still developing an array of tests that it is aiming to offer in its clinical center.
Wong said that for rare, Mendelian disease, he is looking to combine around 100 diseases into one test, and would likely use either exome or whole-genome sequencing, since that would give BGI the option of adding additional diseases to the panel.
Wong said that he would like to work with the Hong Kong department of health to validate such a test, but this is still in discussion.
To diagnose more complex disorders, Wong said he would likely use a capture technique being developed by researchers at BGI-Shenzhen, dubbed All-in-One, that would capture the exome, regulatory regions, the MHC locus, and population-specific tag SNPs (IS 11/16/2011).
Wong said that further down the road, BGI would develop cancer panels that the center would offer. These could be for early detection or monitoring of cancer, as well as to screen a patient for the best course of treatment. Likely, the team would develop different targeted sequencing-based panels for different types of cancer, Wong said.
Clinical Sequencing, BGI's Future
While BGI has so far not focused on any specific area for its sequencing projects — it is involved in clinical sequencing projects, microbial sequencing projects, and plant and animal sequencing projects — Wong anticipated that once the clinical center is mature, clinical sequencing will represent around 70 percent of BGI's business.
Already, BGI has sequenced more than 38,000 human genomes, including 4,500 cancer genomes, over 25,000 individuals with complex diseases, 1,000 monogenic disease genomes, and over 7,000 individuals for population-based studies, said executive director Wang Jun during a talk at the conference in Shenzhen this week. The goal, Wang said, is to sequence one million human genomes.
Additionally it has announced several recent collaborations with a clinical bent, including establishing a joint genome center at Children's Hospital Philadelphia, BGI@CHOP. Hakon Hakonarson, the director of the Center for Applied Genomics at CHOP, said at the Shenzhen meeting that the goal is to create a CLIA-certified and CAP-accredited high-throughput sequencing center that will offer sequencing-based diagnostics.
The Center for Applied Genomics at CHOP currently has 150,000 genotyped samples, and Hakonarson said his team plans to sequence all of them. Additionally, it has electronic medical records extending at least 12 years for around 60,000 children. Many of these families would also be recruited for sequencing projects as well, focusing first on those with undiagnosed Mendelian diseases.
BGI is also collaborating with the University of Copenhagen on several clinical projects, including the Sino-Danish Breast Cancer project and a project to sequence 50,000 people in Denmark.
The Sino-Danish Breast Cancer project is a collaboration between Aarhus University, the University of Southern Denmark, the Technical University of Denmark, the Danish Breast Cancer Cooperative Group, the University of Copenhagen, the Beijing Institute of Genomics, and BGI. The goal is to find biomarkers that predict resistance to endocrine therapy and chemotherapy.
Among other techniques, the group is employing exome sequencing, RNA-seq, and methylation sequencing, which is being done at BGI, to find markers of drug resistance.
The project to sequence 50,000 residents of Denmark, also called the 1% Danes' Genome Project, will begin in February 2012, with goal of building a database of sequence data to provide cohort data for disease research, and to eventually help guide a strategy for incorporating personal genomic information into health care.
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