September 1, 2011 (Vol. 31, No. 15)
BGI Americas Provides Sales and Customer Support in North, South, and Central America
When a deadly foodborne strain of Escherichia coli recently killed dozens of people in Europe, researchers at BGI (formerly Beijing Genomics Institute) teamed up with collaborators at the University Medical Centre Hamburg-Eppendorf to sequence the microbe’s genome. They determined that the new infectious strain, called O104:H4, carries disease-causing genes from two other pathogenic E. coli and several antibiotic resistance genes, and it produces a Shiga-like toxin.
BGI experts also developed, and made freely available, a PCR diagnostic detection protocol and synthesized primers that rapidly identify O104:H4 within two to three hours.
BGI started in 1999 as part of the Human Genome Project; BGI Americas was founded in April 2010 as a commercial interface. BGI co-founders Huanming Yang, Ph.D., and Wang Jian, Ph.D., left the Chinese Academy of Sciences to build BGI, headquartered in Shenzhen, China. BGI contributed 1% of the Human Genome Project and was a core center for the International HapMap Consortium.
About 3,000 genetic researchers, computer programmers, and bioinformaticians operate 137 Illumina HiSeq 2000 sequencers and 27 Life Technologies SOLiD sequencers, and analyze the output. These next-generation sequencers churn out 5 terabases per day, equivalent to 1,500 human genomes. The data-processing center contains 50,000 CPUs with 200 terabytes of RAM.
The size of BGI guarantees a rapid turnaround and cost effectiveness, according to Dr. Yang. Due to the breadth of BGI’s capabilities, “we offer a comprehensive set of services, including a full range of genomic sequencing (whole genome, de novo, target region, and exome), transcriptomics, epigenomics, metagenomics, and proteomics,” he adds.
The bioinformatic experts at BGI not only provide significant data analysis but also invent new technologies such as SOAP (short oligonucleotide analysis package), a software system for analyzing next-generation sequence data.
BGI is nominally nonprofit, and for-profit relationships set up by BGI Americas with pharmaceutical companies and other clients offset the nonprofit programs. Pharmaceutical firms, universities, and research institutes in the United States provide an important market for BGI. Currently, BGI serves 15 of the top 20 pharmaceutical companies.
“Genomics is international and having a presence in the U.S. gives us closer proximity to nurture and build upon those valued relationships,” says Dr. Yang. Currently, 40 people work for BGI Americas and staff will be added as needed.
BGI Americas focuses on sales and customer support teams and it is branching out to establish service laboratories. Among the first is a partnership with the University of California-Davis (UC Davis) to sequence genomes important in the areas of food security, human and animal health, and biodiversity and environmental health.
Pharmaceutical companies that use BGI’s services speed their discovery programs and avoid the costs of buying sequencing equipment and informatic services, Dr. Yang says. “We can help pharmaceutical companies identify drug targets, locate better biomarkers, enhance patient selection for clinical trials, and optimize bioproduction,” he adds. The next promising areas are personalized medicine and the clinical diagnostics market.
BGI Americas offers fee-for-service capabilities in North, South, and Central America. Samples will be analyzed in Hong Kong, but the office in Cambridge can coordinate the shipping and paperwork. The returned report contains not only sequencing data but also annotation, mapping, analysis, or whatever the customer specifies. A similar facility in Copenhagen, Denmark, serves European clients.
BGI has a wide range of projects under way. One of the most recently completed was a collaborative study with GT Life Sciences that unveiled the genomic sequence of the Chinese hamster ovary (CHO) K1 cell line. According to the companies, it was the first published cell-line genome decoded by de novo sequencing and assembly.
The researchers embarked on the genome-scale assessment of CHO-K1 genes involved in protein glycosylation pathways because differential glycosylation can substantially affect functional activity and immune responses. Through their research they identified homologs to 99% of the human glycosylation-associated genes in the CHO-K1 genome, with 53% of them expressed.
The high coverage of homologs provides a unique opportunity for glycoform manipulation in CHO cells. The genome of CHO-K1 also provided insight into viral susceptibility genes and found that key genes associated with viral entry are not expressed in CHO-K1.
“The CHO-K1 genome provides the foundation for studies of other CHO cell lines and is a major step forward in the application of genomics in the production of biopharmaceuticals,” says Jun Wang, executive director of BGI.
Another ongoing project is work being done as part of the International Cancer Genome Consortium. BGI has been contracted to sequence 200 matched samples from people with gastric cancer, as well as healthy controls. Gastric cancer occurs at a high rate in the Chinese population and tumor cells mutate quickly and differ genetically from each other. To understand these genetic changes, BGI researchers developed a new single-cell sequencing method in which a single tumor cell is amplified and sequenced to study the heterogeneity within tumors, and cellular evolution.
BGI also launched the 1,000 Mendelian Disorders program to study diseases caused by a single gene malfunction. Among the first is spinocerebellar ataxia, a neurodegenerative disease. A mutation in the gene TGM6 was identified among four generations of a Chinese family with cases of spinocerebellar ataxia, whereas 500 healthy people do not have the mutation. Such information could lead to new diagnostics and therapies for genetic disorders.
BGI has close relationships with organizations worldwide. The genomic data generated from collaborations advances basic research. Scientists across many fields use this data to develop better crops and livestock and to design diagnostic tools and therapies for cancer and other diseases. “Genomics is in its infancy and presents unimaginable challenges,” says Dr. Yang.