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.