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BGI's Denmark Team Focuses on Clinical Exomes While Parent Company Drives Down WGS Costs

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NEW YORK (GenomeWeb) – Since it was founded in Copenhagen in 2010 as one of BGI's first outposts abroad, BGI Europe has been providing sequencing services to customers in Europe and beyond, both through its own laboratory and BGI's facilities in China.

In January, the Copenhagen laboratory obtained ISO 15189:2012 accreditation for medical laboratories, increasing its attractiveness for customers involved in translational research and clinical testing, and later this year with a Dutch collaborator, it plans to start offering a complete exome sequencing service for inherited disease diagnostics that will include the clinical interpretation.

In the meantime, BGI Europe's parent company, BGI Genomics, has been pushing the price of whole-genome sequencing to a record low, announcing a limited-time offer for a $600 genome last month that involves sequencing on its new BGISEQ-500 platform in China.

BGI Europe was founded in 2010, around the same time as the BGI Americas branch, to offer sequencing and bioinformatics services in the region. At the time, BGI said that it planned to invest $10 million and hire 20 to 50 people initially to build its Danish offshoot, and to add between 50 and 100 staffers over several years. 

One of the reasons for choosing Denmark as its headquarters was that Huanming (Henry) Yang, co-founder of BGI and chairman of its board, had obtained his PhD from the University of Copenhagen in the 1980s and retained personal connections to the Danish academic research community. In addition, English is widely spoken in the country, facilitating business across Europe, said Ryan Liu, general manager of BGI Europe.   

In 2011, BGI Europe joined a number of collaborators in a project to establish a Danish Platform for Large-scale Sequencing and Bioinformatics, since then renamed GenomeDenmark, to develop a cancer vaccine and build a map of the Danish genome. Shortly after, it opened its lab at the Copenhagen Bio Science Park (COBIS), located near Copenhagen University Hospital and other university departments.

Six years later, BGI Europe remains located at COBIS, which houses more than 80 other life science companies, where it occupies laboratory and office space on two floors. Its current team comprises about 20 members, more than half of them laboratory staff. In addition, BGI bioinformaticians from China regularly join the Copenhagen team for limited time periods, and BGI Europe has additional sales staff across the continent. For comparison, the entire BGI group has more than 5,000 employees.

The majority of the Copenhagen group is originally from China — and all of the signs in the laboratory are in English and Chinese — but the team has become more international in recent years, Liu said.

Most of BGI Europe's customers are academic research institutions, but they also include clinical laboratories and private companies. Customers are located all across Europe, as well as in some nearby countries, including Turkey and the Middle East. Many customers are not permitted to ship clinical samples outside the European Union, said Matt Poulter, BGI's Copenhagen-based global marketing manager.

The Copenhagen lab focuses primarily on exome sequencing services, having produced more than 10,000 exomes over the years, although it also offers transcriptome sequencing services and several clinical gene panels.

The typical turnaround time for exomes is two to three weeks, according to Kevin Sun, director of BGI's Copenhagen laboratory, which he said is shorter than that of competitors. In urgent cases, exomes can be completed within a week, he added.

Pricing for exomes depends on metrics such as volume, turnaround time, and capture kit used and usually ranges from $500 to $1,000 per sample, Liu said.

BGI Europe typically employs Amazon Web Services to deliver exome data to customers via the cloud, though it can use whatever data delivery option a customer prefers. Through BGI Online, BGI also offers cloud-based analysis services: last month, for example, the company said it is working with the Broad Institute, Intel, and Alibaba Cloud to provide cloud-based access to the GATK4 software package through BGI Online.

Starting later this year, the Copenhagen lab plans to offer complete diagnostic exome sequencing for rare diseases that includes the interpretation, a service that will be primarily geared at pediatric hospitals in Europe. Sequencing for this will be done in Copenhagen, and the interpretation will be provided by Genome Diagnostic Nijmegen, a diagnostics lab that is part of Radboud University Medical Center in the Netherlands, a long-standing customer of BGI Europe.

BGI also recently invested in genome interpretation company Congenica in the UK and is exploring ways to work more closely with that firm in the international market, Poulter said. BGI already offers Congenica's Sapientia software in China through BGI Online, he added.

The Copenhagen lab also offers a BRCA 1 and 2 panel test, a 21-gene breast and ovarian cancer panel test, and a panel for maturity-onset diabetes of the young (MODY), a monogenic form of diabetes. The lab has sequenced thousands of MODY samples for Danish customers and plans to offer this service more widely in Europe going forward, Poulter said. BRCA testing has been a growing and competitive market, he said, and BGI's BRCA panel has seen good uptake in Turkey, for example. Mendelian disease carrier screening is another test offered by the lab, though there has not been much interest so far.

The lab is equipped with an Illumina HiSeq 2000 and a HiSeq 4000, which recently replaced a number of decommissioned HiSeqs 2000. Those platforms are primarily used for exome sequencing services. In addition, the lab maintains a Thermo Fisher Scientific Ion Proton, which is used for smaller tests with faster turnaround times, such as the breast cancer and diabetes panels. Currently, there are no plans to bring BGI's new BGISEQ-500 sequencer to Copenhagen.

An Agilent Bravo automated liquid handling platform ensures that the lab can prepare 200 libraries of sequencing per day.

Samples for whole-genome sequencing are shipped to BGI's large-scale sequencing centers. "There are certain economies of scale and cost efficiencies available from the Chinese laboratories that we don't have here," Poulter said. Typically, for logistical reasons, they go to BGI's Hong Kong laboratory, which operates HiSeq 2500, HiSeq 4000, and Ion Proton sequencers.

Likewise, all samples for noninvasive prenatal testing with BGI's NIFTY test, which BGI markets to hospitals, private clinics, and doctors across Europe, are shipped directly to the Hong Kong laboratory for analysis.

However, depending on a customer's needs, whole-genome sequencing can also be conducted in one of BGI's laboratories in mainland China, for example its Shenzhen lab, which has both an Illumina X Ten and BGISEQ-500 sequencers installed. 

Last month, BGI started offering whole-genome sequencing on the BGISEQ-500 for $600, about 40 percent below the current "street price" of $1,000 for a genome. The offer, which runs until the end of June and has a turnaround time of three weeks, includes library prep; sequencing at 30X average coverage, with 90 percent of the genome covered at 20X or more; and standard analysis.

In the long term, whole-genome sequencing is likely where customers are going to move, according to Lui. "At the moment, the reason people don't choose whole-genome sequencing is, either they can't afford whole-genome sequencing or they can't process so much data," he said. "So, once they can afford it, and they can process that much data, of course they will choose WGS."

European customers can also access other sequencing platforms through BGI's China laboratories, such as Pacific Biosciences, as well as other sequencing services. On the BGISEQ-500, for example, BGI currently also offers low-cost transcriptome sequencing, small RNA sequencing, and ChIP sequencing, Poulter said.

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