NEW YORK (GenomeWeb) – In an effort to integrate sequencing technology it acquired from Complete Genomics in 2013 into its global service offerings, BGI of China is launching sequencing services on the BGISEQ-500 platform for the first time this year.
At a conference this week, the company also said it has been developing the technology further to enable a "$100 genome" and will start evaluating it as part of internal research projects later this year.
"What you're seeing here is that the technology that was developed at Complete Genomics is now going mainstream," Johan Christiaanse, director of marketing for BGI's global genomic services, said in an interview.
Services on the BGISEQ-500 — quantitative RNA-seq in the next quarter, followed by whole-genome sequencing later this year — are designed to undercut prices of similar services offered by BGI and others on platforms from market leader Illumina, he said. BGI developed the instrument internally, and thus does not need to purchase consumables from an external vendor. "With our own technology, we basically take the middleman away," he said.
BGI unveiled the BGISEQ-500, a desktop sequencer which uses combinatorial probe-anchor synthesis and DNA nanoball arrays — technology originally developed by BGI subsidiary Complete Genomics — in late 2015. The instrument can generate up to 300 gigabases of data per run with paired-end 100-base pair reads. Last year, the China Food and Drug Administration approved registration of the BGISEQ-500 as a medical device, opening it for use in clinical genetic testing.
Over the past year, the company ran a number of RNA sequencing pilot studies on the BGISEQ-500 in collaboration with customers. This included a study of microRNA sequencing with researchers at Saarland University in Germany, which was published in Clinical Epigenetics last fall. Another recently published study in insects, led by researchers at the Chinese Academy of Sciences, used the platform to confirm gene expression profiles, Christiaanse said.
With the beta testing results in hand, BGI is now ready to launch quantitative RNA-seq services on the platform globally. The service, which will generate at least 20 million single-end 50-base pair reads per sample, will be performed at BGI's laboratories in Wuhan and Shenzhen, as well as at its CAP-accredited laboratory in Hong Kong. The three labs currently house approximately 150 BGISEQ-500 instruments between them, Christiaanse said. Eventually, BGI plans to offer the BGISEQ-500 service at its service labs outside of China, he added, for example in Philadelphia and in Copenhagen.
Another 150 or so BGISEQ-500 instruments are installed at the China National GeneBank, a nonprofit research institute in Shenzhen that BGI founded with the Chinese government, and more than 200 BGISEQ-500 machines have been installed at customer labs throughout China, while no BGISEQ-500 has been sold outside of China yet, he said.
The target price for a quantitative RNA-seq sample will be $300 or less, which Christiaanse said is getting close to prices for Illumina or Agilent gene expression arrays, and the turnaround time is on the order of three to four weeks.
Agilent, by comparison, charges between $700 and $1,200 for custom gene expression arrays that can fit between one and eight samples each. However, NGS-based gene expression analysis has higher sensitivity and a better dynamic range than arrays, and the data can be reanalyzed later for additional genes. "Those are all significant benefits and those are now becoming available at the same price point as an array," Christiaanse said.
On GenoHub, a platform that allows NGS providers to market their services, the least expensive comparable RNA sequencing service, providing 20 million 75-base single-end reads on an Illumina NextSeq 500, currently costs $400 per sample.
In the meantime, BGI is initiating a number of customer collaborations for early-access whole-genome sequencing services on the BGISEQ-500. Those studies, which will generate paired-end 100-base-pair reads, are planned for the first half of the year, Christiaanse said. Depending on their outcome, BGI might launch whole-genome sequencing services commercially in the second half of the year. BGI also plans to publish several internal whole-genome sequencing projects conducted on the BGISEQ-500, he added.
Pricing for whole-genome sequencing is expected to be as low as $600 per sample for a human genome at 30-fold coverage, he said, which would include only raw data without bioinformatic analysis and would require a minimum order. This price, he said, would be about 40 percent less than the $1,000 "going street price" for a "base" human genome sequenced on an Illumina platform. Genohub, for example, currently lists $1,300 as the lowest price for a 30-fold human genome, sequenced with paired-end reads on an Illumina HiSeq X.
While BGI has no concrete plans yet for offering services other than quantitative RNA-seq and whole-genome sequencing on the BGISEQ-500, the "logical follow-on" would be exome and full transcriptome sequencing services, Christiaanse said. "Once you master the paired-end 100 [base pair reads], you can expand from that."
BGI will also continue to provide sequencing services on its Illumina, Pacific Biosciences, and Thermo Fisher Scientific sequencers, he said, as many customers need to complete studies begun on those platforms.
Meanwhile, researchers at BGI's Complete Genomics are pushing the technology further to enable whole-genome sequencing for $100 per sample. According to a presentation this week by Complete Genomics CSO Rade Drmanac at the Precision Medicine World Conference in Mountain View, California, the company is working on a DNA-nanoball-based "cluster sequencing system" that will be able to analyze around 100,000 genomes per year at less than $100 per genome.
A single fluidics system will serve more than 10 imaging systems and robotics will transfer the sequencing arrays between the two. Imaging will be fast and involve advanced XY stages and cameras with a capacity of 2 gigapixels per second, according to the presentation, which will enable the use of high-density DNA arrays. Also, the use of consumables will be reduced tenfold, and the system will be able to generate high-quality reads of 300 to 400 base pairs.
Drmanac said in an email that the technology will be available "in the not too distant future" but that there is currently no timeline for its commercial release. He said BGI expects to evaluate the technology this year for internal research projects that require whole-genome sequencing of large numbers of samples. He declined to discuss technical details of the new system at this time.