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Beijing Institute of Genomics Researchers Make Progress toward Low-cost NGS System

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This article was originally published June 27.

NEW YORK (GenomeWeb) – Researchers at the Beijing Institute of Genomics, Chinese Academy of Sciences are developing a next-generation sequencing system that will be sold by Zhongke Zixin, a subsidiary of Zixin Pharmaceutical.

The instrument will be beta tested by 20 early access customers, all at the Chinese Academy of Sciences, beginning this year and mass production will begin in 2015, Jun Yu, the principal scientist behind the project and associate director and professor of the Beijing Institute of Genomics, told In Sequence.

Dubbed BIGIS-4, it is a benchtop system that uses the same pyrosequencing chemistry as Roche's 454 systems. Yu told In Sequence that the Beijing Institute of Genomics holds a patent on the pyrosequencing technology used that has "no conflict with Roche's 454," and it also holds over 50 patents on the device itself.

Researchers published a study in 2011 demonstrating a prototype of BIGIS-4 in the journal Science China. In that study, they sequenced and assembled the Glaciecola mesophilia bacterial genome, generating over 150,000 reads with an average read length of 406 bp. They reported an accuracy of 99.5 percent with similar homopolymer issues as the 454 chemistry. The researchers generated an assembly consisting of 157 contigs with an N50 size of 61 kb. Mean genome coverage was 11.9x and the reads covered 99.4 percent of the genome.

As described in the study, the system consists of four reaction modules housed in separate chambers that share one fluidics system. Depending on the throughput requirements, the user can run just one reaction module, or up to all four modules. In the Science China study, for instance, the researchers used just one chamber to sequence the Glaciecola mesophila genome.

Since that study, Yu said that read lengths have increased to between 700 bp and 1,000 bp and will eventually surpass 1 kb. Accuracy will be on par or better than the 454, he said.

In addition, while the study described four reaction modules that would enable a flexible throughput, the first release of BIGIS-4 will have one reaction module and later editions will have more reaction modules, Yu said.

Throughput has also increased since the study and the system will have two run modes — a 400 mb regular run and a 1 gb elongated run. The BIGIS-4 will cost less than $1 million CNY ($160,745), Yu said.

The main applications of BIGIS-4 will be targeted sequencing and bacterial sequencing with hospitals, clinical laboratories, and small research labs as the targeted end users. Yu said that the group is working with the China Food and Drug Administration to identify specific "applications that require CFDA approval together with the machine." The machine by itself would not be CFDA approved, he added.

The reported accuracy of 99.5 percent in the Science China study is "in the ball park with [sequencing-by-synthesis] technology," according to Vince Magrini, director of the technology development group at Washington University's Genome Institute. However, whether the sequencer gains traction will come down to "the actual difference in costs" — dollars per mb or pennies per gb, he said. Magrini added that as Illumina's paired-end reads increase in length — the MiSeq will soon have paired 300 bp reads — 500 bp to 1,000 bp single-end reads may not offer great enough advantages to convince potential users to switch platforms or to lure new customers. "If you want longer reads, then go long," he said.

Yu said that he thought the BIGIS-4 system would be geared toward a niche market that is not currently served by existing sequencing platforms. And although the platform will initially be beta tested in China, he said there are plans to market it abroad as well.

James Hadfield, who heads the genomics core facility at the University of Cambridge, Cancer Research UK Cambridge Institute, agreed with Magrini that BIGIS-4 may not offer enough advantages to make a dent in the highly competitive next-gen sequencing market. "Even if the machine is cheaper to buy and run than 454," it will struggle to compete against Illumina, Thermo Fisher's Life Technologies, Pacific Biosciences, and now Oxford Nanopore, he told IS.

Elaborating on his CoreGenomics blog, he added that while there may be pressure in China to develop a next-gen sequencing instrument that is cheaper than the HiSeq, BGI's purchase of Complete Genomics may give it the edge to accomplish such a feat.

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