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MGI Tech Launches New Ultra-High-Speed, Mid-to-Low Throughput Sequencer

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BALTIMORE – MGI Tech, a Chinese sequencing technology company affiliated with BGI, this month launched DNBSeq-G99, a new ultra-high-speed, mid-to-low throughput sequencer that the company claims is its fastest sequencer to date.

The ninth sequencing platform released by MGI, DNBSeq-G99 promises to deliver a sequencing run with 150-base paired-end reads (PE150) within 12 hours, an MGI spokesperson said in an email. "It is simple enough, flexible enough, and can achieve outstanding sequencing speed," the spokesperson said. "We have tried large-scale condition optimization and parameter training under technical limits to finally develop such [a] product."

Similar to other sequencers in the DNBSeq franchise, DNBSeq-G99 is based on MGI's proprietary DNBSeq technology, a DNA nanoball-based sequencing approach. However, the company said one innovation of DNBSeq-G99 is that it is the first platform to adopt so-called "triangular matrix signal spots," a triangular patterned array with a 600-nm pitch-to-pitch distance to enable a higher density of signal sites per unit area on the sequencing flow cell. Compared with its previous flow cell, which arranges the signal spots with a distance of 715 nm in a squared pattern, the number of DNA nanoball loads per unit area increased by 68 percent, MGI said.

The instrument is also equipped with high-resolution microscope lens and optical system to further improve the capture efficiency of the signal, the company said, adding that these improvements "help to increase data throughput, while simultaneously reducing imaging area and time." Additionally, the "innovative" sequencing chemistry allows DNBSeq-G99 to achieve a "super-fast" cycle time of two minutes during sequencing, with only 10 seconds required for the fluorescence reaction during the incorporation stage while achieving rapid leveling.

Overall, with these improvements, DNBSeq-G99 can deliver a PE150 run within 12 hours with a data output of 8 Gb to 48 Gb per run, the company said.

In terms of hardware and consumables, DNBSeq-G99, which can fit on the benchtop, is designed to utilize pre-loaded reagent cartridges, MGI said, while additional reagents can be added by "a simple press-to-load maneuver." MGI also highlighted that the instrument has two flow cells, which feature their own flow cell bins, reagent compartments, and configuration options and can be operated independently without interference.

The company said DNBSeq-G99 currently supports sequencing read lengths including paired-end 50 bp (PE50), single-end 100 bp (SE100), and PE150, while reagent kits for longer read lengths, such as single-end 400 bp (SE400) and paired-end 300 bp (PE300), are in the development pipeline.

At present, MGI said DNBSeq-G99 is available in two models. The first model allows automatic analysis and output of the sequencing data through the integrated computing modules while providing users with "secure and reliable localized data storage and calculation." Meanwhile, the second model solely supports the standardized output of sequencing data, which users can analyze on their own.

In terms of DNBSEQ-G99's accuracy, MGI said internal results using Escherichia coli samples indicate a sequencing error rate of as low as 0.2 percent based on the statistical results of 92 runs within 12 instruments. However, the spokesperson noted that the error rate "is an algorithmic evaluation in the MGI summary report and does not represent advanced analysis results."

MGI did not disclose a specific sticker price for the instrument, citing that the price varies among different regions and countries and that the company has a "different price policy by different areas." The company also did not specify the per-Gb cost for DNBSEQ-G99, although the spokesperson claimed it to be "competitive."

In a user experience webinar hosted by MGI on Monday, Yuting Yi, head of R&D at GenePlus — a Chinese cancer genetic testing company that was founded by ex-BGI executives and has previously received investments from BGI — showcased DNBSeq-G99 data for oncology applications.

In one experiment, Yi's group tested DNBSeq-G99 with 10 cancer formalin-fixed paraffin-embedded (FFPE) and 13 plasma circulating tumor DNA (ctDNA) samples in several PE150 runs.

Overall, Yi said DNBSeq-G99 delivered "excellent" performance, with the platform producing at least 108 million reads in each run and Q30 above 94 for all runs. In addition, she showed that the instrument was able to accurately detect single-nucleotide variants (SNVs), indels, copy number variants (CNVs), and structural variants (SVs) in both FFPE and ctDNA samples.

Her team also applied DNBSeq-G99 for metagenomic next-generation sequencing (NGS) on eight bronchoalveolar lavage fluid samples. The results from two single-end 50bp (SE50) runs showed that both runs delivered at least 125 million reads, achieving a Q30 of 96. Additionally, Yi showed that when performing targeted NGS on 12 samples, DNBSeq-G99 generated a total of 126 million reads, with an above 90 Q30.

Miao Zhu, a research scientist at Chinese cancer genomics company Geneseeq, also reported results from his group, where DNBSeq-G99 was compared head-to-head with the Illumina NextSeq 550, MGISeq-2000, and versions of MGISeq-200 using 120 samples that included white blood cell, FFPE, and plasma samples.

According to Zhu, the preliminary results showed that DNBSeq-G99 delivered a lower decoded ratio compared with the other platforms, although the platform had a higher Q30. Additionally, when compared with manual curation, DNBSeq-G99 achieved a higher positive predictive value (PPV) for detecting mutations than other platforms. Moreover, the instrument performed similarly to NextSeq 550 when it comes to CNV detection.

Application-wise, MGI said DNBSeq-G99 can be deployed for oncology panels, small panel genetic disease detection, whole-exome sequencing, oncology targeted methylation panels, RNA sequencing, metagenomics for pathogen detection, and many others. In the future, the release of longer read-length chemistries, such as SE400 and PE300, will also unlock more application possibilities for the platform.

To that end, earlier this month, China Center for Disease Control and Prevention officials also used DNBSeq-G99 as well as nanopore sequencing from Oxford Nanopore Technologies to help identify the first imported monkeypox case in the country.

Currently, DNBSeq-G99 is mainly available in China, and MGI said it is gearing up to launch the instrument in Asia-Pacific and the Americas in the first half of 2023 followed by Europe and Africa in the second half of next year.

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