In a exciting full packed session at AGBT conference, MGI, the subsidiary of China’s BGI, claims to have broken the barrier to achieve a $100 Genome!
MGI says, its T7 sequencing platform with a newly developed chemistry can reduce the sequencing costs up to 5 -fold from its previous best of $500 to $100.
More genomes together?
To get the $100 genome, MGI names new system as DNABSeq. It combines DNBs- small, densely packed balls of DNA generated by rolling circle replication—and a patterned array of “sticky spots” to capture the DNBs. The new DNABSeq has ’70 billion’ such ‘sticky spots’ capture as against its previous high of ‘7 billion’.
With a surface that is five times larger and a doubling of the number of spots, more genomes can be sequenced on each run. Indeed, the Tx can sequence up to 700 genomes on a single run, a capacity that is an order of magnitude larger than any sequencer on the market today.
It takes a full capacity run of 700 genomes to achieve the $100 price point.
The new system has a new mechanism to handle the fluidics of big arrays. Rather than a conventional flowcell system, the DNABSeq T7 system uses a robotic arm , which dips a large ‘panel’ in a series of solutions, thereby reducing reagents cost.
The new ‘Tool’
CoolMPS (MPS stands for massively parallel sequencing) is the first nucleobase-specific antibody-based sequencing chemistry.
The CoolMPS chemistry introduces unlabeled Reversibly Terminated Nucleotides and four natural nucleobase-specific fluorescently labeled antibodies in its sequencing process to recognize the incorporated bases. In this process, the natural ‘scarless’ bases are added in each sequencing cycle. This enables greater accuracy and longer reads.
MGI attaches the dye on the antibody (the amines are labeled) and the antibodies recognize the nucleotides. They need no linkers and there is no dye when the nucleotides are being incorporated. Drmanac says that it is very cheap, highly specific and there is no cross talk.
Another innovation is the use of only two filters(no Red dye), so cross talk is minimized. There is also twice the amount of light and no bleeding from DNB to DNB. They add two antibodies at a time, take an image, and then take add the other two antibodies. This, as per MGI, is the increased cause of accuracy. MGI says, their sequencing has an error rate of 1 in 170kb bases incorporated.
The $100 costs is only for someone who already own the DNABSeq- sequencer. It means the costs is for reagents only and rules out all other expenses. Additionally, one will need to run 700 genomes together to achieve $100 efficiency.
It wont be hard to say, that this instrument will only be feasible to large population based genomic centers.
This new innovation is clearly an attempt to shake the sequencing market which has been long dominated by Illumina and the cost of sequencing set at $1000 for a long time. A different sequencing structure to attempt a $100 genome, will lead to new attempts to reduce the cost further and maybe design some new formats to achieve cost reduction.
The article is adapted from MIT Technology review. AGBT feb 2020