AGBT16 day 4: a new sequencing chemistry from Nanostring

Saturday, February 13, 2016 11:47:

Joe Beecham Nanostring “New optical barcode chemistry's power 3D biology & sequencing-simultaneous DNA, RNA, & protein analysis and low error-rate targeted sequencing” A sequencing system with no library prep or amplification - this is a pretty cool project. Joe is presenting something quite early on but wants to engage with the community on building out this chemistry.

How does it work: Capture probes are laid down on the surface of the flowcell, DNA is hybridised directly and you sequence towards the 5' end with 6pb probes. These are tagged with a fluorescent optical barcode that can be decoded cyclically (somewhat similar to Illumina''s beadarray chips?). Each cycle identifies both the base and position. The first probe is removed and the cycle is then repeated until you have the DNA sequence. Initial experiments on BRAF V600E sequencing had raw single pass error rates of about 2%. Joe suggested that less than 5x coverage from a single molecule would be required to reach a consensus sequence accuracy of 99.99% (Q40).

Read lengths can potentially be very long. Joe described long DNA molecules being stretched out and probes landing randomly along the same molecule to sequence the whole thing. As this is a simple capture hyb of the sample it could be applied to RNA and be one of the first direct RNA-sequencers.

When is it coming: Like Illumina's Firefly Joe is making the same statements as Jay did, we are going to have to wait for the full commercialisation, which may be several years away, look out for more data during 2017.