seqWell CSO Joe Mellor gave me a quick tour of their new transposase library prep product for Oxford Nanopore sequencers. Since the early days of ONT, users have had two basic choices for genome library prep: rapid method relying on transposase or the ligation kits. Rapid is so stupid simple even I can do it (just don't ask for my yields!); ligation requires more molecular biology skill due to multiple enzyme steps as well as bead cleanups. Ligation had higher yields than rapid - so simple but lower yield rapid or much more complicated but higher yield ligation? seqWell's approach is only slightly more complex than the rapid kit, offers a large number of barcodes, and has flowcell yields on par with ligation.
What's the trick? DNA samples are first tagmented with seqWell's TnX transposase enzyme, delivering sample-specific barcodes. seqWell has a huge stock of barcode oligos, so is happy to offer them in blocks of 96. The key change is that the transposome is biotinylated, enabling a single bead cleanup to capture the tagmented DNA and leave behind unmodified DNA. This is a key aspect of Tn5 transposases - they don't really turn over but instead stay latched onto the DNA they have attacked. Once enrichment for the tagmented material is complete, a quick ligation adds the ONT leader complex.
seqWell's kit improves flowcell yields by removing all the non-productive DNA; apparently these molecules interfere with productive ones. It's not immediately obvious why this would be so - if a DNA molecule lacks an adapter then it shouldn't interact with motors - but the effect is real. It will be interesting to see this kit in the wild and have some experienced nanopore community users report on how great the effect is.
This kit also marks a milestone in ONT opening up to collaboration in the library prep space. In the past, ONT would list favored suppliers (or blacklist unfavored ones) of components such as ligase or purification matrices, but ONT would retain full control over the nanopore-specific biochemistry. Now they are sharing the spotlight with seqWell, gaining access to potentially superior technology as well as eliminating the cost and trouble of stocking a large library of barcodes.
I hope this represents a general spirit of openness at ONT. I certainly believe there are many outside the company with interesting ideas that would help sell more ONT reagents and flowcells, but which would be more likely to develop if kept in more vigorous startups rather than a maturing company like ONT.
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