DOI

(This is an opinion piece, a bit different from what I normally post here. My next post will return to my normal mini-study fare.)

I’ve been using Oxford Nanopore sequencing since 2016, and it’s been a ride! At the start, the data was rough – sequencing yields were low and read error rates were >10%. An ONT-only bacterial genome assembly from 2016 had tens of thousands of errors. But each year, it got better. By 2024, ONT-only bacterial genome assemblies had reached near perfection (and sometimes actual perfection). The read error rate in 2024 was lower than the assembly error rate in 2016. Riding that steady wave of improvement was fun.

But I can now say that at least for my domain (bacterial whole-genome sequencing), ONT today feels mostly the same as ONT from two years ago, and that’s not something I’ve ever felt before. Their last basecalling model update was 8 months ago, and it wasn’t dramatic. That ‘fun’ feeling is diminishing.

This is both good and bad. I work in academic research, but I also have many colleagues in public health, and I think we represent two ends of a spectrum. For me, ONT’s rapid development and improvement was great! It created new opportunities, new problems to solve, and let me work on the cutting edge.1 But on the public health side, ONT’s constantly-changing landscape was frustrating. Nobody wanted to spend time and effort developing and validating a pipeline that would be out-of-date in a year’s time. Now with the increased stability, some of my public health colleagues are comfortable replacing old Illumina-based workflows with ONT-based alternatives.2 While I do see the advantages to a slower pace of change, I sometimes pine for the ‘good old days’.3

While I’ve been feeling this sentiment for a while, this post was motivated by ONT’s recent announcement that the P2 Solo will be discontinued.4 The P2 Solo allowed PromethION flowcells to be run on an affordable computer, and its discontinuation could put high-throughput ONT sequencing out of financial reach for many academic labs.5 It’s bad news for researchers that use ONT. I’ve seen a lot of surprise and frustration in the community around this decision, and I’ll add my voice to the others requesting that ONT please reconsider.

As many have already pointed out, the P2 Solo’s discontinuation feels counter to the company’s motto: ‘To enable the analysis of anything, by anyone, anywhere’. By raising the cost of in-house sequencing, this could push more users to third-party sequencing providers which will erode the DIY appeal that drew many labs to ONT in the first place. I can think of many other tech companies who were the cool new underdogs until they became just another big corporation driven by shareholder value, so I hope ONT doesn’t lose what made it special.

A disclaimer: everything I’ve written is from the perspective of bacterial isolate WGS, and users in other fields may have a different experience. I do really like ONT sequencing – it’s a great technology that I would like to keep using. Going forward, I just hope ONT can walk the tightrope: producing a stable product that can be relied upon, while also continuing to push the envelope and support researchers like me.

Footnotes

  1. ONT has benefitted from a strong feedback loop: they shared their new developments early, and researchers like me developed protocols, software tools and validation. In effect, the academic community often acted as an informal extension of their R&D. ↩

  2. ONT has many benefits in bacterial genomics, such as being able to clearly distinguish plasmids (which often carry antimicrobial resistance) that Illumina sequencing cannot. ↩

  3. I nostalgically remember Clive Brown (former ONT CTO) giving enthusiastic talks full of ambitious roadmaps and big ideas. Many of these never materialised (whatever happened to outie sequencing?), but it nevertheless added to the excitement around the technology. ↩

  4. Announcement is here (requires an ONT community login). ↩

  5. The P2 Solo doesn’t include compute for basecalling, which kept its cost down. We do our basecalling on a ‘gaming’ computer named OnION. The alternative to the P2 Solo (which ONT is keeping) is the P2 Integrated, which includes a big NVIDIA GPU and is much more expensive. ↩