Let me start by saying that what I’ve written below are opinions formed after many conversations with many different people, including some from ONT, over the last 2-3 years. I don’t want anyone to think I am stealing their ideas – but I think it’s important to get them out there.
Oxford Nanopore’s technology, currently available in the MinION device, is the only sequencing technology to directly sequence an actual strand of DNA. Every other technology sequences incorporation events into a template strand (including Sanger, Illumina, Ion and PacBio) – and invariably those incorporation events involve the canonical bases, A, G, C and T. However, in nature, DNA is much more complicated than that – there are base modifications and base analogues. The MinION (and other ONT sequencers) is the only sequencer that directly detects those modifications and analogues. However, what we do when we “base call” the raw ONT data is to compress it from natural-DNA-space into canonical-AGCT-space, and whenever we compress we lose signal, and that lost signal turns up in the system as noise – as so-called “error”. People talk about the error rate of the MinION being around 10% – but not all of it is error, some of it is signal, signal for something we don’t quite understand yet so we’re interpreting it (wrongly) as AGCT.
That’s one of the exciting things about nanopore sequencing that no-one is talking about. Oxford Nanopore’s sequencers could possibly reveal a whole new alphabet for DNA that we didn’t know about before – and my bet is that it’ll explain some of what we currently struggle to understand in genetics and genomics.