Sequencing DNA with Nanopores

As we have already mentioned, Daniel has recently moved his blog Genetic Future over to the Wired science blogging network. While Daniel is off flying around Europe introducing his newborn to mozzarella and skiing, I have written a guest post for Genetic Future entitled An Introduction to Nanopore Sequencing.

I have been meaning to write about nanopore sequencing for quite a while (if you don’t know what nanopore sequencing is at all, go read the post!). What prompted me to write this was a CGI video made by Oxford Nanopore that managed to sum up nicely some of the basic theory behind nanopore sequencing:

As a DNA sequencing method, nanopore sequencing is very different to current generation techniques, and it is also a very diverse field, with people working on lots of different membranes, nanopores, control methods and so on. The applications of nanopore sequencing are also pretty broad, with the potential for sequencing DNA, RNA or proteins, along with non-sequencing detection methods. Nanopore sequencing could be a real game-changer, either in the near or the more distance future.

This is what I like about nanopore sequencing; it really is a whole new world. We don’t know what nanopores will do well, and what they won’t. We know that it has the potential for massively fast sequencing; the video for Oxford Nanopore mentions “hundreds of thousands of wells”, and with an occupancy of 35% (optimum poisson occupancy) and a ratcheting rate of 50 bases/second (the sort of process speeds talked about in recent publications), we are talking about a few high quality (30X) human genomes per day, even without further speed-ups; but could machines be built to keep this number of wells running and measure them accurately at this rate? We know that the base quality is theoretically independent of read length, and with no big laser frying the enzymes, read lengths could grow to tens of kilobases or more; but we don’t know what sort of read-length limiting processes will be in play, and how well you can get around them. What sort of weird error modes will creep up from this new means of measuring DNA? What sort of bioinformatic techniques will need to be developed to cope with the sort of data produced? Exciting times.

Anyway, go read the Wired Genetic Future post for a somewhat less rambling introduction to nanopore sequencing.