Monday, 02 September 2013 at 5:13 pm

I've been attending the UK NGS/Genomic Sciences meetings since it started 4 years ago. While there are great talks every year, this year, they were able to get Clive Brown to do the keynote talk about Oxford Nanopore. For people in the NGS field, I don't think I need to say much about what Nanopore is (check out Oxford Nanopore's website for more details).

Before the talk, Clive put up a slide telling people he prefers there to be no tweets about the talk since he will be covering a great deal of technical details (which he did). I found that kind of strange. It seems like he doesn't want the content of his talk to be public? Why not just have all of us sign a NDA if that's the case? However, I will comply with his request and will not write much about the technical aspects of his talk. Instead, I will talk about what I think about Oxford Nanopore and its potential impact on the field.


Sequencers as appliances

At the end of the talk, someone asked Clive if they've tested the Nanopore on any real organisms, not just their internal test samples. His answer was basically that he was more interested about making sure the Nanopore was consistent and correct with their test sample; at the end of the day, he was making a piece of scientific instrument, not promising biological data.

It sounds like Oxford Nanopore is looking to create an appliance rather than a whole complicated sequencing system/pipeline. They want to create a product that people can plug in and use straightaway without much fuss. The machine will pump out sequencing information and what people choose to do with the data afterwards is their business. I personally think it's the right way to go.

I can imagine labs using minIon much like how a they would use a PCR machine. You want to see if your plasmid has the correct insert? Instead of cutting the plasmid and running a gel, just stick the plasmid into the minIon and check if any of the sequences that's coming out looks correct. You want to make sure you've amplified the correct product in your PCR? Stick it into the minIon and see. Apparently the samples that goes in the machine are even reusable; so no more aliquotting your precious samples just to see if they are correct. Obviously, I am discounting the sample preparation steps in these examples, but one can dream.


Streaming data

One thing I gathered from the talk is that the Nanopore can produce a shit-ton of data depending on how long you keep it running. It doesn't perform a single pre-defined run and plop a pile of data onto the computer. It continuously sequences and streams the resulting data to the user. This will have significant impact on how we analyze data.

How much data is too much? How much is enough? How do we deal with streaming data? Do we have to start constructing incremental models? For example, if we create an assembly with 1 million reads, can we somehow incrementally supplement the initial assembly with another 1 million reads as they stream in? Or are we going to have to keep re-assembling all the data?

The streaming data reminded me of an Innocentive challenge that's awarding 1 million bucks to identify organisms from a stream of DNA sequences. Given a stream of sequencing information from a metagenomic sample, when can we conclusively say whether certain populations of bacteria are in the sample? Streaming data is also something Titus Brown has been talking about for a while now.

Will the Nanopore keep re-sequencing samples as you leave the machine on? While that's great for genomes, how will that work for RNA-seq? If the Nanopore will just keep re-sequencing cDNA reads, then the expression data won't be correct. Is it possible to get it to sequencing a molecule just once? Are there are any biases in which molecules tend to go into the pore?


Privacy?

This might seem like a sci-fi cliche, but on Clive's last slide, he talked about the prevalance and ease of DNA fingerprinting if Nanopore works. I immediately imagined an Orwellian future where nanopore sequencing machines are installed everywhere that will suck up organic material (skin flakes, hairs, whatever) and then automatically sequence them and identify people nearby.

This also reminded me of an article I read a while back about banks tagging bank robbers with a DNA fog without the robbers' knowledge for later identification. In 20 years, are we going to get tagged with region specific DNA fogs and have our geographic positions tracked by these nanopore machines? I am probably just paranoid...?








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