February 24, 2012

Oxford Nanopore: A new meaning for Hole Genome Sequencing?

Two weeks ago I asked what Oxford Nanopore Technologies (ONT) was up to, and one week ago that they introduced their two new sequencing devices at the AGBT conference. This week, I review the press reactions in the seven days since ONT's announcement.

Share price development of leading sequencing companies on Friday, February 17th, when Oxford Nanopore introduced their new sequencers. Complete Genomics, Illumina, Pacific Biosciences, Life Technologies. For comparison, Nasdaq and Dow Jones.

ONT's $500-$900 tiny minION sequencer made it into several mainstream news outlets, especially in the UK, where the company is based. Coverage of ONT's announcement appeared in the Financial Times, the Guardian, and Nature. In the US, the ONT announcement made it into the New York Times.

The best technical summaries come from blogs, including Pathogens: Genes and Genomes, Core Genomics, and Omics! Omics!.

ONT is the first company to market nanopore sequencing, but it is unlikely to stay the only one for very long. Bio-IT World published information on rival nanopore sequencing company Genia Technologies, which plans to launch its device in 2013. Two other companies that are working on similar devices are Noblegen and Nabsys, promising a healthy dose of competition.

February 17, 2012

Who are the sequencing superpowers?

As with many other things, the United States are the world leader when it comes to sequencing capacity. There are more sequencing machines in the US than in the next ten countries combined. However, this is not a great surprise, as the US expenditure on Research and Development (R&D) is also much higher than that of any other country.

The question I'm asking here is how the sequencing capacity of US and other countries compares to their R&D expenditure.

Number of DNA sequencing machines for each $1bn spent on R&D

I interpret the resulting numbers as a proxy of how important sequencing is compared to other R&D activity.

Clearly, Australia is punching above its weight in terms of sequencing capacity and considering its research budget, followed by the UK.

In my opinion, the more interesting observation is the low number (34) of sequencers in Japan, compared to that country's vast research expenditure ($144bn). Seems like any Illumina salesmen reading this should book their next flight to Tokyo now.

Some notes on methodology

The number of sequencing machines per country comes from a website created by James Hadfield and Nick Loman. The data relies on self-reporting, and is unlikely to be entirely accurate.

Data on R&D expenditure by country comes from reports by Battelle and UNESCO. I included only countries with 10 sequencers or more, and for which R&D expenditure from 2010 or later is available. I made no distinction distinction between sequencers, treating a Pac Bio the same than an IonTorrent.

I'd also like to thank Saeed Al Turki for a discussion leading up to this post. His country, Saudi Arabia, would probably beat Australia by a wide margin on the chart above. I decided against including it, as no recent R&D expenditure data is available.

February 10, 2012

What's Oxford Nanopore up to?

"With Oxford Nanopore's Technology, it may well be possible to sequence a genome for less than $100". This is was what Graham Richards said when he gave a talk here in Cambridge last October. He should know: He founded the Technology Transfer office in Oxford, which has been involved in Oxford Nanopore Technologies (ONT) from the start. He thinks that the company could be the first billion-pound business to be spun out from Oxford University. A recent valuation is already coming close with $1bn.

So far, ONT has not exactly been open about the specifics of its sequencing technology. This is likely to change very soon. On February 15th, the annual Advances in Genome Biology and Technology (AGBT) kicks off in Florida, and ONT is expected to make an announcement. A press release on ONT's website promises first sequencing data and a demonstration of "disruptive features". 

ONT is working on two types on nanopore sequencing technology at the same time. In both cases, nucleotides are electronically identified as they pass through a protein nanopore. The difference between the two technologies is that in strand sequencing, the whole DNA molecule passes through the nanopore, whilst in exonuclease sequencing, an enzyme located in front of the nanopore cleaves nucleotides off the DNA one by one, which then pass through the nanopore individually.

The technology presented at the AGBT conference will be strand sequencing. It is unclear what the status of the exonuclease sequencing is, and whether ONT plans to take it forward.

Any guesses what we can expect from Oxford Nanopore at AGBT, and in the next few months?

February 2, 2012

PGD: The third way?

Apart from prenatal and carrier tests, which I discussed in my last two posts, there is a third option: Preimplantation genetic diagnosis (PGD). Here, the mother's eggs are fertilised in a test tube, just like in standard in virto fertilisation (IVF). The genotype of the resulting embryos is determined, and those that are likely to develop disorders are screened out. Only one or two embryos that are judged to be least likely to develop a disorder are implanted into the mother's uterus and allowed to develop further.

Currently, most IGV clinics select embryos based on factors such as size and healthy appearance. There is no company that I could find during 15 minutes of googling that offers a sequencing-based PGD solution, and only two that provide an array-based solution: BlueGnome and Natera.

Sequencing-based tests are more common for prenatal diagnosis, but currently only detect trisomies. There are fewer companies marketing PGD tests than carrier or prenatal tests. Source: Genomeweb.com and Company websites

This is surprising, as such technology would in principle allow screening for a similarly large number of disorders than carrier tests, and even positive screening, as imagined in the film Gattaca. The most likely reason for this lack of competition is in my opinion that ethical and technical hurdles remain.

An alternative explanation is that the PGD market is severely limited by people preferring to make babies the traditional way.