July 27, 2012

How useful is sequencing for forensics?

Between 2007 and 2009 police in Germany were frantically looking for a criminal. Although her identity was not known, it was clear that she was dangerous: DNA evidence from 40 crime scenes, including several murder scenes, could be linked to her.

Despite immense efforts lasting more than two years, they did not succeed. Eventually, they had to admit that the reason why they had found DNA from the same woman in all those crime scenes was that the cotton swabs used in the investigation were all contaminated by the same cotton swab factory worker.

This episode of forensic history illustrates how much law enforcement has come to rely on DNA evidence. The centrepiece of this effort are national DNA databases, which have acronyms like CODIS (USA), NDNAD (UK), or  FNAEG (France). Each of those databases contains millions of unique DNA profiles.

Whilst DNA is central to modern forensics, DNA sequencing is not: The profiles in the databases are obtained using capillary electrophoresis of polymorphic loci called VNTRs. Is this likely to change with the arrival of more affordable sequencers?

 
Arthur Eisenberg, who established one of the world's first forensics labs, thinks so. In a recent interview published on Genomeweb, he envisages a future where all forensic DNA testing is done using sequencing.

More widespread use of sequencing in forensics could have a number of benefits. Firstly, sequencing would return information on DNA polymorphisms other than just VNTRs. This includes SNPs, which are much more common than VNTRs. SNPs are informative of traits like eye colour, hair colour, and race, and could be used for facial composites (although this would not be legal in some countries, including Germany).

Another advantage of sequencing is that it can be applied to a wider range of forensic samples than VNTR profiling. Shed hair is recovered from a lot of crime scenes, but cannot be analysed using VNTR profiling because it usually does not contain nuclear DNA. It does however contain mitochondrial DNA, which is already used for forensic investigations.

A major challenge for sequencing is backwards compatibility. Existing VNTR-based forensic databases already have millions of entries, which are not easily comparable to the output of most next generation sequencing (NGS) machines. The reason is that NGS sequencers can typically only read 100-200 bases at a time, whilst for gaining reliable information on VNTRs read lengths of 400 bases or more are required. This is likely to become less of a problem in the next few years, as read lengths increase.

Another remaining challenge is that NGS is not sufficiently reproducible to be admitted as evidence in a court of law. The same barrier exists for the widespread adoption of NGS in the clinic, where reproducibility is essential as well, but cannot yet be demonstrated for NGS-based tests either.

In summary, the hurdles for the widespread adoption of DNA sequencing in forensics seem to be technical, and solvable.

If you have a view on whether sequencing has a future in forensics, please do not hesitate to post your comment below.

July 20, 2012

How is commercial sequencing getting on?

For DNA sequencing to fulfil its promise, it has to be become more than a tool of academic research. It has to enter the clinic, and eventually other areas where it can prove its worth, such as forensics or hygiene monitoring. How far along this path is it?

The graph below partly answer this question. It shows the twelve for-profit companies with the largest number of next generation sequencers.

The twelve for-profit companies with the most next generation sequencers. BGI has aspects both of a for-profit business and an academic research centre. Data from Omics Maps

Compared to the large academic sequencing centres like the Broad Institute with its 101 sequencers or the TGI with its 62 devices, the private sector is far behind in terms of sequencing capacity. The only exception is the BGI, which is somewhere in between a for-profit business and an academic sequencing facility.

To me, the encouraging thing in the graph above is the diversity of business models behind the companies. Although businesses providing sequencing services dominate (the BGI, Macrogen, DNAVision, Shanghai Biochip, Beckman Coulter GenomicsGATC, Takara, and Genotypic fall into this category), there are also agribusiness companies (Monsanto and Keygene) and health care providers (the Mayo Clinic and SAIC-Frederick). This indicates that sequencing is well on its way to leave its academic cradle and move on.

Note

The graph above is based on Omics Maps data from January and the figures have changed since then. Specifically, Source Bioscience (UK) and Fasteris (Switzerland) also have four sequencers and should therefore be shown alongside Genotypic. Expression Analysis (USA), which is owned by Quintiles, may have 12 NGS devices, and DNAVision may have sold two of their sequencers (see comments below).

July 13, 2012

What is going on with Canada?

Of the 8 million inhabitants of the Canadian province of Quebec, 6 million can trace their ancestry back to a founder population of only a few thousand settlers who arrived from France in the 17th century. This means that Quebec has a relatively homogeneous population, making it an exciting place for anyone trying to find genes associated with disease.

However, the only commercial attempt to capitalise on this founder population was by a company called Genizon, which failed last year. Genizon's approach resembled that of DeCODE, whose discovery of a variant apparently protecting against Alzheimer's disease made headlines this week. Whether this success is enough to rekindle interest in Quebec's founder population is questionable.

So what about the state of genomics in Canada as a whole?

In other countries, they paint their flag on pickup trucks and airplanes

Academic research in the field is relatively well financed. A lot of the funding comes from Genome Canada, a federal organisation that was established in 2000. It pays for numerous large-scale sequencing projects carried out in Canada, often via one of its regional centres such as the the McGill University and Génome Québec Center in Montreal.

Around half of the funding of Genome Canada comes from the federal government. The other half comes from the provincial governments, international funding bodies, and other sources. Since its inception, Genome Canada has received around C$1bn in federal funding, which is equivalent to C$90m per year. According to the recently announced federal budget, it will have to make do with much less soon: For the next two years, it will only receive annualised funding of C$30m.

How about the private sector? According to Omics Maps, there are currently no businesses running next generation sequencers in Canada. This means that despite large investments in genomics, no large for-profit sequencing service providers have emerged yet.

This does not mean Canada is a desert when it comes to genomics businesses: For example, GenoLogics produces laboratory information management systems (LIMS) specifically for sequencing and genomics, SQI develops diagnostics based on microarrays, and DNA LandMarks supplies genomics research services to the agricultural industry.

There will be more

This post is a part of a series on genomics in different countries, which has already covered France, Germany, and Japan. In the next few months, I will also cover Britain, China, and, if I am brave enough, the United States.

July 6, 2012

Is the NGS market a duopoly?

There are plenty of examples of two organisations dominating a market: Airbus and Boeing in passenger aircraft, Pepsi and Coca Cola in soft drinks, Microsoft and Apple in operating systems, Democrats and Republicans in American politics.

In this post, I ask how close the next generation sequencing (NGS) market is to being dominated by the Illumina and Life Technologies duopoly.


The size of the NGS market in 2011 was around $1bn, according to several industry sources. There are six companies that are currently active in the market. In decreasing order of NGS revenues, these are Illumina, Life Technologies, Roche, Complete Genomics, Pacific Biosciences, and Intelligent Bio-Systems/Qiagen.

Three of those companies - Complete Genomics, Pacific Biosciences, and Intelligent Bio-Systems - have revenues that are negligible compared to the size of the overall NGS market. Their combined sales amount to less than 3% of the total, and current trends do not indicate rapid growth for any of them.

Estimating the market share of the other three companies is trickier, as they also have business outside of sequencing. Neither of them breaks out its NGS revenues in its financial statements.

Based on the financial information that is available, Roche probably earned revenues of less than $100m from its 454 sequencing technology in 2011. This would be equivalent to 10% of the market or less, and is set to decline even more if recent trends are anything to go by.

This leaves Illumina and Life Technologies commanding at least 87% of the market together. Illumina is the clear leader with a market share of around 60%, which leaves around 27% for Life Technologies.

Nevertheless, the dominance of Illumina and Life Technologies looks precarious. As I mentioned two weeks ago, there are a dozen companies scrambling to enter the market, and some of them are working on rather disruptive technology.