March 30, 2012

Hygiene monitoring by sequencing - which applications?

The microbial testing market is large, and it is growing. It was worth a respectable $5.5bn in 2011. The part of the microbial testing market to which sequencing would be most relevant is the automated testing segment, which was worth $3.2bn, and is forecast to grow at an annualised rate of 8% in the next years.

Size of the microbial testing market, in US Dollar. Automated Microbial Testing is the market segment which is most relevant to sequencing technology

Last week, I theorised that the unique advantage of microbial testing by sequencing would be the ability to distinguish between harmful and harmless microbes. This week, I consider how this could be relevant to the three largest applications of microbial testing: the food industry, hospital hygiene, and water quality monitoring.

Market segments by application, Automated Microbial Testing, 2011

The food industry is the largest consumer of automated microbial tests. This market is likely to keep growing, driven by shifting industry food safety priorities, increasing regulation and increasing worldwide consumption of processed food.Common hazards such as aflatoxins, Salmonella and Listeria, that currently lead to thousands of product recalls per year, have microbial origins and could be detected by sequencing.
Sequencing is well suited to detect hospital-specific pathogens for two reasons. Firstly, a sequence database can easily be updated should newly arising pathogenic strains be identified. Secondly, sequencing can distinguish between closely related strains of bacteria, such as MRSA and the closely related but harmless and common strains of Staphylococcus aureus.
DNA sequencing may also be the ideal choice for monitoring water quality. Apart from safeguarding drinking water supplies, sequencing could also be used to monitor irrigation water supplies and environmental waters.
Other opportunities may be found in the aviation, marine, automotive and petroleum sectors, where bacterial contamination of equipment and fuel can cause problems, in cosmetics manufacturing, where microbial contamination is an important reason for product waste, and in biodefence. I'm sure there are other opportunities I have not thought of as well - any suggestions?

March 23, 2012

Will hygiene monitoring be the next big application for DNA sequencing?

Genome sequencing appears destined to become a standard clinical test. But what about applications of sequencing beyond health care?

Detecting microbial contamination is vital to ensure the safety of food, drinking water, or cosmetics, in biodefence, hospitals, and many other fields. A perfect monitoring system would be sensitive enough to quickly detect contamination by potentially dangerous microbes, and specific enough to avoid false alarms. There are reasons to believe that DNA sequencing could provide such a system.

Until now sequencing has been too expensive to be practical, but this is changing rapidly. I believe that as a result, hygiene monitoring could be one of the first commercially viable applications of sequencing outside of its traditional uses in research and the clinic.
Sequencing would be a uniquely valuable technology whenever it is necessary to distinguish between harmful and harmless microbes. For example, the bacterium E. coli is mostly harmless and can commonly be found in the gut of healthy humans. However, some strains can cause serious food poisoning and lead to human suffering and economic damage: The pathogenic O104:H4 strain of E. coli caused 50 deaths and $2.8bn in damages in Europe last summer. Distinguishing between strains is vital for many applications, and can in principle be achieved by sequencing.
Tests that detect the presence of any form of microbe indiscriminately already exist. There are also technologies that are specific for single microbial strains. Sequencing, at least initially, is more likely to be useful in applications where perfect sterility cannot be enforced, and where there is more than one microbial strain that could be harmful.

In my post next week, I will ask what the markets are for which these conditions apply, and where, as a consequence, early adoption of sequencing-based technologies for microbial monitoring is likely to make sense.

March 16, 2012

What is going on with Germany?

Germany is economically less centralised than other European countries. Unlike Paris or London in France or the United Kingdom, there is no single city that dominates business.

The same applies to German research institutions, which are spread throughout the country. This may be the reason why Germany does not have a flagship dedicated sequencing centre such as the Sanger Institute in the UK. Instead, its sequencing capacity, although similar to that of the UK, is more distributed amongst different research facilities.

One of those is the excellent Max Planck Society. Its institutes for Evolutionary Anthropology and Molecular Genetics have large sequencing capacity and use it to produce excellent research.

In the private sector, the sequencing services company GATC Biotech stands out. If you had to pick a stereotypical German company, you couldn't do better than GATC. With 150 employees it is solidly Mittelstand, it is family owned and managed, it is innovative, and it is headquartered in the entrepreneurial state of Baden-Württemberg. It is also successful: In its European market, GTAC competes with international industry behemoth BGI.

German Euro Coin

Apart from sequencing, GATC is also active in the prenatal diagnostics space. Its daughter company LifeCodexx is about to market its PraenaTest, which uses technology that is similar to and partly licenced from Sequenom's MaterniT21 test.

To my knowledge, the PraenaTest is the first commercially available sequencing-based prenatal test in Europe. This is surprising, given Germany's conservative attitude towards more controversial biotechnology. German legislation reflects this. For example, preimplantation genetic diagnosis is more tightly regulated than in many other countries.

But GATC has dealt with cumbersome legislation before. When it was founded in 1990 as Europe's first sequencing company, its name was inspired by the four DNA bases. It soon had to find out that according to German corporate law, such abbreviations are not permitted for company names.  The founders circumvented this by simply claiming that GATC instead stands for Gesellschaft für Analyse-Technik und Consulting (Society for Analytical Technology and Consulting).

March 9, 2012

The sequencing data deluge, just another inaccurate apocalyptic prediction?

Sequencing data management is big business.

The business model of companies in that space is based on the well-publicised fact that it takes a lot of disk space to store sequencing data, and that it may be advantageous for many organisations to outsource the management of that data.

Surely, this means that data storage is going to be a major issue for genomics?

I would like to argue that things may not get as bad as often feared.

First, it's necessary to explain why sequencing data currently takes so much disk space. A human genome is around 3 billion bases long, and storing it should therefore take no more than 3 gigabytes (GB). In reality, around 100 GB are needed. That's more than you could get on the newest iPad.

The reason for this is the nature of the data generated by most sequencing machines. They can only sequence segments of DNA that are no more than a few hundred bases long. As a result, each base needs to be sequenced several times to make sure that there are no gaps between segments. Another reason for sequencing bases multiple times is to make sure that the sequencing machine has made no errors.

Therefore, the large amount of data generated by sequencing is at least in part due to the limitations of currently used technology. There are four reasons why this is likely to change and why in the future less disk space may be required for store a genome:

  • Currently all sequencing data is stored. For many applications, this may not be necessary. Instead, a lot of disk space could be saved by only storing information on where the genome differs from what can be expected
  • New sequencing technologies could lead to less sequencing data being generated per genome. Lower error rates would mean that each base has to be sequenced fewer times in order to be sure that no error has been made
  • New technologies that can sequence longer fragments at a time could also reduce the amount of data generated per genome
  • Currently used data formats contain a lot of redundant information. New data formats making use of compression algorithms could save a lot of disk space

Taken together, this implies that the amount of disk space per genome is likely to decrease.

I still think that the overall demand for disk space for sequencing data will grow, but that growth will be driven by the number of genomes being sequenced, not by the storage requirement per genome.

March 2, 2012

What is going on with Japan?

Considering that Japan is one of the world's most important scientific nations, its DNA sequencing capacity is surprisingly low. There are more sequencing machines in the Netherlands or in Spain, both of which spend only a fraction of what Japan does on research and development (R&D).

In this post, I ask whether sequencing in Japan really is as neglected as this suggests, or whether the reality is less gloomy.

Is the scarcity of sequencing machines due to  Japan focussing on things other than the life sciences? Hardly: Japan is considered to rank amongst the five leading countries in the world in healthcare, medical science, the life sciences, and biotechnology. According to the OECD, there are more biotechnology companies in Japan than in any other country except the United States.

If weakness in the life sciences generally is not the reason, what causes Nippon's neglect of sequencing? The answer seems to be a recent lack of growth in the biotechnology and medical sectors, combined with a scarcity of public funding for genomics.

For example Takara, a large biotechnology company that offers sequencing services on several Illumina and SOLiD machines, has seen sales stagnate for years. The (at least perceived) lack of funding for genomics in the public sector becomes apparent from the case of Yusuke Nakamura, a highly cited Japanese geneticist. Earlier this year, he quit his positions as the head of the government's Office of Medical Innovation and at Tokyo University for the University of Chicago. Nakamura says that what he perceived to be a lack of government support for genomics contributed to his decision to leave the country.

The outlook for sequencing for Japan in not all dark. For example, Hokkaido System Science, a company that provides DNA synthesis and sequencing services, is flourishing and aims to expand internationally. And then there is of course Riken, Japan's flagship natural sciences research institute, whose impressive infrastructure includes ten next generation sequencers.

Will Japan's genomics revival come from a large government push, from the private sector, or not at all? For now, it seems impossible to tell.

Future plans

I am also considering reviewing the state of DNA sequencing in Canada, China, France, Germany, the United Kingdom,  and, if I feel up the challenge, the United States. Would there be any interest in this?