Keeping up with genomics

It is among one of the most ambitious scientific programmes ever undertaken - the human genome project has started to revolutionise the way we think about human biology and medicine. The discipline of genomics is developing at a rapid rate - here Dr Amanda Collis tells us what’s new in genomic technologies

It took 13 years for the human genome project to be completed, at a cost of billions of pounds, and using the most powerful tools available at the time. In the years since its completion in 2003, the technology for sequencing has taken huge leaps forward in efficiency and affordability – it is now possible to sequence an entire human genome in under a week and at a cost of only a few thousand pounds. New technology has meant that genome sequencing is now an efficient and commonly-used tool, which is increasingly affordable.

This progress is thanks in no small part to technology developed on the basis of Biotechnology and Biological Sciences Research Council (BBSRC)-funded work by Professors Shankar Balasubramanian and David Klenerman, at the University of Cambridge. Work that led to the establishment and subsequent sale of spin-out company Solexa Sequencing whose sequencing platform, now sold by US-based company Illumina, reduced the time taken to sequence a genome by around 10,000 times.

BBSRC recently carried out a review of these so-called next generation sequencing technologies to examine the potential impacts that they might have on research in biosciences1. They also looked at how these technologies are currently being used and what the needs of the UK bioscience community are for access to next generation sequencing.

The review shows that this technology is working well to support the UK’s world-class bioscience base. There are new areas of research opening up as a result. For example, it is possible to look at genomes on a population level – we can sequence and compare the genomes of many individuals from the same species, which is a powerful way of identifying any genetic basis for useful or desirable traits as well as potential vulnerabilities and weaknesses. This will be particularly important in crop improvement research in the coming years as we face the need to grow more food in the context of a changing environment.

There are also some challenges to address. A strong and well-coordinated community of researchers with skills and training in mathematics and computing will be crucial to make the most of opportunities for genomics research. And a concerted effort to develop software for data analysis is also vital to ensure that the best possible value is drawn from this capability in the UK.

Professor Ottoline Leyser, University of Cambridge, who chaired the review said: "Next generation sequencing has huge potential to contribute to global issues that require solutions based on excellent bioscience research, such as food security, biofuels and healthy ageing.”
 
"At present, supply and demand for next generation sequencing access is balanced but we must monitor this very carefully to ensure that this remains the case. The review suggests that having a small number of centralised resources, such as The Genome Analysis Centre, enables us to meet demand with a great degree of flexibility – we can expand only as much as we need to at any one time in response to the needs of the whole community. But some smaller, specialised local provision is also likely to be important."

"To derive maximum value from current and future investments in genome research, we need to ensure coordination across the UK community. This will facilitate knowledge exchange; help to establish best practice; and ensure efficient use of technological and other resources. And BBSRC and The Genome Analysis Centre are in a good position to facilitate this.”

"It is also clear that training researchers in mathematics and computing so that they are able to work easily with large datasets from day one of their careers is becoming an essential part of maintaining the UK's capability in bioscience research."

Professor Douglas Kell, BBSRC Chief Executive said: “This review is very useful for BBSRC. It offers us the opportunity to ensure that there is effective uptake of this technology across our community. We can also see areas where more work and investment may be required. These may include training and skills development for researchers and also the development of new bioinformatics tools to deal with the huge volumes of data that is being produced; we often talk about the risk of ‘data deluge’ and this is a real life example where we can make a difference to ensure value is extracted from large data sets.”

The raw information from a complete human genome sequence represents data on the scale of tens of terabytes – ten terabytes of data would require over 14,000 compact discs for storage. We can solve this with high capacity data storage facilities, some of which are centralised and shared among the research community already. But just storing the data is not sufficient – researchers also need to be able to have fast access and the ability to share the information. Using a standard fast internet connection it is now possible to transfer 1 gigabyte of data in about one minute – 10 terabytes would take a week!

At present the UK is doing well with respect to data storage and availability but this will be an ever changing landscape, inevitably in the direction of greater need for capacity. To this end, BBSRC is involved in ELIXIR – the European Life-science Infrastructure for Biological Information. This is a pan-European initiative that aims to operate a sustainable infrastructure for biological information in Europe. BBSRC leads the funding strategy for this project and was pleased to welcome the news in February 2011 that funding has been earmarked from the UK’s Large Facilities Capital Fund with a view to constructing ELIXIR’s central hub at EMBL-EBI in Hinxton near Cambridge. BBSRC has already contributed £10M and the Medical Research Council, the Natural Environment Research Council and the Wellcome Trust also support ELIXIR. ELIXIR works through a network of nodes distributed throughout Europe and coordinated at EMBL-EBI. Denmark, Finland, Spain and Sweden have also already committed funds towards developing the network.

Professor Janet Thornton, Director of EMBL-EBI and coordinator of ELIXIR said: “This is the first step towards building a distributed infrastructure for biological information throughout Europe. By providing public access to the wealth of knowledge generated by the global research community, we will empower researchers in academia and industry to solve some of society’s most pressing problems”.

Professor Douglas Kell, added: “Storing and curating such data in central locations is the best and most efficient way to make them available in digestible forms. To benefit from the information they contain we have to be able to mine such data for answers to many of the current problems in chemical, molecular and sub-cellular biology, and also to apply them in the context of systems and predictive models. To this end, ELIXIR offers essential services to the modern life sciences community, and these need both to be expanded and to be maintained. Only in this way can we make the most of previous and future investments in research in biology and biotechnology.”

Genomics research has huge potential to lead to major advances in some of the grand challenges we are facing:

Food security
With a global population set to reach nine billion by 2050 and facing the need to live with environmental change, we have to increase the amount of available food in a sustainable way. To this end, easy access to the genomes of animals, plants, insects and pathogens will advance research for crop improvement and improved health, welfare, and productivity of livestock.

Healthy ageing
In the UK we are experiencing a scenario where lifespan is increasing at a greater rate than health span. Genomics research – the emerging population genomics field in particular – gives us access to understanding diseases of old age; drive earlier diagnosis; and improve disease prevention and management.

Bioenergy and industrial biotechnology
Information about certain plants, bacteria and animals can aid the development of new plant-based sources for sustainable bioenergy. And access to the very diverse genomes of plants and microbes supports research into other industrial biotechnology applications, for example, to develop alternatives to oil-based plastics, costly pharmaceutical precursors, and high tech materials.

So this is very good news for the bioscience community. Next generation sequencing technology has become a ubiquitous and efficient tool; the current supply and demand for the technology is balanced; centralised resources such as The Genome Analysis Centre are a tremendous asset; data storage and availability is also working well; and the possibilities for data intensive bioscience are huge.

It is also vitally important that the availability of equipment and data storage must keep pace with increasing use. The community of researchers must coordinate research and resources to establish best practice, facilitate knowledge exchange and derive maximum value from investments. Skilled people are required to increase our capabilities in data analysis and interpretation, which means that training will be vital. We also need improved software so that researchers no longer have to be able to carry out computer programming in order to make use of next generation sequencing data. BBSRC will be taking on the recommendations from the review and is already establishing measures to address some of the challenges.