Background: Oxford University and research in big data and drug discovery

3 May 2013

The Li Ka Shing Centre for Health Information and Discovery is launched today at Oxford University. When completed, the Centre will house over 600 scientists attempting to define disease more accurately, identify targets for novel drug therapy, utilise a wide range of health-related datasets to better understand disease and response to therapy, and realise some of the many benefits that will emerge from the genomics revolution.

Oxford University has a great deal of expertise in these areas already, and a number of examples are given below.

1) Gathering health data to give new answers
2) Genome sequencing in medicine
3) Disease surveillance
4) Drug discovery
5) Imaging

1) Gathering health data to give new answers

While the scale, speed and accessibility of big data are all new, there is a history to this type of research in Oxford. It goes back to the work of Sir Richard Doll, who discovered the link between smoking and cancer and pioneered the use of large clinical studies to give the best medical evidence.

The Million Women Study is a national study of women's health involving more than 1 million middle-aged women. Coordinated by Oxford researchers, it is the largest study of its kind in the world. Its sheer size means the study is able aims to answer many questions about the factors affecting women's health; factors such as hormone replacement therapy (HRT), use of the pill, childbirth and breastfeeding, diet, obesity and exercise.
The Million Women Study has provided the largest-ever study of smoking among women in the UK, showing that female smokers lose at least 10 years of life on average. But stopping before the age of 40 – and preferably well before the age of 40 – avoids more than 90% of the increased risk of dying caused by continuing to smoke. The study has also calculated that 6,000 cancers a year, or five per cent of all cancers in women, can be attributed to being overweight or obese.
The Million Women Study was instrumental in changing guidelines on the use of HRT, along with the Women's Health Initiative trial from the USA. Because HRT use is linked to higher rates of breast and other cancers, and of stroke, it is now recommended that HRT should be generally used for only a few years to relieve menopausal symptoms. As a result of changes in HRT prescribing, it is thought that many thousands of breast cancers may have been prevented.
http://www.millionwomenstudy.org/introduction/
http://www.ox.ac.uk/media/news_stories/2012/121027.html
http://www.ox.ac.uk/media/news_stories/2007/071107_1.html

In terms of comprehensive data on a nation's health and wellbeing, it is hard to beat UK Biobank. Half a million British adults have contributed blood and urine samples, had their height, weight and many other things measured, answered questions on lifestyle and diet, and given information on their medical histories. Led by Professor Sir Rory Collins of Oxford University, the project will also follow how the health of these 500,000 people changes over time using data from primary care, hospital statistics, and cancer and death registers.
Data will be anonymised and available to approved scientists wanting to study the causes, prevention and treatment of many common diseases. Plans are underway to image 100,000 of the participants, genotype the half million, and find out much more about their lives (occupation, environment, cognitive function, activity levels etc).
http://www.ukbiobank.ac.uk/about-biobank-uk/
http://www.ox.ac.uk/media/news_stories/2012/120330.html

A daily pill of low-dose aspirin could help prevent many types of common cancers, Oxford University researchers have found. Their studies have also raised the possibility that aspirin could also be effective as a treatment for those with cancer by reduce the chances of tumours spreading to other parts of the body. These findings were only made possible by mining the records of past clinical trials of aspirin for heart disease, and cross referencing these with UK registries of cancers and deaths.
The scientists argue that new trials are still required to confirm the benefits of daily aspirin would outweigh other risks, such as increased numbers of stomach bleeds, but that such trials should be done urgently.
Separately, the Clinical Trial Service Unit at Oxford is running the ASCEND trial of aspirin in 15,000 patients, funded by the British Heart Foundation. This prospective trial should be able to address this question.
http://www.ox.ac.uk/media/news_stories/2012/120321.html

2) Genome sequencing in medicine

The cost and speed of reading out a person’s entire DNA code – all 3 billion letters of it – continues to come down at pace, meaning it is beginning to be used in medicine. Oxford University scientists are at the forefront of such efforts, exploring how sequencing someone's genetic code can be helpful to doctors. They are showing how the latest DNA sequencing techniques can identify the causes of rare disorders, aid diagnosis, or predict responses to treatment – particularly in cancer, where the genetic changes present in the tumour can determine what treatment is best for the patient.

The first person in the UK to have their entire DNA read to identify the cause of a disease was a four year old girl. Oxford scientists, by sequencing the genomes of her family, were able to detect a genetic mutation that appears to have occurred spontaneously and caused a serious condition. Craniosynostosis is a disorder affecting 1 in 2,500 children which results in the premature fusion of the bony plates of the skull, hindering expansion of the skull and restricting brain growth. The condition requires surgery to solve the potentially life-threatening problems caused by raised intracranial pressure and difficulties with breathing. Genome sequencing provided the family with an explanation for their daughter's condition and allowed genetic counselling to be given. The parents could be told the risk of the condition would be low for any further children they might have, but advice for the daughter when she comes to thinking about having children would be very important.
http://www.ox.ac.uk/media/news_stories/2011/110803_3.html

Oxford scientists have recently introduced a 46 gene test on the NHS that can help predict how an individual patient’s tumour might respond to treatment. Mutations in these genes may be driving the growth of the tumour, and knowing certain mutations are present in cancer cells can potentially determine which treatment a patient should receive. It's the first such test using the latest DNA sequencing techniques to be launched as an NHS service, thanks to a partnership between scientists at the University of Oxford and Oxford University Hospitals NHS Trust. The researchers say the £300 test marks a step change in introducing next-generation DNA sequencing technology into the NHS, and heralds the arrival of genomic medicine.
http://www.ox.ac.uk/media/news_stories/2013/130325.html

Oxford University researchers are nearing the point of having sequenced in depth the genomes of 500 people with a range of diseases – including cancer, immunological disorders, and rare inherited diseases. This landmark project led by Professor Peter Donnelly is being conducted with Illumina, a leading manufacturer of DNA sequencing systems. The project has been designed to explore how whole-genome sequencing might be used in informing diagnosis and treatment decisions for individual patients in years to come. One example from the project is the identification of two new bowel cancer genes: genome sequencing among families with a strong history of developing the disease found that rare DNA faults in two genes were strongly linked to bowel cancer.
http://www.ox.ac.uk/media/news_stories/2011/110803_3.html
http://www.ox.ac.uk/media/news_stories/2012/121224.html

3) Disease surveillance

The recent emergence of malaria parasites that are resistant to our most effective antimalarial drug, artemisinin, is a great threat to worldwide efforts to control malaria. As a result of resistance, the effectiveness of this key drug is weakening in some parts of South East Asia, and if this resistance spreads more widely to other areas of the world it could threaten hundreds of thousands of lives. A worldwide collaboration, led by Professor Dominic Kwiatkowski of Oxford University, has just published a study showing that drug resistance can be detected and tracked by surveying the genomes of malaria parasite populations using the latest DNA sequencing technologies. Tracking artemisinin resistance from where it has emerged in a small corner of Cambodia through genetic monitoring could help guide public health measures to halt the spread of resistance.
http://www.ox.ac.uk/media/news_stories/2013/130429.html

Collecting and merging data from the field is allowing detailed maps of malaria risk to be generated – giving new understanding that is critical for targeted public health measures. And the same approach has recently given us the first reliable estimate of the worldwide burden of dengue.
http://www.ox.ac.uk/international/international_collaboration_and_research/oxfords_partnerships_in_global_health/p/public_health_patterns_of_disease/malariamap.html
http://www.ox.ac.uk/media/news_stories/2013/130408.html

Genome sequencing techniques are also able to track infections and monitor outbreaks of disease at home in the UK. Scientists at Oxford have been pioneering this approach, for example in deducing how hospital-acquired infections like C. difficile are spread, plotting the connections between TB cases in Birmingham, and were first to publish on how fast bench-top sequencers can be used for tracking pathogens. The advantage is clear: measures can then be taken to halt outbreaks rapidly or lessen the chances of spread of hospital acquired infections.
http://www.ox.ac.uk/media/news_stories/2012/120208.html
http://www.ox.ac.uk/media/news_stories/2012/121115_2.html
http://www.ox.ac.uk/media/news_stories/2012/120306.html

An example showing the value of being able to combine different sets of data, is the use of Google Earth to track the spread of typhoid in Kathmandu, Nepal. Oxford University researchers based in Nepal and Vietnam combined DNA sequencing technology and GPS signalling to map typhoid cases in Google Earth and trace the source of outbreaks. With 2013 marking the 200th anniversary of John Snow's birth, this is a modern equivalent of his work to map cases of cholera in Soho, London.
http://www.ox.ac.uk/media/news_stories/2011/111018.html

4) Drug discovery

The Structural Genomics Consortium is a public-private partnership that primes the development of new medicines for disease like cancer, diabetes, obesity, and psychiatric disorders by carrying out basic science of relevance to drug discovery.
Since it was founded in 2004, it has been working to significantly speed and scale up the process of determining the structure of proteins relevant to human diseases, generating more than 10% of the global output in this field. This is an important step in understanding how best to design drugs against these proteins. More recently, the centre in Oxford under Professor Chas Bountra has extended its work to generate antibodies and compounds that bind to the proteins – a crucial starting point in the drug discovery process.
The SGC, which includes 8 large pharmaceutical companies, is committed to place all information, data, reagents and know-how into the public domain, immediately and without restriction and without any patent protection – enabling, quicker and more efficient drug discovery by sharing the information.
http://www.ox.ac.uk/media/science_blog/111021.html
http://www.thesgc.org/about/what_is_the_sgc

While enormous strides have been made in investigating the biological pathways underlying disease, it is not a simple matter to understand which of these is most relevant or most suitable for the design of new drugs targeting the disease. It is this challenge, the new Target Discovery Institute will address. Research will focus on generating and verifying the best candidate drugs before they get anywhere near testing in patients, using the latest technologies to test large numbers of compounds in cells in the lab that are relevant to disease.
http://www.tdi.ox.ac.uk/home

5) Imaging

The Centre for Functional Magnetic Resonance Imaging of the Brain at Oxford is at the forefront of efforts to analyse data from large numbers of MRI scans of the brain. FMRIB is one of the lead centres in the human connectome project, an international effort to map the neural networks in the brain – essentially giving the brain's wiring diagram.
Led by Washington University, University of Minnesota, and Oxford University, the project will map human brain circuitry in 1,200 healthy adults, and has recently released its first major dataset. They will use this data to understand variations in people with age, gender, and genetic factors, and reveal connections to behaviour.
UK Biobank also aims to image 100,000 of its volunteers – both neuroimaging and heart imaging. This will be by far the largest imaging study ever carried out by about a factor of ten. An initial phase has recently been announced, and FMRIB will lead the neuroimaging effort.
http://www.ox.ac.uk/media/science_blog/220210.html
http://www.fmrib.ox.ac.uk/research/@@researchtheme?remote=http://www.ndcn.ox.ac.uk/research/analysis-group
http://humanconnectome.org/
http://humanconnectome.org/about/pressroom/press-releases/human-connectome-project-releases-major-dataset-brain-connectivity/
http://www.ukbiobank.ac.uk/2012/11/uk-biobank-welcomes-imaging-funding/