IDBS Data Management Blog

The battle has long raged over the impact of nature (in the form of genetics) vs Nurture (in the form of environmental factors) on an individual’s susceptibility to disease. Clearly both play a huge part in deciding the expressed phenotype, but scientists always struggled to explain the variation in phenotype found between identical genomes even in the same lab conditions or between twins raised in the same household.

The reason for these variations may well be due to the unknown purpose of large sections of DNA previously believed to be ‘Junk’ (also known as Dark Matter). New research shows that 80% of the genome is now biologically relevant as opposed to the 2% of protein coding genes that were previously the regions focussed on.

These findings were identified by the Encode project (The Encyclopaedia of DNA Elements), which recently published 30 connected open access journal papers based on the work of 400 scientists from 32 labs in the UK, US, Spain, Singapore and Japan. Started 5 years ago the project has cost $288 million and was set up to explain the findings of the 2003 Human Genome Project, which highlighted only 2% of genes were involved in producing blood, bone and tissues. The work was based on more than 1600 experiments and 180 different cell types.

The project identified four million gene ‘switches’ or regulatory genes, which are areas of DNA that control when genes are turned on and off in a cell and hence how much of any particular protein is produced. It was of particular interest that these switches were often not located close to the gene encoding regions of DNA, explaining the assumption that these other regions were Junk. This had been questioned for some time has and now been proved incorrect.

It seems regulatory genes are of significance for rare diseases, such as Crohn’s disease, as well as more common diseases such as cancer. Considerable early excitement surrounded mistakes in single gene or monogenic disease such as sicklecell anaemia, but the complexity of human biology has proved that the majority of disease is polygenic. The impact of mistakes in regulatory genes is much more significant and is suspected to be 5-10 times more impactful than mistakes in coding genes. For example, cancer defects in 20 regulatory genes surface repeatedly in 17 major cancer types, providing new avenues for drug targets and personalized treatments.

Use of these new findings in medical treatment is still a long way off. This project demonstrates why basic, fundamental research is key to understanding the building blocks of life. As we continue our journey into the mysteries of human existence and disease susceptibility, the incredible foundation of our lives that is DNA continues to amaze us with its sophistication and complexity.

Friday January 20, 2012 was a proud day for the Healthcare team at IDBS as our new US Healthcare Center of Excellence was opened by Massachusetts Governor Deval Patrick in front of a crowd of local dignitaries, press and analysts, customers and, of course, our employees.

New gene sequencing technologies have – in the space of only 12 years – reduced the cost of sequencing a human genome from $3bn to $1000. To apply this data to clinical decision support requires new approaches to data management and understanding of genetics in the clinic. Our translational medicine solutions provide an enabling capability.

We see tremendous opportunity for Massachusetts and the rest of North America, as a result of the Meaningful Use Program, to advance scientifically and clinically from the growing availability of electronic medical records, but clinical and genetic data needs to be pulled together and made consumable by those who can take action for the benefit of patients.

Forward-looking organizations we speak with are looking for ways to use data from the clinic to accelerate research and then to apply the genetic and genomic understanding back into the clinic. With our ground breaking new systems, such as the ORIS project at King’s Health Partners, we are delivering this critical piece of the personalized medicine puzzle.

We believe it is critical to unite diagnostics, pharmaceutical, academic centers and now hospital environments to create a collaborative genomically-centered ecosystem that is focused on improving patient care and research. Our new Center of Excellence is the hub around which we are building these systems in the US.

2012 may not be the year that genetics is routinely used in making clinical decisions in every hospital but it promises to be a pivotal year for personalized medicine. The rapidly dropping cost of genome sequencing, now around $4000 per person and the growing availability of electronic patient data is providing a huge opportunity to improve patient outcomes and reduce the incidence of adverse drug events. In Minnesota, US, the Mayo Clinic has begun a study to systematically sequence every patient, with a parallel study testing genetic variants associated with drug metabolism. Both studies will be used to drive the routine use of genetic data in clinical decision-making and will enable a better understanding of the impact on cost and effectiveness of care.

Major initiatives in the UK, such as the Cancer Research UK Stratified Medicine Initiative, are routinely collecting patient and genetic data and the Technology Strategy Board is funding development of low cost genetic screens to be used by the NHS, as well as funding work like IDBS’ Acropolis project that will enable cloud-based collaborative research projects to be run on genetic and patient data.

We await the outcome of these projects with much excitement and, based on the growing number of requests to support clinical use of genetic data in addition to our translational research capabilities, we expect to be very busy in the next 12 months.

I read with interest yesterday’s report in the Lancet highlighting the spiralling global costs of cancer treatment, with 12 million people diagnosed with cancer worldwide costing £185bn ($295bn) per year. The report goes on to say that most developed countries are spending between 4% and 7% of their healthcare budgets just on treating cancer.

The complexity of the market is partially to blame for this growing expense – there were 35 approved cancer drugs in 1970, now there are nearly 100, not to mention the additional imaging and biomarker options that are increasingly available to better diagnose disease and monitor treatment efficacy.

We all know that successful, affordable treatment of cancer requires analysis of patient data to compare treatments, side effects and outcomes. What this takes is access to high quality data about a patient’s medical history, treatments and lab results. This is a significant data integration challenge requiring data extraction from multiple systems and clinically orientated integration of that data. Importantly appropriate pseudonymisation of patient records is also vital in using such information for research purposes.

This is still a major problem for Healthcare organisations, governments, payers and providers. Here’s a typical question we need to be able to answer today:

“How many patients with Triple Negative Breast Cancer were treated with Cytoxan and Taxol and what are their outcomes, ethnicity, exercise, drinking, smoking, and dietary profiles? And then let’s look at their genomic profiles.” 

Access to this type of data and analytics, such as Kaplan Meier survival curves, is essential to improved outcomes for cancer patients.

Too often though this is just too hard, because it is a task of epic proportions, pulling data together from files and basic spreadsheets.

We can all celebrate the success of HER2 tests for Herceptin and KRAS for Vectibix, in fact the report mentions a Japanese KRAS study that showed a £32m ($51m) per year saving for treatment of colorectal cancer using this test. However, Personalised Medicine is still a long way off, and while IDBS is helping advance these capabilities, we are also able to support more immediate needs to improve treatment selection and outcomes.

Here at IDBS we are actively supporting the integration and analysis of patient data with many of the leaders in this field of study, including King’s Health Partners in the UK and Windber Medical Center in the USA. Our systems enable clinicians and clinical researchers to quickly select groups (or cohorts) of patients and see a timeline of their diagnosis, treatment, risks and outcomes. This is enabling technology for clinicians worldwide and more importantly for today’s and tomorrow’s cancer patients.

I’ve really enjoyed seeing the Cancer Research UK Stratified Medicine Programme getting so much coverage around the globe. This initiative will blaze the trail for the wider adoption of genetic testing to support diagnosis and treatment of various cancers including breast, colorectal, lung, prostate, ovarian and skin cancer.

The 2 year program will see 9,000 samples and associated clinical data systematically captured and genetically tested for known cancer variants with a view to building a comprehensive warehouse of cancer data. This will then form a research resource to better understand the genetic basis for diagnosis and disease treatment, and in the future support clinical decision-making.

The Cancer Research UK project is part of a larger Stratified Medicines Innovation Platform funded by the Technology Strategy Board and other bodies to advance personalised medicine in the UK.

We at IDBS are proud to be leading one of these projects, designed to support industry and academic collaboration in stratified medicines based on high quality, longitudinal patient information and associated genetics. The Acropolis project will focus on the secure infrastructure to analyse and share this data, leading to improved disease understanding and patient outcomes.

We wish the project team well because this is by no means a trivial undertaking and highlights many of the difficulties faced by academic medical centres around the world in bringing together critical data to support translational medicine research.

The project team face many challenges in bringing these disparate data sets together, not least of which is capturing patient data from the clinical systems it is stored in. This information is frequently distributed across electronic medical records, laboratory systems, PACs and cancer information systems requiring sophisticated informatics to extract the source data and format it consistently. Information governance and protected health information compliance are also key areas to address as is integration with biobanks and incorporation of genetic tests results from standardised procedures.

We will be cheering our sister project on and continuing to provide support to the Cancer Research UK team as we begin the journey towards personalised medicine in the UK.