Tricky gene mutations detected by free, fast, easy-to-use new software


Scientists have developed an easy-to-use software tool that can detect important genetic mutations that previously needed to be identified by a separate test.

The software, called DECoN, accurately and quickly detects changes in copy number of blocks of DNA called exons, by analysing sequencing data already generated to identify smaller gene changes.

It was developed by researchers at The Institute of Cancer Research, London, and the Wellcome Trust Centre for Human Genetics, Oxford.

Most gene mutations are small DNA changes within an exon. These small changes are readily detected by DNA sequencing tests.

But sometimes whole exons are deleted or duplicated. These are called exon copy number variants (exon CNVs), and they are not easily picked up by standard DNA sequencing tests.

It is vital to be able to find these variants because they are an important cause of disease. For example, about 10 percent of the BRCA1 mutations that predispose women to breast and ovarian cancer are exon CNVs. In clinical testing laboratories a separate test has traditionally been used to detect exon CNVs, but this adds considerable time and cost, and is not available for all genes.

Using DECoN (which stands for Detection of Exon Copy Number variants), the researchers took advantage of the high density of sequencing data available in new gene panels to accurately detect deletions or duplications of exons. DECoN does this automatically, adding only 30 minutes to the data analysis of up to 96 samples, and without costing any more.

The team performed extensive evaluations of DECoN including in more than 1,900 clinical BRCA tests where it successfully detected all the exon CNVs.

Study leader Professor Nazneen Rahman, Head of Cancer Genetics at The Institute of Cancer Research, London, and The Royal Marsden Hospital Foundation Trust, said "DECoN has transformed our gene testing pipeline, making it more efficient and more effective, whilst also making it much faster and cheaper. Previously we had to do an additional slow and expensive test to detect these tricky mutations. Now they are automatically detected by DECoN during the data analysis process."

Professor Gerton Lunter at the Wellcome Trust Centre for Human Genetics in Oxford, who led the software development, said "This was an outstanding collaboration for us. It is hugely rewarding to see our work having a real impact for patients."

DECoN was developed through the Wellcome-funded Mainstreaming Cancer Genetics programme and Transforming Genetic Medicine Initiative. A key element of these programmes is to develop tools that can be easily and freely used around the world.

A paper detailing the development, evaluation and implementation of DECoN was published today in Wellcome Open Research, a newly launched publishing platform that promotes fast, open publication of any useful work by Wellcome researchers.

Professor Rahman added: "It's very important to us that our work can be as impactful as possible. We have made an easy-to-use version of DECoN freely available from and the source code is also available."

"We took advantage of the new Wellcome Open Research publication platform to publish our DECoN paper. The paper was freely available for anyone to read and download within two weeks of submitting it. If we had chosen the traditional publishing route it would have taken months. We plan to use Wellcome Open Research for much of our work. We are excited about the faster, broader impact we will have through using the platform."


For more information please contact Sophia McCully on 020 7153 5136 or [email protected] For enquiries out of hours, please call 07595 963 613.

Notes to editors

About DECoN

DECoN was developed, validated and implemented by the Mainstreaming Cancer Genetics Programme and the Transforming Genetic Medicine Initiative. Both are funded by Wellcome. DECoN detects deletions and duplications of exons, which are termed exon CNVs, through analysis of next-generation sequencing (NGS) data. DECoN was first evaluated through testing 96 samples with known exon CNV status and achieved 100% sensitivity and 99% specificity. Extensive simulations were also performed which showed that DECoN performance is excellent, giving >98% sensitivity and specificity for all typical NGS run parameters. DECoN performance was also validated in a real-world setting in a clinical testing laboratory, and is now used routinely to detect exon CNVs in cancer predisposition gene testing in theTGLclinical laboratory.

Mainstreaming Cancer Genetics programme:

Transforming Genetic Medicine Initiative:


About The Institute of Cancer Research, London

The Institute of Cancer Research, London, is one of the world's most influential cancer research institutes.

Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.

The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.

As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.

The ICR's mission is to make the discoveries that defeat cancer

About The Wellcome Trust Centre for Human Genetics

The Wellcome Trust Centre for Human Genetics is one of the leading international centres for the study of the genetic basis of common human diseases.

As well as hosting high-profile groups pursuing the genetic basis of diabetes, cardiovascular, and infectious disease, and neuropsychiatric phenotypes (amongst others), the WTCHG has led the efforts of the Wellcome Trust Case Control Consortium and been responsible for advancing the application of large-scale genetic analysis to the dissection of common human phenotypes. The Centre also houses leading research groups in statistical genetics and structural biology in a lively interdisciplinary environment. The Centre provides core facilities in genomics, bioinformatics and statistical genetics, imaging, and chromosome dynamics.

Presently the WTCHG has around 470 scientists and support staff and had a £20.3M grant turnover in 2010/11. For more information please visit:

About Wellcome

Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate.

About Wellcome Open Research

Wellcome Open Research provides all Wellcome researchers with a place to rapidly publish any results they think are worth sharing. All articles benefit from immediate publication, transparent refereeing and the inclusion of all source data.

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Sophia McCully
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