Dr Hurles was Principal Investigator of the Deciphering Developmental Disorders (DDD) study, established between the UK National Health Service and the Wellcome Trust Sanger Institute and the largest of its kind in the world. It has analysed the exomes of around 14,000 children with severe, undiagnosed developmental disorders as well as their parents. DDD is providing diagnoses for around a third of these families and has identified clusters of affected children that have similar clinical characteristics and shared damaging genetic variants in the same gene.
To support the DDD study a powerful software platform was developed, leveraging the web portal developed as part of the DECIPHER data sharing initiative that is coordinated at the Sanger Institute and used by a global network of clinical centres. This software formed the original basis for Congenica’s Sapientia™ technology, a clinically validated genomics interpretation platform.
Need for data sharing
Even though the main DDD programme has been completed; analysis of the data is continuing and Dr Hurles says: “We are getting to a position where we can start to characterise the overall genetic architecture of developmental disorders.
“This is a significant development and will be valuable from a public health perspective. It will enable an estimate to be made of the contribution of the different types of disorder and, through extrapolation, to show how prevalent a disease is in the general population.
“Many of these genetic diseases are so rare that a clinician may see only one or two cases in their career. Being able to compare their patient’s genetics to this growing body of knowledge is a major step forward in helping consultants determine a definitive diagnosis.
“Even though this is a large study, we still need to share data,” says Dr Hurles. “There are some disorders where we only have one child with a particular condition; by making sequence variants visible through the DECIPHER web portal we have enabled clinicians to connect patients with the same mutation and as a result define new disorders.”
Open standards to support systematic clinical interpretation
Sapientia provides clinicians and scientists with the tools to interpret mutations found using gene panels, exomes and genomes and links them to clinical phenotpyes displayed by the patient. It provides a list of filtered, potential disease-causing variants that can be assigned pathogenicity by users.
Dr Hurles explains: “Developing a consistent industry-wide approach for retaining this evidence would be a very powerful way to ensure interoperability over time. For Sapientia we are keen to have an open set of standards, which would allow us to capture this information systematically from different sources.”
Dr Hurles says: “For genetic analysis to have a real outcome in precision medicine we need to have common ways to communicate that don’t require clinicians to have specialist knowledge. Improving consistency and data sharing is key to this and these are the principles we are using within Sapientia.”
Congenica will host an Education Event at the annual meeting of the American Society of Human Genetics on October 20th from 13:00-14:30 in Room 9 of the East Building of the convention centre. The symposium will include talks from clinicians
• Dominic McMullan FRCPath, Consultant Clinical Scientist, Head of Germ-line Programme, Birmingham Women’s Hospital NHS Foundation Trust
• Dr Simon Ramsden, Section Head of Constitutional Genetics,Manchester Centre for Genomic Medicine
• Dr Hywel Williams, Senior Research Associate, Great Ormond Street Institute of Child Health, University College London
They will also be present in the main exhibition hall, at exhibition stand #230.