NEURO-GENSEQ - Informatics interrogation for rapid precision genetic diagnosis

Congenica and FutureNeuro have announced the first stage of their ground-breaking partnership to develop new, automated tools to assist in the diagnosis of epilepsy, whilst integrating them with Ireland’s Electronic Health Record (EHR) system.

The partnership will develop a cutting-edge clinical decision platform for epilepsy, harnessing the power of Congenica’s clinical genomics analysis software, Sapientia, to better target and diagnose epilepsy in patients.

Run over two years, the project will operate out of the FutureNeuro lab in Dublin, which is an SFI Research Centre dedicated to developing new technologies and solutions for the treatment, diagnosis and monitoring of chronic and rare neurological diseases.

Congenica will develop new tools that will come together to create a diagnostic support platform spanning the entire workflow from DNA sequencing to integrating the final data with the Irish national electronic health record (EHR).

The first stage of the project will centre upon the transfer of numerous epilepsy exomes and genome-wide association study (GWAS) datasets, into Sapientia. Further data will be uploaded in the form of more GWAS and whole exome sequence (WES) datasets, all of which will be available to the clinical scientists throughout their research, combined with Sapientia’s existing knowledge base of high quality epilepsy data.

Security of the data will be ensured by Sapientia’s own robust, secure cloud-based environment, which encrypts all data and connections both in transit and at rest, but also by careful collaboration between FutureNeuro’s and Congenica’s in-house quality control experts.

Ant Rogers, Head of Bioinformatics at Congenica, said: “The ultimate goal of the project will be the development of a bioinformatics pipeline within Sapientia to detect somatic mutations in epilepsy, specifically malformations of cortical development (MCD), which are an important pathological feature of the condition. In fact, MCD’s are thought to be the root of as much as 40% of refractory childhood epilepsy.”

“Presently, the tests to diagnose epilepsy, such as EEG’s, CT scans or MRI’s amongst others, are slow, inaccurate and only available or applicable after someone has started experiencing seizures, which in many cases may be too late. We are very excited about the new project with FutureNeuro SFI Research Centre and what these breakthroughs could mean for patients and their families around the world.” He continued.

In the long term, the project will see Sapientia, which was born out of a pioneering research project at the Sanger institute, being enhanced to help clinicians and geneticists interrogate DNA sequences for somatic epilepsy in a clinical context. These enhancements will be integrated with the Irish EHR and will be crucial to developing diagnoses and treatments for patients with neurological conditions.

David Henshall, FutureNeuro’s Centre Manager, said: “FutureNeuro brings together an exceptional team of scientists, clinicians and other experts to address the urgent needs of patients with chronic and rare neurological diseases such as epilepsy and motorneurone disease. In a globally unique way, the Centre will undertake cutting-edge research on diagnosis and treatment of neurological disorders that leverages the emerging electronic healthcare infrastructure in Ireland. With our industry partners and hospital network, we can more quickly translate research into effective diagnostic supports, treatments and monitoring systems that will benefit the lives of patients living with these debilitating and often devastating conditions that impact more than 700,000 people in Ireland.”

Epilepsy affects more than 50 million people worldwide, making it one of the most common neurological conditions. Though it can be managed, the condition can be particularly damaging to children who may only display symptoms upon their first fit, which carries a high potential risk of brain damage to the patient. It is in the early diagnoses of such cases that the project would see its greatest impacts as the first fit carries the highest risk of catastrophic consequences.

Dr. Charles Steward, Congenica’s scientific lead on the project said: “In the future, the work we do will help establish if a child has a de novo mutation or not, meaning that recurrence risk is low in other children. It will help to allow prenatal diagnosis for future children and to tailor treatments, such as drug repurposing, based on a disease defined by a gene’s erroneous sequence. Furthermore, when a patient is referred to a clinician, there will be

much richer data sources to inform on the consultation. For example, these would be things like electronic health records that integrate results of genomic sequencing with other data sources, such as MRI.”

Ireland’s science strategy, known as innovation 2020, aims to build the total investment in research and development, in both the public and private sectors, to 2.5% of their gross national product (GNP). SFI announced in May of this year that it will invest €72 million over the next six years in four new world-class SFI Research Centres in Ireland.

SFI’s Director General, Dr. Mark ferguson, said: “Our existing 12 SFI Research Centres are outstanding international examples of applied and basic combined (ABC) research. They are making important scientific advances, enhancing enterprise and industry, developing critical skills, supporting regional development, and enhancing Ireland's international reputation. They are drivers of Ireland's increased rankings in research and innovation over the last number of years. They are also an important engine for the economy; companies engaged with the SFI Research Centres are located all over Ireland and the world. The commitment of industry and academic bodies to come together to develop these new SFI Research Centres clearly demonstrates the potential economic and societal impact of the planned research.”