This year’s report, ‘Generation Genome’, from the UK Chief Medical officer, Professor Dame Sally Davies, emphasises the important role of genomics for transforming the future of our healthcare system. The CMO’s annual 2016 report sets out current approaches and future challenges for fully implementing genomics in a clinical setting.

We chat to Prof Philip Beales MD FRCP FMedSci, Congenica’s Medical Director and an expert contributor to the report, who shares his thoughts on what it means to be the generation genome whilst also highlighting what we still have to achieve to ensure genomics medicine benefits patient care.

What is the importance of this report to UK healthcare?

We have seen major advances in the field of genomic research over the last decade. The use of sequencing technologies to study the DNA of large numbers of individuals has helped scientists learn more about the genetic causes of disease, to identify potential risk factors and to help provide firm diagnoses where it may not have been previously possible. Genomics is increasingly on the radar for general healthcare and we are seeing the beginning of the movement of genomics into mainstream healthcare.

What are the challenges to those in genomics healthcare today?

The report rightly states that there remain several genetic diseases for which we still haven’t categorically identified the cause. A major challenge in defining these orphan conditions is the complexity of DNA: billions of bases (“letters”) make up one patient’s DNA (“genome”). Spelling differences in a genome, known as genetic variants, are what separate us from each other; they are what make us unique. Sometimes these changes can cause disease, but identifying exactly which variant(s) in the DNA are responsible can be a complex process and is a major bottleneck in bringing genetic data to the clinic.

Having access to the genomes of more people will increase our understanding of the consequences of genetic variants. The ever-decreasing cost of DNA sequencing means it is now possible to achieve this. Projects such as the Deciphering Developmental Disorders (DDD) study and the 100,000 Genomes Project aim to sequence (decode) many individuals with rare disorders to provide accurate genetic diagnoses. Both projects are highlighted in the report as examples of how the UK is leading the field in utilising genomic data for clinical benefit. The DDD study, led by Congenica’s Scientific director, Matt Hurles, has leveraged the combined expertise from the NHS and the Wellcome Trust Sanger Institute to utilise genomic technologies in identifying genetic causes of developmental disorders and providing diagnoses for the families involved. Importantly, the data is responsibly shared to improve diagnostic outcomes worldwide.

The 100,000 genomes project, of which Congenica is a partner, is another UK-based large-scale genomic project. In this project, every single base in a DNA molecule is being sequenced using a technology known as whole-genome sequencing. Having access to every base in the genome of each patient has the potential to considerably improve diagnostic yield (the ability to pinpoint the cause of a disorder). The aim of the 100,000 Genomes Project is to provide diagnoses where this has previously been missing and in addition to better understand the genetic basis of malignant cancer in order to move towards a more personalised medicine approach.

More data, however, brings with it more challenges. Not only is there a real need for comprehensive and efficient analysis of genetic data but how this vast amount of genetic data can be computationally stored is not yet known.

What does this mean for the future of clinical genomics?

Leading on from the report, there are still a number of questions that need to be addressed. Specifically, who will take responsibility for storage, analysis and interpretation of sequence data is not yet clear.

Genomics England’s 100,000 Genome Project, alongside partners including Congenica, are beginning to address these issues. Specialised analysis platforms are needed to make variant interpretation more efficient and more cost effective. Here at Congenica, we facilitate the shift towards genomic approaches becoming mainstream in the clinic by providing streamlined interpretation platforms. Sapientia is part of the pipeline for analysing the entire genome of an individual (known as whole genome sequencing) and screening variants to generate a list of potentially disease-causing mutations. Sapientia enables clinicians to both analyse and consolidate large amounts of data to enable them to make informed decisions about the diagnosis of a patient based on the available genetic data.

The report highlights the importance of genomic analyses for rare disease and cancer but eventually, we hope to increase our understanding of common complex diseases such as diabetes and asthma. These disorders are caused by many different variants combined with environmental and lifestyle factors, making it complex to identify not only the disease-causing variants but also the combination in which they act. We have already learnt a great deal from research in these areas but future DNA analysis of much larger groups of patients will further help our understanding of the causes of such complex disorders.

Other areas will benefit from advances in genomics but also bring additional challenges. For example, in rapid screening for acutely sick children in intensive care, as with the Rapid Paediatric Sequencing (RaPS) Project at UCL Great Ormond Street Institute of Child Health, fast and accurate genome analysis is needed. It is imperative to focus sequencing technologies on identifying variants that have a high penetrance (a high chance of causing disease) and those that are currently treatable. We must develop the best approaches for reporting actionable genetic findings to patients and their families.

Ultimately, to fully establish genomics as a leading tool in healthcare, we need to focus on maximising the benefit to patients given the information available to us.

Philip Beales will be speaking in a roundtable “Precision Medicine: Advancing Patient Care through Genomic Data” at the Precision Medicine World Congress on 21-24 August 2017 in San Diego. Find out more about the conference here.