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.”

Congenica welcomes Chinese trade delegation to Cambridge Headquarters.

A delegation of eminent government and business representatives from one of China’s most vibrant and innovative cities has visited Congenica, at their Cambridge HQ, to discuss potential future collaborations as the exciting start-up expands into China.

The delegation was led by Qingdao’s Mayor, Meng Fanli, who was accompanied by representatives of the Qingdao Municipal Government, Qingdao Bureau of Commerce, the President of Qingdao’s Sino-German Eco Park, Qingdao Foreign Affairs Office and members of the Beijing Genomics Institute (BGI), the latter of whom are both a partner of Congenica and have recently opened offices in the city.

The meeting, held at Congenica international headquarters at the Wellcome Trust Genome Campus, Cambridge, focused on an overview of Congenica’s gold standard clinical genomic analysis platform, Sapientia, from the company’s President Dr. Tom Weaver. Mayor Meng then went on to speak about Qingdao's vibrant and expanding science parks, increasing foreign capital and direct investment alongside major Chinese businesses, prestigious universities and direct global transport links.

“We have made a promise to the people to increase their standards of living and we have done that, but we have more to do. People’s demands have also increased so we will promise to provide genetic testing for all newborns in Qingdao. With BGI and their partner, Congenica we expect to complete this project.” Said Mayor Meng.

Qingdao has a history of trade and innovation both internationally and domestically. With its nearby international ports and airports, proximity to North and South Korea and also major domestic hubs such as Tianjin, Beijing and Shanghai, mean that it is consistently one of the highest GDP cities in the country. Chinese internet giant Baidu has recently signed a deal with the municipal government to turn it into China’s first smart city.

The other cities receiving attention from the central government and also vying to be the location of Congenica’s Chinese headquarters are Nanchang, Jiangxi, Ningbo, Zhejiang, and Suzhou, Jiangsu.

“The UK is widely respected around the world for our research and innovation,” said Rt Hon David Willetts MP, Minister of State for Universities and Science from 2010 to 2014. “By supporting the development of innovation capacity in other countries we can make it easier for UK businesses and universities to build links with counterparts overseas. The UK Science Park Association is a good example of this. Their work with the Chinese Association of University-based Science Parks has been highly valued by the Chinese Government.”

Mayor Meng and his delegation went on to London where he spoke the following day at the Qingdao Forum on UK - China Trade and Investment. “It is very impressive to see the use of innovation in supporting long term economic growth for England. Our mission is to support the economic development of China for its people, especially healthcare, through new technologies and ideas.”

Congenica addresses genetic testing of inherited diseases at 2nd International 4P Health Summit Forum 2017 in China

Congenica has continued to embrace their global mantle as they presented at a leading Chinese personalised medicine conference, which also hosted the renowned Leroy Hood of the Institute for Systems Biology and the P4 Medicine Institute. The event was attended by hundreds of prominent Chinese geneticists, clinicians and scientists gathered in the southern city of Tonglu, Zhejiang on Nov 14th, 2017.

Dr. Bai Shizhong, President of the China Health Promotion Foundation and Dr. Zhang Shibin, Chairman of the Chinese Health Management Association Steering Committee performed the opening ceremony highlighting the growing evidence of how genetics is playing an ever increasing role in wellness and diagnosing diseases.

Personalised medicine has been growing in eminence in China as the country modernises its vast healthcare system. Combined with the declining cost of sequencing a human genome and a greater understanding of genetic basis of diseases, the country’s scientists are driven to bring together the best minds, technologies and ideas in the field of genomics.

Congenica’s expertise in diagnosing inherited diseases by analyzing patient derived genomic data was highlighted at this forum. The company’s Chief Business Officer, Dr Shikha O'Brien, presented the ground-breaking work being done by the U.K. based company utilising their gold standard clinical genomics analysis platform, Sapientia. Dr. O’Brien spoke about the prevalence of rare diseases around the world and the sheer scale of sufferers in China - estimated to be around 16 million people. She then went on to show how Congenica’s clinical expertise in rare diseases combined with the interpretation technology platform can empower China’s genetic experts and hospitals to truly make an impact on the country’s healthcare.

Dr. O’Brien, said: “We are delighted to be part of this thought leadership in China and presenting at this conference. This is an opportunity for us as a community to realize the benefits of fast moving technologies in genomics. Accurate and fast interpretation of genomic data remains a bottleneck and Congenica’s technology is addressing that gap with demonstrated success across a wide variety of applications in diagnoses of rare disease.”

Dr O’Brien presented several examples where Sapientia platform was critical in a fast turnaround with clinically actionable reports in rare disease pediatric patients for whom fast and accurate diagnosis is key. She provided additional examples where the Sapientia platform is being used in diagnostics and pharmaceutical drug discovery as well as clinical trials design using genetics based risk factors in patient cohorts.

The conference also saw a number of presentations from members of the Chinese Academy of Sciences’ Hundred Talents Project, for which Dr. Hood was a researcher earlier in his career. The project describes itself as; ‘the backbone program for attracting and training academic and technological leaders’ both from domestic graduates and those attracted back from overseas, by offering benefits and preferential treatment in their professional and private lives.

Tonglu has seen a high level of investment in recent years, culminating with the construction of the Kona Tai 4P Medical Health Industry Park amongst a number of other high profile projects. Zhu Hua, Secretary of the County Party Committee, said: “Tonglu is a new talent city with a bright future. With the concept of talent as the first resource, science and technology as the first productive force, and innovation as the first driving force, we will create the best talent ecology.”

A number of awards were also presented at the conference to outstanding Chinese scientists and entrepreneurs in healthcare and its associated fields.

Sanger Institute welcomes San Diego trade delegation

Congressman Peters addresses representatives of Genomics England, Illumina and Edico amongst others

The Wellcome Sanger Trust welcomed a US Congressman and trade delegation from the city dubbed, ‘America’s genomics capital’, for a discourse on innovation and enterprise in the life sciences, last week(18/10).

The delegation was composed of a mixture of government and business representatives from the UK and San Diego, including the city’s Regional Economic Development Corporation (SDREDC), who organised the event, Genomics England, Edico Genome, Congenica and led Congressman, Scott Peters (Dem. CA-52).

San Diego has re-invented itself over the previous decades as a 21st century smart city, embracing science, technology, engineering and mathematics (STEM) in its business, education and amenity planning and now challenges San Francisco as a centre for trade and technology on the west coast.

The two cities hold key positions in both the current life science industries and in the history of the discipline as a whole. Both were the sites of key events on the science’s timeline and home to the biggest names in the industry. They have created environments which attract lots of venture capital and are magnets for talent. Supported by high quality universities and institutes, they are perfect locations to grow spin-outs and start-ups such as Congenica.

“I think we are all impressed by the parallels between Cambridge and San Diego. Two vibrant, dynamic cities both excited about science and innovation, particularly in the genetics and STEM fields. Life sciences have $5.6 billion of economic impact in our city and that includes heavyweights like Illumina but also relative newcomers such as Edico who has proved its processor with an impressive growth trajectory through their work with Congenica.” Said. rep. Peters.

Before the Congressman spoke the gathered representatives of government and industry had heard from Prof. Joanna Hackett, Chief Commercial Officer of Genomics England, who said: “There are three groups here today who have saved a lot of lives. Congenica, Edico and Genomics England. Whole genome sequencing will become routine clinical care, our project has proved its clinical utility. Genomics England is very good at getting the patients, our population is very rich, but we need to rely on other companies to extract and interpret the data and that is where the great work of our partners such as Congenica comes in.”

Life sciences are highly prized industries for modern cities. The jobs created in these sectors tend to be high wage and knowledge intensive but still provide a highly deployable skillset. They are strong attractors of talent and drivers of education as well as having some of the highest numbers of spin-out companies to keep the market growing and diverse.

The city boasts a huge number of ultra-modern solutions such as one of the world’s largest internet of things (IoT) networks which includes smart buildings, streetlights and utility metres. The city has embraced the electric car with 727 charging stations, with a number being directly powered by solar energy and more than 14,000 vehicles on the road. All of this and future innovation is underpinned by a reinvigorated education system capped by the city's university, UC San Diego which is part of the famous University of California group that includes Berkeley and UCLA.

Rebecca Hemenway, Senior Director of New Product and Business Development at Edico Genome told the audience: “The Human Genome Project took 13 years and $2billion to give a result. Now, it's very different. In fact, we hold the world record for performing the fastest genetic diagnosis at 26 hours from beginning to end. It is very important to have a streamlined and efficient workflow and that was why we established our partnership with Congenica. We expedite and they interpret.”

Closing the talks was Congenica’s Chairman, Dr. Andy Richards, who said: “Doing something like this, revolutionising healthcare, requires real ambition. Genomics England was a brave move on the part of the UK but it has unequivocally shown that genomics can make a real difference in healthcare. As much as our sector was born of the competition between Craig Venter and the private sector against institutes like the one we stand in now. It has been collaboration which has brought us to where we are today and which will take us to greater heights in the future.”

Congenica has been expanding into new territories over recent years and have seen their first strategic appointments on both the east and west coasts of the US, with most of them being based out of San Diego. The Cambridge based company has also seen its initial appointments in China too, where they also have partner organisations in the form of the Beijing Genomics Institute.

Precision Medicine: Advancing Patient Care through Genomic Data

A fundamental shift in medical education is needed in order for doctors and patients to benefit most from advances in precision medicine and information technology. This was the consensus view from the experts at Precision Medicine Leaders’ Summit held in San Diego on the 23rd February.

During a round-table hosted by UK-based clinical genomic analysis software developer Congenica and chaired by Dr. Phil Beales, consultant physician, Professor of Medical and Molecular Genetics at the UCL Institute of Child Health (ICH), and Congenica’s Chief Medical Officer, a range of experts from across industry, government and business discussed some of the most pressing matters raised.

The key messages from the panel were the high need for education and training in all hospitals and clinics in order to keep pace with the shifting face of modern medicine, genomics, bioinformatics, and personalised medicine and to understand the changing needs of practitioners so that research efforts can meet these transitive requirements and the equally evolving role of computational sciences in bioinformatics and interpretation.

Artificial Intelligence in Precision Medicine

The delegates had heard earlier in the day from Atul Butte, PhD, Director of the Institute of Computational Health Sciences at University of California San Francisco, who is working closely with the Chan-Zuckerberg Initiative, on the growing role of computing and A.I. in precision medicine.

“Do you think there really is a place for A.I. in delivering personalised medicine, or is it all just hype?” Asked Dr. Beales.

Rourke Yeakley, “I would say ‘yes’, especially in how it can get rid of bias. One of the things we do in terms of AI is that we bring in research so it’s an integration with clinical information that’s not just based on the patient’s information and thus we get recommended treatment points. Outside of my work in the ER, I also work for an AI company and core to everything we’re trying to do is clinical decision making, specifically trying to understand how we can incorporate genomic data to influence those decisions.”

“You could even eliminate unnecessary tests, a lot of physicians would love to reduce the numbers of tests, but, they worry they may get into trouble for not running these ‘routine’ tests. However, if the AI insisted and its decisions were accepted then malpractice cases would decrease and you would see a reduction in the numbers of tests, a relief to the patient and a burden off the doctor.” Continued Dr. Yeakley.

The human brain is inherently good at recognising big patterns though not always the smaller or more subtle ones. The growths and advances in medicine over the last few decades have been aimed at increasing the amount of data and knowledge to increase the scale of patterns and stratify patients but modern advances in genomics and increasing focuses on rare diseases have brought small deviations and small patterns to the forefront. Whereas even the most experienced specialist may only be able to remember a few hundred patients and their symptoms, a competent A.I. system could bring to the fore patterns and clues from entire datasets with a fraction of the time and resources.

“I like that idea, A.I. is there to help, to support – it is not replacing anyone or anything it's simply helping out and raising the limitations on what’s possible.” Summed up Nick.

Adoption of New Technologies

The delegates went on to discuss adoption of such technologies. For instance adoption of electronic medical records in the UK National Health Service (NHS). “Explaining to the NHS why they need electronic medical records is one thing. Long gone are the days of people being born in Edinburgh and dying in Edinburgh – they need communication between the different NHS systems, especially now that they’re devolved. But, explaining the value in it rather than the cost of it can be another thing.” Said Hilda Mwangi who is a U.S. based, International Business Development Officer for the UK government’s Department for International Trade.

“In the UK, with the 100K genomes project, the only reason it worked as well as it did was because there was a mandate,” responded Nick Lench, Congenica’s Chief Operating Officer.

“But what propels that mandate?” Asked Shikha O’Brien, Congenica’s Chief Business Officer, “it’s money. Unless people see profitability in something or, at least, it equates to value for them, it’s never going to get done. The system has to show that there is monetisation on that value. What the industry needs is validated studies, so, I think it is yet to be demonstrated, this integration of all of this data put together in one seamless way that can benefit the patient. Then, that is when the NHS or organisations like the NHS outside of the UK are going to see value in it.”

“I think part of it has to come from industry and doctors and the growth of private hospitals will drive that. If the private hospitals show profitability and better healthcare because of, for example, connected records – would that push the NHS to do it?” Posited Ms. Mwangi, adding, “So, this is where industry has to step in to engage systems like this for their patients or their parts of the NHS. Sure, the conversation will come back around to cost and value but that is where companies like Congenica can come and get involved in those discussions between physicians and organisations.”

Defining the Transition to Precision Medicine

“The great thing is that we’re the generation that’s defining this transition and we can be the people that define what needs to get taught and how it will get taught. It’s not just genetics, its regulatory, its compliance, it’s the outcomes, for example, how do we handle secondary findings? It’s just so much about amalgamation of all this information.” Stated Shikha O’Brien.

“This is the transition we’re going through right now and it is about education and knowledge around genomics and how it needs to be brought deeper into the standard curriculum. This isn’t a new debate, I attended a conference last year at Stanford and the main topic there was also – ‘how education needs to incorporate more genetics’.” She continued.

“I think that’s where you have to take it into the schools and colleges. You have to educate the kids and then the kids grow up and go on to university and they’re ready for the change, some of them may even be the change. However, if you are already a physician practising primary care what’s the motivation to learn about genomics?” Said Nick Lench. “There are multiple generations involved in this.”

Dr. Beales said: “So, in many ways we’re moving beyond genomics now. We’re here at a precision medicine conference and it's more about looking at longitudinal data on individuals and applying that to their individual health care to make it personalised.”

“But where does this data go?” Asked Shikha, “does it get channelled back into clinical trials? Does it become part of something else either in the wider industry or at the specific hospital? We don’t know but when we do have this kind of data it is often a retrospective analysis. How can we be prospective about such things, especially now that we are in the genomics era? How, as a community or an industry, do we get together and bridge that gap with genomics, pharmacogenomics and pharmaceuticals to then hand that information to a practising physician in a form that can be of direct benefit to their patients or institutions?”

American Society of Human Genomics Annual Meeting 2017

The American Society of Human Genetics (ASHG) 2017 Annual Meeting took place over five days (17th -21st October) in Orlando, FL. Encompassing all levels and aspects of the industry from pure research to commercial start-ups, scientists from across the globe heard talks, took part in discussions and networked with fellow geneticists. The Society also announced its annual prize winners and introduced a number of leading geneticists from the developing world.

The biggest name of the week was that of Microsoft co-founder and trustee of the Bill & Melinda Gates Foundation, Bill Gates, who spoke with Francis Collins, Director of the US National Institutes of Health, at this year’s Presidential Symposium. The 90 minute discussion took place on the Wednesday night and was the most popular event of the week by far, attracting 32,000 viewers online and most of the 7479 attendees.

Peter C. Scarcheri, PhD and chair of the ASHG 2017 program committee said: “We are excited to engage with Dr. Collins and Mr. Gates on the latest breakthroughs, efforts and challenges in our field as well as explore future opportunities.”

The Gates Foundation has pledged tens of millions of dollars to support genomics and healthcare in the developing. Some of the money has gone directly into projects overseas focused on matters including farming and animal health, epidemic containment and identification such as with the 2014 west Africa ebola outbreak and disease prevention in sub-Saharan Africa.

ASHG also uses its annual meeting to recognise research taking place around the world that will significantly impact the industry. Amongst this year's prize winners were scientists working on new breakthroughs in the use of personal omics in precision and preventative medicine, and the molecular causes behind ciliary disorders, as well as a plethora of other exciting projects.

Dr. Matt Hurles of the Sanger Institute in Cambridge, UK spoke about his pioneering work with the Deciphering Developmental Disorders project (DDD) which recruited 12,000 patients with developmental delay for array comparative genomic hybridisation analysis and exome sequencing. The interpretation and understanding of this data has had far reaching impact in the industry.

Cambridge based clinical genomics analysis company Congenica welcomed speakers from some of the world’s leading genomics markets at their exhibitor symposium: ‘Impacting Clinical Diagnostics Using Rapid and Accurate Whole Exome Analysis’. Each of the talks reflected the global reach, influence and application of their gold standard clinical genomics analysis platform, Sapientia.

Dr. Yuan Yuan Fu, Clinical Scientist at Fuwai Hospital, Beijing has been using Sapientia to analyse the whole exome sequence (WES) data from cardiovascular patients in the Chinese capital. Her presentation focused on two case studies. The first of an 18 year old man who was diagnosed with de novo dilated cardiomyopathy after his WES data was analysed.

The second case study focused on a more complex condition that was initially suspected to be Marfan Syndrome (MFS), due to the patient's phenotypic symptoms and tall stature. They first looked at using aortopathy and multiplex ligation-dependent probe amplification (MPLA) testing for FBN1 and TGFBR2 genes but both of these were negative. WES was applied and Sapientia was used to analyse the results, which discovered a CBS gene mutation with autosomal recessive inheritance and phenotypes similar to MFS, but was in fact the far rarer homocystinuria. Without Sapientia, the diagnostic odyssey to accurately identify this variant would be extremely long - if it was completed at all - using traditional methods.

From the New York Genome Center (one of America’s leading not for profit genomics research institutes), came Dr. Avinash Abhyankar. He told the story of a family who had lost a child at 15 months of age without receiving a diagnosis. Two years on the couple were planning to try for another baby. The only tissue sample available from the child was a dried blood spot, which was used to run WES. The results were analysed with Sapientia and variants prioritised to produce the resulting diagnosis of ASNS Deficiency - a severe neurological disorder that shows its onset in-utero or at birth.

From Britain’s world famous Great Ormond Street Hospital for Children came Senior Clinical Scientist, Dr Natalie Chandler, who works to provide and expand prenatal clinical diagnostic services in a range of rare paediatric specialities. The centre dealt with over 30,000 samples during the 2016-2017 period, in particular non-invasive prenatal diagnosis (NIPD) and fetal exomes. The centre uses Sapientia to provide rapid trio clinical exome sequencing analysis using an exomiser to prioritise variants within the panel and rank how the gene fits with the human phenotype ontology (HPO) terms.

A case study was shown of a patient who presented for a scan at 24 weeks of gestation. Sapientia was used and the variant was identified and classified as clearly pathogenic. The time from referral to a diagnosis of 3M Syndrome was just 12 days.

Over the week attendees heard from many exciting and fascinating speakers, from national projects to niche specialisations and open source data sharing.

MyGene2 caught many people’s attention with what they described as, ‘a web platform for radically open data sharing that’s free, public and searchable to empower undiagnosed patients to leverage and share clinical research sequence data’, in their presentation.

A number of different national programmes were presented, Australia, Japan and Qatar and also breakthroughs in how people share data. The Broad Institute’s Heidi Rehm spoke out about the need to create a comprehensive international data base: “I look forward to a time when we have deciphered all the causes of disorders with a genetic basis and are able to effectively treat, manage and often prevent the morbidity and mortality associated with rare disease. My favourite part of this is watching how quickly we are making a difference to the lives of patients.”

Biotexel’s Genomic Medicine 2017 Conference

Cutting edge science took centre stage at Biotexel’s Genomic Medicine 2017 conference, which was held in Cambridge last week [26th & 27th September] bringing together leading minds from groundbreaking genomic studies and commercial genomic medicine companies.

The two day event, held at the University of Cambridge’s Murray Edwards College, boasted such prestigious speakers as Prof. Carlos Caldos, Prof. Eamonn Maher & Dr Lucy Raymond. Talks focused on emerging methods in genomics, the challenges of large cohort studies, and the new progress towards treating & understanding various cancers, as well as the relative benefits of whole exome sequencing versus whole genome sequencing.

Impact of Genomic Medicine on the Patient Odyssey

Dr. Lucy Raymond, Professor of Medical Genetics and Neurodevelopment at Cambridge University, spoke about the impact of genomic medicine on the patient odyssey, commenting: “In clinical practice, diagnosis is still too slow. We have come a long way. It wasn’t long ago that we were using PCR’s and Sanger Sequencing. The length of time needed has come down drastically but it needs to come down more. Diagnostic yields may still not be as high as we’d like but every success saves costs for the NHS, stress for the parents and, ideally, the life of a child.”

Two other speakers who captured the imaginations of the attendees were, firstly, Dr. Manju Kurian of Great Ormond Street Hospital, who spoke about personalised medicine approaches to childhood neurological disorder, and secondly, Dr. Carlos Caldas, Director of Cambridge Breast Cancer Research Unit, who talked about the progress that his clinic has been able to make by providing genomic profiling.

The Mutational Landscape of Cancer Genomics

Breast cancer in particular was a disease that informed a lot of the talks and debates, with Serena Nik-Zainal of the University of Cambridge and the Sanger Institute, speaking about her lab’s ongoing work to exploit the mutational landscape of cancer genomes for clinical applications.

She said: “The central dogma in a lot of cancer research has been finding the driver mutations. But in cancer things are always mutating, even in health, the human body is always mutating, its natural. We are constantly identifying mutational signatures. Unfortunately we are finding that no two patients have the same drivers and no two tumours have the same signatures.”

“We have been using whole genome sequencing to profile and analyse women with breast cancer and it has been big data that is leading to breakthroughs. We are fine tuning genomic precision medicine.” She added.

The event was a great success with delegates not only fascinated by all of the speakers but with much left to debate at the various networking events.

Dr. James Hadfield, Head of Genomics at Cancer Research UK Cambridge Institute, summed up everyone’s feelings when he said: “We have heard a lot about the great impact what we all do is having on people’s lives and as technology and research move on we will have even more of an impact. Knowing this certainly makes it easy to get out of bed each morning.”

Wellcome Trust big data analytics symposium

Cambridge, UK. - Across the life sciences, statistics and analytics are the crucial elements in understanding and capitalizing on the genomics revolution and in driving forwards personalized medicine. That is the message left with the attendees of the Wellcome Trust Genome Campus symposium on Big Data Analytics for Genetics in Personalized Medicine, on Saturday 9th September.

Clinicians, doctors, researchers and students gathered at the Francis Crick Auditorium in the bright, early autumn sun to await the day’s talks by some prominent experts from world renowned institutions.

The presentation that created the most buzz on the day was a rallying call for the need to crowd-source and globally collaborate on variant curation from Broad Institute Member, Dr. Heidi Rehm, who spoke about standards and approaches to support genomic variant interpretation. This has recently become tragically topical as, in the US, there has been the first lawsuit over a misdiagnosed variant.

Dr. Rehm told the audience: “We are seeking to redefine clinical relevance and disease validity clarification through a semi-quantitative system, aggregating clinical evidence and giving variants a validity score. At the moment, too many genes which are reported as related don’t have enough supporting information. What we do have is a huge number of experts from whom we can essentially crowdsource this. The database is open to the public and follows all ACMG rules and uses industry accepted ideas and terminology. Submissions have to show how they came to their conclusions and then we work as a community to resolve conflicts and discordance. In fact, so far, we’ve resolved 72% of the 300 conflicting variants we’ve faced so far. Systematically we can reassess outliers, support clinicians and affect patients.”

The next came from University of Southern California’s Associate Professor in the Department for Preventative Medicine, Dr. Kimberly Siegmund who spoke about using statistical approaches to investigate changes in the mutational processes during the growth and development of a cancer or tumour.

She said: “We know tumours share ancestry, that they all have a tumour initiating event. We can learn about the mutation process and sequence tumours to build a catalogue from which we can then infer patterns and draw contextual data from neighbouring bases. This gives us multinominal probability.”

Dr Seigmund’s lab undertakes multi region sampling and whole exome sequencing with a minimum of three runs to understand the diseases trunk and branch mutations and try to glean any de novo mutations contained within to add to the catalogue using a descriptive framework.

Underpinning these ideas was a phrase from the day’s first speaker, Dr. Chris Spencer, head of innovation at Genomics PLC who spoke generally on improving healthcare with genomics. He said: “Genetics is the best chance in a generation to make a major shift to better healthcare, at the very least, to improve the efficiency of the doctor’s toolbox. Over the next 10 years, as a global industry, we will be sequencing millions if not billions of genomes but unless we make use of that data it will be useless. Frankly, even if all the sequencing machines in the world blew up this afternoon, we would still have enough data to be working on for the next 50 years!”

After the intermission, things took a turn to the technical. First, attendees heard from Dr. George Davy Smith, Professor of Clinical Epidemiology at the University of Bristol, UK, who spoke about Mendelian randomisation in a data rich environment.

Dr. Davy Smith utilized a number of formulae and graphs focusing on utilising resources such as the UK Biobank to more deeply understand factors of disease progression and how pleiotropy can influence outcomes but that variants may still be data derived.

The last speaker of the day was Dr. Hae Kyung Im, Assistant Professor of Genetic Medicine at the University of Chicago, USA, who spoke about integrating GWAS, omics and electronic medical records to dissect disease biology.

“Recent progress has allowed us to generate huge amounts of HTS data and to be able to interpret this data. At Chicago we are ambitious and we want to characterise the phenotypic consequence of all human genes.” She said.

Dr. Im went on to talk about her new project, The Human Knockout Project, which is a systematic effort to understand the disruption of any given genes and to learn more about why some drugs do not work on some groups.

The day overall was a great success. Complemented by the lovely weather, the conducive staff and inspiring exhibitions attendees and speakers alike enjoyed a stimulating and interesting range of discussions and debates.