Genomics for Rare Diseases: Going Global and Shifting the Care Paradigm

The use of genomics in rare disease diagnosis and treatment is going global

The benefits of genomics in rare diseases are increasingly making a difference to patients, their families, and their physicians, and they are being scaled globally.

The trend of accelerating the use of genomics in rare disease diagnosis and treatment is going global, driven by the important goal of reaching all people around the world, no matter where they live.

Active programs have now been deployed and exist in many populous countries around the world.

For instance, WuXi NextCODE has established active collaborative efforts in three continents, most recently adding Fudan Children’s Hospital as a partner in its efforts to lead whole genome diagnostics for rare diseases in China.

Over the coming weeks, I expect WuXi NextCODE to continue have news of its dedicated efforts to spread the application of genomics for rare diseases to all geographies.

Diagnosing Rare Diseases: Genomics Shifts the Paradigm

Rare diseases are an area of significant advancement for genomics, as the opportunity for improved diagnosis and treatment through the use of genomics is truly remarkable.

According to the National Institutes of Health (NIH), there are over 7,000 rare diseases affecting between 25 and 30 million Americans, which is nearly 1 in 10 people, making the overall prevalence of rare diseases significant. Since NIH believes that approximately 80 percent of rare diseases have genetic origins, the potential for genomic sequencing, interpretation, and analysis to offer a solution here is truly game-changing.

Every day there are new cases of children with “unknown” diseases, many of which are likely related to a hereditary genetic disorder. Sadly, these children and their families often spend years undergoing testing and experimental treatments for a wide range of diseases in an attempt to properly diagnose and treat them; usually, this so-called “diagnostic odyssey” is accompanied by a very high financial and emotional burden.

Genomics offers the potential to deliver a correct and precise diagnosis for rare diseases that have identifiable genetic causes. Indeed, case studies are rapidly accumulating that show that, by offering genomic sequencing and analysis services to patients with a suspected rare genetic disease, mutations that might be causing the disease may be identified, and thus correct treatment can be employed much earlier to eliminate the burden of a long-term diagnostic and treatment odyssey.  A recent article in Bloomberg BusinessWeek highlighted medical histories of two patients who recently received a diagnosis informed by genomics. In both these representative examples, genomic analyses provided an end to the burden, cost, and stress of their multidecade-long diagnostic odyssey:

  • Jackie Smith, 35, spent the 32 years from age 3 unable to receive a correct diagnosis that could account for her weak limbs and turned-in ankles, despite seeing many doctors on numerous occasions. Indeed, Jackie’s parents were told to “take the 3-year-old girl home and enjoy her while they could” …”[her disease] would probably kill her before she was old enough to drive.”  This past February, using genomic interpretation and analyses from Wuxi NextCODE, Claritas Genomics definitively identified her condition as centronuclear myopathy in less than three weeks.
  • Dustin Bennett, 24, would tremble and violently jerk for hours or days at a time and had been developmentally delayed since childhood. After dozens of doctor visits and incorrect diagnoses—seizures, muscle disorders, mental health problems—a Mayo Clinic genomic-based analysis showed he has episodic ataxia type I, a neurological disease characterized by hours-long attacks with no clear trigger. Dustin, a 24-year-old who functions at a first-grade level, is now on the second round of a medication doctors say should help reduce the frequency and severity of his episodes.

The benefits of genomics in rare diseases – to individuals, their families, and their physicians – are increasingly making a difference to patients.  These benefits are being seen in case after case – and they are being scaled globally, as leading medical centers in many countries around the world are using genomics to support their efforts in diagnosing and treating rare diseases.  I believe passionately in the game-changing potential of genomics to help rare disease patients and I am dedicated to advancing world-leading genomics globally to uncover new solutions for patients.

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Genomics Offers Game-Changing Solution to Rare Disease Diagnosis, Costs

Hannes Smarason Wuxi NextCODE

As genomics is used more and supported by ever-more robust analysis and interpretation, its potential to offer a solution to diagnosing rare diseases is truly game-changing.

I believe strongly and have previously blogged on the potential for genomics to shift the care paradigm for rare diseases, and here I’d like to detail in particular the huge potential value genomics can add to rare disease diagnosis. According to the National Institutes of Health (NIH), there are over 7,000 rare diseases affecting between 25 and 30 million Americans, which is nearly 1 in 10 people, making the overall prevalence of rare diseases significant. Rare diseases can be chronic, progressive, debilitating, disabling, severe, and life-threatening.

When a patient presents with a spectrum of unusual symptoms, a costly scramble naturally begins to diagnose the patient’s disease. Some people refer to this diagnosis process for rare diseases as a “diagnostic odyssey,” as patients and their families are subjected to test after test while being handed from one doctor to another, oftentimes to medical centers far from their home. Too often, this odyssey yields no concrete diagnosis or—worse—misdiagnosis. The direct medical costs can be significant, and the indirect costs—the frustration and disillusion felt by the patients and the family—can be extraordinary.

Since NIH believes that approximately 80 percent of rare diseases have genetic origins, the potential for genomic sequencing, interpretation, and analysis to offer a solution here is truly game-changing. A recent article in Bloomberg BusinessWeek highlighted medical histories of two patients who recently received a diagnosis informed by genomics. In both these examples, genomic analyses provided an end to the burden, cost, and stress of their multidecade-long diagnostic odyssey:

  • Jackie Smith, 35, spent the 32 years from age 3 unable to receive a correct diagnosis that could account for her weak limbs and turned-in ankles, despite seeing many doctors on numerous occasions. Indeed, Jackie’s parents were told to “take the 3-year-old girl home and enjoy her while they could”…”[her disease] would probably kill her before she was old enough to drive.”  This past February, using genomic interpretation and analyses from Wuxi NextCODE, Claritas Genomics definitively identified her condition as centronuclear myopathy in less than three weeks.
  • Dustin Bennett, 24, would tremble and violently jerk for hours or days at a time and had been developmentally delayed since childhood. After dozens of doctor visits and incorrect diagnoses—seizures, muscle disorders, mental health problems—a Mayo Clinic genomic-based analysis showed he has episodic ataxia type I, a neurological disease characterized by hours-long attacks with no clear trigger. Dustin, a 24-year-old who functions at a first-grade level, is now on the second round of a medication doctors say should help reduce the frequency and severity of his episodes.

As genomics is used more and supported by ever-more robust analysis and interpretation, I expect these types of clear successes to become even more commonplace. And the value to the healthcare system and the patient is clear, expressed powerfully in the Bloomberg BusinessWeek piece:

While there isn’t yet a cure, Smith is participating in research that may one day lead to treatments or more supportive care. “Just being connected feels good. I felt alone for a long time,” she says. “And I want to do it for the bigger picture, too. Not just for myself, but so I can be counted.”

 

Bringing Together Core Technologies Unlocks Genomic Data to Improve Healthcare

genome analysis technologies

Within the “3-legged stool” of genomics-enabling technologies, lower-cost genome sequencing has reached a point of strong commercial viability, and the remaining two legs—genomic analysis tools database storage—are rapidly evolving to support the use of genomic information in medical care.

The adoption of genome sequencing technology is rapidly expanding as medical centers around the world embrace its utility in informing healthcare decisions—an emerging reality of personalized medicine.

There are three important areas of technology that are driving the use of genomic data in healthcare:  genome sequencing, genomic analysis tools, and database storage.

The first of these—genome sequencing—has advanced to the point that it is more widely accessible, with the cost of sequencing at nearly $1,000 or less. This lower cost of genome sequencing has reached a critical milestone to enable the use of sequencing as a mass-market product for medical care.

The second and third core genomic technologies—genomic analysis tools and database storage—are in the midst of evolution. Their progress and integration are critical for the next stage of adoption of genomic data into health care.

The rapidly evolving legs of the “3-legged stool” of genomics technology are genomic analysis tools and database storage.

  • Genomic Analysis Tools: Since the human genome was first sequenced more than a decade ago, an increasingly robust body of research has showcased the links between mutations identified in the genome and disease risk. Informatics tools have been developed by medical centers and genomics companies to apply to whole-genome samples. Increasingly, these genome analysis tools will need to adapt to the steady pace of new genomic linkages to disease and to operate at a level approaching “big data.”
  • Database Storage for Human Genomes: There are a growing number of robust databases of human genomes, including data for healthy people or those with certain diseases. When properly analyzed, these databases offer the potential to provide the medical community with a reference library against which to compare genetic data. Large-scale, high-quality databases are an essential element to cross-reference a patient genome to guide more informed medical decisions.

Recently, two leading genomics companies—WuXi and NextCODE Health—have combined their technology capabilities in these two areas. WuXi has industry-leading capabilities to analyze, store, and manage the vast amounts of genomic data. NextCODE Health brings a leading-edge system for sequence-based clinical diagnostic applications and genome analysis.

The combination of WuXi’s foundational genomic database storage and management and NextCODE’s sophisticated genome analysis tools will integrated the key components that are most rapidly evolving to apply genomics to medical care.

Initiatives like these advance the state-of-the-art in genomic analysis and database storage, bringing us to the heart of helping the world to fully harness personalized medicine and providing tools directly to doctors to provide better diagnostics and treatments to patients.

The progress to date has been amazing. Yet the opportunities ahead are even more extraordinary to improve the speed, accuracy, and accessibility of genomic information to improve human health.

A New Era, New Vision for WuXi and NextCODE Health

WuXi-NextCODE

WuXi PharmaTech has acquired NextCODE Health to create WuXi NextCODE Genomics, a global leader in genomic medicine. Pairing WuXi’s technology and existing reach with NextCODE’s leading analytics and database promises to advance the pace of genomics research today.

In the fast-paced genomics community, we continually look for new opportunities and strategies to enhance the value of genomics and use the increasingly robust body of genomic data for the advancement of clinical medicine.

We’re excited to announce a new, ambitious vision to do just that, with WuXi’s acquisition of NextCODE Health. NextCODE will be merged with WuXi’s existing Genome Center in wholly-owned subsidiary called WuXi NextCODE Genomics, with unique, comprehensive and global capabilities for using genomic data to deliver better medicine and improve healthcare.

WuXi, a Shanghai-based genomic laboratory service partner for companies in the pharma and biotech community, has already been collaborating with NextCODE to provide analysis services to customers of the WuXi Genome Center. Now, with the in-house capability to analyze, store, and manage the vast amount of genomic data, NextCODE’s industry-leading genome sequence analysis platform will expand WuXi’s core next-generation sequencing benefits and services.

Pairing WuXi’s technology and existing reach with NextCODE’s leading analytics and database promises to advance the pace of genomics research today. More importantly, however, this new era for NextCODE brings exciting opportunities to maximize the most advanced tools available today and contribute to major advances in genomic medicine.

Global Projects Move Genomic Medicine to the Next Level

nextcode-genomics-england-hannes-smarason

NextCODE takes top marks in Genomics England analysis and interpretation “bake-off:” NextCODE’s proven population-scale platform delivered the best results in rare disease and cancer clinical interpretation, as well as secondary analysis and variant refinement.

New genomics-based technologies and tools are making their way into a range of exciting research programs and clinical studies around the world. Leading-edge organizations are quickly adopting hardware for sequencing and systems for collecting genomic data. Now, the focus has turned to analysis and interpretation – the critical component necessary to gain the insights from the sequence data that will transform medicine.

Earlier this year, Genomics England announced investments for broad sequencing and analysis of 100,000 human genomes. At the time, Genomics England had selected Illumina as its sequencing partner and was coordinating resources and centers to support the effort, including resourcing for analysis and interpretation. [See blog post here]. Other initiatives, such as the Qatar genomics program and the initiatives by Longevity and Regeneron also represent the accelerated progress in seeking medical advancements from genomic data insights. [See blog post here.]

This week, Genomics England announced a select group of companies with advanced capabilities to move to the next stage of evaluation to provide clinical interpretation for the 100K Genomes Project. At the tip top was NextCODE, which received top marks by Genomics England for its analytical capabilities across all the categories evaluated: rare disease interpretation, secondary pipeline analysis and cancer interpretation. [See press release here.] The company’s advanced Genomically-Ordered Relational database, or GOR, combined with its clinical and discovery interfaces offer the most advanced and reliable capabilities to support the ambitious tasks undertaken by Genomics England, and are already proven at population scale. [Read more on the GOR database here.]

The coming months will be a very exciting time for genomic medicine, with interpretation taking the spotlight as we take leaps toward the next stage of personalized medicine.

Genome Data Interpretation: How to Ease the Bottleneck

Bloomberg NextCODE Hannes Smarason

Bloomberg BNA Business’ “Diagnostic Testing & Emerging Technologies,” highlights how NextCODE is providing a qualitatively different way to store and analyze genomic information to meet growing opportunities in personalized medicine.

With advances in sequencing technology and reduced costs, more and more data are generated every day on the genetic basis of disease. The challenge has become how to derive meaningful information from these mountains of data.

While various systems have been established in recent years to store the large amounts of genomic data from patients’ DNA, a remaining obstacle is to “break the bottleneck” so that researchers can process the vast data in multiple human genomes in order to identify and isolate a small, useful piece of information about disease. Conventional databases and algorithms have not been able to efficiently and reliably identify subset information among the millions of genetic markers in order to inform clinical decisions. This has become a major data management roadblock.

The key is to find new approaches for databases and algorithms that accommodate the unique ways that genomic information is analyzed and interpreted. As discussed in Bloomberg BNA, Diagnostic Testing & Emerging Technologies, NextCODE is already easing this bottleneck by providing a qualitatively different way to store and analyze genomic information and apply it to meet the growing opportunities for personalized medicine.

NextCODE’s Genomically Ordered Relational (or GOR) database infrastructure is a truly different way of storing this huge amount of data. The principle is very simple: rather than store sequence and reference data in vast unwieldy files, it ties data directly to its specific genomic position. As a result, the algorithms are vastly more efficient compared to a traditional relational database because they can isolate by location in the genome. That makes analysis faster, more powerful, and radically more efficient, both in terms of clinicians’ and researchers’ time, as well as computer infrastructure, I/O, and CPU usage.

This holistic approach applies broadly to the priorities of genome scientists around the world, helping them eliminate the data management bottleneck to identify more culprits to many inherited diseases, more quickly and cost effectively.

Read more about NextCODE’s work here.

Trends in Sequencing and Analysis Today Leading to Tomorrow’s Clinical Advances

The insights we’re gaining from sequencing and analysis techniques are delivering new advances in healthcare with ever greater speed and precision.

The challenge for programs seeking to accelerate their research discoveries with genomic data is how to analyze the wealth of information—to make it clinically relevant and rapidly deliver reliable insights to better inform patient care.

The insights we’re gaining from sequencing and analysis techniques are delivering new advances in healthcare with ever greater speed and precision. It’s a particularly exciting time to be a part of this evolving industry, with continual opportunities for new clinical applications of these technologies and platforms.

Companies like Illumina and others who are delivering next-generation sequencing technologies are gaining global exposure. New partnerships and programs are placing these advanced techniques into the hands of the world’s leading clinicians and researchers, who are then applying them to some of today’s greatest medical challenges.  Recently, plans to integrate sequencing technologies have been announced by world renowned organizations like the Baylor College of Medicine in the U.S., Genomics England, and Sidra Medical and Research Center in Qatar.

The challenge for these and other programs seeking to accelerate their research discoveries with genomic data is how to analyze this wealth of information – to make it clinically relevant and rapidly deliver reliable insights to better inform patient care.

NextCODE Health is working to advance this piece of the puzzle with its Genomically Ordered Relational (GOR) database and its clinical and discovery interfaces (the Clinical Sequence Analyzer​™ and Sequence Miner™).  Combining next-generation sequencing techniques with increasingly robust analysis tools, NextCODE Health is helping to accelerate global research progress today to deliver unprecedented advances in patient care in the years just ahead.

Pioneering Genome Sequencing Effort in England Aims to Shape the Future of Global Medicine

£300 million in new investments for Genomics England

Genomics England 100,000 Genomes Project

Genomics England was set up by the UK Department of Health to deliver the 100,000 Genomes Project. Initially the focus will be on rare disease, cancer, and infectious disease. The project is currently in its pilot phase and will be completed by the end of 2017.

These are exciting times for large-scale sequencing projects. Last week, U.K. Prime Minister David Cameron announced over £300 million ($509.4 million) in new investments for Genomics England, which aims to sequence, analyze, and store the genomes of 100,000 UK National Health Service (NHS) patients by 2017. The investments include about £162 million ($275.1 million) from Illumina Inc. (NASDAQ:ILMN), the partner for the sequencing element of the project. In turn, Genomics England will pay Illumina about £78 million ($132.4 million) for its services.

At the same time, the Wellcome Trust will put £27 million ($45.8 million) into a new sequencing hub at its genome campus in Cambridge; the Medical Research Council, or MRC, is investing £24 million ($40.7 million) to support data analysis and interpretation, and the NHS will make £20 million ($34 million) available for the establishment of patient sequencing centers.

This is a prime example of how the implementation of sequencing technologies promises to drive a revolution in the structure of medical research. These new projects aim to capture more data on human DNA than ever before, with the goal of advancing care and solving healthcare challenges.

The 100,000 Genomes Project, developed by the NHS, has the potential to significantly influence the global community through its plans to integrate sequencing data into standard medical practice.

Genomics England plans to generate 100,000 whole genome sequences from NHS patients with cancer, rare diseases, and other conditions, and to share the resulting data for research and development purposes. In the early phases, the program will also seek to develop standards for consent, sample storage, data generation and variant analysis that may be useful for many other organizations conducting large-scale projects within public health systems.

The project is enlisting the help of organizations from around the world to undertake this significant effort. In fact, it recently selected Illumina to conduct the sequencing efforts and is evaluating technologies for storing, annotating, and interpreting the data so that it can be used  for both clinical diagnostics and drug discovery, development, and delivery to the right patients.

The challenges of analyzing data on such a large scale are formidable, but the end result carries great potential to address some of the significant unmet medical needs. NextCODE’s technology has already accomplished analytics on this scale based on its work with the Icelandic population through deCODE genetics. It’s an exciting prospect for advancing the future of genomics-driven medicine and one to watch.

Seeking Genomic Answers to Autism and Rare, Idiopathic Diseases

rare-diseases-hannes-smarasonAs more is learned about autism spectrum disorders, more questions seem to arise. Yet with DNA sequencing, researchers are able to investigate the genetic roots of this and other diseases that are not yet well understood. It’s another instance in which genomics can shed light upon the workings of that most important organ system—the brain—which is so difficult to analyze.

Institutions around the world have sought to fill in pieces of the autism puzzle with links to other disorders and diagnostic insights, and these efforts have in recent years uncovered a number of possible genetic triggers and pathways. Yet the causes and manifestation of these diseases remain largely elusive.

University College Dublin’s Academic Centre on Rare Diseases (ACoRD) in Ireland, which is world renowned for its discoveries in rare genetics, is using NextCODE’s genome analysis technology to power large-scale, sequencing-based diagnostics programs and genome discovery efforts to study autism and rare pediatric disorders.

Recognizing the enormous potential of large-scale sequencing to mine whole genomes and accelerate discoveries in rare genetic diseases, ACoRD will focus on some of the most challenging areas to inform and provide new directions for research that may help lead to diagnosis, treatment, and even prevention for these disorders. In using NextCODE technology both for analyzing as well as storing large-scale genomic data, ACoRD is well positioned to become a focal point for multinational research and clinical diagnosis in conditions that require the gathering and collective analysis of genomes from many participants in many countries.

Four Factors for Improving Genomic Data for Personalized Medicine

advancing the use of genomic data for personalized medicine

The pace of progress has been astounding with advances in the use of genomic information to provide faster, more accurate, and more in-depth information to enable personalized patient care.

We’ve come a long way in improving the way that a patient’s genome sequence data is analyzed and interpreted to realize the full potential of personalized medicine. Here are four factors helping to overcome barriers and achieve new milestones for using genomic data to provide faster, more accurate, and more in-depth information to guide clinicians in delivering personalized care for patients.

Factor #1: Fast database query of the genome

Problem: Relational database architectures make it possible to store large quantities of sequencing data, but querying whole genome data can be time-consuming and take days to weeks.

Solution: The GOR (Genomic Ordered Relations) database is able to query whole-genome sequences in real time. The reason is that GOR understands the genome in terms of chromosomes, its natural structure, rather than as a continuous string of sequence. That’s both intuitive and innovative. When searching for a variant, tools in the GOR architecture don’t have to scan each individual’s entire sequence; they retrieve the variant straight from its location. Annotation data – information on what diseases or conditions variants have been linked to – are also stored in the same way. The GOR database was pioneered a decade ago by deCODE genetics, one of the first organizations to manage truly large genetic datasets, and is now being used by NextCODE for clinical applications of genomic data.

Factor #2: Fast, reliable identification of disease-causing variants

Problem: Many sequencing analysis pipelines are only powered to process data in a compressed format called Variant Call Format (VCF) files. These comprise only a tiny fraction of the genome, and being working only with VCF files makes it difficult to correct common alignment and allele-calling errors. That can result in both false positive and negative results, or to missing the key causative variants altogether.

Solution: The foundation for improved sensitivity and specificity is the ability to use VCF data on top of the raw sequence data from which it was derived. NextCODE’s pipeline and clinical interfaces, powered by GOR, give users the ability to go back to and visualize raw sequence data at a click. This approach enables genomic analysis and interpretation by seeking out disease-causing genetic variants, either in specific patients, or for research studies in a clinical setting.

Factor #3: Patient genomic information at the fingertips of the clinician

Problem: Many of today’s genomic interpretation tools are too complex and difficult to use by clinicians who may have minimal experience with genetic informatics tools.

Solution: All of the complex informatics required by a clinical analysis tool should disappear at the fingertips of a clinician. It starts by having a robust foundation to the informatics platform, and using the GOR database architecture enables rapid cycling between personal sequence data and broad clinical knowledge. The result is the Clinical Sequence Analyzer (CSA) in which clinicians can simply type in a patient’s symptoms, and CSA will search the patient’s whole genome for variants that may be relevant.

Factor #4: Applying the full power of whole-genome sequencing to cancer tumor analysis

Problem: Many of today’s approaches to the analysis of cancer genomes only look at the immediate next step for a course of treatment, an important capability but only part of a holistic view of a the genetic profile of a patient’s cancer and what can be done to fight it.

Solution: The Tumor Mutation Analyzer makes a more holistic approach possible, analyzing a whole exome or whole genome sequence from a patient’s own genome and from tumor cells. Comparing the two it is possible to isolate the variants likely to be cancer drivers. The distinguishing feature of TMA is the depth of the data it stores and the unprecedented level of detail it provides to more accurately identify variations. This level of detail is especially important in cancer genetics, where the chances of finding previously unknown variants are very high, and even if a mutation is successfully targeted with a course of treatment, another potential driver is often waiting in the wings.

The pace of progress has been astounding with advances in the use of genomic information for patient care. How will the path continue in the future? Stay tuned.