Tag Archives: Claritas Genomics

Speeding Diagnosis of Rare Diseases

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WuXi NextCODE Claritas

Claritas Genomics combines physician experience with next-generation sequencing and WuXi NextCODE’s analytics to accelerate rare disease diagnosis.

It’s one of the most heartbreaking and frustrating things for parents and pediatricians. When a child presents with a constellation of symptoms that doesn’t point to a known disease, what do you do?

Typically, these kids undergo a battery of tests, some of which will eventually be for single genes suspected to play a role in their health problems. But what if those tests come up negative? That leaves the families and doctors wringing their hands as they wonder what to do next.

That was the case with a patient at Boston Children’s Hospital (BCH). He was a boy who, at six months, wasn’t sitting up, smiling, or doing most of the things babies his age typically do. Instead, he seemed “rigid” to his mom, and then he developed a severe respiratory virus and was hospitalized. He also had repeated seizures and eventually needed a tracheotomy—a tube placed through an incision in his throat to help him breath.

Usually, such kids then begin going through what is known as a “diagnostic odyssey”—a long and arduous journey from doctor to doctor and lab to lab.

BCH doctors are trying a new approach. In 2013, the hospital spun out Claritas Genomics, a specialized genetics diagnostics business that combines the experience of the hospital’s physicians with the power of next-generation sequencing and WuXi NextCODE’s advanced analytics. Timothy Yu, a neurologist and researcher at BCH, helped found Claritas to provide a more holistic approach to rare disease.

WuXi NextCODE’s advanced analytics play a key role in improving the speed and efficiency of such diagnostics. Reading the genome isn’t the major challenge anymore—now the issue is finding the relevant mutations in those three billion base pairs.

The data from a single genome can comprise more than 100 gigabytes, which is enough to fill the hard drive on a good laptop computer. Even the exome, which comprises the parts of the genome that encode proteins, can be 15 gigabytes. To diagnose a rare disease, doctors need to find sequence variations and then scour the research to find out what those actually do. That used to take months to years, and many of the variants were simply classified as being of “unknown significance,” without any further information or the ability to check again as the field of knowledge grew.

WuXi NextCODE’s system has begun to make this a click-and-search task. Our knowledgebase can mine all publicly available global reference datasets simultaneously and in real time to show all there is to know about any given variant and its likely biological impact. By keeping the data in a WuXi NextCODE research database, such as the one BCH is growing every day, our system can also quickly rerun the analysis and provide new information as soon as it becomes known.

Claritas is continually expanding the range of its services. Most recently, the group received conditional approval from the New York Department of Health for three new “region of interest assays” as well as one for mitochondrial DNA. That brings the number of Claritas’s approved tests in that state up to six and means more patients in New York will benefit from this new technology.

Children at BCH with ambiguous diagnoses now regularly undergo a whole exome scan early in their clinical journey. The data is then triaged. It is examined first for the most obvious mutations and then more data is progressively analyzed as necessary. With the consent of parents and security measures for privacy, that data can also become part of research datasets at BCH and other major hospitals around the world, so that the growing data pool can benefit that child and others.

This combination of expertise and technology helped Claritas Genomics find an answer for that baby boy and his family mentioned earlier. Heather Olson, the boy’s treating neurologist, had the boy’s exome scanned through Claritas Genomics, and 130 genetic variations were identified that could have caused one or more of the symptoms. WuXi NextCODE’s system helped narrow that down to only six variants that could have possibly been passed on by the boy’s parents. Olson and Yu finally focused on one, a mutation of the BRAT1 gene, which served as a diagnosis. A paper published by Yu, Olson, and colleagues, which describes this mutation and children affected by it, should help other physicians make this diagnosis more quickly in the future.

Yu presented more on Claritas’s novel platform recently at Boston’s Bio-IT World meeting. He explained how the platform helps doctors to much more quickly and accurately diagnose kids with diseases not previously described.

“Thanks to the speed of the platform, we can get a whole clinical exome completed in as little as two weeks,” he said.

The growing database of genetic variants and their effects also means more patients will get an actual diagnosis, rather than walking away still wondering what could be going on.

The ability to diagnose more cases is a start to unravelling the causes of the estimated 7,000 different rare diseases estimated to exist. And it’s a necessary first step towards developing new therapies for those conditions, too.

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

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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.

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

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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.”

 

Genetics-Based Advances in Rare Diseases: Ideas into Action

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NextCODE Health-Claritas Genomics

Claritas Genomics and NextCODE have established a collaboration to support rare disease clinical care.  Combining robust sequencing with integrated diagnostic capabilities, the partnership aims to accelerate and augment the services provided to leading pediatric care organizations.

Today we have a tremendous opportunity to use the data being generated from genome sequencing to address the mysteries of rare genetic diseases affecting children. Though these diseases individually are rare, according to Global Genes, an estimated 7,000 different types of rare diseases affect more than 30 million people in the U.S., roughly half of whom are children.

To conduct diagnostic testing for pediatric genetic disorders, leading children’s hospitals are collaborating with specialized laboratories, including Claritas Genomics, a recognized leader in specialized pediatric genetic testing affiliated with Boston Children’s Hospital, part of the Harvard Medical School system.

The real opportunity lies in the analysis of raw genomic sequence data to identify patterns or markers of a rare disease. While it has been theoretically possible to use genomic sequencing to diagnose most rare diseases, a major hurdle has been in integrating dynamic informatics tools that can quickly interpret the data into accurate diagnostic insights and, ultimately, treatment options.

This is why Claritas Genomics and NextCODE have today established a collaboration, enhancing their collective capabilities to support rare disease clinical care. Combining robust sequencing with integrated diagnostic capabilities, the partnership will aim to accelerate and augment the services provided to leading pediatric care organizations.  Claritas has established a wide range of tests for genes known to be associated with pediatric disorders, which NextCODE is integrating into its clinical interface, resulting in accurate, reliable clinical reports. Learn more about NextCODE’s pioneering activities here.

Enabling this rapid, integrated approach to genomics-based care for rare diseases holds great promise for the community and for the many families who are anxiously seeking answers to these mysterious diseases.