Category Archives: rare diseases

Rare Disease Day Spotlight: Dr. Christina Waters on how WuXi NextCODE is Using Global Genomics to Advance Diagnosis and Treatment

Posted on by

As we continue to build and expand the leading global platform for storing, sharing, and interpreting massive sets of genomic data, rare diseases are becoming an increasing focus for us.

So, today, on Rare Disease Day, we want to spotlight the role of Dr. Christina Waters, our new Senior Vice President for Rare Disease.

Christina founded the non-profit RARE Science in 2013.  With RARE Science she has succeeded in creating a framework to power rare disease research and bring together families across 38 countries who share one of the almost 400 conditions the organization is working on. Joining WuXi NextCODE has allowed Waters to help us increase our focus on rare diseases and take her non-profit’s goals to scale and help more patients with rare diseases receive definitive diagnoses and more effective treatments.

“The reality of rare disease means we must work globally if we are going to have enough patients in any of our studies to have an impact,” she explains.

Rare conditions are, after all, much harder to study because in any given place fewer people have them.  For some conditions, the number of known patients is fewer than 100 worldwide.

Still, overall, there are many rare conditions – about 7,000 and affecting hundreds of millions of people worldwide. Over half of rare disease patients are children, 30% of which will die before their fifth birthday.

Learn more about Christina and her aims for rare disease patients.

Share on Tumblr
0
email

Using AI to Understand and Make Use of the Genetic Roots of Obesity

Posted on by

This week, we announced a breakthrough partnership applying artificial intelligence to the study of genetic variants associated with obesity. Rare metabolic syndromes cause excessive weight gain in some patients. These conditions are very difficult to treat and lead to related health risks. Now, WuXi NextCODE is working with Rhythm Pharmaceuticals to use AI to help advance the development of drugs to treat such patients.

We’re excited to be doing this work because several key genes are known in the MC4R pathway, which helps regulate weight by increasing energy expenditure and reducing appetite. We’re now working with Rhythm to determine which of these variants correlate with the greatest impact on risk of developing obesity through this pathway.

This is one of the frontiers of rare disease research, and we hope to make rapid progress with our novel AI tools, including our proprietary DeepCODESM algorithm for variant scoring. Learn more about this intriguing research here.

WuXi NextCODE Appoints Christina Waters to Expand Reach and Impact of the Global Platform for Rare Disease

Posted on by

Dr. Christina Waters’ expertise in translational medicine and building global networks and cohorts will extend the reach and benefits directly to patients, families, and disease organizations.

Connecting patients, advocacy organizations, researchers, and healthcare systems through world-leading genomics and massive data – to advance diagnosis, research and new therapies

  • WuXi NextCODE’s platform is the engine of choice for large-scale sequence-based rare disease diagnostics and research efforts on three continents
  • Dr Waters’ expertise in translational medicine and building global networks and cohorts will extend the reach and benefits directly to patients, families, and disease organizations

14 December 2017 – WuXi NextCODE today announced the appointment of Dr Christina Waters as senior vice president, focusing on our rare disease programs. Dr Waters will apply her two decades of experience to grow the company’s rare disease platform by reaching out to and integrating patients and patient communities, leveraging our capabilities and those of our partners to benefit even more people around the world.

WuXi NextCODE presently serves as the diagnostics engine for major research hospitals and national health systems and genome projects in the US, China, UK, Ireland, Singapore and Qatar, and has assembled the world’s leading knowledgebase of genome variation for diagnosing rare disease. Under Dr Waters’ leadership the company aims to extend the breadth and impact of its platform by using existing networks and global social media to identify and connect rare disease patients wherever they are. WuXi NextCODE plans to employ the full range of its capabilities – from sequencing through interpretation, AI and large-scale discovery – to generate new datasets, communities and cohorts that will make it possible to diagnose more cases, understand the biology of rare disorders, and drive therapeutic development.

“A central part of our mission as a company is to apply genomics to solve rare disease and we are thrilled that Christina Waters is joining us to realize this vision,” said Hannes Smarason, CEO. “Building on our large-scale work, she is going take our platform to the next level: putting it directly at the service of patients and families in urgent need. Connected with each other and armed with sequence and medical data, we and patients, partnering with research institutions, healthcare systems and pharmaceutical companies, are going to be able to solve and eventually treat more rare disease cases.”

“I am excited to be joining WuXi NextCODE at this promising moment in the genomics revolution,” said Dr Waters. “Pharmaceutical companies have very clear criteria for the data they need to begin working on developing new drugs but many families are on their own, scattered all over the world. WuXi NextCODE has the platform that can connect patients’ and families’ data globally to create a critical mass of knowledge for diagnosing more diseases and the cohorts for uncovering the biology and undertaking therapeutic development. We are uniquely placed to be the trusted partner for generating and assembling the data required. This is going to help countless families and I feel privileged to have the chance to help drive this effort.”

Dr Waters is founder and CEO of Rare Science, a non-profit staffed entirely by volunteers that serves as a resource and research hub working to find diagnoses and treatments for some 3000 children and their families with more than 350 rare disorders in 38 countries. She has been responsible for leading medical research in a broad range of organizations ranging from academia and disease – from non-profits to biotech and large pharmaceutical companies, including Novartis, aTyr Pharma, Cell Therapeutics and the Multiple Myeloma Research Foundation.
She holds a BS in molecular biology from San Diego State University, a PhD in genetics from UC Davis, an MBA from the Anderson School of Management at UCLA, and was awarded postdoctoral fellowships at UC Berkeley and CalTech.

Pioneering Rare Disease Diagnostics in China—An Interview with Fudan Children’s Hospital Clinicians at ASHG17

Posted on by
wuxi-nextcode-fudan-university

The first year of WuXi NextCODE’s partnership with Fudan Children’s Hospital has delivered 11,000 clinical reports and a diagnosis rate of 33%, matching the throughput and success rate of the world’s leading laboratories.

One year ago, WuXi NextCODE (WXNC) and the Children’s Hospital of Fudan University (CHFU) launched a joint laboratory to put the global gold standard in sequence-based rare disease diagnostics at the service of patients in China. In the first year of that joint effort, the partnership delivered some 11,000 clinical reports—with more than 1,000 new reports now being generated each month—and a diagnosis rate of 33%. This matches the throughput and success rate of the leading laboratories in the world.

Dr Lin Yang of CHFU presented a summary of this remarkable progress at WXNC’s breakfast session on rare disease at the ASHG17 meeting held recently in Orlando. Afterwards, WXNC’s global communications lead, Edward Farmer, sat down to talk about this collaboration and what it means for patients, with Associate Professor and Laboratory Director Dr. Huijin Wang from the clinical team; Dr. Bing Bing Wu, director of the medical diagnostics laboratory; and Assistant Professor Dr Xinran Dong, who leads the bioinformatics team, as well as WXNC Chief Scientific Officer, Jeff Gulcher.

Edward Farmer: It’s a real pleasure to have with us our colleagues from Fudan and to be able to hear about this collaboration in rare disease diagnostics and genome-based testing in the neonatal unit. To start us off, Jeff, can you tell us how this partnership came about and how you see its importance to rare disease diagnostics in China and worldwide?

Jeff Gulcher: It’s been a fantastic partnership that started about two-and-a-half years ago, when we began discussing the possibility of creating a joint laboratory. The aim was to take advantage of WXNC’s technology and sequencing expertise together with Fudan’s expertise, both on the medical side and the interpretation side. The goal was to enable whole exome or medical exome sequencing of very sick children. In parallel, we decided to see if sequencing is useful in the neonatal ICU setting.

Through this partnership, we’ve now sequenced a large number of children and worked together to make diagnoses. Our medical genetics teams have worked closely together to interpret these cases, and in about one-third of the cases, we’ve been able to deliver diagnoses that were not suspected by the treating physician. In many cases, that has led to different treatments, with better outcomes for the children.

Together, we have now sequenced over 11,000 pediatric cases, including some 2,500 neonatal ICU cases, and we are very pleased with this partnership.

Edward Farmer: We have with us several senior people from Fudan. Huijin, let’s begin with you, as director of our joint laboratory. Can you share with us your impressions of this partnership so far and some of your results?

Huijin Wang: We have had a very good experience with this collaboration. We have many cases and, each week, we have a case meeting with the Cambridge WXNC team and we discuss the data and variant curation for the more difficult ones. The results have been impactful for the patients. In many cases, we can deliver a clinical diagnosis, and some of these offer real treatment options.

I remember one case that first came to the neurological clinic with seizures and hypoglycemia. This child had presented with recurrent hypoglycemia at a very early age and was in the NICU. We sequenced the family and found a recessive variant in the FBP1 gene, which the patient had inherited from both parents.

After this diagnosis, the doctor was able to discuss the problem with the family and advise them on how to limit the child’s diet to avoid hypoglycemia. The child is now doing well and no longer experiencing hypoglycemic episodes. And his family came back later and planned to have another child, and we referred them for prenatal diagnosis, and they were able to have another child who is healthy. This was a very successful case and is the sort of story that encourages us and shows us the value of the work we are doing.

Edward Farmer: That is an encouraging result. Lin, as an attending physician, how do you see the impact of introducing this technology into China at scale?

Lin Yang: We have more and more children at our hospital with birth defects or congenital malformations, so we really want to get a diagnosis and whatever possible treatment for them, including new treatments when available.

The collaboration between our hospital and WXNC starts with us deciding whether the case is likely to be the result of a genetic disorder. If it is, we do pre-testing counseling for the whole family before taking DNA samples. We then use WXNC’s capabilities for the sequencing and analysis of the results. Finally, we need to interpret the sequencing results and report them to the parents. It is often very difficult for parents to understand “what is a gene,” “what is a mutation,” “what is the disorder,” and “how can your child benefit from a molecular diagnosis?” So that is a critical part of our work.

But more and more patients are choosing molecular diagnosis and, if they get a correct diagnosis early, they may find a useful and more targeted treatment earlier.

In the NICU, we have some patients that have immune deficiency disorders. These can be very serious conditions, as the children suffer from repeated infections. It is very hard on the whole family. For such cases, if you have a specific diagnosis, there is often a cure. This is very good news for these families in the NICU, as they now have the possibility of getting a molecular diagnosis and then a treatment.

Edward Farmer: Are there any specific examples or cases that you can share with us?

Lin Yang: I had a newborn patient who had very low platelet counts and petachiae (red spots from small bleeds) on his face and body. We found that he has a mutation in the WAS gene, inherited from his mother’s side of the family, which means that his bone marrow is not producing enough platelets. But with a hematopoietic cell transplantation [HCT, which can include bone marrow] from a relative or closely matched donor, he has every chance of being cured of the disease and becoming a healthy boy. He is now waiting for a matched donor.

Edward Farmer: Huijin, you’ve done amazing work so far, and I know you are only getting started, but I wonder what proportion of the patients you see are able to benefit from the work of your lab and the collaboration with WXNC?

Huijin Wang: Currently, we are delivering a diagnosis to about 30% of patients, and we are able to recommend specific clinical treatment for about 20% of our patients.

And very often, we can give some guidance, if not a cure. Sometimes just knowing exactly what the diagnosis is gives patients peace of mind and new options. For example, many can go to a specialty clinic. But just knowing the diagnosis is often a comfort.

There is also a big need, and as a national center of excellence our diagnostics can help people across the country. About 80% of our patients come from outside of Shanghai, so with a diagnosis, they can go back to where they live and take some action there.

Lin Yang: There is also a difference among different diseases. I think we are now able to provide actionable results to about 50% of patients with neuromuscular disorders, and for respiratory maybe something less than that. For NICU, it’s maybe 15% that get a diagnosis, but we want to boost all of these.

We can benefit many more patients with this technology. In our hospital and with the WXNC collaboration, we can see an increasing number of patients. But there are a lot of undiagnosed patients, and in many places, there is not yet access to molecular diagnostics, so we hope this capability spreads to other parts of the country as well.

Edward Farmer: And Xinran, as we’re talking about building the scale and reach of molecular diagnostics, perhaps you can tell us a bit about how you are dealing with all of this data.

Xinran Dong: We have collected a lot of data. And from my bioinformatics perspective, one of the things that the WXNC collaboration is helping us to do is to make good use of the data, both for our clinical cases and for research.

I see part of my job as helping to build this into one of the biggest databases on rare disease in China and maybe the world. This is going to help patients today and advance the discovery of new genes.

Edward Farmer: Clearly there is no lack of ambition here. I want to thank you all for your time, and we look forward to sharing more stories of our work together.

Why We Need Big Infrastructure For Tackling Rare Disease

Posted on by
Hannes Smarason big data rare diseases

Having bigger databases, and having a mechanism that flags genomic variants, is key to optimizing patient care for entire families

Uncovering the genetics of schizophrenia is vital but challenging. As I wrote in my last post, mutations in more than 100 spots in the genome have been linked to the condition. But which ones actually play a role in the disease, and which ones are just there for the ride—innocent bystanders that just happen to occur alongside the real culprits? That’s the crucial question for scientists seeking new treatments for this condition, among them leading researchers and clinicians at our close partner, Boston Children’s Hospital (BCH).

One thing we’ve learned recently is that even a small amount of knowledge about genetic underpinnings of disease can have a big potential benefit for patients. For example, the 16p13.11 region deletion I described in that last post ended up being very important for several patients later, particularly one father and his son, recently described by our colleagues at BCH. This case highlights the importance of expanding the scope and scale of such research, and of updating and alerting patients as more is discovered—not just in schizophrenia, but across rare disease.

In their previous work, the BCH team used chromosomal microarray analysis to determine that a young boy with symptoms of schizophrenia, including psychosis, was missing an entire chunk of DNA—one copy of the chromosomal region 16p13.11, which spans several genes.

Schizophrenia in children is rare, and some researchers believe it could be an extreme variation of the disease, and so might hold important clues for the treatment of this condition in both young and old. A search of our and BCH’s databases showed that several other young patients also showed variations in that region. Just as important, it was confirmed that a parent of one of those patients also carried that deletion, and it seemed likely that another parent (not available for testing, but with reported symptoms of schizophrenia) also likely carried the deletion.

Clearly 16p13.11 seemed to be emerging as a “hotspot” for variations linked to psychosis. But the scientists were only finding this because they could go back and search the databases, and they were working their way backwards from pediatric cases to learn information that might have been medically relevant to the parents as well. All this suggests that having bigger databases, and having a mechanism that flags such variants, is key to optimizing patient care for entire families.

One case uncovered by the BCH scientists, regarding a young man who we will call Jack, brought this into sharp focus. As a teenager, Jack had undergone detailed genetic screening at BCH because of symptoms that included learning disabilities and recurrent seizures. It was determined that he had a 16p13.11 deletion, but at the time of his screening, that mutation hadn’t yet been linked to psychosis. So it became just one more detail in Jack’s medical record.

Separately, a few years later, Jack’s father was diagnosed with ADHD and treated with a high dose of mixed amphetamine salts. Within a few weeks Jack’s father experienced a manic-psychotic episode. He was prescribed an anti-psychotic and eventually recovered. Unfortunately, his son was deeply affected by his father’s breakdown and became withdrawn and depressed. Eventually, Jack also developed psychotic symptoms, which were so serious he was hospitalized.

Jack’s symptoms, thankfully, responded to anti-psychotic medication, but his doctors wondered if there was any connection between the breakdowns suffered by the father and son.

A check of Jack’s medical record revealed the 16p13.11 deletion. And seeing that detail after the link had been made between 16p13.11 and psychosis, his doctors immediately speculated that it might be a cause of Jack’s symptoms. Further, they suspected that mutation could be the “linchpin” causing psychosis in the father and the son. Jack’s father was tested, and he also carries a 16p13.11 deletion.

So here’s the lesson: if Jack’s doctors had known about the link between 16p13.11 and psychosis as soon as it emerged, they might have also suggested testing Jack’s father. If they had, the BCH doctors “believe that the psychosis could have been averted in both father and son.”

In light of this case, the BCH researchers write that they see a keen need for broad, integrated, and sophisticated infrastructure to support genomics-driven precision medicine. They have several recommendations, including that physicians need to receive regularly updated risk information about specific mutations; genetic reports on parents who are “carriers” but seem unaffected should note that problems could arise later, and families that include carriers of variations that increase risk should be monitored and given counseling.

Such activities will be well supported by tools such as WuXi NextCODE’s Genomically Ordered Relational (GOR) database and global platform for diagnosing rare disease and building a global knowledgebase. This can act as one of the key spokes in the “wheel” of genomic diagnostic process. But we also need to build in others, such as means to automatically alert doctors to important knowledge updates, monitor patient records, and connect doctors to specialists who can help refine a diagnosis as new discoveries are made. We and our partners at BCH are committed to helping create these tools.

*  *  *  *  *  *  *  *  *  *  *  *

Headed to ASHG? If you are attending ASHG this month, join us to hear more about how rare disease studies can inform our understand of common diseases at two of our “Genomes for Breakfast” events: “Using Population Genomics to Understand Common and Rare Disease” (Oct. 18), and “Using NGS to Diagnose Rare Disease—Experiences from Three Continents” (Oct. 19).

From Rare to Common: How Rare Diseases Could Advance Schizophrenia Treatment

Posted on by

Rapidly advancing our understanding of rare diseases is a key area of focus for us at WuXiNextCODE. We believe genomics can both transform our ability to understand and diagnose rare conditions, and that this is going to point us is the direction of developing new treatments. At the same time, there is a growing body of evidence and even approved new therapies that show that an understanding of rare diseases can also shed new light on the genetics of complex diseases, such as heart disease, arthritis, and schizophrenia.

Understanding complex diseases is a mammoth challenge because multiple genes are usually involved as well as environmental factors. It’s particularly hard with neurologic conditions. No animal models can really mimic what happens in people’s brains, and human studies usually only provide hints of the information needed to identify potential treatments.

But rare diseases are often caused by single variants that perturb specific and identifiable biological pathways. That’s why recent genetic studies of rare types of early-onset psychosis have inspired so much interest among researchers studying schizophrenia. This disease affects more than 50 million people worldwide, but early-onset cases are very rare, suggesting they may be extreme manifestations.

A new line of inquiry into this condition emerged after a group of our close collaborators at Boston Children’s Hospital, including a scientist now at WuXi NextCODE, used chromosomal microarray analysis and whole exome sequencing in a six-year-old with profound symptoms of psychosis. They discovered this patient had a variation in the ATP1A3 gene, which was not previously associated with schizophrenic symptoms. The team wondered: was that mutation helping cause his symptoms? Would the same mutation be found in other children with early-onset schizophrenia? Could this new lead point to a biological pathway common to many people, young and old, with these same symptoms?

That would be a real breakthrough, both for this child and potentially for many other people.

The Puzzle of Schizophrenia Genetics

Schizophrenia is one of the most serious and common mental illnesses. It is often very difficult to treat, in part because of available drugs’ side effects. There are already about a dozen anti-psychotics on the market for this condition. Besides causing serious side effects, treatment must also usually be life-long. Doctors often have to try different drugs until they find something that works and which the patient can tolerate. Even then, the patient’s response can change over time.

The genetics of the disease are still not well understood. Studies of families and populations show it is heritable – the more affected close relatives someone has, the more likely that person will develop it. Many families are afflicted by both schizophrenia and bipolar disease, suggesting the two conditions are biologically related.  Both conditions seem to be associated with multiple mutations to possibly dozens of genes. Still, even in identical twins – who share exactly the same mutations – it’s not uncommon for only one twin to be affected.  Clearly, there is something other than genes afoot.

Scientists, notably including our colleagues at deCODE genetics, have put their fingers on a few genes and key pathways. Another large genomic study, with more than 30,000 cases and 100,000 controls, pointed to over 100 potential spots in the genome with mutations associated with schizophrenia. Both have found an association with mutations in a region called MHC (Major Histocompatibility Complex), a result that reinforced a then percolating idea that schizophrenia might be related to immune dysfunction.  And then just this week, Chinese researchers reported a new trove of suggestive genetic factors. But despite these massive gene hunts, we are still far from a complete picture of what genes cause this disease and how.

A Promising New Lead?

As described in the BCH blog Vector, The BCH team who found that ATp1A3 mutation in the six-year-old boy decided to do some more digging. The chromosomal microarray analysis showed that he was missing an entire chunk of DNA – one copy of the chromosomal region 16p13.11.  Next, they searched their database and found several other children with variations in that area.  One had a duplication of the 16p13.11 region, rather than a deletion. She had started experiencing hallucinations at the age of 4.  Those findings prompted the BCH researchers to launch a large-scale study, which has already enrolled at least 50 children with early-onset psychosis and will be able to leverage WuXi NextCODE’s informatics and global knowledgebase to find more cases, at BCH and beyond.

The researchers hope that ultimately their studies will not only help children with early-onset schizophrenia but also point to the biological pathways that cause the more prevalent form of the disease, which usually strikes adolescents and young adults.

Such research will hopefully provide firm leads on novel pathways that can be used to identify new drug targets. There is a tremendous need for new medicines. Most of the antipsychotic drugs we have today were developed back in the 1950s and act on the dopamine and/or serotonin receptors. They don’t improve all of patients’ symptoms, and as noted earlier, they can have serious side effects.

By uncovering new biological pathways, groups like the researchers at BCH, able to leverage massive global genomic data like that we are able to provide, aim to uncover such targets and begin the journey to providing better options for patients with rare and common diseases alike.

If you are attending ASHG this month, join us to hear more about how rare disease studies can inform our understanding of common diseases at two of our “Genomes for Breakfast” events:  Using Population Genomics to Understand Common and Rare Disease (Oct. 18), and Using NGS to Diagnose Rare Disease – Experiences from three continents (Oct. 19).

 

 

 

Let’s Speed the Genomic Revolution, UK CMO Says

Posted on by
Sally Davies genomics

Whatever path various societies take to tap the power of the genome to improve human health, a recent report from England’s Chief Medical Officer, Dame Sally Davies, calls out key elements for realizing that future sooner rather than later.

England’s Chief Medical Officer wants to build on the success of Genomics England’s 100,000 Genomes Project and take her country swiftly into the age of precision medicine. The goal is to get patients optimal treatment more quickly and with fewer side effects. That means using genomics to more accurately guide prescribing—initially for cancer, infections, and rare diseases—but increasingly for all conditions and overall wellness and prevention.

Dame Sally Davies’ vision is anchored in the work that Genomics England is engaged in today and to which WuXi NextCODE and other leading genomics organizations have contributed. It’s a rallying cry that many voices are joining and underpins our work not only in England, but also similar efforts we are helping to advance in countries near and far, from Ireland to Singapore.

Her call is particularly forceful in three areas that she rightly singles out as critical to realizing the potential of precision medicine to revolutionize healthcare:

  • Industrial scale: Genomics has in many ways been treated and developed as a “cottage industry,” yielding important advances. But the need is massive scale in the era of population health (e.g., whole-genome sequencing, or WGS).
  • Privacy AND data sharing: Dame Sally wants to provide and ensure high standards of privacy protection for genomic data but is adamant that this should not come at the price of stifling the data sharing and large-scale collaboration that will transform medical care and many patients’ lives. She wants to move beyond “genetic exceptionalism,” which holds that genomic data is fundamentally different or more valuable than other data. Like other sensitive data, we can protect genomic data well and use it for public benefit.
  • Public engagement: She calls for a new “social contract” in which we, as individuals and members of society, recognize that all of us will benefit if we allow data about our genomes to be studied. That holds whether we are talking within our own countries or globally.

In England, as elsewhere, these shifts require the input of political leaders, regulators, and a range of healthcare professionals, including researchers as well as care providers. Crucially, such a transformation also requires a level of commitment on the part of patients throughout the National Health Service (NHS) and citizenry in general. If England takes this bold step forward, it could have tremendous effects. But “NHS must act fast to keep its place at the forefront of global science,” said Davies. “This technology has the potential to change medicine forever.”

To date, more than 30,000 people have had their genomes sequenced as part of the 100,000 Genomes Project. But there are 55 million people in the UK, and Dame Sally would like to see genomic testing become as normal as blood tests and biopsies for cancer patients: She wants to “democratize” genomic medicine, making it available to every patient that needs it.

We share and are, indeed, taking part in helping to realize much of Dame Sally’s vision as we work to accelerate Genomics England’s work and engage with our partners globally. As we know, different societies have different models of healthcare and different approaches to research and care delivery. But the ability for people anywhere to tap into the power of the genome to improve their health is at the very core of our own mission as an organization, and we applaud Dame Sally for calling out some of the key elements for realizing that future sooner rather than later.

Whatever path different societies choose to follow toward precision medicine, her recent report provides one enlightening view of a starting point for making the leap.

Speeding Diagnosis of Rare Diseases

Posted on by
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.

Genomics: Forging Patient-Centric Communities

Posted on by
patient-centric-communities-hannes-smarason

Genomics has become a foundation for virtual patient-centric communities involving patients, caregivers, clinicians, and researchers worldwide.

In recent years, genomics has become a foundation for virtual patient-centric communities – communities built on the Internet and through social media that:

  • Connect people touched by a disease or disorder; or
  • Reach out to broad populations affected by rare diseases, many of whom are undiagnosed.

These patient-centric communities are dedicated to sharing information and providing support in order to break down the barriers of isolation and uncertainty that can compromise care and adversely affect quality of life for patients and their families.  As we learn more about the genetic variations that contribute to diverse conditions, virtual communities that are fueled by genomics contribute an ever-expanding resource.

Virtual communities have greatly affected patients and caregivers worldwide, and the relationships forged through genomics are essential to clinicians and researchers as well.  Genomics not only serves to link patients to each other but also to connect those patients to research initiatives that use genetic sequencing to diagnose conditions and guide treatment, thus improving patient outcomes today while influencing research for better therapies tomorrow.

RareConnect, for example, is an online platform that connects patients, caregivers, clinicians, and researchers in more than eighty disease-specific communities.  Another leader in this arena is PatientsLikeMe, which has activities that encompass more than 400,000 members with over 2,500 conditions.  Many diseases and conditions are identified by genetic abnormalities or characteristics.  Participants in RareConnect, PatientsLikeMe, and similar sites are drawn in part to the ways in which genomics could contribute to an accurate diagnosis, a novel treatment, and ultimately a cure.

The use of genomics to build communities has been especially important for rare diseases.  For patients and caregivers affected by the rarest of rare diseases – the disorders so rare that only a handful of known cases exist worldwide – the transformative role of genomics is that much more powerful.

An excellent article in The Atlantic tells the story of one young woman whose experience illustrates this phenomenon.  A genomic study identified the genetic mutation that underlies Lilly Grossman’s movement disorder.  The information provided by genomics has enabled the formation of a virtual community.

Lilly’s case has acted as a magnet for others with the same mutation. Families with the same problem read about Lilly’s case and contacted the Grossmans. Doctors and geneticists looked at their own patients and saw a new explanation behind puzzling symptoms. Before, there were isolated pockets of people around the world, dealing with their own problems, alone for all they knew. Now, there’s a community.

The connections forged through genomics are essential to patients, often children, and their caregivers, often families.  Genomics can provide the vital link, the piece of information that identifies individuals with similar experiences – the community of people who understand.  Patient-centric communities are one way in which the increasing availability of cost-effective genetic sequencing is transforming patient experiences, shortening diagnostic odysseys, and improving clinical care.

Many such communities are also critical for advocacy and fundraising.  Parent Project Muscular Dystrophy (PPMD), for instance, has worked effectively to promote Duchenne muscular dystrophy research and speed the discovery of potential treatments. PPMD has demonstrated how parents and caregivers can effect meaningful change, raising both awareness and financial resources – and even being a leading voice in support of FDA approval of therapeutics.

The intersection of genomics and social media increasingly drives progress, too. The Charlotte & Gwyneth Gray Foundation, for example, has raised an estimated $3.5 million to support CLN6-Batten disease research – through a crowdfunding initiative launched less than a year ago.

And coalitions of patient-centric communities can achieve significant advances through the power of numbers. Thus Genetic Alliance, a network of more than 10,000 organizations, was a key player in passage of the Genetic Information Nondiscrimination Act and in development of the National Patient-Centered Clinical Research Network.

Initiatives run the gamut from efforts to identify a handful of individuals with rare diseases to projects that aim to enroll thousands of participants.  Earlier this month, the University of Washington launched MyGene2, a site where families with rare conditions can publicly post their stories, establishing connections not only with those who share similar stories but also with clinicians and researchers.  At the other end of the spectrum, 23andMe has partnered with a number of Parkinson’s community groups on a project to gather genetic data from more than 11,000 individuals.

And, in the last year, the Simons Foundation Autism Research Initiative (SFARI) launched SPARK, a project to collect genomic information from 50,000 people with autism and their families.  At WuXi NextCODE we are delighted to participate in this endeavor by providing direct online access to the data.

Genomics has played a critical role in the evolution of patient-centric communities.  Groups that have developed resources and advice for patients and families are increasingly collaborating with clinicians and researchers.  Through voluntary contributions of personal knowledge – and genomic data – participants in patient communities are expanding the impact of genomics on medicine.  The growing power of virtual communities has facilitated numerous initiatives to improve patient outcomes through improved diagnosis, optimized standards of care, and new directions for promising research.

From rare diseases to disorders that affect millions, all stakeholders increasingly use genomics to translate individual experiences and expertise into meaningful improvements in the lives of patients and their caregivers.  Genomics sits at the powerful nexus between evidenced-based medicine and the empowered patient.  At WuXi NextCODE we are proud to advance the role of genomics not only in patient care but also in the evolution of strong, effective patient-centric communities.

Marking Progress in Genomics: Reflections and Prospects

Posted on by

Progress in Genomics WuXi NextCODEAs leaders of our field gather in Vancouver for the annual American Society of Human Genetics Meeting (ASHG 2016), it is an excellent time to take stock of the past and clarify our perspectives for the future. For the field of genomics, this is an opportunity both to reflect on our accomplishments over the last few years and to consider what we can achieve in the years ahead.

Indeed, our accomplishments have been numerous and our goals are ambitious, yet achievable. Here, I would like to summarize five significant ways in which our work in genomics has been revolutionizing medicine and improving patient outcomes.  In addition, I would like to share my thoughts about five areas in which I believe our field can drive meaningful change over the next few years.

What We Have Achieved
1. Improvements in Sequencing Technology and Analytical Tools
The ever-increasing volume of genomic data is testimony to the dramatic increases in sequencing speed and efficiency over recent years.  At the same time, novel methods of analysis, like the powerful genomics platform employed here at WuXi NextCODE, have considerably advanced our understanding of genetic variations and their clinical significance.

2. Transformations in Cancer Treatment
As I have discussed here, the expanding use of genomic data to guide treatment decisions in oncology is transforming the way clinicians approach cancer treatment.  In addition, our growing understanding of genetic predispositions for certain cancers is helping high-risk individuals make informed choices about preventive care.

3. Progress in Rare Diseases
Genomic data has brought new hope to families struggling with rare diseases by shortening diagnostic odysseys, guiding treatment, and building communities.  I provide examples of the game-changing power of genomics in the diagnosis of rare diseases here.

4. Empowerment of Patients and Consumers
Patients and consumers are increasingly informed about the innovative and meaningful ways in which genomic data can guide healthcare decisions.  The successes in our field are empowering individuals to pursue personalized medicine and generating interest in direct-to-consumer testing.  I offer my thoughts about DTC genetic testing here.

5. Innovations in Cloud-Based Analysis
The vast and ever-growing quantity of genomic data and related information necessitates new approaches to storage and analysis.  As I have previously discussed, cloud-based computing is essential to continued success in genomics.  WuXi NextCODE’s Exchange is at the forefront of the accelerated research made possible by real-time collaboration and analysis in the cloud.

What We Can Achieve in the Years Ahead

1. Effective Communication and Collaboration
Realizing the full potential of big data and cloud-based computing will require new efforts to dismantle “data silos.”  I am encouraged by recent initiatives to facilitate collaboration in cancer research, and – as I have recently discussed – call upon researchers and clinicians throughout the field of genomics to improve communication among all stakeholders.

2. Policies for Research with Patient Data
Our field derives its greatest power from careful analysis of genomic data, and access to data is critical to effecting meaningful change in healthcare.  In order to gather this game-changing data – from patients, from consumers, and from population-wide studies – we need to develop and embrace policies that lead to consider the ‘biorights’ of patients.  Individuals who wish to contribute information for research should have the opportunity to do so, and all parties should clearly communicate the purposes and extent of data-sharing.

3. Integration for Clinical Trials
I perceive significant movement toward the development of clinical trials that test the efficacy of treatments tailored to specific genetic anomalies – and use genetic information to screen participants.  This is an area in which genomics will dramatically accelerate the development of personalized therapies that will surely improve patient outcomes.

4. Actionable Information from Population-Wide Genomic Studies
I believe that in the near future we will reap significant rewards from projects that gather population-wide genomic information.  Analysis of the data we are collecting around the world, which I describe here, is an essential step to reshaping healthcare practices worldwide.

5. Globalization of Genomic Products: ‘Think Globally, Act Locally’
The power of genomic information is now known throughout the globe, and can be applied in a multitude of positive ways.  With such widespread potential, individual countries and cultures will choose to advance and roll-out genomics in their own distinct ways for the benefit of their citizens.  Companies that develop genomic products will need to adapt and design their products for use in specific markets.  At WuXi NextCODE, the first focus of our product portfolio for individual patients and families is in China, where we are delivering three offerings: population-optimized diagnostics, carrier screening, and whole-genomic wellness scans.

Together these initiatives build upon our recent accomplishments and further the creation of data and analysis necessary for meaningful change in healthcare.

The genomic revolution in medicine that we envisage will be achieved through applied use of research and development that is:

  • Fueled by big data, including data provided by informed consumers and patients and data derived from population-wide studies;
  • Supported by clinical trials crafted to assess the safety and efficacy of treatments tailored to individual characteristics; and
  • Enabled by collaborative work and effective communication.

At WuXi NextCODE, we are energized by the prospects for genomics in the years to come. We are proud to be at the cutting edge, providing the tools and resources that researchers and clinicians need to harness the transformative power of genomic data. And—importantly—we are confident that our field will continue to drive meaningful changes in healthcare that improve patient outcomes.