Tag Archives: genomics

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

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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.

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New Breast Cancer Study Underscores the Need for More Sequencing

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Gene sequencing for breast cancer. More than the usual suspects at play.

Ever since actress Angelina Jolie’s highly publicized preventive mastectomy ignited discussion about BRCA 1 and BRCA2, almost everyone has heard about these genes and how they can increase risk of breast cancer.  Some people even refer to them as “the breast cancer genes.” But how genes cause this disease is much more complicated than just through the most well known BRCA mutations, as a recent study in JAMA of Ashkenazi Jewish women has demonstrated. http://jamanetwork.com/journals/jamaoncology/fullarticle/2644652

This intriguing study raises a crucial question: How much sequencing is enough when diagnosing breast cancer in the age of targeted therapies? The number of these therapies keeps growing, as does our knowledge of the links between what drugs work for women with particular mutations. But at what point should we say we have uncovered enough mutations to make a proper diagnosis? And in a field in which we know there’s a lot we don’t know, is there such a thing as enough?

The good thing is that sequencing costs are going down. “It used to be that just testing for a single gene cost several thousand dollars,” says Jim Lund, Director of Tumor Product Development at WuXi NextCODE.  “Now a panel of genes costs that and whole exome sequencing is slightly more.” At the same time, the number of mutations that are discovered and studied is increasing – in the genomes of patients and the genomes of their tumors.

The data here has a message about data itself: in principle, we should be generating as much sequencing data as possible. By generating it, storing it for vast numbers of patients and their healthy relatives, creating more comprehensive databases of all disease-linked variants, and then reanalyzing patient and tumor samples as more is learned, we can improve the risk assessment and the speed and accuracy of diagnosis for patients everywhere. Since we can do this, the question isn’t whether we can afford to do more sequencing, but why anyone would argue that we can afford not to.

The researchers who led the recent JAMA study used multiplex genomic sequencing on breast tumor samples from 1007 patients. They tested for a total of 23 known and candidate genes.  It has been well documented that women of Ashkenazi descent have a higher risk of breast and ovarian cancer, and that is at least in part because of three particular BRCA1 and BRCA2 mutations. These are called founder mutations, because they probably originated among some of the earliest members of this ethnic group, and have been propagated because of a strong history of marriage within the same community.

But the researchers working on this study wanted to know if there were mutations in other genes besides BRCA that made it more likely these particular women would develop breast cancer. The patients were from 12 major cancer centers; had a first diagnosis of invasive breast cancer; self-identified as having Ashkenazi Jewish ancestry; and had all participated in the New York Breast Cancer Study (NYBCS).

Surprisingly, only 104 of the patients were carrying one of the infamous founder alleles. Seven patients had non-founder mutations in BRCA1 or BRCA2, and 31 had mutations in other genes linked to increased risk of breast cancer, including CHEK2. The vast majority of these women carried none of the mutations that are “obvious suspects” for breast cancer. “We do not know why those women got breast cancer,” says Shannon T. Bailey, Associate Director of Cancer Genetics at WuXi NextCODE.

It’s important to note that thousands of different cancer-predisposing mutations have been found in BRCA1 and BRCA2 alone. Every population studied to date includes people with such mutations.  The three founder mutations that have been established as being common among Ashkenazis are estimated to account for about 10% of breast cancers in this group. The rest of BRCA1 and BRCA2 mutations are considered extremely rare under any circumstances.

“If you look at the genes on the panel used in this study, it looks as if they are mostly associated with DNA damage and there are no cell cycle regulating genes included,” says Bailey. “But there are all kinds of mutations that cause breast cancer, even in noncoding regulatory zones.” As a result, even the best designed panel may fall short.

That’s why this study is so important. It tells us that even with founder mutations, family history matters but it doesn’t yet always tell you everything you’d like to know. Of the women with the founder BRCA mutations, only about half had a mother or sister with breast or ovarian cancer.  It’s also already well known that just carrying a BRCA1 or BRCA2 mutation is no guarantee the patient will get cancer. For reasons we don’t yet understand, these mutations raise overall risk, but not everyone who carries one will develop the disease. So while BRCA mutations are important, we need lots more information about other genes too.

The authors of this JAMA report suggest that Ashkenazi patients with breast cancers should have “comprehensive sequencing,” including, perhaps, complete sequencing of BRCA1 and BRCA2 and possibly testing for other breast cancer genes as well.

And what about other patients?  WuXi NextCODE’s Lund points out that even the most highly regarded recommendations for breast cancer testing do not cite specific panels. Those recommendations come from the U.S. Government Task Force [https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/brca-related-cancer-risk-assessment-genetic-counseling-and-genetic-testing] and the NCCN Clinical Practice Guidelines. Women with a family history will likely get more comprehensive testing, but beyond that it is not clear exactly how to proceed in every case.

At WuXi NextCODE we believe that this is clear evidence pointing to the value of doing more sequencing across all ethnic groups – for healthy individuals, patients, and their tumors, and pushing towards sequencing as standard of care. This would expand our knowledge of the genetic risk factors for breast and other cancers; provide vast new cohorts for research; and deliver the most actionable insights to patients, from risk assessment through diagnosis and then ongoing as new discoveries are made.

All of the participants in this JAMA study consented to have their sequence data used to advance research. They are already helping to do that, and this is just one study of thousands that are now underway and that are helping us to expand our data- and knowledgebases with the ultimate aim of delivering even better outcomes for all people and patients everywhere.

Domain Expertise: Jumpstarting Artificial Intelligence in Biomedicine

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Is artificial intelligence the “single most transformative technology in modern history?” That’s the view of Tom Chittenden, who leads WuXiNextCODE’s AI program. And Tom is not alone in his enthusiasm, as numerous analysts are predicting this technology will be one of the fastest growing fields in the world.

In recent talks at Boston’s BioIT World and the EmTech conference in Hong Kong, Tom described some of the strides we’ve been making with our DeepCODE AI tools. Their power is in part thanks to a novel, causal statistical-learning method and deep-learning classification strategy. But another advantage is that they were built on—and are extending the reach of—our global platform for genomic data. That means that Tom’s team has that rare combination of both of the key ingredients to AI making an impact in biomedicine: cutting-edge algorithms AND deep domain expertise and access to the biggest datasets.

Tom—who also holds appointments at Harvard, MIT, and Boston Children’s Hospital—and his growing team have the former in spades; our platform and expertise in genomics provide a key edge in the latter. Our platform has been built over more than 20 years and today underpins the majority of the world’s largest genomics efforts and includes all major global reference databases. It stores, manages, and integrates any type of genomic data and correlates it with phenotype, ‘omics’, biology, outcome, and virtually any other type of data that may be relevant to a particular medical challenge.

That means that we can routinely train and test our AI tools on some of the most comprehensive data sets in the world, such as that in The Cancer Genome Atlas (TCGA). “Today we can take ‘omics data and clinical information and map those to curated resources such as SNOMED CT and biomedical ontologies, and then use AI to identify patterns that lead us to novel findings,” Tom says.

This is a powerful approach to tease out which of hundreds of genetic variants are really involved in a particular disease, based on which ones are actually associated with aberrant expression pathways. You may find hundreds of genetic mutations in a single type of breast cancer tumor, for example, but it is determining which ones are drivers of the disease that matters.

Put simply, AI can lead us to both better diagnoses and easier discovery of more and better drug targets, by taking a range of genomic data and marrying it to clinical information and scientific knowledge. AI is not just going to better match patients to the right drugs, it is going to help further our understanding of the relationships between genes and complex molecular signaling networks, one of the most challenging arenas in our field and the most sought-after starting point for discovering validated pathways and targets.

Valuable insights in real-world medical challenges are already emerging from this AI effort uniquely developed on and applied to the genomic and medical data that counts.

WuXi NextCODE  recently presented preliminary data from analyses using our novel AI technology to diagnose subtypes of tumors. Our DeepCODE tools were validated on six patient-derived tumor xenografts from mouse models, and then tested against approximately 8,200 human tumors from a collection of 22 cancer types in The National Cancer Institute’s TCGA collection. That study included five ‘omics data types. We achieved 98% accuracy overall, and our analyses of human breast and lung cancer subtypes were accurate in 96% and 99% of cases, respectively. This points to an improvement over current methods for matching patients to treatments for their particular cancer, and we have refined that accuracy further still. This capability is also going to be central to the development of liquid biopsies.

http://hannessmarason.com/blog/2017/04/04/a-perfect-pairing-ai-and-precision-medicine/

In another oncology study, using the same multi-omics data, DeepCODE identified a signal predictive of survival across 21 cancers, pointing to novel and holistic pathways for developing broad oncotherapies.

A recent study published in Nature, meanwhile, describes a potential new role for a well-known growth factor. That report, led by Yale University scientist Michael Simons, looked at blood vessel growth regulation—a crucial process in some very common conditions, including cardiovascular disease and cancer. Our Shanghai team provided RNA sequencing for this study. Our Cambridge AI team drove some of the key insights pointing to novel disease mechanisms.

Simons’ team studied knockout mice, whose fibroblast growth factor (FGF) receptor genes were turned off. They proved, for the first time, that FGFs have a key role in blood vessel growth, uncovering some metabolic processes that were “a complete surprise,” according to scientists on the team. Further, they mapped out pathways that could help provide new drug leads.

http://hannessmarason.com/blog/2017/05/15/bringing-artificial-intelligence-cardiovascular-medicine-cancer-genomics-action/

Our AI team is just getting started. We’re looking forward to many more intriguing findings from this group as they leverage their expertise and massive amounts of the relevant data to improve medicine and healthcare.

Bringing Artificial Intelligence to Cardiovascular Medicine and Cancer: Genomics in Action

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WuXi NextCODE Nature

A Yale research team, with contributions from WuXi NextCODE’s artificial intelligence (AI) and sequencing teams, has discovered a novel mechanism regulating how blood vessels grow.

Artificial Intelligence (AI) can already catch a criminal and identify the right patients for certain types of surgery. But those challenges involve relatively few parameters compared to number of parameters or features involved in linking the 3 billion bases in the human genome with other ‘omics data and all the complexity of human biology. For that very reason, the promise of AI in genomics is as necessary as it is enticing, and WuXi NextCODE is committed to pushing the frontier of this emerging field.

This week, I am encouraged by results from a study published in the latest edition of Nature, which describes how a well-known growth factor may play a previously unknown role in some important diseases. That report, led by Yale University scientist Michael Simons, investigates blood vessel growth regulation—a crucial process in some very common conditions, including cardiovascular disease and cancer. Our Shanghai team provided RNA sequencing for this study. Our Cambridge AI team applied some of the most advanced statistic in their toolset to take the data analysis to the next level.

Simons’ team studied knock out mice, whose fibroblast growth factor (FGF) receptor genes were turned off. The scientists were able to prove, for the first time, that FGFs have a key role in blood vessel growth, uncovering some metabolic processes that were “a complete surprise,” according to scientists on the team. Further, they mapped out pathways that could help provide new drug leads.

It’s inspiring to see scientists from around the world using top-notch technology to collaborate on pivotal research questions. This study involved scientists in six different countries.

This FGF study also comes on the heels of our recent announcement about how our deepCODE approach classified 27 different tumor types with greater than 95% accuracy when applied across approximately 9,000 human tumors from The Cancer Genome Atlas (TCGA) collection. [LINK: https://www.wuxinextcode.com/highlights/posters-at-aacr/#/brief–using-ai]

With the rapid rate of progress, it’s not surprising that AI is finding success in genomics. Today’s informatics capabilities allow for assimilating larger and larger datasets with AI applications, and the field is evolving at a rapid pace. Google alone published more than 200 papers on AI in 2016. Like us, they use a deep learning approach.

From facial recognition to genomic solutions
Each AI problem has a different scale. In facial recognition, AI applications analyze relatively few features in the human face (about two dozen). Digital scans of the human eye that use AI techniques are able to segment patients before eye surgeries, and this entails algorithms that consider hundreds of features.

Genomics, of course, involves looking at any number of feature sets among billions of possibilities. It’s an immense challenge, but I think it’s perfectly suited to AI. And with deep-learning tools, we can fish out many more insights than with traditional analyses.

Our goal is to see how AI can help researchers achieve better results in identifying and evaluating new medicines, pinpointing risk factors and disease drivers, finding new combination therapies that work better than single drugs, and more. Our deepCODE tools comprise a novel, multinomial statistical-learning method and deep learning classification strategy. It’s an advanced approach to AI.

This week’s Nature paper is another encouraging sign.

Many of the stickiest problems in medicine are longstanding. The role of FGFs in blood vessel development was poorly understood until now. This group’s findings may help open new avenues of research.

Our team is always seeking to tackle problems with the latest approaches and technologies. Now, in the age of big data, it makes sense to start letting computers do more and more of the work, even some of the actual thinking. Certainly, we pick the questions and frame them. But then, let’s load the data and let the machines help us find the answers. If we can polish this process, and apply it to a growing number of problems, new answers and insights are sure to come.

Genomics: Forging Patient-Centric Communities

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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

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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.

Genomic Information and the Importance of Communication

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Communicating clinically useful results both to doctors and patients will drive success

genomics-communications-hannes-smarasonAround the world, researchers and clinicians are taking on the challenge of integrating genomic analysis into medical practice. Physicians and patients are increasingly aware of the potential utility of genomic data. As genomics continues to become a more powerful tool in healthcare, there is a clear and compelling need for a commitment to excellence in communication.

At WuXi NextCODE, we are proud to provide sequencing and analysis resources that help doctors:

  • Shorten diagnostic odysseys, as I have discussed here; and
  • Improve treatment choices, as I have discussed here.

Maximizing the opportunities afforded by the ‘big data’ of genomics necessitates collaboration and communication, which I discuss in more detail here. As part of our genomics business, we are dedicated to the highest standards of communication – indeed, we view effective communication as central to how our technologies will improve health in both the near and the long term.

The task of harnessing the vast and expanding quantity of genomic data to improve clinical care requires interpretation and discovery powered to translate the data into clinically useful information. Leveraging that information to improve patient outcomes also requires clear and accurate communication:

  • Between researchers and clinicians;
  • Between specialists in different medical fields;

And, increasingly,

  • Between doctors and patients.

As the recent CLARITY Undiagnosed competition highlighted, applying genomic data to medical practice involves interpreting the sequenced genomes and identifying molecular diagnoses – and a third step: communicating clinically useful results both to doctors and to patients.

The CLARITY challenge winners, including WuXi NextCODE, were explicitly recognized for the quality and clinical utility of their reports.

Studies and surveys have shown that many people favor greater access to genetic information. Individuals want analysis of their genomes in order to:

  • Reveal their unique risk factors for inherited diseases;
  • Pinpoint a diagnosis if they are ill; and
  • Guide their decisions if they are seeking treatment.

Genomics is helping to inform patients in all these ways.

In addition, genomics demonstrates enormous potential to empower individuals.

The hundreds of thousands of people who purchase genomic testing through direct-to-consumer businesses like 23andMe are demonstrating a robust enthusiasm for gathering genomic information. And patients enrolled in clinical trials and donors participating in population-wide genomic studies express a desire to be more informed. Patients and consumers consistently seek resources that transform their personal genomic signatures into information they can use to make better healthcare and lifestyle decisions.

And most patients and consumers are willing – often eager – to share their genomic information to aid medical research and discovery. 23andMe reports, for example, that 80% of its customers consent to share their genomes for research.

It is unmistakably clear that, in the not-too-distant future, every individual in many countries around the world will have their genome sequenced. Throughout a person’s life, medical professionals will be able to access genomic information to guide health decisions – from identifying inherited conditions to assessing risk for complex diseases to calculating appropriate treatments, drugs, and even dosages for truly personalized healthcare.

The more effectively we communicate – the more we share information within the research community and parlay that into clinically useful information for patients – the greater the benefit to all.

As much as people understandably prefer simple, definitive answers to questions about their personal health, the information that genomics provides can be complex and even ambiguous. A genetic variant might be identified, for example, that can be tied to family medical history and translated into a probability or likelihood. This was the case for Angelina Jolie Pitt, who noted in her New York Times piece that her genomic analyses “gave [her] an estimated 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer.” Percentage risks are nuanced, and individual perceptions of acceptable risk vary considerably. It is therefore difficult to define precisely the circumstances under which a genetic variant becomes clinically actionable.

Or a genetic variant might be identified which gives physicians clues but does not explicitly identify a specific disease. For example, a patient seeking a diagnosis may have a genetic variant that correlates to a number of diseases involving dysregulation of lipid metabolism. Identifying the variant provides physicians and caregivers with a clear direction for further analysis and treatment, but does not yield a conclusive diagnosis or prognosis.

Or a genetic variant might be identified which has yet to be understood as causing or playing a role in disease. Such a variant may occur by chance and have no medical relevance, or its meaning may be uncovered as science in the field advances. But for the person who is having the genomic information analyzed today, it offers no actionable information.

As all of these examples illustrate, effective communication about genomic information can be a significant challenge. There is a risk that poor communication will be a barrier to the adoption of genomic medicine, but if we strive to communicate clearly with patients and the public, our successes will likely accelerate more widespread use of genomics. The role of genomics in transforming health care will grow exponentially as we all endeavor to improve communication with patients, their families, and the public at large.

Our work at WuXi NextCODE is advancing the transformation of medical practice through genomics. As part of that vision, we recognize the critical importance of facilitating effective communication among all stakeholders. We provide the resources that enable researchers and clinicians to identify disease and inform treatment decisions. And we strive to add additional value by communicating about genomic information accurately and proactively, all with the ultimate goal of meaningfully improving patient outcomes.

Genomics: Big Data Leading to Big Opportunities

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The Big Data of Genomics

WuXi NextCODE Exchange

The big data of genomics will continue to expand, and our approaches to analyzing genomic data need to continue to evolve to meet the growing demands of clinicians and researchers. Cloud-based platforms such as WuXi NextCODE’s Exchange are essential to address the fundamental big data challenge of genomics.

Beyond question, we are in the midst of an explosion of “Big Data” in many facets of human endeavors. In fact, data-storage leader IBM asserts that roughly 2.5 quintillion bytes of data are generated every day and 90% of the world’s data was created in the last two years.

An outpouring of articles in scientific journals and major newspapers has highlighted the promising potential of big data in medicine, including a special section in the current issue of Nature.  Genomics has become a major source of the growth of such big data, particularly as the cost of sequencing genomes has plummeted. The raw sequence data for just one person’s whole genome use as much as 100GB—and already hundreds of thousands of individual genomes have been sequenced.  With more than 2,500 high-throughput sequencing instruments currently used in 55 countries across the globe, more genomes are added every day. The aggregate amount of genomic data is growing explosively, and next-generation sequencing (NGS) sequencing data are estimated to have doubled in volume annually since 2007.

The accumulation of genomic data is a worldwide phenomenon.  Impressive population-wide sequencing efforts are leading the way, from 100,000 genomes in England, Saudi Arabia, and Iceland to 350,000 in Qatar to a million in both China and the U.S.

And earlier this month, the CEO of the Cleveland Clinic predicted that soon children will routinely have their whole genomes sequenced at birth, implying a near-future in which 10s of millions of new genomes are sequenced annually.

Turning Data into Resources

But sequencing genomes is not enough, and the creation of genomic big data is just the beginning.

Thanks to the analysis of big data in genomics and associated informatics, we are seeing meaningful progress in cancer care and the diagnosis of rare diseases, as I have discussed here and here. We clearly have a tremendous opportunity to use the big data of genomics to continue to drive a revolution in healthcare.

Yet there is a broad consensus that a ‘data bottleneck’ is hampering collaboration and discovery. Not all researchers and physicians confronting the current onslaught of genomic big data can readily determine how to use genetic information to prevent or treat disease. To succeed, researchers and physicians clearly need resources that:

  • Draw together useful data from disparate sources;
  • Facilitate analysis and collaboration; and
  • Improve clinical practice.

The power of genomic analysis needs to expand outward from major research centers and hospitals to the myriad clinics and community hospitals where many patients receive care. To have the greatest impact on the broadest population, clinicians throughout the world’s health systems need access to the big data generated by DNA sequencing, even—or perhaps especially—if they are not affiliated with research institutions. They also need to be able to make sense of the data they have access to.

Answers in the Cloud

Sequencing provides the raw data to uncover the genetic variants that contribute to disease. But the datasets are too big to transfer repeatedly—and too big even for smaller hospitals, labs, or clinics to store onsite. Key medical advancements require not only big data, but also tools and resources to generate, interpret, and share analysis of millions of genomes.

Cloud-based platforms—such as WuXi NextCODE’s Exchange—are essential to address the fundamental big data challenge of genomics. Collaboration in the cloud works to dismantle existing “data silos”—genomic information hosted only on local servers and analyzed on idiosyncratic, closed platforms. The NextCODE Exchange, in contrast, is a browser-based hub that affords secure, seamless collaboration with colleagues around the world. Moreover, users get access to NextCODE’s tools for making the critical links between variation in the genome and disease and other phenotypes, backed by harmonized links to the the most important public reference data.

And cloud-based computing is inherently scalable: resources for data storage and analysis expand as needed, allowing researchers and physicians to leverage massive datasets to improve patient care in the clinic. The big data of genomics will continue to expand, and our approaches to analyzing genomic data need to continue to evolve to meet the growing demands of clinicians and researchers.

At WuXi NextCODE, we have built upon our heritage of conducting the largest analysis of genomic data (deCODE’s path-breaking Icelandic analysis) by assembling an ever-growing database of human genomes. We are committed to driving the movement of sequence data into patient diagnosis and care through user-friendly, leading-edge analysis and informatics. I am confident that data analysis and collaboration in the cloud will revolutionize healthcare, and exceptionally proud that WuXi NextCODE’s Exchange is at the forefront of this exciting advancement.

FDA Approval Moves DTC Genetic Testing Forward

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DTC genetic testing, Hannes Smarason

23andMe is relaunching its direct-to-consumer genetic tests in the U.S. with the approval of the FDA to provide consumers “carrier status” information on 36 genes that can cause rare diseases. I am optimistic that DTC genetic testing will expand its impact over time, ultimately having a tremendous impact on human health globally.

Today, genomics industry maverick, 23andMe, is relaunching its direct-to-consumer (DTC) genetic testing in the U.S., with the approval of the FDA to inform consumers whether they carry a genetic variant for one of 36 rare diseases that could potentially be passed on to their children. In addition to this carrier status information that now meets FDA standards, reports from the newly launched 23andMe test will include information on wellness, traits, and ancestry.

A big positive step forward

For the genomics industry as a whole, this is a significant step forward as the FDA’s decisions have global influence. Indeed, this is a landmark FDA decision, as it is the first time ever that the FDA has allowed such a broad spectrum of medically relevant genetic information to be provided directly to consumers. Both the FDA and 23andMe deserve credit for working through the challenges that, less than two years ago, resulted in the FDA ordering 23andMe to stop marketing its genetic testing kits in the U.S. That the FDA—one of the world’s most thoughtful medical regulatory agencies—has come so far so fast is indicative of the potential it likely sees in DTC genetic testing improving the health of U.S citizens.

A larger journey ahead for direct-to-consumer genetic testing

Moving forward, there are at least two important directions that—in collaboration with the appropriate regulatory agencies, such as the FDA—I think DTC genetic testing will advance:

• DTC genetic testing will expand its reach globally; and
• DTC genetic testing will likely expand the medical impact of its reported results.

DTC genetic testing will expand its reach globally.

Catalyzed by demand for improved health, DTC genetic testing services will inevitably become accessible to much of the world’s population over the decades to come. To be successful, these services will need to be customized by geography and culture and approved by the appropriate local governmental agencies. While the genome is shared by all humans, it is naïve to think that DTC genetic testing services will be the same across all people living anywhere. It is incumbent on industry participants to align their DTC reports and services to best meet the needs of the specific customers in specific countries and geographies—and to do so in a spirit of cooperation with the appropriate governmental health regulators.

DTC genetic testing will likely expand the medical impact of its reported results.

As noted, today’s FDA approval for 23andMe to be able report on carrier status is a significant step forward, but more health data remains to be gleaned—and reported—from an individual’s genomic data. From 23andMe’s announcement, you can see the foreshadowing of what may ultimately be possible:

About [23andMe’s] Carrier Status Tests
[23andMe’s tests] can be used to determine carrier status in adults from saliva collected using an FDA-cleared collection device (Oragene DX model OGD.500.001), but cannot determine if you have two copies of the genetic variant. Each test is most relevant for people of certain ethnicities. The tests are not intended to diagnose a disease, or tell you anything about your risk for developing a disease in the future. On their own, carrier status tests are not intended to tell you anything about the health of your fetus, or your newborn child’s risk of developing a particular disease later in life.

Clearly, working with regulators such as the FDA, and others, such as thoughtful genetic counselors, there is a future potential for the right service to be able to report on people’s risk for developing specific diseases. Informed, health-conscious consumers are very likely to demand access to this information—and millions of individuals have already paid significant sums out of their own pockets to have their genomes sequenced and analyzed. Indeed, from news reports covering 23andMe, we know that when ordered by the FDA to stop providing health information such as the disease risk, their rate of new customer sign-ups dropped by more than half.

I am very optimistic that DTC genetic testing will expand its impact over time, overcoming skepticism and ultimately having a tremendous impact on human health globally. I am proud that our team at WuXi NextCODE will be a part of making this exciting future happen, and today I am especially proud that WuXi Ventures recently invested in 23andMe, making us active supporters of its current and noteworthy success.

Genomics in Cancer: Continuing to Push the Leading Edge

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genomics in cancer - hannes smarason

Genomics is helping to prevent and treat cancer at an accelerating rate, supporting the goal of oncologists to dramatically improve cancer patient outcomes.

The progress in the use of genomics to help prevent and treat cancer continues to grow at a pace that is impressive. Indeed, there is expanded use of genomics to drive patient care and improve outcomes across an ever-expanding number of cancers by a growing number of oncologists.

Genomic Knowledge Can Clearly Drive Better Care

Applying genomics to cancer treatment is a powerful clinical application, as genomics can provide a window into how to best treat a patient’s particular cancer as it:

  1. may help better understand the genetics of the tumor itself, and
  2. can provide insight into how cancerous tumors may grow and spread over time.

With a genomic-based approach to cancer care, oncologists can more personally tailor anti-cancer treatments to an individual tumor’s mutations, thus molecularly targeting the specific cancer’s Achilles heel. Already, there are well-documented successes of molecularly targeted anti-cancer agents, such as cancer drugs that target certain genes—HER2, EFGR, ALK, and others.

In 2015, the pace of adoption of genomics in clinical oncology has advanced significantly. Recent evidence of the accelerating use of genomics to help fight cancer includes:

  • Evolving from ‘why’ to ‘how’ to use genomics at leading cancer centers. At the top cancer care facilities, genomics has become part of the programmatic approach to provide certain cancer patients with optimal care—care that is fundamentally designed to lead to the best outcomes. The question for leading medical centers globally has evolved over the last few years from “do we need genomics?” to “for which cancer types and at what stages of cancer treatment and diagnosis can we best use genomic sequencing and analysis?”—an evolution from “why?” to “how?” at a very fundamental level. The accelerating use and deployment of genomics by leading medical facilities validates that they are deriving significant value from genomics, and that value is resulting ultimately in meaningfully advancing better care for cancer patients.
  • Expanding potential applications of genomics within different types of cancers, broadening the types of cancers and tumors that can potentially benefit from genomics. Researchers and clinicians continue to publish a wealth of information validating the potential of genomics to improve outcomes in certain types of cancer patients. In 2015 alone, highlights of these advancements include certain prostate cancers, brain cancers, rare types of pediatric kidney cancers, and even potential targets in certain non-small cell lung cancers.
  • Broadening acceptance in cancer prevention. Driven in part by the education of oncologists and physicians generally and in part by the empowerment of knowledgeable patients, people are seeking and benefiting from genetic tests that reveal their personal risk for certain tumors (such as BRCA for breast or ovarian cancers). The idea of using genomic analysis to predict an individual’s cancer risk by comparing their genome with databases of confirmed genetic mutations linked to disease is—for certain individuals with specific family histories and genetics—driving appropriate medical decisions for patients who may be at high risk for certain cancers.
  • Powering clinical trials with genomics. The use of genomics in cancer clinical trials – whether for inclusion in data-gathering or even screening of patients—has gone from rare to commonplace over recent years, and is improving knowledge around the safety and efficacy of drugs in cancer and beyond. Two large-scale cancer trials have been initiated in 2015 with the bold goal of substantially advancing the understanding and use of genomics in cancer care. The anti-cancer treatments being tested in both trials were selected for their activity on a specific molecular target, independent of tumor location and histology. The two trials are actively enrolling and are (1) an American Society of Clinical Oncology (ASCO)-sponsored study, called TAPUR (Targeted Agent and Profiling Utilization Registry) and National Cancer Institute (NCI) and is called NCI-MATCH (Molecular Analysis for Therapy Choice). These trials and any subsequent follow-on trials will doubtless provide insightful information to drive the growing use of genomics in improving cancer care.

In summary, genomics is helping to prevent and treat cancer at an accelerating rate, supporting the goal of oncologists to dramatically improve cancer patient outcomes. There are at least four frontiers where we can see substantial progress in the use of genomics in cancer care, including expanded use in leading medical centers, increased potential applications within cancer, widespread acceptance in cancer prevention, and an increase in the use of genomics within clinical trials. I am personally committed to continue to drive and accelerate this genomic revolution to continue to bring true progress in improving cancer care to patients in need globally.