September 26, 2016

GlobeNewswire "UnDx Consortium to Present at 14th Annual Future in Review Conference"

August 17, 2016

Bioscience Technology "Consortium Meets to Explore Multidisciplinary Approach to Precision Medicine"

August 16, 2016

Genetic Engineering & Biotechnology News "Precision Med Team Sets Sights on Rare Disease Therapies"

August 16, 2016

CenterWatch News "UnDx Consortium to focus on precision medicine"

August 15, 2016

Yahoo Finance "Precision Medicine Put to the Test: UnDx Consortium Gathers to Examine New Hypotheses for Undiagnosed Patients"

August 15, 2016

GenomeWeb "Five Companies Form UnDx Precision Medicine Consortium"

July 25, 2016

American Gut Project "Can the Gut Microbiome Be Used to Provide Valuable Information to Undiagnosed Patients?"

The UnDx Consortium speaks to participant DeAunne Denmark


1.   Tell us about your life living with an undiagnosed disease, and your journey finding answers to this point.

The experience of several years with an undiagnosed disease has been the most difficult time of my life. It has been far harder than nine years of MD/PhD training, or any of the other physical, mental, or emotional challenges I’d faced so far. It has been especially difficult during what was supposed to be a prime time in life - still relatively young and just at the beginning of an exciting career. Like probably all illnesses, being undiagnosed can be extremely isolating. It is impossible, even for those closest to you, to understand the depths of insecurity, helplessness, desperation, and discouragement that can creep into your life. As well as the disease struggle, you now live every day with physical and mental compromise in basic functions that most everyone around you takes for granted. I also took these basic functions for granted before this. Through it, though, I’ve come to value health and simple aspects of wellness more than ever. I appreciate the amazing nature of our bodies to keep us alive as they do. That’s been a wonderful gift.

Some people have kindly reflected that it must take a lot of courage and persistence to keep moving forward in spite of the barriers, dead-ends, dismissal, and obscurity - not to mention relentless fatigue. Of course, it’s always lovely to hear and I greatly appreciate it. But I also imagine most people would do the same if their own life was at stake. I’ve been both reassured, and very humbled, to see how strong our basic instincts are to do whatever it takes to carry on, even in the worst of circumstances.

2.   What are the greatest factors limiting our ability to find answers for patients living with undiagnosed diseases currently?

One of the biggest limitations in my view is that we aren’t yet applying in the clinic, technologies that are currently available and widely used in research. It’s been extremely frustrating for me as a patient to know that I could analyze my own samples as a scientist in the lab to a greater degree than any of my doctors had access to or even were familiar with much of the time. Further, even if I was able to contribute samples to a research project, neither I nor my doctors would typically get the data returned to help inform a clinical decision. Helping to bridge or even close these gaps between researchers, clinicians, and patients has always been one of my main goals as a clinician-scientist, and even more so now that I’m seeing it from the perspective of a patient.

3.   The UNDX Consortium is exploring whether bringing these new technologies together to focus on a single problem will expand our understanding. What questions or hypotheses do you have, going into the project?

I admit to bias on this, but am nonetheless convinced at this point that clinical use of these technologies will bring enormous benefit to patients, and at an overall cost savings to the system. It’s critical, of course, that this assertion be tested. But just to know that there is more to try, to explore, that new discoveries are happening every day and that there is real potential for answers and treatment, has provided me strength to persist through the most difficult times. For me, it has truly been a source of hope. I’d love to know what the Consortium envisions as the best possible outcome, and what they’d like the change in medicine to be as a result of this project. How can we take this from the cutting-edge to the standard of care?

4.   How will the Consortium help advance the development of personalized medicine?

In many ways, I believe! First, by showing the power of technologies like these to shed light on some of the most wicked and devastating human conditions. Also by demonstrating the kind of collaborations and data integration that can achieve clinically meaningful understanding, and that these are both feasible and scalable, even cost-effective. What’s being done here is an example of tremendous progress not just for undiagnosed disease, but also in helping reshape the ways we support health and treat disease as a whole.

American Gut - UnDx Consortium Collaborator


1.   Tell us about your technology.

The American Gut Project (AGP), as part of the Earth Microbiome Project (EMP), utilizes techniques developed and benchmarked for EMP and the Human Microbiome Project. Most samples submitted to AGP are processed for bacterial marker gene (16S rRNA) sequencing and analysis (protocol information can be found here). Sequences are analyzed utilizing a tool called Quantitative Insights Into Microbial Ecology (QIIME), originally developed in the Knight lab. AGP specific protocols can be found here.

2.   What potential does it hold for those with undiagnosed diseases?

In the past decade, microbiome research has seen a huge boon, with hundreds of research groups identifying potential connections between the microbiome and countless diseases, from obesity to IBD to autism. While we don’t yet know whether microbiome dysbiosis is a cause or effect of disease, in some cases, targeting the microbiome does lead to alleviation of symptoms or improvement in the overall health condition. If connections can be identified between the microbiome and undiagnosed diseases, we may be able to learn more about the nature of the disease and may potentially target the microbiome as a treatment strategy to improve quality of life for patients.

3.   Why have you joined the UnDx Consortium?

We believe the microbiome is key to human health. If there is a connection between the microbiome and a disease state, we want to identify it, and then figure out how to improve health for people suffering for that disease.

4.   What is your contribution to the UnDx Consortium project?

We are performing 16S marker gene sequencing (and later metagenomics sequencing) on stool samples collected from patients and their non-affected family members.

5.   The Consortium is exploring whether bringing these new technologies together to focus on a single problem will expand our understanding. What questions or hypotheses do you have, going into the project?

We wonder whether the connection between stool microbes and metabolites and blood metabolites plays a significant role in disease, and whether the connection between stool and blood can only be observed if the blood and stool samples are collected at the same time. We would also like to see whether specific SNPs or other genetic variations are correlated with disease, and if so, are certain microbial taxonomies or metabolites also correlated with disease-indicated genetic variants.

6.   What are you looking to learn from the UnDx Consortium? How does the project connect back into building your business?

We are excited to participate in such a large scale collaborative effort bringing together experts from several fields. We expect this experience to inform future large-scale collaborations. It’s not easy to coordinate such disparate groups (both in terms of expertise and geographical location); doing so successfully with the UnDx will enable us to partake in more large-scale collaborations and ensure those collaborations runs smoothly.

7.   How will the Consortium help advance the development of precision medicine?

One of the biggest missing pieces in precision medicine is the numbers of samples to analyze and guide decision making, and the other critical missing piece is the willingness of participants to share data due to privacy concerns. The UnDx is tackling both of these problems in a very proactive way. I hope that what UnDx is doing will lay the groundwork to encourage other groups to do the same-only then can we move precision medicine forward

GenPro - UnDx Consortium Collaborator


1.   Tell us about your technology.

Genome Profiling (“GenPro”) is a molecular information company focused on the discovery of novel epigenetic biomarkers and their translation into: precision clinical assays for drug responsiveness, patient stratification and disease diagnosis; new pathway, MOA and epigenetic therapeutic target insights; and more. Our ground-breaking application of epigenetic information to next-generation human health applications is enabled by proprietary analytics and big-data computational processing for gene methylation quantification to elucidate multi-site methylation signatures (EpiMarkersTM) from next generation sequencing data. Through milestone-based collaboration agreements we apply these capabilities to assist biopharma and medical research institutions accelerate the discovery, development and commercialization of game-changing health and longevity improvement products across many diseases.

2.   What potential does it hold for those with undiagnosed diseases?

Epigenetic signals layered onto all human genomes determine much of the subtle physiological differences that exist between individuals. Our analyses can identify subtle chemical (DNA methylation) changes between individuals and potentially help to pinpoint areas of altered gene expression regulation that may indicate abnormal changes in cellular functions associated with disease progression.

3.   Have you worked with undiagnosed diseases before? 

This is our first opportunity to apply our capabilities to multiple undiagnosed disease patients.

4.   Why have you joined the UnDx Consortium? 

We were inspired by the opportunity to potentially contribute something meaningful alongside other leading-edge complementary technologies to triage such a complex, costly, and debilitating health challenge being faced by so many people, their families and clinicians. Our view is that if GenPro can elucidate some novel epigenetic insights that would contribute to a solution that helps one, let alone several UnDx patients it would be a worthwhile endeavor. We were also motivated by the opportunity to learn through a unified initiative about how our capabilities combined with the other esteemed organizations who are participating could be more broadly applicable to other chronic and life-threatening diseases.

5.   What is your contribution to the UnDx Consortium project? 

GenPro is committed to apply our epigenetic biomarker discovery analytics platform to produce quantitative gene methylation profiles from the Next Generation Sequencing data from each patient, analyze the gene methylation data for new molecular insights that are distinguishing in the UnDx patients versus controls, identify the top CpG sites and the genes that they are associated with that are responsible for the differentiating characteristics; and provide new insights into likely gene pathways and MOA’s that could be helpful to other members of the consortium and it’s medical and scientific advisors.

6.   The Consortium is exploring whether bringing these new technologies together to focus on a single problem will expand our understanding. What questions or hypotheses do you have, going into the project? 

Our hypothesis is that through this special opportunity we and our consortium members will learn a tremendous amount in a very short period of time that will result in actions and hopefully outcomes that could be beneficial to the participating patients and to each member’s business.

7.   What are you looking to learn from the UnDx Consortium? How does the project connect back into building your business? 

We believe there are numerous business building benefits to GenPro by participating in this consortium that include but are not limited to: a.) developing new insights into how our technology needs to evolve to fully exploit opportunities at the nexus of other complementary technologies and approaches; b.) meeting and interacting with other renown thought and technology leaders and the likely innovation that could spawn from that; c.) the potential positive visibility and credibility that could accrue to the consortium and its collaborators as success evolves; and more.

8.   How will the Consortium help advance the development of precision medicine? 

The very different levels of patient data compiled by consortium members provide a unique opportunity to integrate patient disease data across hierarchical levels of biological function, from molecular genetics, to metabolism to microbiome ‘ecosystem’ structure and function.

9.   What’s your relationship to the other UnDx Consortium partners? 

It is limited at the moment, although Illumina technology generates the vast majority of the next generation sequencing data that GenPro applies its analytics to for gene methylation quantification, novel epigenetic biomarker discovery, and the other information we provide. This study will bring us much closer together, which is one of the motivating aspects for our participation.

KromaTiD - UnDx Consortium Collaborator


1.   Tell us about your technology.

Using highly specific genomic probes and unique methods, KromaTiD’s proprietary directional Genomic Hybridization or dGH™ technology detects structural rearrangements to the genome by directly imaging changes to the chromosomes.

2.   What potential does it hold for those with undiagnosed diseases?

Structural rearrangements to the genome can in some cases cause diseases. Combining dGH with sequencing and array studies provides a more complete genetic profile and increases the chance of discovering the elusive cause of an undiagnosed disease.

3.   What is your contribution to the UnDx Consortium project?

KromaTiD is screening a portion of the genome of all the patients in the project for undiscovered structural rearrangements. Additionally, where previous studies have identified genes that may be involved in the disease, we will screen those genes for any changes with high resolution gene tracking assays

4.   The Consortium is exploring whether bringing these new technologies together to focus on a single problem will expand our understanding. What questions or hypotheses do you have, going into the project?

We believe, and are testing with this project, that integrating the results of high quality sequencing into our design process will allow us to produce highly targeted assays that can resolve fine structural changes to genes. Changes that may be involved in the underlying disease process.

5.   What are you looking to learn from the UnDx Consortium? How does the project connect back into building your business?

We believe that our dGH platform is an essential tool in the researcher’s toolbox and we are excited to pair dGH with other leading technologies. This approach—combining different data from a range of platforms—is already being adopted by a number of our customers and we believe will continue to grow.

6.   How will the Consortium help advance the development of personalized medicine?

This approach, understanding the root cause of a condition is fundamental to personalized medicine and the necessary first step towards targeted treatments. The techniques we and other consortium members develop for these patients can be applied to larger studies and a wider range of patients.

Metabolon - UnDx Consortium Collaborator


1.   Tell us about your technology.

Metabolomics has emerged as a powerful technology for precision medicine because of its ability to analyze underlying disease processes. Metabolic pathways are more completely understood than almost any other aspect of human biology, and they have been integral for mapping many complex physiological processes like muscle and cancer metabolism. Metabolomics measures all of the metabolites within these pathways. This is a critical reason why a growing number of large precision medicine and next-generation sequencing (NGS) initiatives have adopted metabolomics as a cornerstone of their programs to link genetics and metabolic profiles to phenotypes or health states. Because metabolomics most closely relates to the phenotype and the genetic influence thereof, it has emerged as a keystone technology. As an emerging first-line technology, metabolomics is adding significant value to the analysis of genetic disorders, inborn errors of metabolism, complex diseases, and large cohorts.

2.   What potential does it hold for those with undiagnosed diseases?

There is growing appreciation that complex illnesses are caused by a combination of genetic and non-genetic factors. Clinicians must take into account the impact of these factors to make an informed diagnosis. Metabolomics reflects the influences of genes, diet, lifestyle, environment and xenobiotics to aid in understanding gene function and how diseases originate. It also provides the biomarkers for health assessment and customized therapy.

3.   Have you worked with undiagnosed diseases before?

Yes, we formed a collaboration with Baylor Genetics Laboratories about two years ago to validate our test for inherited metabolic diseases (aka inborn errors of metabolism). Using only one small plasma sample, our test can identify 65 diseases, making it an ideal first-line screening tool. We are also conducting research into the biomarkers involved in complex diseases such as ME/CFS.

4.   Why have you joined the UnDx Consortium?

Despite all the research so far, there is still much work to be done if we hope to unravel the mystery surrounding undiagnosed diseases. We’ve had the opportunity to work with many people who are affected and know how important it is for them to finally have some answers. We think it will take the collective focus of a group like the Consortium to make significant progress in this area.

5.   What is your contribution to the UnDx Consortium project?

Metabolon is the world’s leading health technology company focused on metabolomics for precision medicine. Our platform technology and proprietary software provide unprecedented insight into biochemical pathways. We screen more than 2,000 metabolites to give a real-time assessment of an individual’s health status, which may set the stage for new ways to diagnose, monitor and provide guidance for treatment.

6.   The Consortium is exploring whether bringing these new technologies together to focus on a single problem will expand our understanding. What questions or hypotheses do you have, going into the project?

Detecting single or multiple perturbations in the levels of specific metabolites has demonstrated diagnostic capabilities. Metabolites provide the intersection between the potential risk of disease (genetic alterations) and the causative nature and treatment of a disease. Metabolon’s ability to scan the global profile of these small molecules in an unbiased manner has resulted in a breath of knowledge regarding potential underlying causes or novel treatments for multiple diseases. We hypothesize that profiling plasma from the UnDx cohort and their respective healthy relatives should result in the identification of new avenues to elucidate the underlying unknown disease state and possible new interventions. Furthermore, the findings from the metabolic profiling should be enhanced by combining them with results of other -omic technologies.

7.   What are you looking to learn from the UnDx Consortium? How does the project connect back into building your business?

Metabolon is participating in the effort to map human health, while also capitalizing on the biomarkers and signatures already derived to assess individual health right now. Whether used for routine health assessment or in conjunction with genetic sequencing, metabolomics must play a vital role in precision medicine, which is a key part of our business.

8.   How will the Consortium help advance the development of precision medicine?

We envision a future contrasted from today’s state where, instead of treating individuals with a one-size-fits-all approach, an extensive suite of biomarkers will point to a vivid palette of disease signatures to which a clinician can react. To reach this state, a precise blueprint of human health is required. While powerful genomic technologies are a front-line approach for constructing this blueprint, the wealth of data they produce has created a bottleneck in the understanding of it. Identifying the key signals within the data that drive traits of interest (e.g. disease, drug response, etc.) and figuring out what these signals mean is a persistent challenge.

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