precisionFDA: A Community Approach for Submitting & Evaluating Diagnostic Tests, Powered by DNAnexus

DNAnexus has been awarded a research and development contract by the FDA’s Office of Health Informatics to build precisionFDA, an open source platform for community sharing of genomic information.

precisionFDA is a new approach for evaluating bioinformatics workflows, and is an integral part of FDA’s work in better understanding diagnostic tests that incorporate next-generation sequencing (NGS) technologies. As a component of the White House’s Precision Medicine Initiative, precisionFDA’s streamlined approach to evaluating NGS-based diagnostics and creation of reference datasets will build a community around best-practices resources and democratize the submission process to the FDA.

The FDA has adopted a community approach to crowd source reference analytical pipelines and datasets for the testing validation process by the community members who will be utilizing them. The DNAnexus Platform will deliver precisionFDA, providing the underlying cloud-based compute and data management infrastructure. In addition, DNAnexus will work with the FDA to build a community around its informatics platform to help drive standards around secondary analysis, the process of mapping, alignment, and variant calling of DNA sequence data.

The value of secondary analysis is undermined when datasets and bioinformatics tools are not harmonized for comparison and reproducibility. precisionFDA, with the help of the genomics community will streamline the process for submitting and validating NGS-based tests. Standardization will improve the evaluation process through consistent data quality, increased integration and reproducibility, and improved data exchange with collaborators.

Key objectives for precisionFDA include:

  • Exploring the use of a cloud-based portal, precisionFDA, to create a community around open-source genomic analysis pipelines, reference data, and analytical processing resources.
  • Determining appropriate and auditable levels of security, privacy, and governance control to ensure the protection of collaborators’ intellectual property and protected information, while enabling interaction within the community.
  • Providing an initial set of reference genomic data models and reference analysis pipelines.
  • Independent genomic analysis and data management work areas that can be kept private or shared with owner’s choice of collaborators, the public, or FDA for vetting or validation .

As a cloud-based informatics platform, precisionFDA will provide open source reference applications, reference datasets, and cloud-based compute and data management resources for the validation of NGS-based tests.

precisionFDA DNAnexus

precisionFDA is slated to provide test developers a flexible method for independently evaluating the accuracy and reproducibility of NGS analysis workflows, and to securely share results with collaborators and the FDA. DNAnexus expects the platform to be used broadly by NGS-based test providers, standards-making bodies, pharmaceutical and biotechnology companies, health care providers, academic medical centers, research consortia, and patient advocacy groups.

We predict that this new model for evaluating NGS-based tests will open up the process to a broader range of community members, who will benefit from open source reference data and applications and pay-for-use compute and storage resources, leveling the playing field for smaller test developers.

We are pleased to share this new and strategically important FDA initiative and look forward to collaborating with the genomics community in shaping this next evolution of precision medicine.

Using Genomics To Improve Patient Care: DNAnexus to Support Both Projects Selected by California Precision Medicine Initiative

dna-art2As Chief Medical Officer at DNAnexus, I’ve come to see my remit in very simple terms: I represent the voice of the patient-participant.

At least, that’s my aspiration. It’s been tremendously heartening to see the centrality of the patient-participant increasingly acknowledged (see here, here), especially in the context of the President’s Precision Medicine Initiative, for example (see here).

As a physician, there are few things more clarifying than the absolute commitment to do your best for the patient in front of you. Even as a resident, I was struck by how many seemingly intractable turf battles could be resolved simply by pausing to ask, “what’s in the best interest of this patient?”

When I set up the PASTEUR translational research training program with Denny Ausiello at Harvard about fifteen years ago, our focus was squarely on the patient; PASTEUR’s core philosophy – embedded in its motto – was: “Our patients as partners in discovery” (see here.)

Today — especially here in Silicon Valley – we are awash in data, and in folks who love, and have remarkable expertise collecting data, working with data, analyzing data.

The challenge, it has long seemed to me, is ensuring that we maintain our focus, and acknowledge data milestones (33 petaflops! One million genomes!) but reserve our greatest respect and joy for accomplishments that impact people – the conclusion of a diagnostic odyssey, the successful treatment of a patient – or even better, the prevention of disease in a high-risk participant.

Not only should technology be measured by its impact on people, but technology should also strive to leverage and bring out the best in the people hoping to use it – which in healthcare means researchers, providers, and participants.

During my training, I was especially moved by the words of pioneering pediatric surgeon Judah Folkman (see here), who preached the importance of inquisitive physicians and inquisitive researchers (and presumably, inquisitive participants) in driving medical progress.

This perspective perfectly captures how I view the DNAnexus platform – not as a magical solution (biology is still hard), but rather as a secure, cloud-based collaboration and analytics tool that can enable inquisitive clinicians, researchers (and increasingly, I hope, participants) to ask thoughtful questions of massive amounts of data, to collaborate easily, and to generate and share new insights that help patients and participants.

In this context, we feel especially honored to be supporting the two demonstration projects that were just selected by the California Initiative to Advance Precision Medicine (CIAPM), a public-private effort launched by Governor Edmund Brown, led by Dr. Atul Butte, and hosted by UCSF (see UCSF’s press release here). Both projects aim to yield quick results for patients.

The first project, led by Charles Chiu, an associate professor of laboratory medicine at UCSF, uses genetic sequencing to identify potentially treatable infections in acutely ill patients; Chiu’s approach was utilized, perhaps most famously, to save the life of Joshua Osborn, a 14-year old boy who had been placed in a medically-induced coma after falling critically ill and experiencing brain swelling for unknown reasons. Genetic testing, using a methodology developed by Chiu and colleagues, identified the causative pathogen, which led to the successful treatment of Joshua and his subsequent recovery.

The current project aims to expand the reach of this approach, initially to additional hospitals within the UC system, and eventually, I hope, to clinics across the nation (and globe). DNAnexus is committed to cloud-enabling the analytic pipeline, ultimately allowing samples and sequencing from a range of sites to be analyzed and securely shared using a common platform. Structurally, this approach of distributed sequencing and centralized analytics – which enables rapid scaling — is very similar to what DNAnexus has also enabled at Natera (see here).

Paul De Kruif’s classic Microbe Hunters (see here) played a critical role in spurring my earliest interest in the excitement and promise of medical research; consequently, it’s been especially gratifying to see the DNAnexus platform applied to accelerate the understanding of infectious disease. The platform has also supported the Ebola research of pioneering Broad Institute investigator Pardis Sabeti and her colleagues (work also supported by the Broad, Illumina and the CDC); see here for a summary, and here for the June 2015 paper in Cell.

The second project, led by David Hausler, a professor of biomedical engineering at UCSC and Ted Goldstein, a research associate at UCSC (and a former VP at Apple), seeks to identify precision treatments for pediatric cancer patients in California based on the genetic characteristics of their disease. This work builds on the UCSC Treehouse Childhood Cancer Project, which enables the combined analysis of cancer datasets.

DNAnexus is currently supporting oncology analysis pipelines at UCSF and Intermountain. I am particularly excited to contribute to the analysis and sharing of oncology data because the opportunity and the need seem especially great. It’s essential that the culture of medical research – including (some might say particularly in) oncology — evolve from one of hoarding data to one that recognizes the urgency – certainly from the patient’s perspective – of sharing data, and catalyzing knowledge turns (to borrow Andy Grove’s term), and accelerating the rate of progress.   We hope that our platform – and the analysis, collaboration, and insight it enables – can contribute impactfully to this process.

As excited as we are to be an industry partner of both teams selected by the CIAPM, we are, as always, focused on execution, and can’t wait to roll up our sleeves and get to work here.

We understand that for both demonstration projects, the ultimate measure of success is not the amount of DNA analyzed, or the amount of computation brought to bear. It’s also not the number of collaborators assembled nor the translational insights generated — though both are important intermediate markers.

Rather, our success metric is the difference we are able to make in the lives of patients and families. Our ambition is the relentless and unwavering pursuit of this goal. Our conscience is all those who continue to count on us and on science to fulfill our solemn commitment.


Dr. Shaywitz is Chief Medical Officer of DNAnexus. He also holds an adjunct appointment as Visiting Scientist in the Department of Biomedical Informatics at Harvard Medical School, and is co-host, with Lisa Suennen, of “Tech Tonics,” a podcast “focused on the people and passion at the intersection of technology and health,” available on iTunes (here).

Natera’s Genetic Testing to Scale with DNAnexus

NateraLogoNEW(2014)CMYKEarlier this year, we announced that Natera, a leader in non-invasive genetic testing, selected the DNAnexus cloud genomics platform to support the company’s portfolio of genetic tests. With the next-generation sequencing (NGS) clinical diagnostic market poised for exponential growth, Natera needed a solution to keep pace with its growing volume of genetic tests and global test delivery issues. At the moment, non-invasive prenatal testing (NIPT) is marketed toward high-risk pregnancies, however Natera is setting its sights on the $2.2 billion average-risk market, which is ready to open in the near future.

Key requirements to grow test portfolio and expand global reach:

  • High security and regulatory requirements: ISO 27001 compliance, HIPAA, CLIA, and Business Associates Agreement (BAA)
  • Cost-effective scaling for production workloads and Service Level Agreement (SLA)
  • Pipeline versioning to ensure all versions coexist and can run side-by-side
  • Control data locality and comply with national health data laws
  • Control over IT budgets and evolving needs

As Natera expands its NGS genetic test market share, it needed a global solution to decentralize the genome sequencing across partner laboratories and centralize the data analysis using the company’s patented SNP-based algorithms in the cloud. Currently, Natera has signed partnerships with a dozen laboratory and distribution partners who are utilizing the company’s genetic services, and has an aggressive plan to expand its footprint post-IPO.

Natera began trading on the NASDAQ (NTRA) July 2, 2015, with a $180 million IPO. The company’s lead product is Panorama™, a safe and non-invasive prenatal screening test that uses a blood sample from a pregnant mother, drawn as early as 9 weeks into the pregnancy, to assess the risk of certain chromosomal conditions that may affect a baby’s health. However, with this new influx of cash, Natera will move into the cancer diagnostics space, leveraging Panorama’s underlying technology to identify cell-free tumor DNA.

In addition to NIPT, the liquid biopsy market is set to explode. Named one of Technology Review’s 10 Breakthrough Technologies for 2015 and predicted to top $19 billion for the oncology market, a liquid biopsy can capture and isolate DNA shed by tumors in the blood. Soon something as simple as a routine blood test could be used to diagnose and treat cancer, instead of taking a sample directly from a tumor. Because cancer treatment requires multiple tumor sampling during the course of treatment, this non-invasive procedure makes it easier to take samples and make adjustments to a treatment plan.

DNAnexus is proud to be the supporting infrastructure, enabling Natera to scale their business to grow the global genetic testing market. The DNAnexus platform serves as a compliant command center capable of cost-effectively supporting multiple testing sites and enabling providers such as Natera with the technical platform to market and monetize their tests globally.

Visit https://www.dnanexus.com/diagnostic-test to learn how DNAnexus works with diagnostic test providers like Natera.