Innovation Fueled by Collaboration and Regulatory Science

In mid-2015 the Food and Drug Administration’s (FDA) Office of Health Informatics awarded DNAnexus a research and development contract to build precisionFDA, an online, cloud-based platform for sharing genomic information. Since its launch, more than 2,000 members of the next-generation sequencing (NGS) community have contributed to this resource by sharing and comparing biomedical data, software tools, and testing methodologies.

It falls under the responsibility of the FDA to ensure new medical treatments and tests meet a high standard for safety and efficacy, while working to get advances to market as quickly as possible. Following the announcement of President Obama’s Precision Medicine Initiative, the genomics community saw an increase in the use of NGS-based technologies in diagnostics, yet no standardized way to evaluate the accuracy of those tests. If new diagnostics were to be developed based on the broad applications of NGS, the approaches needed to be understood, and proved reliable, before they could be applied in clinical contexts.

The FDA took a forward-thinking approach to the regulation of genomic-based technologies and sponsored the development of the precisionFDA platform to, in the words of FDA leaders, “foster innovation and develop regulatory science around NGS tests,” and accelerate the implementation of precision medicine. Instead of government regulators establishing and imposing a set of performance standards for NGS tests with the typical top-down approach, precisionFDA seeks to empower the genomics community to develop regulatory science, through a collaborative and secure online platform.

The collaborative nature of precisionFDA lets researchers perform analyses on the same datasets, compare approaches, figure out what is successful, and determine where refinements can be made. The platform provides a flexible environment for test developers to leverage the findings from these collaborations to evaluate the accuracy and reproducibility of NGS analysis workflows, and share those results with the FDA and the rest of the community. The power of this approach is that the FDA remains at the epicenter of ongoing discussions, enabling the community to continue innovating, while keeping a pulse on the rapidly evolving genomics research space.

Robert Califf, former FDA Commissioner, penned an op-ed piece on his way out of office: How The FDA Will Help Lead the Next Medical Revolution. Califf believes that with precisionFDA, the agency can simultaneously meet the goals of protecting patients and advancing genomic medicine. Regulatory oversight can often be seen as a hindrance to innovation in healthcare, but the former commissioner believes that with this novel approach to regulation, the FDA will play a big role in realizing the potential of basing an individual’s’ treatment plan on their unique characteristics and genetic profile.

PrecisionFDA was founded upon the principles of collaboration and creating networks of stakeholders from industry, academia, and government. This platform is a successful example of how innovative regulation can spur progress by giving the key community stakeholders the ability to work together to define regulatory science.

In recent years, improvements in NGS technology have enhanced our ability to interrogate the human genome with high-specificity and bring those insights together with clinical patient data, which has pushed us closer to delivering on the promise of precision medicine. In order to keep pace with these technological advancements, it is crucial to harness the network effect of scientific collaboration. By empowering the community members with regulatory input, innovation can be stimulated instead of suppressed, and these innovations in turn will improve upon the quality of genomic tests and lead to advancements in health outcomes for patients.

George Asimenos, VP at DNAnexus will be presenting on precisionFDA at Molecular Med Tri-Conference in San Francisco as part of the Best Practice in Personalized and Translational Medicine short course. Hear the presentation Monday February 20th from 8am-11am.

Learn more and get involved at precision.fda.gov.

New Org Admin Tools Available on DNAnexus

We are excited to announce the release of the Org Admin Interface, a new suite of tools to help manage groups of users and shared resources on the DNAnexus Platform.

What is an “Org”?

An Org, or Organization, is a DNAnexus entity that is used to manage a group of users. At a high level, Orgs can be used to associate users, projects, and other resources with one another in a way that models real-world collaborations. Orgs simplify management of data access, sharing, and billing.

Org Admins are users who are authorized to manage Org membership, configure access and projects associated with the Org, and oversee billing.

How do I use the Org Admin tools?

If you are the admin of an Org, you will be able to access the interface from the header of the DNAnexus Platform. From there, you’ll be able to navigate to all the Orgs you manage.

To learn more about Orgs on DNAnexus and how to use the Org Admin tools, please see the following guides:

Introduction to Orgs

Using the Org Admin tools

How do I create an Org?

If you would like to create an Org for your team, please contact support@dnanexus.com. One of our scientists will be happy to work with you to set up an org structure appropriate for your team.

I am a member of an Org. What tools are available for me?

Members can be granted access levels that vary, from basic access to shared projects and apps to the ability to create new projects billed to an Org. We have provided a guide for interacting with Orgs as a member here.

As always, if you have any questions or feedback about the Org Admin tools, please do not hesitate to contact us at support@dnanexus.com.

Sentieon on DNAnexus: License-Free Access Through April 7th

Test drive Sentieon’s pipelines on DNAnexus and see how you can achieve faster and more cost-efficient results with equivalent or improved accuracy and consistency

Editor’s Note: This blog post is written by Brendan Gallagher, Business Development Director at Sentieon.

We are excited to officially announce our collaboration with DNAnexus and the availability of our tools on the scalable cloud-based DNAnexus Platform. At Sentieon, we are enabling  precision data for precision medicine by improving upon industry-leading bioinformatics tools. Our suite of secondary analysis tools produce equivalent or improved results while running much faster and more cost-efficient than GATK, MuTect and MuTect2 bioinformatics tools.

For a 2 month period, DNAnexus users will have license-free access to test, validate, and use:

  • DNAseq (BWA + GATK 3.5) – From FASTQ / BAM to VCF
  • TNseq (BWA + MuTect or MuTect2) – From FASTQ to VCF
  • Rapid DNAseq (BWA + GATK 3.5) – From FASTQ to VCF in 1 hour

Register today to take advantage of this time-limited and license-free opportunity to access Sentieon pipelines on DNAnexus! General commercial availability begins April 8th.

Sentieon tools produce equivalent results to GATK/MuTect/MuTect2 suite of tools by using mathematical methods identical to the Broad Institute’s Best Practice Workflow pipeline. Sentieon has improved the efficiency of the computation algorithms and engineered robust software implementations to speed up the pipeline while providing equivalent or improved accuracy and 100% consistency.

Delivering Better  Results

On the same compute infrastructure, Sentieon software is an order of magnitude faster in terms of core-hours, while producing 100% consistent results with no run-to-run difference. Sentieon software does not down-sample in high-coverage regions, enabling rigorous analysis for deep-coverage sequence data. By removing the down-sampling and other run-to-run error sources, Sentieon tools also improve the accuracy and quality of the results.

SPEED

Sentieon DNAseq processes a 30x NA12878 Genome from fastq to gVCF in ~6 hours and 15 minutes on a single 32 virtual core instance on the DNAnexus platform.  Sentieon and DNAnexus are also offering a rapid-turnaround distributed version of the app that can complete a 30x genome in approximately 1 hour while adding minimal additional compute cost.  

In our 2015 white paper comparing DNAseq to then-current GATK version 3.3, we showed that Sentieon DNAseq has a runtime improvement of 20-50x while producing identical results. Download the white paper.

The figure below shows the performance of our current version matching BWA-GATK3.5 on the DNAnexus Platform from FASTQ to VCF:

CONSISTENCY

Sentieon is 100% consistent and has no run-to-run variation You will get the same result every time you run an individual sample.

Sentieon Concordance to GATK – Identical within GATK’s run to run difference

The above figure shows the concordance analysis in our white paper. Over 99.8% of the variant calls produced by GATK 3.3 and Sentieon DNAseq were identical. After removing the differences from GATK downsampling, the variant calls were over 99.99% concordant. Learn more.

The same concordance performance is maintained in our current DNAseq version as compared to GATK3.5.

COST

With Sentieon, you can process a 30x genome from FASTQ to VCF for the previous price of an exome.  DNAseq costs 5x less for whole exome sequencing (WES) and 7x less for whole genome sequencing (WGS) than GATK3 run on the DNAnexus Platform.  For cost comparison purposes, please contact sales@dnanexus.com.

But don’t take my word for it.

Sentieon has been a top performer in many independent studies, and  last year, we were recognized for accuracy and consistency in the precisionFDA community challenges: precisionFDA Consistency Challenge and precisionFDA Truth Challenge.

Furthermore, Sentieon software enables large cohort joint calls with tens of thousands of whole genomes without intermediate file merging, enabling much easier and much more efficient population-scale studies.

So go ahead, register here to try it out, and let us know what you think. 

Email me anytime at brendan.gallagher@sentieon.com or talk to the DNAnexus team. 

This is the start of a nice partnership as DNAnexus and Sentieon will continue to collaborate on the acceleration and improvement of genomic analysis by providing our customers with the most accurate and cost-conscious tools. We look forward to expanding the tools available on DNAnexus in the future.