Rady Children’s Quest to Finding That Needle in a Haystack

Rady Children’s Institute for Genomic Medicine (RCIGM), located in San Diego, has announced a pioneering effort to deliver life-changing genetic diagnoses for children suffering from rare diseases. Led by president and CEO, Dr. Stephen Kingsmore, Rady is building an end-to-end clinical whole genome data analysis solution, built on the DNAnexus Platform, for children’s hospitals nationally.

The impact of diagnosis by WGS is often life changing. The team routinely tests critically ill children for over 5,000 diseases, of which more than 500 have highly effective treatments. For example, if the test reveals a mutation in a gene involved in digestion, causing the inability to process a particular nutrient thereby leading to buildup of a poisonous byproduct, a simple change in diet can limit the effects of the disease. The sooner this condition can be diagnosed the less damage the child will suffer. In these cases, minutes literally matter.

Dr. Kingsmore’s vision is to ensure genome-powered diagnosis is accessible to every child who needs it. Building a world-class pipeline at a single hospital isn’t enough. RCIGM needed a solution that could scale and be deployed at institutions around the world. DNAnexus provides the technology and expertise that allows RCIGM to grow an innovative pediatric-focused genomics network, distribute its clinical tools and collaborate with colleagues in a secure and compliant environment.

This work was done as part of RCIGM’s collaboration with the The Newborn Sequencing In Genomic medicine and public HealTh (NSIGHT) program. NSIGHT addresses how genomic sequencing can replicate or augment known screening results for newborn disorders, what knowledge sequencing can provide for conditions not currently screened, and what additional clinical information could be learned from sequencing relevant to the clinical care of newborns. The NSIGHT program is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Human Genome Research Institute (NHGRI), components of the National Institutes of Health.

DNAnexus provides a flexible platform that connects Edico Genome’s ultra-fast variant calling algorithms with Fabric Genomics’ interpretation software, and integrates seamlessly with Rady Children’s custom data interpretation portal. Users monitor jobs, organize and share data, and compare patients’ data to a diagnostic resource within the network. At DNAnexus, we are proud to support Dr. Kingsmore and RCGIM’s endeavor to prevent, diagnose, and treat childhood diseases through genomics research.

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.

Bringing Together Genomics and Patient Data in the Cloud

Please join us Tuesday, February 7, at 10am PT (1pm ET) to hear leading genetics expert, Dr. Jeffrey Reid, Executive Director and Head of Genome Informatics at the Regeneron Genetics Center (RGC), discuss RGC’s integrated approach across genetic trait architectures and phenotypes, the underlying cloud infrastructure that makes the center’s collaboration with multiple institutions possible, and key lessons learned from RGC’s pioneering genomic sequencing study.

Webinar Details
Title: Beyond 100,000 Exomes: Insights & Lessons from Large-Scale Sequencing in the Cloud
Speaker: Jeffrey Reid, Ph.D., Executive Director, Head of Genome Informatics, Regeneron Genetics Center
Date: Tuesday, February 7, 2017
Time: 10:00 AM PT, 1:00 PM ET

Despite growing investment in biopharma research and development, the number of new drugs is not increasing. It is estimated that more than 90% of drugs that enter Phase I clinical trials fail. Among failures in Phase II clinical trials, 51% are due to lack of efficacy and 19% due to toxicity. These statistics suggest that pre-clinical models may be poor predictors of benefit, and together with data on genetically-informed development programs, indicate that human genetics data can substantially improve the likelihood of success for new therapeutics.

Regeneron has a long history of commitment to genetics-based  science, and a track record of integrating human genetics into successful development programs, delivering new medicines to patients. Therefore, the company has made substantial investment in the Regeneron Genetics Center, a cloud-based large-scale sequencing and analysis effort supporting Regeneron development programs. The RGC is a natural extension of this decades-long commitment to genetics at Regeneron, integrating large-scale, diverse data types and fostering collaboration with a wide array of stakeholders, including biopharma, healthcare providers, research institutes, and patient advocacy groups.

The Regeneron Genetics Center has sequenced more than 120,000 people so far, and has created one of the world’s most comprehensive genetics databases pairing sequence data and de-identified electronic health records. The RGC research program involves trait architectures and phenotype collaboration across a network of more than 30 research and healthcare provider institutions. Securely and easily sharing data and tools at scale with so many partners is a major challenge. In order to enable frictionless collaboration across these disparate labs, Regeneron selected DNAnexus to provide the cloud-based bioinformatics platform necessary to securely share large-scale sequencing data and tools.

In this presentation Dr. Reid will explain the RGC vision for genetics-driven drug development, describe the automation and uniquely enabling infrastructure of the RGC, and discuss in detail some of the informatics innovations and early biological insights that have already come out of the RGC’s collaborative efforts.