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.

ACMG: A Look at Applying Genomic Data to Clinical Reports

The annual American College of Medical Geneticists (ACMG) conference meets this week (March 21-25, 2017) in Phoenix, Arizona, providing an outstanding forum to learn how genetics and genomics are being integrated into medical and clinical practice. Eric Venner, from the Human Genome Sequencing Center (HGSC) at Baylor College of Medicine, will present the following poster (Abstract Number 368): Generating Clinical Reports from Genomic Data on the Cloud-based Neptune Platform  on Friday March 24th 10:30AM-12:00PM

In order to meet the demand for timely and cost-efficient clinical reporting, HGSC developed Neptune, an automated analytical platform to sign out and deliver clinical reports. The process starts when a clinical site uploads a test requisition to the HIPAA compliant environment on DNAnexus. Next, de-identified samples are analyzed with HGSC’s variant calling pipeline, Mercury, which feeds into the reporting pipeline, Neptune. Variants of putative clinical relevance are identified for manual review and possible addition to a VIP database of clinically relevant variation. The VIP database currently holds 20,872 SNPs and 3,946 indels, as well as a curated set of copy number variants.

Neptune’s manual review interface was designed with a clinical geneticist in mind. Users can login, curate variants in their samples, update the VIP database accordingly and create clinical reports. Early applications include reporting for the NIH Electronic Medical Records and Genomics (eMERGE) Network III where more than 14,500 samples and a panel of 109 genes will be processed over the course of three years.

eMERGE is a national network that combines DNA biorepositories with electronic medical record (EMR) systems for large scale, high-throughput genetic research to support investigating how personalized treatments impact patient care. Research so far has led to significant discoveries across a wide range of diseases, including prostate cancer, leukemia, and diabetes.  DNAnexus and the Human Genome Sequencing Center (HGSC) at Baylor College of Medicine worked to build the eMERGE Commons, a data repository where genomic data are merged with patient electronic medical records (EMR), as well as analysis results and bioinformatics tools to be accessed and applied by eMERGE researchers.

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.