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.

DNAnexus Celebrates National DNA Day

Known as National DNA Day, April 25th commemorates the discovery of the double helix structure by James Watson and Francis Crick in 1953 and the completion of the Human Genome Project in 2003. This dual celebration of two monumental milestones offers the opportunity to celebrate the latest advances in genomic research, and reflect on the fevered pace of discovery since the first human genome was sequenced.  

In the decade-and-a-half since the completion of the Human Genome Project, significant advancements in genome sequencing and analysis technologies have greatly reduced the cost of sequencing. Researchers can now sequence more genomes, and therefore create larger datasets to parse through in search of their needle-in-the-haystack discovery.

Computational innovation has been key to meeting the demands of the mountains of data pouring out of sequencing machines. Beyond creating scalable platforms to manage the growing datasets of genomic information, there is a pressing need for tools that allow researchers to integrate disparate data types — including genotypic and phenotypic data — and collaborate with other researchers within and between organizations.

What seemed to be aspirational in 2008 — to create the largest public database of human variation and genotype data with the 1,000 Genome Project– has been surpassed many fold. The DiscovEHR collaboration between Regeneron Genetics Center and Geisinger Health system, for example, joins together next-generation sequencing (NGS) data from 250,000 exomes with longitudinal electronic health records for the discovery of genetic variation. Two large-scale studies from this collaboration were recently published in the journal Science and discussed the analyses of genetic and phenotypic data from more than 50,000 patients.

Regeneron is also embarking on a joint project with GlaxoSmithKline (GSK) and the UK Biobank, where the genetic variants of 500,000 people will be analyzed. AstraZeneca announced a similar initiative, which will sequence more than 2 million genomes over the next 10 years to inform discovery and development. The vast trove of genomic data that is generated from these research projects empowers scientists and clinicians to study the role that our genome can play in complex diseases.

This genome-based research has help pushed us closer to the promise of precision medicine. Today, the genetic basis of some 5,000 rare disorders is known, enabling researchers to get a deeper understanding of the disease, develop improved diagnostics, and create more targeted and effective therapeutics. Now more than 100 FDA-approved drugs are packaged with genomic information that tells doctors to test their patients for genetic variants linked to efficacy, dose, and adverse side effects.

It is remarkable to see how technological innovation has lead to groundbreaking advances in genomics. Already in the first third of 2017, there have been a number of important discoveries. Take a look at the National Human Genome Research Institute’s (NHGRI) compilation of Notable Accomplishments in Genomic Medicine. At DNAnexus, we are inspired by progress, and are excited to be a part of the genomics revolution.

Join the discussion and participate in NHGRI’s Twitter Chat today at 10am PST (1pm EST). Search the hashtags #DNADayChat or #DNADay17. Special guests Dr. Francis Collins and Dr. Kathleen Rubins will be answering your questions about genomics.

Webinar: Trio Analysis with Sentieon Rapid DNAseq on DNAnexus

Please join us Thursday, May 18 at 11am PST (2pm EST) for an educational webinar on trio analysis and cohort joint genotyping using Rapid DNAseq, Sentieon’s variant discovery tool.

Sentieon and DNAnexus are collaborating to make tools available to accelerate genome analysis, while reducing costs for researchers. By leveraging the power and scalability of the cloud,  rapid runtimes for joint genotyping easily scale to thousands of samples. Additionally, using the variant discovery pipelines on DNAnexus, you can obtain identical results to GATK, MuTect, or MuTect2 at a fraction of the cost. Our customers are already experiencing a more than 10-fold increase in processing speed and cost savings of 5-7x.

This webinar will demonstrate the power of running Sentieon Rapid DNAseq on DNAnexus for variant calling of a 30x whole-genome trio in just about one hour. Using the single multi-sample VCF generated from this data, it is possible to identify de novo variants, the parental origin of interesting inherited mutations, and examine the carrier status of individuals for rare recessive mutations.

Webinar Details
Title: Rapid Trio Analysis and Cohort Joint Genotyping with Sentieon on DNAnexus
Speaker: Don Freed, PhD, Bioinformatics Scientist, Sentieon
Date: Thursday, May 18, 2017
Time: 11:00 AM PT, 2:00 PM ET

Attendees will learn how to:

  • Rapidly run joint genotyping and identify de novo mutations from a trio in about one hour
  • Achieve deterministic variant calls, with no run-to-run differences and no down-sampling in high coverage regions
  • Perform accelerated analysis on cohorts of thousands of samples