Scientists to Present Study Data on RainDance Technologies’ Microdroplet Platform at ASHG

RainDance Technologies, Inc., a private company pioneering microdroplet-based technologies for single-molecule and single-cell analysis, today announced that scientists from The Scripps Research Institute, the Translational Genomics Research Institute (TGen) and Emory University will present data highlighting the broad utility of the company’s innovative microdroplet platform during the 60th Annual Meeting of the American Society of Human Genetics (ASHG), taking place in Washington, D.C. this week.

Daniel Salomon, MD (Scripps), Matthew Huentelman, PhD (TGen) and Michael Zwick, PhD (Emory) will present data at ASHG across diverse human disease research areas including genome-wide association (GWA) follow-on studies, DNA methylation analysis and the identification of X-linked genetic variation.

“RainDance Technologies has developed a robust and flexible targeted sequencing platform that continues to prove its value across basic and medically important genomic research applications by offering single-molecule resolution and unparalleled genomic coverage at nano-scale levels,” said Roopom Banerjee, President and CEO of RainDance Technologies. “As data from these studies show, scientists can successfully apply our microdroplet technology to identify rare variants and enhance their understanding of the origins and pathways of complex diseases such as autism, Alzheimer’s and X-linked mental retardation.”

Drs. Salomon and Huentelman will present at the RainDance workshop Thursday, November 4 from 1:00 to 2:00 p.m. ET and Dr. Zwick will present Friday, November 5 at 10:15 a.m. ET during the Concurrent Platform Session III. The company will also be demonstrating its microdroplet technology platform and expanded capabilities at its exposition booth (#604) during the meeting.

DNA Methylation Analysis at Scripps

DNA methylation is a chemical modification of DNA that has been associated with nearly every human biological process and, as a result, has become a growing area of scientific investigation. Of particular medical interest is the methylation of specific DNA sequence motifs known as CpG (C-phosphate-G ) islands.

At The Scripps Research Institute, Associate Professor Daniel R. Salomon, MD is studying the functional genomics of human kidney, liver and islet cell transplantation. The primary objective of this work is the discovery of biomarkers aimed at improving transplant outcomes and the management of immunosuppression.

Using the RainDance platform, Dr. Salomon is investigating cytosine methylation of DNA CpG dinucleotides in gene promoters and their role in epigenetic modification that regulates gene transcription. Because CpG island sequences are similar, the ability to specifically enrich for a CpG upstream of a target gene is challenging, particularly for methods that rely on probe hybridization alone. The RainDance microdroplet-based PCR Methyl-Seq capabilities and proprietary primer design algorithm help overcome this hurdle by providing the capacity to specifically enrich for a CpG upstream of a specific gene.

“While many methods exist to interrogate methylation states, none offer large-scale, targeted, single CpG resolution,” said Dr. Salomon. “We have recently developed an approach combining bisulfite treatment followed by RainDance microdroplet PCR and next-generation sequencing to assay the methylation state of 50 genes in a single run. The levels of coverage we’ve achieved in these studies using this method are very promising and lead us to believe that we could easily increase the total number of genes covered in a single run to over 2,000 – making this a practical solution to accelerate and scale up our DNA methylation research.”

GWA Follow-on Studies at TGen

While GWA studies have led to progress in defining the possible genetic basis of disease, they have only identified a small fraction of heritable variation in disease risk. To deepen the understanding of the mutations that explain the rest, the need for follow-up studies to identify rare variants and copy number variations has become clearer.

At TGen, Matthew Huentelman, PhD, Investigator in the Neurobehavioral Research Unit, is studying the genomics of neurological traits and conditions to better understand, diagnose, and treat human diseases of the nervous system including Alzheimer’s disease.

To identify novel risk factors associated with Alzheimer’s disease, Dr. Huentelman’s team recently performed a GWA study. In a sub-set of the cohort selected for neutral risk at the APOE locus, they detected a significant association in SNPs located within TOMM40 and APOC1, two genes that flank APOE. To better understand this important disease risk locus they resequenced a collection of 192 individuals from their cohort using the RainDance platform for the targeted sequencing of 110Kb of the genome centered on the APOE gene.

“Isolating a large contiguous locus poses a significant challenge for many targeted sequencing methods, mostly due to the large percentage of repetitive elements in the human genome,” said Dr. Huentelman. “With the RainDance platform, we could design primers flanking repetitive regions, allowing these repetitive loci to be sequenced with the same efficiency as unique sequences. Our preliminary data suggest that it is one of the most viable solutions for determining all sequence variants in a contiguous locus.”

X-Linked Variation Research at Emory University

X-linked diseases are monogenic disorders that are associated with defective genes on the X chromosome. More than 300 human diseases, including some types of autism and mental retardation, have been linked to the X chromosome.

At Emory University, Assistant Professor Michael Zwick, PhD is employing the latest genomic technologies to identify genetic variants contributing to autism susceptibility, with a special emphasis on variants located on the human X chromosome. The primary goal of this research is to advance the understanding of how variation in the human genome contributes to this complex condition.

“The central challenges in human genetics lie in efficiently identifying, annotating and interpreting how genetic variation influences complex human diseases,” said Dr. Zwick. “The RainDance technology has provided us a robust platform for generating target DNA for next-generation sequencing to identify X-linked genetic variation that we believe contributes to autism and X-linked mental retardation. The high-quality DNA sequence data that we are producing and analyzing will aid in the development of better detection tools that will allow researchers and, someday clinicians, to rapidly and cost-effectively identify disease causing variants in some of the most devastating human conditions.”

The RainDance RDT 1000 aids in accelerating human health and disease research through a proprietary microdroplet-based PCR technology that enables “digital biology” at unprecedented picoliter-scale levels, capable of generating more than 1 million individual reactions in less than 10 minutes. Providing a fully-automated, highly reliable and robust system, the RDT 1000 dramatically simplifies customer workflows, shortens turnaround times and lowers cost. As a result, the RDT 1000 is finding broad application across basic and medically important genomic research focused on the prediction and prevention of human disease.



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