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WashU Researchers Using NanoString nCounter Platform in Large Diabetes Study

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Washington University School of Medicine’s Genome Sequencing Center will use NanoString Technologies’ nCounter Analysis digital gene-expression system through an early-access program to study the genetic underpinning of obesity and diabetes, the company said last week.
 
James Cheverud, a professor of physical anthropology in the school’s Department of Anatomy and Neurobiology,will use the technology to validate the expression signatures of more than 50 diabetes genes across 15 tissues in over 900 samples.
 
More specifically, Cheverud will use the nCounter “to measure the levels of gene expression in a variety of tissues at loci in genomic regions that have been found to have genetic effects on levels of obesity and diabetes in crosses of LG/J (Large) and SM/J (Small) mice,” a spokesperson for the School of Medicine told Pharmacogenomics Reporter this week in an e-mail.
 
Ultimately, Cheverud and his team aim to identify the “molecular basis of genetic variations responsible for normal levels of variation in obesity and diabetes-related traits.”
 
The company has begun taking commercial orders for the research-use-only system, which includes a fully automated sample-prep station, a digital analyzer, molecular barcodes, and reagents. The system uses these molecular barcodes, or CodeSets, and single-molecule imaging to assay hundreds of gene transcripts per reaction. According to NanoString, one feature that is unique to the nCounter is its ability to detect fractional fold change differences.
 
The nCounter Analysis System would most likely compete with Applied Biosystems Taqman system. NanoString plans to market its technology platform to researchers who want “TaqMan-like performance with the ability to multiplex hundreds of genes per sample.”
 
A spokesperson for NanoString told Pharmacogenomics Reporter this week that the nCounter Analysis System is sensitive enough for a 0.5 fM spike control, which corresponds to a single copy per cell, more than 90 percent of the time. NanoString also guarantees that 90 percent of the time its system can detect a 1.5x fold change for transcripts detected at greater than 5 copies per cell. 
 
“However, in routine practice our performance is much better than our guaranteed specifications,” the NanoString spokesperson said. “We often are able to quantify a 1.2x fold change at a level of a single copy per cell. We are also able to routinely detect our 0.25 fM (0.5 copies per cell) spike and often can detect our 0.1 fM (0.25 copies per cell) spike.”
 
The spokesperson for the University said that Cheverud and his team have seen the data generated by NanoString’s system and are impressed. “We … expect to get the same quality of data for our lab,” the spokesperson said.
 

“When you consider the labor component, the savings with the nCounter Analysis System are even more dramatic.”

Since the nCounter enables researchers to multiplex many gene targets in a single sample, Cheverud and his team also stand to save time and money.
 
“In this study, if we were to use qPCR the study would have required 55,000 individual reactions,” the University spokesperson said. “With the nCounter platform, we can get the same number of data points in 900 reactions.”
 
“There is a significant difference in the amount of labor needed to perform the experiment,” the spokesperson added. “For this study in particular, the nCounter Analysis System will save us tens of thousands of dollars.”
 
The nCounter will enable Cheverud and his team to complete their study in 900 reactions in less than a month with a single system and a part-time technician, according to NanoString.
 
Cheverud’s study is being funded by the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. Results from the study are slated for publication by this summer.
 
The WashU placement is NanoString’s second early-access project. The first was to CalTech researcher Eric Davidson’s lab. Davidson plans to use the platform to study developmental biology on gene-regulatory networks in the sea urchin.
 
“The system is not currently available through any CLIA labs. We have just launched our early-access program and have started to take orders for commercial units,” the company spokesperson said. The company does not yet have plans to submit the system for US Food and Drug Administration approval.
 
However, “we do see the benefits of the [FDA regulatory] system for diagnostics, specifically the performance and ease-of-use aspects of the system,” the spokesperson continued. “How we move into the diagnostics market is in discussion but not in our immediate plans.”
 
For the time being, the company is marketing the system “to microarray users for validation of their gene signatures, researchers who are studying specific pathways, and to researchers who would like TaqMan-like performance with the ability to multiplex hundreds of genes per sample,” the company spokesperson said.

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