Clinical OMICS

MAY-JUN 2018

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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www.clinicalomics.com May/June 2018 Clinical OMICs 29 ple, in real settings, in real diseases states," he explained. Having access to fresher samples is one reason to take the research into the field. "The closer we can get to the disease, the better chance we have of making an impact." Reid anticipates that RNA- seq technology is on the verge of being portable enough to go into the field (See sidebar). Everything from instrumentation to software is devel- oping rapidly, he said. Reid also said that the methods used to understand the malaria parasite will likely be used to understand and create atlases for other disease vectors. Path Ahead It is clear to those using single-cell analysis in basic research that the path ahead includes using the techniques in the clinic. "As the technologies become more stable, there will be a lot of opportunities for clinical appli- cations," Navin said. These include early detection by sampling for can- cer markers in urine, prostate fluid, and the like. It also includes non-in- vasive monitoring of rare circulating tumor cells, as well as personalizing treatment decisions using specific markers. These methods will be par- ticularly useful in the case of samples that today would be labeled QNS, or 'quantity not sufficient.' "Even with QNS samples, these methods allow you to get high-quality datasets to guide treatment decisions." Preparing scRNA-seq for the Clinic & the Field In 2015, high-throughput single cell RNA- seq was described in two independent publications by Allon Klein (In-Drop) Evan Macosko (Drop-Seq). These methods al- lowed the simultaneous transcriptional profiling of thousands of individual cells at unprecedented resolution in one single ex- periment. At the time, Molecular Cell pub- lished an article by Jan Junker and Alexan- der van Oudenaarden which declared that single-cell transcriptomics had "entered the age of mass production." Enter instrument manufacturers who have since been working to offer their se- quencing customers high-throughput, scRNA-seq platforms that are easier to use and increasingly portable. They anticipate, based on the increasingly long list of poten- tial applications, that single-cell analysis will one day be used in the clinic and in the field for precision diagnosis, monitoring, and treatment of a range of human diseases. Today, scRNA-seq platforms are commer- cially available from Dolomite Bio, Bio-Rad, and 10X Genomics—to name a few. Dolo- mite Bio recently launched its latest Drop- Seq platform, the Nadia Instrument and the Nadia Innovate. The Nadia Instrument, in particular, is compact and designed to be easy to use. The Nadia Innovate allows for user-defined single-cell protocols. "The Nadia product family represents a huge leap forward in democratizing single-cell research and enabling potential clinical applications," said Heike Fiegler, Ph.D., vice president of biology at Dolomite Bio. Christopher Love, Ph.D., was a co-se- nior author of the Seq-Well paper. He said Seq-Well's simplicity makes it possible for researchers to prepare samples in chal- lenging environments, such as Biosafety Level-3 or -4 facilities. It will also help re- searchers wanting to collect and prepare samples in remote locations around the world. "Seq-Well removes the need to ship samples and potential artifacts or concerns from that process," said Love, who is a pro- fessor of chemical engineering at MIT. He also added that Seq-Well's low cost and ability to be analyzed using next-genera- tion sequencing (NGS) make prospective banking and large-scale studies feasible. "Its sample efficiency makes it possible to process samples with a low concentration of cells, such as cerebrospinal fluid draws." These attributes will make Seq-Well, or something like it, useful for clinical appli- cations because samples can be prepared in a small clinic or a foreign country and shipped to a laboratory for analysis. Scientists at instrumentation giant Illu- mina see the single-cell market as maturing rapidly. "Although single-cell sequencing is still a relatively early stage market, adoption is quickly accelerating," said Gary Schroth, Ph.D., vice president, genomic applications, Illumina. The focus is shifting away from whole–transcriptome analysis using NGS, the company said. "Today, additional meth- ods are being enabled to address a broad- er set of applications such as DNA somatic profiling, epigenomic characterization by measuring chromatin accessibility (ATAC- seq), and even protein expression (CITE- seq). As the market matures, we expect adoption of the tools and techniques by biotech and pharma customers conduct- ing target and biomarker discovery, and diagnostic testing labs seeking higher res- olution methodologies to better diagnosis and treat disease."—Camille Mojica Rey n The Nadia instrument from Dolomite Bio is one among many commercial tools developed in recent years to help spur single-cell research. SCIEPRO/SCIENCE PHOTO LIBRARY / Getty Images

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