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Single-Cell Genomics Market Poised to Take Off, Driven by NGS, qPCR

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Next-generation sequencing is helping to drive the emerging market in single-cell genomics, according to a report by Culver City, Calif.-based market research firm DeciBio.

The single-cell genomics market is expected to more than triple by 2015, with next-gen sequencing representing around $100 million of that in 2015 and growing to $300 million by 2018.

Historically, single-cell genomics has been dominated by microarray technology and PCR, senior author of the report, David Cavanaugh, told In Sequence. But increasingly, qPCR and next-gen sequencing are taking over.

While the market as a whole is growing rapidly, Cavanaugh said, not every facet is experiencing growth. "It's a very heterogeneous market," he said, with some aspects like next-gen sequencing growing very fast, but with other portions, like microarrays, slowing down.

"We really see qPCR and NGS being the predominant genomic tools used," he said. Cavanaugh added that single-cell genomics, while still a niche market, is at a tipping point.

"The workflow is pretty challenging and has historically been low throughput and manual," he said. The workflow can be divided up into three parts, Cavanaugh said, including cell isolation, sample preparation, and genomic analysis.

"Very few people have expertise across the entire workflow," he said. For instance, cell isolation techniques like flow cytometry have been the realm of cell biologists who were not "well-positioned to think about the challenges of sample prep on low amounts of DNA or RNA," he said.

Increasingly, though, companies like Fluidigm are developing tools that automate much of that process and enable the front ends and back ends to be integrated, he said.

Additionally, the launch of institutions dedicated specifically to single-cell genomics is helping to drive the technology forward. For example, Fluidigm and the Broad Institute established a joint Single-Cell Genomics Center last year. East Boothbay, Maine-based Bigelow Genomics, which was founded in 2009 to offer cell sorting, cell lysis, and whole-genome amplification, recently added next-gen sequencing of single cells to its service offerings (IS 4/3/2012).

Currently, academic laboratories make up the vast majority of the single-cell market. But, DeciBio estimates that as the technology evolves, the market will spread to other areas like applied sciences and especially clinical customers.

The two main driving application areas are using single-cell genomics for very rare cells, like unculturable bacteria, embryos, and circulating tumor cells; and to analyze genomic variation from heterogenous samples like tumors, where the genomic makeup of individual cells can vary within the same tumor.

In the context of analyzing rare cells, Cavanaugh said that next-gen sequencing would likely be the primary tool, since it offers a hypothesis-free approach. For looking at genomic variation at the single-cell level, both next-gen sequencing and qPCR will be valuable. For instance, in the case of studying a tumor with known driver genes, qPCR could be used to look at the differences in expression between metastatic and non-metastatic cells, Cavanaugh said.

Within the research setting, single-cell sequencing has been gaining in popularity for sequencing unculturable bacterial species. For instance, at this year's US Department of Energy-Joint Genome Institute's user meeting, researchers from JGI and the Broad Institute each demonstrated single-cell sequencing approaches for studying bacteria (IS 4/3/2013).

And a number of researchers highlighted single-cell sequencing techniques at last year's Biology of Genomes meeting at Cold Spring Harbor Laboratory in New York (IS 5/12/2012).

In addition, the National Institutes of Health last year awarded three groups from the University of California, San Diego (IS 11/27/2012), the University of Pennsylvania (IS 12/4/2012), and the University of Southern California (IS 12/11/2012) five-year grants between $9 million and $10 million each under its Single Cell Analysis Program for single-cell transcriptome sequencing projects.

Clinically, using single-cell genomics techniques to analyze circulating tumor cells is the "most near-term opportunity," according to the DeciBio report.

Indeed, researchers at Cold Spring Harbor are testing single-cell sequencing of biopsy samples, surgical samples, and circulating tumor cells from prostrate cancer patients to see whether using the technique to analyze copy number change can help inform earlier diagnosis (CSN 9/7/2011).

Single-cell sequencing in preimplantation genetic diagnosis may ultimately end up being the first clinical use of the technology. For instance, Dagan Wells from the University of Oxford, who also collaborates with preimplantation diagnosis firm Reprogenetics, has designed a single-cell sequencing-based test to screen embryos for chromosomal aneuploidies and is currently conducting a clinical trial of the test. (CSN 2/27/2013).

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