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BIOMARKET TRENDS Biobusiness Single-Cell Genomics Poised for Growth Market Potential Is Being Unlocked by Several Promising Technologies David Cavanaugh Single-cell genomics is a fast growing, emerging approach in which genomic technologies are applied at the level of single cells, rather than an entire population of cells. Ever since Robert Hooke discovered the frst cell in the 17th Century, scientists have been looking to better understand this basic unit of life. Despite the rapid evolution of genomic technologies over the past decade, the ability to interrogate the genomics of a single cell remained very challenging. Historically, many scientists believed that groups of very "similar" cells would have limited genomic variation, supporting the use of a cell population approach. However, recent single-cell genomic experiments have demonstrated that even seemingly identical cells can have signifcant genomic variations. These variations can play a critical role in human health and disease (Figure 1). Over the past few years, there has been an explosion of single-cell genomics publications (growing at more than 40% per year: Figure 2). The segments of microbiology, basic cell biology, and stem cell biology represented the majority of these publications. Single-cell approaches have been enabling for microbiologists given that microbes, particularly novel microbes, can be challenging to culture to a suffcient population size to conduct traditional population-level genomic approaches. The emergence of single-cell genomics has enabled microbiologists to identify and analyze individual microbes at the genomic level. Interestingly, single-cell genomics has also been adopted by traditional cell biologists inDavid Cavanaugh (cavanaugh@decibio. com) is a partner at DeciBio. Web: www.decibio.com. terested in complementing their existing cell biology approaches (e.g., fow cytometry, patch clamp) with genomic analysis. For stem cell biologists, single-cell genomics is a disruptive technology to better understand cell programming and differentiation. In the last few years, there has been an emergence of publications in specifc disease areas, especially oncology, neurology, and immunology in which single-cell genomics has enabled an understanding of intrapopulation heterogeneity (e.g., tumor cell heterogeneity) and rare subpopulations (e.g., CD34+ and CD133+ hematopoietic stem cells). Conducting single-cell genomics experiments has been challenging given that it requires the manual integration of a number of workfow steps, historically conducted by different research subspecialties, creating a "cross-functional skill gap." In step one, single cells must be isolated from bodily fuids or tissue, typically using technologies such as fow cytometry, laser capture microdissection, or micromanipulation. These technologies have been historically under the purview of cell biologists, not geneticists. Next, isolated single cells must be managed into separate compartments (so that their DNA/RNA does not mix) and then of single cells (e.g., Nugen's Ovation® OneDirect System). Similar to qPCR in the 1990s, all the right drivers are in place—high scientifc interest, rapidly growing number of publications, optimized instruments and reagents—to really "unlock" the single-cell genomics market. As a result, DeciBio believes that this market has reached an infection point and will experience rapid growth over the next fve or so years, with many segments growing at greater than 40% annually. DeciBio's recently published "Single Cell Genomics (SCG): Market Size, Segmentation, Growth, Competition and Trends" market report provides detailed information about this rapidly growing market, highlighting some segments that are expected to more than double in size each year for the next three years (Figure 3). the DNA/RNA of each single cell needs to be amplifed for downstream genomic analysis. (Current genomic analysis technologies are typically not sensitive enough to work with DNA/RNA from a single cell without amplifcation). Finally, during the third step the DNA/RNA is analyzed using genomic technologies such as qPCR or sequencing. The latter two steps are typically under the purview of geneticists, not cell biologists. The combination of a lack of a system to integrate all steps of this workfow and the existence of a cross-functional skill gap among scientists has signifcantly limited the adoption of single-cell genomics to date. The good news is that the single-cell genomics workfow is rapidly improving through integration of steps, optimized single-cell reagents, and higher throughput. Most notably, Fluidigm has launched the C1™ Single-Cell Auto Prep System, which integrates cell isolation and sample prep into one instrument with the ability to integrate downstream with its BioMark™ HD qPCR platform for gene expression analysis. This represents the frst end-to-end solution for single-cell qPCR and has the capacity to conduct analysis on 96 individual cells at a time. Nanostring offers a protocol to conduct gene expression on single cells in suspension, thus integrating steps two and three. Additionally, other companies have launched reagents optimized for genomic amplifcation Figure 2. Single-cell genomics publications have exploded recently Figure 3. Single-cell genomics market poised for rapid growth Figure 1. Single-cell genomics can identify variations masked by population studies NEWS Products & Services >Thermo Fisher Scientifc has inked an exclusive agreement with Toyko's Mitsui Knowledge Industry (MKI) for the worldwide marketing and distribution of MKI's Lipid Search software for the interpretation of lipidomic research data. The software supports Thermo Scientific Orbitrap and hybrid Orbitrap systems as well as triple quadrupole mass spectrometers. It processes data from both infusion MS/MS and LC-MS/MS data, and uses MS2 and/or MS3 data to identify lipids from a database of more than one million species. >Debiopharm Group and Quartz Bio have entered into a year-long collab- oration through which the latter firm will apply its bioinformatics expertise to support the former's translational projects, ranging from next-generation sequencing to clinical biomarker analysis. >AstraZeneca has agreed to license Optibrium's StarDrop™ software, which highlights high-quality compounds. According to Optibrium, its software reduces the time it takes to choose effective leads and transform them into candidate drugs. Under the terms of the agreement, the pharma giant will also have access to the software firm's ADME-QSAR and Auto-Modeller™ modules. >AB Sciex, Genedata, and LECO are partnering to deliver a software system that will enable metabolomics researchers to process and analyze experimental data across different GC/MS and LC/MS platforms, the companies said. Previous collaborative efforts among the three firms produced the latest version of Genedata Expressionist® MSX software, an endto-end solution for the analysis of mass spectrometry data generated through metabolomics experiments. >San Diego-based Pfenex division Reagent Proteins has entered into a nonexclusive agreement with Canadian firm BioVectra, through which the latter will cooperate in the sales and distribu- Genetic Engineering & Biotechnology News tion of the former's range of more than 5,000 catalog protein products. >Following its acquisition of Celsis In Vitro Technologies (Celsis IVT) for an undisclosed price, Bioreclamation Group is now BioreclamationIVT— a "one-stop shop offering a complete range of biological tools needed to pursue new drug discovery and development," according to the firm. BioreclamationIVT will offer a combination of Celsis IVT and Bioreclamation products, which enable scientists to better understand the pharmacokinetics, metabolism, and toxicity of the compounds they are investigating. n | GENengnews.com | August 2013 | 15