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      Is Open Access

      Microfluidics for genome-wide studies involving next generation sequencing

      review-article
      1 , 2 , 2 , a)
      Biomicrofluidics
      AIP Publishing LLC

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          Abstract

          Next-generation sequencing (NGS) has revolutionized how molecular biology studies are conducted. Its decreasing cost and increasing throughput permit profiling of genomic, transcriptomic, and epigenomic features for a wide range of applications. Microfluidics has been proven to be highly complementary to NGS technology with its unique capabilities for handling small volumes of samples and providing platforms for automation, integration, and multiplexing. In this article, we review recent progress on applying microfluidics to facilitate genome-wide studies. We emphasize on several technical aspects of NGS and how they benefit from coupling with microfluidic technology. We also summarize recent efforts on developing microfluidic technology for genomic, transcriptomic, and epigenomic studies, with emphasis on single cell analysis. We envision rapid growth in these directions, driven by the needs for testing scarce primary cell samples from patients in the context of precision medicine.

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          Most cited references163

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          Epigenetics in cancer.

          Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Global changes in the epigenetic landscape are a hallmark of cancer. The initiation and progression of cancer, traditionally seen as a genetic disease, is now realized to involve epigenetic abnormalities along with genetic alterations. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer including DNA methylation, histone modifications, nucleosome positioning and non-coding RNAs, specifically microRNA expression. The reversible nature of epigenetic aberrations has led to the emergence of the promising field of epigenetic therapy, which is already making progress with the recent FDA approval of three epigenetic drugs for cancer treatment. In this review, we discuss the current understanding of alterations in the epigenetic landscape that occur in cancer compared with normal cells, the roles of these changes in cancer initiation and progression, including the cancer stem cell model, and the potential use of this knowledge in designing more effective treatment strategies.
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            The impact of next-generation sequencing technology on genetics.

            If one accepts that the fundamental pursuit of genetics is to determine the genotypes that explain phenotypes, the meteoric increase of DNA sequence information applied toward that pursuit has nowhere to go but up. The recent introduction of instruments capable of producing millions of DNA sequence reads in a single run is rapidly changing the landscape of genetics, providing the ability to answer questions with heretofore unimaginable speed. These technologies will provide an inexpensive, genome-wide sequence readout as an endpoint to applications ranging from chromatin immunoprecipitation, mutation mapping and polymorphism discovery to noncoding RNA discovery. Here I survey next-generation sequencing technologies and consider how they can provide a more complete picture of how the genome shapes the organism.
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              Droplet microfluidics.

              Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of "digital fluidic" operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors, resulting in decreased reaction times. This, coupled with the precise generation and repeatability of droplet operations, has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as microreactors ranging from the nano- to femtoliter range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. This review will focus on the various droplet operations, as well as the numerous applications of the system. Due to advantages unique to droplet-based systems, this technology has the potential to provide novel solutions to today's biomedical engineering challenges for advanced diagnostics and therapeutics.

                Author and article information

                Journal
                Biomicrofluidics
                Biomicrofluidics
                BIOMGB
                Biomicrofluidics
                AIP Publishing LLC
                1932-1058
                10 March 2017
                March 2017
                10 March 2017
                : 11
                : 2
                : 021501
                Affiliations
                [1 ]Department of Biomedical Engineering and Mechanics, Virginia Tech , Blacksburg, Virginia 24061, USA
                [2 ]Department of Chemical Engineering, Virginia Tech , Blacksburg, Virginia 24061, USA
                Author notes
                [a)]

                Author to whom correspondence should be addressed. Electronic mail: changlu@ 123456vt.edu

                Author information
                http://orcid.org/0000-0003-2565-3609
                Article
                1.4978426 005702BMF R-17009R
                10.1063/1.4978426
                5346105
                7c349765-c638-4083-bcd8-27866d7e04f5
                © 2017 Author(s).

                1932-1058/2017/11(2)/021501/24

                All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 06 January 2017
                : 16 February 2017
                Page count
                Pages: 24
                Funding
                Funded by: National Human Genome Research Institute (NHGRI) http://dx.doi.org/10.13039/100000051
                Award ID: HG008623
                Award ID: HG009256
                Funded by: National Cancer Institute (NCI) http://dx.doi.org/10.13039/100000054
                Award ID: CA174577
                Funded by: National Institute of Biomedical Imaging and Bioengineering (NIBIB) http://dx.doi.org/10.13039/100000070
                Award ID: EB017235
                Award ID: EB019123
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