Next Generation Sequencing, also known as high-throughput sequencing, is revolutionizing the field of genomics. Next Generation Sequencing enables scientists to sequence DNA and RNA much more quickly and cost-effectively than previous sequencing technologies. This new sequencing approach promises to accelerate both basic genomic research as well as translational medical applications.
The Rise of Next Generation Sequencing Technologies
Previous Sanger sequencing techniques could sequence only one strand of DNA at a time and were low-throughput. Next Generation Sequencing platforms, by contrast, utilize various techniques to sequence DNA in a massively parallel way. Some of the most prominent Next Generation Sequencing technologies include Illumina sequencing by synthesis, Ion Torrent semiconductor sequencing, and Pacific Biosciences single molecule real-time sequencing.
These platforms take advantage of innovations such as DNA amplification techniques, DNA cluster generation, fluorescence-based detection, and semiconductor chip technologies to sequence millions to billions of fragments of DNA simultaneously. The vastly increased throughput allows researchers to sequence entire genomes, transcriptomes, metagenomes, and more at a fraction of the cost of Sanger sequencing. Since the first Next Generation Sequencing platform was announced in 2005, throughput and data yields have increased exponentially while costs have dropped dramatically.
New Insights into Genetics and Genomics
Armed with these powerful new sequencing tools, researchers have begun sequencing entire genomes from thousands of individuals worldwide to advance our understanding of human genetics and genomics. Large-scale genome sequencing projects like the 1000 Genomes Project have mapped genetic variation across thousands of human genomes to discover SNPs, indels, and structural variants.
Next Generation Sequencing is also enabling new insights into human diseases through projects like The Cancer Genome Atlas, which is sequencing and analyzing huge numbers of tumor genomes to better understand cancer mutations. Medical genomics is also advancing rapidly, with Next Generation Sequencing being applied to clinical diagnostics for conditions that have a genetic component. Researchers are sequencing the genomes of patients to pinpoint disease-causing mutations faster than ever before.
Transcriptomics and Epigenetics
Next Generation Sequencing technologies are revolutionizing other areas of genomics beyond whole genome and exome sequencing. RNA sequencing, also known as RNA-seq, allows comprehensive analysis of the transcriptome at a depth and scale not possible before Next Generation Sequencing. Scientists are using RNA-seq to explore alternative splicing, gene fusions, differential gene expression, and the functional impact of genetic variants on the transcriptome.
Next Generation Sequencing is also being applied to epigenomics research through whole genome bisulfite sequencing and chromatin immunoprecipitation sequencing. These approaches enable high-resolution mapping of DNA methylation patterns and histone modifications across genomes. Combined with genomics and transcriptomics data, this new layer of epigenetic information is helping to unravel how gene regulation and expression are controlled in health and disease.
Microbiome and Single Cell Research
Exciting new research areas are also being enabled and revolutionized by Next Generation Sequencing. Metagenomic analysis using Next Generation Sequencing is allowing comprehensive investigation of microbial communities in various environments like the human microbiome. Researchers have just started to tap the potential of such studies to understand our symbiotic relationships with microbial partners and how they impact health and disease.
Next Generation Sequencing approaches are also empowering new single cell approaches like single cell DNA sequencing and single cell RNA sequencing. They allow genomics and transcriptomics to be investigated at the single cell level rather than averaging effects over bulk populations. Studying cells individually can uncover important new heterogeneities that were previously masked in bulk studies, with implications for developmental biology, cancer evolution, and more.
The Future of Genomics
Next Generation Sequencing is absolutely core to the future of genomics research and its medical applications. With further exponential increases in throughput and even lower costs projected, Next Generation Sequencing will become ubiquitous in applications from routine healthcare to biotechnology. Genome sequencing is poised to become part of preventative healthcare through comprehensively profiling individual genomes, microbiomes, and more for personalized risk assessment.
Genomic sequencing will deliver new insights into diseases and open up an era of more personalized treatments tailored to a patient's genomic and molecular profile. Genomics will also revolutionize agriculture through applications such as genome-wide selection and microbiome engineering. As the power and affordability of Next Generation Sequencing keeps accelerating, its transformational impact will only continue to grow across biomedicine and many other fields in the coming decade and beyond. The future of genomics is digital.
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