DNA sequencing technology has progressed at an unprecedented pace
Since the mapping of the first human genome in 2003, DNA sequencing technology has advanced rapidly. The “Next Generation Sequencing” or NGS has reduced the time and cost of DNA sequencing by orders of magnitude compared to “First Generation” Sanger sequencing. This new sequencing approach is enabling genomic research and applications at an unprecedented scale.
Massively Parallel Sequencing Revolutionized DNA Sequencing
NGS achieves high-throughput and low costs by massively parallelizing the sequencing process. Instead of sequencing DNA fragments one at a time, NGS platforms sequence millions of DNA fragments simultaneously. They do this using specialized biochemical techniques to amplify and read DNA sequences across many individual reactions occurring in parallel.
Two major approaches used in Next Generation Sequencing are sequencing by synthesis and sequencing by ligation. In sequencing by synthesis, each DNA fragment is amplified by generating many copies, then DNA nucleotides are added one at a time while imaging identifies the incorporated nucleotide. In sequencing by ligation, DNA fragments are immobilized on solid surfaces and fluorescently labeled oligonucleotides are sequentially ligated before imaging. Both achieve massively parallel sequencing of thousands to billions of DNA fragments concurrently.
Decreasing Costs Have Fueled Genomic Research and Applications
A major impact of NGS has been rapidly declining DNA sequencing costs. Where the first human genome cost over $2.7 billion to sequence in 2003 using Sanger sequencing, NGS can now sequence an entire human genome for under $1,000. This thousand-fold reduction in sequencing costs has enabled personalized genomic medicine applications and scaled genomic science projects that were previously impossible.
Notable large-scale projects fueled by low-cost NGS include the 1000 Genomes Project, Cancer Genome Atlas, Human Genome Diversity Project, Genome Archives, and Earth BioGenome Project. Scientists can now sequence DNA from species ranging from humans to plants to microbes at an unprecedented scale. Genomic variation is being mapped across human populations for association studies. Cancer genomes are sequenced to uncover new therapeutic vulnerabilities.
New Diagnostic Applications and Continued Declining Cost
Beyond research, next generation sequencing has enabled clinical diagnostic applications by sequencing complete human genomes or focused gene panels rapidly and cheaply. This allows determining disease risks or diagnosing genetic conditions from a single blood or saliva sample. Companies offer NGS-based carrier screening panels, tumor testing, microbiome analysis, and non-invasive prenatal testing.
As NGS technology continues to improve, costs are projected to continue decreasing. Some estimate the cost of a human genome may drop below $100 within a few years. This will fuel further research projects and clinical applications that leverage genomic data. Whole genome sequencing may become a routine component of preventive healthcare and diagnostics. Conditions previously difficult to diagnose may be identified through NGS.
Beyond DNA, Applications in Transcriptomics and Epigenomics
While primarily known for DNA and genome sequencing, NGS methods have expanded applications in related fields. RNA sequencing allows analysis of gene expression levels genome-wide through sequencing of cDNA. This massively parallel “RNA-Seq” has replaced microarrays for transcriptomics and is revolutionizing our understanding of gene regulation.
NGS also enables large-scale methylome and epigenetics studies by sequencing DNA after treatment to preserve methylation patterns or histone marks. Technologies like ChIP-Seq examine how proteins interact with DNA. Single-cell RNA-Seq and ATAC-Seq allow analysis of individual cells. Such applications will provide insight into development, disease mechanisms, and cellular heterogeneity.
Next Generation Sequencing has transformed genomics research capabilities by enabling massively parallel, low-cost DNA sequencing. Beyond continuing to reduce sequencing costs, the technology will likely yield new capabilities like long-read sequencing, portable sequencers, and real-time sequencing. These developments will allow greater insights from genomics and expansion of clinical applications that leverage the power of NGS.
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