Next Generation Sequencing: Unlocking Genetic Mysteries Faster Than Ever Before

 

Next Generation Sequencing

The Dawn of a New Era in DNA Sequencing

Since the completion of the Human Genome Project in 2003, DNA sequencing has revolutionized our understanding of human genetics and disease. However, the laboratory techniques used in the project, such as Sanger sequencing, were expensive and labor-intensive, generating sequencing data at a relatively slow pace. This all changed with the advent of next-generation sequencing (NGS) technologies in 2005. NGS employs various high-throughput platforms that allow scientists to sequence DNA and RNA much more rapidly than previous methods.

Massively Parallel Sequencing 

One of the key innovations of NGS is its ability to sequence millions of DNA fragments simultaneously. This is achieved through methods such as sequencing-by-synthesis, in which DNA fragments are amplified on a solid surface and fluorescently labeled nucleotides are added one at a time while a camera captures the incorporation in real time. Alternatively, ion semiconductor sequencing observes changes in pH as single nucleotides are incorporated into strands. Importantly, these parallelized approaches allow entire human genomes to be sequenced within a single day for just a few thousand dollars - a dramatic decrease compared to the billions of dollars and over ten years it took to complete the original Human Genome Project.

Revolutionizing Genetic Research

NGS has had widespread impacts on biomedical research. For example, genome-wide association studies using Next Generation Sequencing  have identified hundreds of genetic variants associated with common diseases such as cancer, diabetes and heart disease. Clinicians can now sequence entire patient exomes or genomes to pinpoint mutations underlying rare genetic disorders. NGS has also opened new doors in non-invasive prenatal testing using cell-free fetal DNA in maternal blood. Microbiologists now sequence bacterial and viral genomes on a large scale to track disease outbreaks in real time. In basic science, NGS fuels discoveries by facilitating transcriptome analyses and characterizing epigenomic markers across the whole genome.

Underpinnings of Precision Medicine

Perhaps most significantly, next generation sequencing is providing insights that will transform medicine into a more personalized model. Already, genomic sequencing is used clinically to match cancer patients with targeted therapies based on their tumor's genetic profile. As sequencing costs continue declining, it will likely become standard practice in the next decade to sequence individuals' whole genomes for predictive, preventative and participatory purposes. Doctors will be able to counsel patients on genetic disease risks, recommend lifestyle changes, and select medications tailored to each person's unique DNA sequence. Genomic data combined with other "omic" profiles such as the proteome and metabolome will give rise to an unprecedented level of precision in disease diagnosis and treatment. Overall, NGS is helping usher in an new era of individualized, predictive and preemptive health care guided by a comprehensive understanding of our genetic makeup.

Technological Advances Drive Discovery

Remarkably, NGS technologies continue improving at an exponential pace. Second and third generation platforms including those from Illumina, Thermo Fisher and Oxford Nanopore can now sequence entire human genomes for under $1000. Emerging long-read technologies are resolving previously intractable genomic regions like repetitive sequences and structural variants. Combining short and long reads provides even higher resolution. Portable devices now allow real-time, on-site sequencing during disease outbreaks. New single-molecule sequencing approaches promise to eliminate amplification biases and push per-base sequencing costs below one cent. Computational methods for analyzing massive genomic datasets are also advancing quickly. As sequencing capabilities progress, our view of human genetic variation and its relationship to health will become increasingly sophisticated. Looking ahead, NGS will remain at the forefront of biomedicine, further opening the book of life and driving new discoveries with profound implications for disease understanding and patient care.

Enabling Groundbreaking Genomics Initiatives

 

Massive population-scale genomic projects leveraging next generation sequencing are now unveiling previously hidden architectures of human genetic diversity and disease risk. Notable examples include the UK Biobank study of 500,000 volunteer genomes and medical records, and the NIH's All of Us initiative that aims to collect genetic and health information from one million Americans. Increasingly comprehensive reference genome datasets like the Genome Aggregation Database (gnomAD) are allowing clinically meaningful variants to be more precisely distinguished from common benign polymorphisms. International consortia are sequencing hundreds of thousands of individuals across diverse global ancestries to uncover novel risk loci and reduce health inequities. These monumental collaborative efforts are transforming our fundamental understanding of human variation, complex traits, disease pathogenesis and many other topics through the sheer power of large-scale genomic datasets. With technologies continuing their relentless pace of advancement, the potential of genomics to improve lives worldwide is closer to being fully realized with each passing year.

 

Gets More Insights on: Next Generation Sequencing