by Next generation sequencing (NGS), also known as high-throughput sequencing, is an innovative DNA sequencing technology that allows large scale, cost-effective and rapid DNA sequencing. Unlike the traditional Sanger sequencing, which is considered first-generation sequencing, NGS enables sequencing of millions to billions of DNA strands concurrently, reducing the time and cost required while increasing throughput.
How NGS Works
NGS works through a process of massively parallel sequencing, wherein many DNA fragments are simultaneously sequenced multiple times. The DNA is first fragmented into shorter sequences that are attached to microscopic beads and amplified using a technique called bridge amplification to generate clusters. Specific fluorescent dyes are then attached to each DNA fragment and imaged using a high-powered microscope. By detecting the specific fluorescence of each fragment, the machine determines the sequence of the DNA fragments. Advanced algorithms are then used to map and assemble the sequenced fragments into full genomes or whole genome sequences.
Applications of NGS in Genomics and Biomedicine
Next Generation Sequencing finds myriad applications in various fields of biology and medicine including genome sequencing, metagenomics, transcriptomics, epigenetics and more. Whole genome sequencing allows studying the entire genome composition, identifying genetic variations associated with diseases and disorders. Cancer genome sequencing helps understand cancer biology and accelerate development of targeted cancer therapies. Pathogen genome sequencing enables tracking disease outbreaks and understanding host-pathogen interactions. Agricultural applications involve sequencing plant and animal genomes to develop better crops and livestock. NGS also has wide applications in precision medicine for predicting individual patient response to drugs and facilitating development of personalized treatment regimens.
Impact on Genetic Disease Research and Clinical Diagnostics
Next Generation Sequencing has revolutionized genetic disease research by enabling rapid identification of disease-causing genetic variants associated with both rare and common inherited disorders. It has facilitated research linking rare genomic variants to rare Mendelian diseases. For example, using NGS technology, researchers identified genetic variants responsible for Miller syndrome, early onset Alzheimer’s disease, Miller-Dieker syndrome and many others in a fraction of the time taken by traditional methods. In clinical diagnostics, NGS-based gene panels and whole exome sequencing are increasingly being used to accurately diagnose genetic diseases and disorders, leading to faster diagnosis and informed treatment decisions. It offers a cost-effective alternative to Sanger sequencing for clinical testing of inherited disorders.
Potential Challenges and Future of Next Generation Sequencing
While NGS has significantly accelerated biological and biomedical research, there are still some challenges involved. The huge amount of complex sequencing data generated requires high computational power and data analysis expertise. Standardizing the diverse sequencing platforms and developing robust bioinformatics tools for analyzing NGS data are ongoing challenges. Data storage, management and sharing of genomic and health information while maintaining patient privacy and confidentiality are important issues that need addressed. Overall, with continuous advances in sequencing technologies producing longer reads at higher throughput and lower costs, NGS is set to revolutionize genomics, medicine and healthcare in the decade to come by enabling precision medicine on a massive scale.
