How Next Generation Sequencing is Revolutizing Genomics?

Next generation sequencing (NGS) has transformed our understanding of biological systems and genetics by providing a comprehensive look into the complex world. But what if it was possible to decode thousands of genomes simultaneously and uncover insights that could transform the fields of biology and medicine? Let us introduce you to the world of genomic exploration, where the boundaries of discovery are being redefined with every technological advancement.

In recent years, next generation sequencing has resulted in the development of better targeted and personalized therapies. In this blog, we take you to the realm of NGS, detailing the basics and workflow of the sequencing method. Also, we shed light on the benefits and latest advancements in the next generation sequencing technology.

What is Next Generation Sequencing?

In essence, next generation sequencing is a technology that determines the sequence of Deoxyribonucleic acid (DNA) or Ribonucleic acid (RNA). The sequenced DNA or RNA using NGS is used to study genetic variations linked to diseases or other biological phenomena. NGS was first introduced in 2005 and was initially called “massively parallel sequencing” as it allowed for simultaneous sequencing of multiple DNA strands. This was a huge advancement over traditional Sanger sequencing, which could sequence only one DNA strand at a time.

The NGS Workflow

The main steps involved in a typical NGS workflow are:

Sample Preparation: The first step involves extracting genomic data from samples. The samples can take the form of saliva, blood, and tissue. During sample preparation, the fragmentation of the DNA into shorter sequences takes place. The DNA fragmentation is followed by ligation, amplification, and enrichment of adapters.

Sequencing: The exact DNA sequencing method depends on the platform being used. Some DNA sequencing methods include sequencing and pyrosequencing by ligation or synthesis. Sequencing by synthesis is a popular technology as it allows for the simultaneous sequencing of large amounts of genomic DNA. Also, it carries out sequencing at high sensitivity to detect a wide range of genetic alterations.

Data Analysis: Finally, bioinformatic tools, analytical methods, and data science platforms are used to control quality and identify pathogenic variants.

Different Next Generation Sequencing Technologies

Here’s an overview of the most common next-generation sequencing technologies:

Whole Genome Sequencing (WGS): This NGS method involves determining the complete sequence of an organism’s genome. In WGS, the DNA is fragmented into smaller pieces and then sequenced. After this, the aligning and assembling of the DNA sequence is done to construct the entire genome. Whole genome sequencing is used to discover genomic variants and study complex DNA traits.

Targeted Sequencing: This sequencing method focuses on specific genomic regions. It uses capture techniques or amplicon-based methods to enrich and sequence specific DNA regions. Targeted sequencing is used to study genetic variations and investigate specific genes linked to diseases.

Whole Exome Sequencing (WES): This next generation sequencing method focuses on the genome’s exonic regions. After fragmentation, WES uses hybridization techniques to capture exonic regions selectively. The captured exonic regions are then sequenced. WES is used to study rare genetic disorders and discover mutations associated with disease.

RNA Sequencing: RNA sequencing offers a comprehensive representation of transcriptome, which is the full range of messenger RNA expressed by an organism. After extraction, the RNA from cells or tissues is converted into complementary DNA and then sequenced. The sequenced data includes information about gene expression levels and transcript variations. RNA sequencing is used to study alternative splicing, identify novel transcripts, and develop antisense and RNAi therapeutics.

Advantages of Next Generating Sequencing

There are several advantages associated with the sequencing of an entire genome. Some of them include:

Scientific Information: Next generation sequencing provides information on genetic variations that may lead to or increase the risk of diseases. Thus, it can enable healthcare professionals to act preemptively before disease development and commence treatment for an undiagnosed disease.

Technical Accuracy: The next generation sequencing procedure is performed with the highest standards. Also, discoveries are constantly being made to improve the data quality for next generation sequencing.

Cost Savings: The cost of sequencing amount of the world’s first genome amounted to billions of dollars. But with technological advances, genome sequencing can now be done in a few hundred dollars.

Types of NGS Applications

Next generation sequencing can be used for multiple applications, including:

• Whole genome sequencing to determine the complete DNA sequence of an organism.
• Whole genome sequencing to focus on the genome’s coding regions.
• Targeted sequencing for studying specific regions of interest in genome
• Epigenomics for evaluating modifications in epigenetics
• RNA sequencing to determine genetic alterations and identify specific cell types.

Latest Developments in Next Generation Sequencing

The nextgen sequencing market has the presence of both established players and new entrants. Companies such as Oxford Technologies Nanopore, Illumina, and Pacific Biosciences are working tirelessly to reduce the cost of the technology. The market for next generation sequencing is growing, with organizations marketing NGS benchtop platforms to bring the technology into as many labs as possible.

Here are some of the latest market developments:

• In March 2024, the World Health Organization (WHO) published a series of recommendations on the use of next-gen sequencing tests for diagnosing drug-resistant tuberculosis (TB). The guidelines are accompanied by a WHO operational handbook offering detailed guidance over evidence-based recommendations.
• In December 2023, Illumina partnered with HaploX for the development of domestically produced sequencing instruements in China. The development marked a new stage in the strategic development between the two firms.

Final Saying

To conclude, NGS is used for analyzing DNA and RNA samples and is a popular technology in functional genomics. Unlike microarray techniques, NGS-based methods provide several advantages, such as higher reproducibility and increased dynamic signal range. In the upcoming years, we can see more industry participants offering advanced next gen sequencing solutions.