Beyond the genome: Unlocking the power of next-generation sequencing (NGS)

• Next-generation sequencing (NGS) has revolutionized genomics by enabling the rapid, accurate, and cost-effective sequencing of genomes
• The applications associated with NGS technology are extensive, spanning fields such as cancer genomics, rare disease diagnosis, and pharmacogenomics
• Advances in AI and machine learning technology are helping improve NGS data analysis, paving the way for precision medicine and personalized healthcare

In April 2003, the Human Genome Project was declared complete, marking a herculean international effort to map and sequence the entire human genome.¹ Fast-forward to today, and things have changed substantially — next-generation sequencing (NGS) now enables what used to take decades to be possible within just a day.²

By breaking DNA into millions of fragments and sequencing them simultaneously, modern NGS techniques enable the rapid analysis and processing of massive amounts of genetic information, offering a broad range of benefits and potential applications.³

However, before we examine the nature of these applications, it’s essential to first review the current NGS landscape.

Next-generation sequencing (NGS), also known as massively parallel sequencing or deep sequencing, describes a DNA sequencing technology that has helped revolutionize the fields of genomic research and diagnostics.² By leveraging NGS, scientists have made it possible to sequence an entire human genome within a single day — a feat that once took years.^1,2

Here’s how the process works:⁴

1. DNA fragmentation and library preparation — lab personnel first fragment genomic DNA into millions of short pieces. They then attach sequencing adapters (short, synthetic DNA sequences) to each of these fragments, creating a DNA library that’s compatible with the sequencing platform.
2. Massively parallel sequencing — the prepared library is loaded onto an NGS instrument, where the lab then sequences millions of DNA fragments simultaneously. Each platform uses slightly different methods to determine the order of nucleotide bases.
3. Data analysis and assembly — after sequencing, powerful bioinformatics tools align the millions of short DNA pieces into a reference genome. These tools essentially reconstruct the complete DNA sequence of the sample, offering a comprehensive digital map of the individual’s or organism’s genome.

The main advantages NGS offers over traditional sequencing methods (like Sanger sequencing) are its speed, scalability, and overall cost-effectiveness.⁵ While older methods could only sequence one DNA fragment at a time, NGS enables the simultaneous analysis of thousands to billions of fragments, making it possible for labs to sequence multiple genes, or even entire genomes, in a single run.^2,3

Another advantage is that NGS is also “hypothesis-free” compared to qPCR or Sanger. NGS techniques like whole genome sequencing or whole exome sequencing sequence the entirety of the organism's genetic material or its protein-coding regions, respectively. Researchers simply ask, "What's here?" rather than asking, "Is this specific gene mutated?"⁶

As time passes, and with continued investment, NGS sequencing will only become faster, more accurate, and more affordable, opening up even more possibilities than are already available in clinical diagnostics, research, and public health.

NGS offers a broad range of applications across the entire healthcare industry, particularly in the fields of oncology, rare and infectious diseases, and prenatal diagnostics.⁷ Clinical and medical laboratories are also poised to benefit significantly as NGS gradually becomes more integrated into routine clinical practice.⁸

Here are just some of the areas where applying NGS could revolutionize laboratory workflows in the years ahead.

NGS sequencing has already transformed oncological practices through its ability to profile tumors comprehensively. Laboratories are now using techniques like whole genome sequencing, whole exome sequencing, and gene panel testing more often to detect mutations, guide targeted therapies, and monitor resistance to treatments.⁷

Lab personnel can also now use liquid biopsies to identify circulating tumor DNA, providing a minimally invasive way to track the progression of cancer.⁹ This precision approach can help lead to the development of personalized treatment plans and, ultimately, improve the delivery of care to patients.⁸

NGS technology is revolutionizing infectious disease surveillance and public health by providing faster and more comprehensive pathogen identification and analysis.¹⁰ Certain countries, such as the US, have integrated pathogen genome sequencing into their public health systems’ infectious disease surveillance strategies already.¹¹

In doing so, this has enabled outbreaks to be detected earlier, transmission pathways to be tracked more easily, and antimicrobial resistance patterns to be recorded and monitored — all of which are critical for delivering timely public health responses.^10,11

For patients with unexplained symptoms or who haven’t responded normally to specific treatments, NGS genomics may be used to help accelerate the diagnosis and treatment of rare and inherited diseases.¹²

Using whole exome sequencing and whole genome sequencing techniques can help identify pathogenic variants within a patient’s genes, minimizing the time it takes to diagnose issues.¹² This ensures patients receive the most appropriate treatments sooner, rather than later.

The growing use of NGS technology in research is also helping to drive discoveries of new genes linked to rare single-gene disorders. Uncovering the genetic factors associated with common, complex diseases directly influences drug delivery, enabling the development of targeted therapies tailored to unique genetic profiles.⁷

The future of NGS genomics looks bright, with current technological advancements and lab trends indicating the development of even faster, cheaper, and more integrated sequencing in the years to come.

Thanks to advances in artificial intelligence and machine learning, the software and tools used to analyze this vast quantity of genomic data are also seeing drastic improvements. Predictive analytics models now enable the accurate identification of disease-associated variants, delivering improved levels of patient care.¹³

Future NGS applications will only continue to grow as well, especially in the context of personalized medicine. While NGS may be a fundamental tool for innovation, quality, and personalization in today’s clinical labs, the possibilities it presents for the future are endless.

When the Human Genome Project concluded in April 2003, critics hailed it as “the most important biomedical research undertaking of the 20th century.”¹ The transformative applications that NGS provides now prove this to be true, sparking a genomic revolution that has reshaped the world of genomics.