The advantages and benefits of NGS for human health research

DNA sequencing technology has advanced significantly over the past two decades, prompting a paradigm shift in the world of life science. Just think how much has changed since the Human Genome Project: In 2003, the first complete sequence of a human genome was delivered at a cost of $2.7 billion, following 13 years of unprecedented collaboration between thousands of scientists.

It was a huge feat at the time, and was achieved thanks to (1st generation) Sanger sequencing technology, a sequencing-by-synthesis approach. At the time, Sanger sequencing was the best resource available. But the technique was limited by its short read length. Now, thanks to Next Generation Sequencing (NGS) technologies, anyone looking to sequence an entire human genome could do so for under $3000, in 1-2 days.

It’s a remarkable example of how far technology has progressed. High-throughput NGS technologies are now accessible to researchers across a vast array of disciplines, providing a platform for DNA and RNA sequencing , with applications that include variant/mutation detection for diagnostic or therapeutic purposes. NGS technology has opened the door to genomic medicine, diagnostic tools for cancer and rare diseases, and novel vaccine approaches that came into the spotlight during the COVID-19 pandemic.

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Now that the era of rapid, affordable DNA sequencing is here, and with genomic medicine setting a new benchmark for healthcare, NGS has never been more essential for human health research. Today, the power of high–throughput NGS technologies is being leveraged by researchers to tackle an increasingly diverse range of unmet needs. In this blog, we explore some of the benefits of NGS technology for human health research.

Benefits of NGS for biomarker discovery

The basis of many diseases and disorders can be linked to our genes, with approximately 10,000 human diseases thought to be caused by a mutation in a single gene. Today, NGS has become the leading platform for the discovery and validation of disease biomarkers through genomic profiling. It brings various benefits to biomarker discovery, including the ability to perform deep sequencing, which enables the detection of low frequency genetic variants, and massively parallel sequencing, which can cover the expanse of the human genome.

NGS can identify mutations in coding and non-coding genomic regions, and can also be used to recognize faulty transcriptome characteristics. This multi-omics approach has provided great value to cancer biomarker discovery in particular, since cancer is a multifaceted genetic disorder, often involving multiple gene mutations as well as changes in transcriptional and epigenetic profiles. These genetic changes can serve as valuable biomarkers for early detection, staging, and detailed molecular characterization of cancer for personalized therapy [1].

NGS benefits in disease diagnostics

After genomic and proteomic biomarkers for a specific disease have been identified, scientists can then also harness NGS as a powerful diagnostic tool. For example, if you wanted to test a patient for a specific cancer, NGS panels can be used to interrogate clinically relevant gene mutations for that specific cancer type. Each panel is designed to interrogate multiple mutations in parallel to deliver a rapid and comprehensive diagnostic platform.

In a diagnostic context, there are various NGS approaches employed depending on the panel and disease. For a well-defined gene panel, a PCR (amplicon) enrichment approach can be used. However, some target mutations, such as genes with GC-rich regions or internal tandem duplicates, pose a challenge for amplicon NGS, and so taking a hybrid-capture approach instead can be advantageous [2].

NGS technology brings great value to disease diagnosis and prognosis by providing rapid, accurate and comprehensive data into the genetic and molecular changes associated with specific diseases or conditions. We are now in a period where this data can then be used to develop personalized treatment plans and improve patient outcomes.

NGS and gene therapy

NGS has been one of the major contributing factors to gene therapy becoming a clinical reality in recent years. Gene therapies based on gene editing technologies like CRISPR-Cas9 are increasingly making it into the clinic, but this couldn’t be achieved without the sequencing power of NGS.

In gene therapy, NGS is often used to identify clinically important mutations prior to the application of targeted therapies. For example, an individual with an inherited condition such as cystic fibrosis or inherited retinal dystrophy may be tested with a targeted NGS panel to identify the key mutations present. Following this, a personalized gene therapy can be developed and delivered to silence, replace, or repair the faulty gene(s) responsible for the disease [3].

Further benefits of NGS are harnessed after gene therapy, where it can be used to confirm whether a transgene sequence has been correctly integrated into a patient, and so assess whether the treatment has been delivered successfully and the gene is being expressed at the desired levels.

NGS is also useful in the identification of potential off-target effects. While gene therapies are designed to target specific genes of clinical relevance, there is always a small chance of unintended mutations elsewhere in the genome. By sequencing the entire genome of cells treated with gene therapy, researchers can identify any off-target effects and assess their potential impact on the patient’s health.

NGS for infectious diseases

It’s not just human genomes that can be interrogated with NGS, the genomes of pathogens can also be sequenced. Next-generation sequencing (NGS) has revolutionized the field of infectious disease prediction and prevention by empowering rapid and accurate identification of pathogens and their genetic characteristics.

One of the main benefits of NGS in the prediction and prevention of infectious disease is the genomic surveillance of pathogens. It can be leveraged to generate population-level data on pathogen genomes by tracking the evolution and spread of pathogens over time and across regions. This information can be used to detect outbreaks early, inform public health interventions, and develop targeted prevention and control strategies. In this way, NGS was central to tracking COVID-19 variants during the pandemic.

NGS was also the driving force behind the successful COVID-19 vaccine campaigns, in which it helped identify antigen regions that could be targeted by vaccines, while also helping to monitor vaccine efficacy and identify emerging vaccine-resistant strains.

A must-have platform for human health research

With an ever-growing list of clinical and human health applications, NGS is here to stay. At Eremid, we recognize that NGS is now an essential platform for genomics research, and have integrated multiple NGS technologies into our genomics services lab to enable a comprehensive range of applications including:

• Whole Genome Re-Sequencing
• De Novo Sequencing
• Low-pass Whole Genome Sequencing
• Target Region Sequencing
• Exome Sequencing

With extensive expertise in the Human Health, AgBiotech, and Food and Nutrition sectors, our world-class scientific team can provide the guidance and sequencing services you need to boost your genomics research.

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References

1. Ventzislava A Hristova & Daniel W Chan, Cancer biomarker discovery and translation: proteomics and beyond. Expert Rev Proteomic. 2019. 16. 2 ,93-103.
2. Dahui Qin. Next-generation sequencing and its clinical application. Cancer Biol Med. 2019. 16. 1,4-10.
3. Monica L Hu, et al. Gene therapy for inherited retinal diseases: progress and possibilities. Clinical & experimental optometry. 2021. 104. 4, 444–454.