The Evolving Role of Next-Generation Sequencing in Precision Medicine

Next-generation sequencing (NGS) has transformed precision medicine by enabling comprehensive genetic analysis at unprecedented speed and scale. Unlike single-gene testing, which examines one gene at a time and may miss complex or multifactorial genetic contributions, NGS allows simultaneous analysis of thousands to millions of DNA fragments. NGS consolidates testing for multiple biomarker types, such as single-nucleotide variants, insertions/deletions, copy number variants, and gene fusions, reducing the need for sequential single-gene assays and minimizing error rates. This capability is critical for identifying rare variants, complex mutations, and biomarkers that guide personalized treatment strategies. The shift from single-gene methods to NGS is driven by the need for faster, more accurate diagnostics in fields like oncology, rare disease research, and reproductive health. NGS significantly accelerates diagnostic turnaround times compared to traditional methods and have evolved so much in the last decade that some NGS systems in the market can now deliver results in as little as 24 hours. Its highly automated workflows and ability to process multiple samples simultaneously enable rapid, precise results, facilitating timely clinical interventions in settings like oncology and rare disease diagnostics.

When to Use WGS, WES, or Targeted NGS

Targeted NGS achieves high sensitivity, detecting nearly all known mutations in oncology, making it a cornerstone of precision diagnostics. Its ability to identify low-frequency variants with high specificity, even in challenging low-input samples like FFPE tissues or circulating tumor DNA (ctDNA), ensures accurate detection of cancer-related mutations, enabling comprehensive genomic profiling in as little as 24 hours.

• Whole-Genome Sequencing (WGS): Analyzes the entire genome, including coding and non-coding regions. WGS is ideal for discovering novel variants or studying complex diseases but generates large datasets requiring significant computational resources. It is also used for aneuploidy detection in preimplantation genetic testing.
• Whole-Exome Sequencing (WES): Focuses on protein-coding regions (approximately 1-2% of the genome), which harbor most disease-causing mutations. WES balances cost and data complexity, making it suitable for rare disease diagnostics.
• Targeted NGS: Sequences specific genes or regions of interest, offering high sensitivity and cost-efficiency. It is preferred for applications requiring deep coverage of known variants, such as cancer profiling or carrier screening. It excels in analyzing degraded samples, such as FFPE tissues, common in clinical research.

The Value of Targeted NGS

Targeted NGS delivers high-depth sequencing of specific genomic regions, maximizing sensitivity and minimizing data processing demands. Its advantages include:

• Cost-Effectiveness: By focusing on clinically relevant genes, targeted NGS reduces sequencing and analysis costs compared to WGS.
• Speed: Rapid, in-house targeted NGS platforms can deliver results in as little as 24 hours, critical for time-sensitive applications like cancer treatment planning.
• Low Input Requirements: Targeted NGS can analyze small or degraded samples, such as FFPE tissues or ctDNA, enabling non-invasive diagnostics.
• High Sensitivity: Deep sequencing ensures detection of low-frequency variants, essential for identifying actionable mutations.

Targeted NGS’s amplicon-based methods enable precise sequencing of homologous genomic regions, such as tumor suppressor genes, and hypervariable regions like T-cell receptor sequences, critical for cancer and immunotherapy research. These features make targeted NGS a powerful tool for clinical laboratories aiming to integrate genomic testing into routine workflows.

Real-World Applications of Targeted NGS

Targeted NGS is significantly advancing medical research and clinical practice by addressing complex challenges across multiple domains. In oncology, targeted NGS enables precise identification of tumor-associated mutations using minimal samples, such as FFPE, facilitating tailored therapeutic strategies. For inherited disease research, NGS panels efficiently detect causative genetic variants. In reproductive health, it supports comprehensive genetic risk assessments, enabling prospective parents to make informed family planning decisions through expanded carrier screening. In infectious disease research, targeted NGS rapidly sequences microbial genomes, aiding in the surveillance of outbreaks and the identification of significant variants. Additionally, it underpins non-invasive cancer monitoring through liquid biopsies, analyzing ctDNA to detect early signs of relapse with high sensitivity. Targeted NGS also contributes to microbiome research by profiling microbial diversity in the human gut, offering valuable data for personalized nutrition and immune health strategies.

These applications are exemplified by recent advancements in clinical and research settings. In oncology, a study in Scientific Reports found that targeted NGS identified mutations in approximately 70% of 422 non-small cell lung cancer samples, supporting the selection of personalized therapies. Across these applications, the technology’s capacity to process low-input samples and deliver rapid, accurate results is transforming the understanding and management of disease.

The Future of NGS

The future of NGS lies in its deeper integration into clinical practice and public health. Advances in automation and bioinformatics are streamlining workflows, reducing hands-on time, and making NGS more accessible to smaller laboratories. Advances in automation have enabled select rapid, targeted in-house NGS systems to reduce hands-on time to as little as 20 minutes, making genomic testing more accessible for smaller labs with limited training resources. Emerging technologies, such as single-cell sequencing and long-read sequencing, promise to enhance resolution and uncover previously undetectable variants. Advances in semiconductor-based NGS may further reduce diagnostic costs, enhancing reliability enabling broader access to genomic testing in resource-limited settings. The increasing integration of artificial intelligence in NGS workflows is enhancing the accuracy and efficiency of variant interpretation, with recent studies highlighting significant improvements across a range of sequencing platforms. As costs continue to decline, NGS is poised to become a standard tool for personalized medicine, enabling equitable access to genomic insights worldwide.

Get acquainted with how rapid, in-house NGS solutions can enhance clinical workflows and discover strategies for integrating genomic testing into your practice today!

Related posts:

A Look at the Billion Dollar Clinical Oncology NGS Market–Part I: Growth Driven by Regional Expansion & Targeted Technologies Considerations for Implementing Next-Generation Sequencing in Real-World Clinical Settings WSJ Health Forum 2022: Psychedelics Set to Take Center Stage in Mental Wellness Pioneers of AI Win Nobel Prize in Physics for Training Neural Networks with Physics

Author

Bernice Lottering