Next-Generation Sequencers: How They Are Transforming Precision Medicine

Next-Generation Sequencing (NGS) has revolutionized the field of genomics by enabling rapid and high-throughput DNA and RNA sequencing. Unlike traditional Sanger sequencing, which sequences DNA one fragment at a time, NGS allows parallel sequencing of millions of DNA fragments, making it faster, cost-effective, and more scalable.

The global Next-Generation Sequencers (NGS) market, valued at US$ 1.2 billion in 2022, is set for significant expansion in the coming years. With a projected CAGR of 8.3% from 2023 to 2031, the market is expected to surpass US$ 2.4 billion by the end of 2031. This growth is driven by increasing applications of NGS in clinical diagnostics, personalized medicine, cancer research, and infectious disease surveillance. Advancements in sequencing technologies, declining costs, and rising demand for high-throughput genomics are further fueling market expansion.

NGS platforms are broadly categorized into benchtop sequencers and floor-standing sequencers. These instruments leverage cutting-edge sequencing technologies, including Whole Genome Sequencing (WGS), Whole Exome Sequencing (WES), and Targeted Sequencing & Resequencing, to support applications in clinical diagnostics, personalized medicine, agriculture, and more.

This article explores the differences between benchtop and floor-standing sequencers, their underlying technologies, and their impact on various scientific domains.

________________________________________

Benchtop Sequencers vs. Floor-Standing Sequencers

NGS instruments are classified based on their size, capacity, and intended usage.

Benchtop Sequencers

Benchtop sequencers are compact, cost-effective, and suitable for small to mid-scale sequencing projects. They are designed for laboratories that require rapid sequencing with moderate throughput. Some of the most popular benchtop sequencers include:

• Illumina MiSeq – Known for its ease of use and high accuracy, it is widely used in microbiome research, targeted sequencing, and small genome sequencing.

• Ion Torrent™ Ion GeneStudio S5 System – Uses semiconductor sequencing technology to deliver fast turnaround times, making it ideal for clinical diagnostics.

• Oxford Nanopore MinION – A portable device that provides real-time sequencing and long-read capabilities, useful for field-based research.

Floor-Standing Sequencers

Floor-standing sequencers are high-throughput machines designed for large-scale sequencing projects. These instruments support extensive genomic studies, population genetics, and complex research applications. Notable floor-standing sequencers include:

• Illumina NovaSeq 6000 – Offers ultra-high throughput, enabling whole-genome sequencing at an unprecedented scale.

• PacBio Sequel IIe – Delivers highly accurate long-read sequencing, essential for resolving complex genomic regions.

• BGI DNBSEQ-T7 – A powerful sequencer that provides rapid sequencing for population-scale studies.

The choice between benchtop and floor-standing sequencers depends on factors like budget, throughput needs, and research goals.

Key Sequencing Technologies: WGS, WES, and Targeted Sequencing & Resequencing

NGS platforms rely on different sequencing approaches based on the study’s objectives.

1. Whole Genome Sequencing (WGS)

WGS is the most comprehensive sequencing approach, providing a complete map of an organism’s DNA. It is widely used in:

• Medical Genomics – Identifying genetic mutations associated with diseases like cancer, neurological disorders, and rare genetic conditions.

• Agrigenomics – Improving crop resilience and livestock breeding through genome analysis.

• Evolutionary Biology – Studying genetic variations across species and tracing evolutionary lineages.

Benchtop vs. Floor-Standing Sequencers for WGS

Benchtop sequencers are suitable for sequencing bacterial and viral genomes due to their lower throughput. Floor-standing sequencers, on the other hand, are essential for sequencing large and complex genomes, such as human or plant genomes, due to their massive data output.

2. Whole Exome Sequencing (WES)

WES focuses on sequencing the exonic regions (protein-coding genes), which constitute about 1–2% of the genome but account for approximately 85% of known disease-causing mutations. WES is widely applied in:

• Genetic Disorder Research – Identifying mutations linked to inherited diseases.

• Oncology – Detecting cancer-associated mutations for precision medicine.

• Pharmacogenomics – Understanding how genetic variants influence drug response.

Benchtop vs. Floor-Standing Sequencers for WES

Benchtop sequencers like the Illumina MiSeq are ideal for targeted applications requiring quick turnaround. For large-scale clinical studies, floor-standing sequencers such as the NovaSeq 6000 offer the necessary throughput and depth.

3. Targeted Sequencing & Resequencing

Targeted sequencing focuses on specific genes or genomic regions, allowing deep coverage and cost-effective analysis. Resequencing is used to compare genetic variations against reference genomes. Applications include:

• Cancer Genomics – Detecting mutations in known oncogenes and tumor suppressor genes.

• Infectious Disease Research – Sequencing viral and bacterial genomes to track outbreaks and resistance mechanisms.

• Prenatal Testing – Screening for genetic disorders in fetuses through non-invasive prenatal testing (NIPT).

Benchtop vs. Floor-Standing Sequencers for Targeted Sequencing

Benchtop sequencers are preferred for small-scale targeted studies, whereas floor-standing sequencers enable the parallel processing of thousands of samples for large population studies.

Advantages and Challenges of Next-Generation Sequencing

Advantages

✅ High Throughput: NGS enables sequencing of millions to billions of DNA fragments simultaneously.

✅ Cost-Effectiveness: The cost of sequencing per base has significantly decreased over the years.

✅ Scalability: Different platforms cater to diverse sequencing needs, from small-scale research to large population genomics.

✅ Precision Medicine Applications: Personalized treatments based on genetic profiles are now a reality due to NGS advancements.

Challenges

❌ Data Management: NGS generates vast amounts of data, requiring advanced bioinformatics tools and high computational power.

❌ Cost of Equipment: While sequencing costs have decreased, initial instrument costs remain high, especially for floor-standing models.

❌ Technical Complexity: Library preparation, sequencing, and data interpretation require skilled personnel.

Future of NGS and Emerging Trends

1. Single-Cell Sequencing

NGS advancements now allow sequencing at the single-cell level, providing deeper insights into cellular heterogeneity and disease mechanisms.

2. Long-Read Sequencing

Platforms like PacBio and Oxford Nanopore are improving long-read sequencing, enabling better resolution of complex genomic regions.

3. AI-Driven Bioinformatics

Artificial intelligence (AI) is playing a crucial role in analyzing massive NGS datasets, accelerating discoveries in genomics.

4. Portable and Point-of-Care Sequencing

Devices like the Oxford Nanopore MinION are making sequencing more accessible, even in remote areas or clinical settings.