Sequencing your way to health – Challenges and opportunities

Sequencing the first human genome was the beginning of a health revolution and since then, with rapid advances, DNA sequencing has evolved from a technology used in research to being an integral part of the clinical diagnostics pipeline. DNA sequencing is used for diagnosis and treatment of cancer, chronic and rare diseases, identifying genetic variations, tracing ancestry, and developing personalized treatments. It also underpins the emerging field of liquid biopsy.

Different types of DNA sequencing have their own advantages and disadvantages, which help determine their application.

First-generation DNA sequencing, Sanger sequencing, is simple, quick, and accurate for small-scale sequencing, confirming variants detected by NGS or sequencing single genes. It has low throughput, short read length, and a higher cost per base compared to NGS.

Next-generation sequencing (NGS) is the second generation of DNA sequencing that can generate millions of short reads simultaneously, allowing for high-throughput and multiplexed sequencing of multiple samples or regions in a single run. This increases the speed and reduces the cost of DNA sequencing. NGS has enabled the development of new applications, such as liquid biopsies, whole-genome sequencing, whole-exome sequencing, targeted gene panels, and CRISPR-based diagnostics. It, however, has lower accuracy than Sanger sequencing, especially for homopolymer regions and GC-rich regions. It also requires high-quality DNA samples and sophisticated bioinformatics tools for data analysis.

Third-generation DNA sequencing is a long-read sequencing technology based on single-molecule sequencing (SMS) that can generate long reads without amplification or fragmentation of the DNA molecules. This has high sensitivity for detecting low-frequency mutations in cfDNA samples and comes at a high cost per base, lower throughput.

NGS is the most commonly used and accounts for close to 60 percent of the DNA sequencing market as the fastest and the cheapest form of gene sequencing. Perhaps the most significant change in the past 12 months has been the lapse of certain core technology patents and the entrance of new players into the sequencing market.

For purchase decisions for DNA sequencers in the diagnostic sector, choosing the right DNA sequencer for a diagnostic laboratory involves balancing technical specifications that include throughput, accuracy, read length, with practical considerations, such as cost and ease of use. In addition to these technical considerations, it is also important to consider the challenges of translating sequencing to the clinic.

Sequencing generates large amounts of data that need to be transferred, stored, analyzed, and interpreted. Adequate computational resources and skills to handle the data is an imperative.

Centralized DNA sequencing facilities and public-private partnerships can provide a cost-effective option to utilize high-throughput sequencers, standardize protocols and procedures for sample and library preparation, quality assessment, data analysis, and reporting.

There is also a need for robust databases and guidelines to provide evidence-based interpretation and clinical recommendations for genomic findings. India, with its population of 1.3 billion genomes, makes up 20 percent of the world’s population, but the DNA sequences of its people only make up about 0.2 percent of global genetic databases This emphasizes the need for India-centric population genomic initiatives.

Advances in DNA sequencing technology and increased applications in clinical diagnosis, drug discovery, and a growing demand for personalized medicine and precision healthcare present significant opportunities for growth and expansion.

The 3.2-billion DNA base pairs sequence is a valuable tool for the diagnostic industry for diagnosing and treating patients more effectively.