Targeted Sequencing in Clinical Research: Advantages and Disadvantages

%argeted sequencing (TS) has become an essential technique in both clinical and research settings, offering several advantages over other sequencing methods. TS is a powerful tool for investigating specific regions of interest in the genome, providing unique insights into disease areas such as oncology, inherited diseases, immunology, and infectious diseases. This approach allows for the targeted sequencing of specific genes, coding regions, and even segments of chromosomes with precision and efficiency.

Advantages of Targeted Sequencing
High Confidence and Accuracy: TS provides high confidence and accuracy in identifying sequence variations in diseases. This is achieved through the amplification of target genes or sequences of interest, ensuring efficient sequencing of the genomic targets.
Reasonable Turnaround Time: TS offers a reasonable turnaround time, making it suitable for rapid molecular diagnosis of diseases, especially during emergencies or global pandemic outbreaks like COVID-19.
Lower Cost: Compared to whole genome sequencing (WGS) and whole exome sequencing (WES), TS panels are more cost-effective. This makes them more accessible for industrial and clinical applications where speed and cost are crucial factors.
Simplified Data Interpretation: TS panels provide excellent coverage depth, which simplifies data interpretation and reduces the level of bioinformatics or computational demand.

Disadvantages of Targeted Sequencing
Limited Coverage: TS panels focus on a particular cluster of genomic regions, which means they may miss important variations outside of these regions. This limited coverage could lead to incomplete or inaccurate results.
Requires Target Enrichment: Before the development and use of TS panels, an additional step of target enrichment is necessary for the genomic regions of interest. This step adds complexity to the process and may introduce potential biases or errors.
Potential for False Interpretations: While TS provides deeper analysis of results than WGS and other survey approaches, there is still a risk of false interpretations due to the depth of coverage. This risk must be carefully managed to ensure accurate results.

Conclusion
Targeted sequencing is a valuable tool in clinical research, offering high confidence and accuracy, a reasonable turnaround time, lower cost, and simplified data interpretation. However, it also has limitations, such as limited coverage, the need for target enrichment, and the potential for false interpretations. As researchers and clinicians continue to develop efficient approaches for the molecular diagnosis of diseases, it is essential to consider both the advantages and disadvantages of TS in the context of specific applications.

Reference:
Pei, X. M., Yeung, M. H. Y., Wong, A. N. N., Tsang, H. F., Yu, A. C. S., Yim, A. K. Y., & Wong, S. C. C. (2023). Targeted sequencing approach and its clinical applications for the molecular diagnosis of human diseases. Cells, 12(3), 493.