In recent years, with the further development of high-throughput sequencing technology, the cost of sequencing has continued to decrease, and whole-exome sequencing (WES) has been increasingly applied to genetic disease detection, which has improved the diagnosis rate of diseases.
However, it comes with the question: does the widely used whole-genome sequencing (WGS) currently suitable for clinical application? It is likely that whole-genome sequencing will subsume genetic testing for individual or even panels of genes, replacing individual genotyping assays with a comprehensive assessment of genetic variation.
- Doctors are too tired to analyze and explain so many VUS, laboratory data analysis and clinical is in disjunction. Is there any reanalysis for undiagnosed cases and re-collection of clinical phenotypes is not yet determined.
- The whole genome sequencing costis high, and the information that could be read out is little. It is still in the scientific research stage, and the clinical application is still early.
- Since clinical applications are considered, the main purpose of clinical diagnosis should consider accuracy, periodicity and cost. Scientific research must use research funding!
- At present, the cost of WGS is still high, and the sequencing, analysis and interpretation is too time consuming. The information useful to patients is similar to the sequencing of exons.
- For single-gene disease, the combination of WES aCGH/SNP-array/CMA has been able to meet most reequipments. Compared with WES, WGS does have a wider coverage, but WGS detects too many variations, such as deep variation in non-coding regions, and a large number of small fragmentsof hundred bp, kb-level deletions/repetitions. These variations are difficult to explain. WGS is not fundamentally different from WES. The most important thing at present is not to expand the genome range of detection, but to expand variants that can be accurately detected, such as repeated amplification of polynucleotides. Compared with the NGS’s WGS for clinical use, it is better to wait for the technical matureness of third generations of sequencing.
- Currently, at least the near future, I personally think that WGS is not suitable for clinical applications. Reason 1, cost considerations. The cost of sequencing a single WGS basically equal to the cost of the current trios’ family, but the positive rate has not increased significantly (data shows 40% of WES and 42% of WGS), and the cost of analysis has increased significantly. Reason 2, without available reference database. Even if more deep intron sites are detected, there is no way to make a pathogenic judgment. Although WGS is superior to WES in terms of detection rate of CNV and SV, low-cost detection method is an alternative.