An Interview Questions for Experts’ Opinions towards WGS In Clinical Field

Background
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?

To answer the question, we invited some clinical specialist WGS to compile this article.

The interview
1.Q: do you think WGS can be used for individual uses?
A: WGS can be used clinically, but there should have more stringent requirements for genetic testing companies for industry qualifications.

1. Q: What’s the difference between WGS and WES?
A: 1) WGS data analysis is easier than WES. It’s relatively less likely to judge wrong. 2) Although everyone is shouting that the cost of whole genome sequencing will decline in the future, from the current situation, the future will still be no enough threatening competitors in a few years. 3) WGS generates a lot of unnecessary information at the same time. Because the amount of data is greatly increased, the time for data analysis will increase and it will be detrimental to the clinical process. Moreover, enterprises have to bear the storage and maintenance costs of these data; 4) WGS results show more unknown variation, which is uncertain and troublesome. 5) WGS generate some information that can be used for research. 6) In general, WGS is currently only suitable for use in a few clinically difficult cases.

2.Q: What your opinion towards application of WGS?

A: I am optimistic about the application of WGS. 1) Interpretation is a big problem: as a diagnostic tool, it requires a strong background in medicine, genetics, and combined with clinical ability. 2) Price is also a problem: sequencing a 100G data might cost thousand dollars. 3) But in some aspects: for example, genetic disease, health genetic risk assessment, WGS is still promising. As to tumor, it is currently not suitable because the whole genome sequencing is insufficiently measured (not deep enough).

3.Q: Why WGS is not broadly used for clinical purpose?
A: ACMG proposes that genetic testing depends on the potency ratio. If the whole genome sequencing is free, every potential patient wants to do it. However, the WGS cost is borne by the patient, the analysis process is complicated, and many of the conclusions obtained are uncertain. The diagnosis of the disease is still trending toward step-by-step testing, from simple to difficult, from cheap to expensive. The necessity of detection cannot only be considered from the perspective of medical diagnosis, but also from economic, social and family effects.

4.Q: Is it difficult to interpret WGS data?
A: As an interpreter, the actual interpretation process of WGS is almost equal to the WES genome-wide CNV. The coverage is more uniform, but some of the variation depth is simple than WES, and some of the sites are not well to be judged. It is a good solution for scientific research, but for the clinical application, considering the current business process, interpretation level and cost performance, WGS is not so good though it should be the next big trend when it’s mature.

5.Q: What’s key for WGS marketing?
A: The key depends on how powerful bioinformation pipeline can be extracted from WGS. Also from the perspective of the testing laboratory, the WGS library construction is significantly simpler and has a shorter cycle (compared to WES). WGS is the future.

6.Q: As a doctor, will you recommend WGS for patient?
A: I think that the cost of WGS is too high. We have not recommended it to a patient yet. It is also true that the results of the analysis are difficult to explain to the patient. It is very good to use this method for scientific research on a few difficult cases.