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Current Bioinformatics


ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

Research Article

Detecting TYMS Tandem Repeat Polymorphism by the PSSD Method Based on Next-generation Sequencing

Author(s): Binsheng He*, Jialiang Yang, Geng Tian, Pingping Bing* and Jidong Lang*

Volume 15, Issue 10, 2020

Page: [1153 - 1159] Pages: 7

DOI: 10.2174/1574893615999200505074805

Price: $65


Background: Thymidylate Synthase (TS) is an important target for folic acid inhibitors such as pemetrexed, which has considerable effects on the first-line treatment, second-line treatment and maintenance therapy for patients with late-stage Non-Small Cell Lung Cancer (NSCLC). Therefore, detecting mutations in the TYMS gene encoding TS is critical in clinical applications. With the development of Next-Generation Sequencing (NGS) technology, the accuracy of TYMS mutation detection is getting higher and higher. However, traditional methods suffer from false positives and false-negatives caused by factors like limited sequencing read length and sequencing errors.

Objective: A method was needed to overcome the short sequencing read length and sequencing errors of NGS to make the detection of TYMS more accurate.

Methods: In this study, we developed a novel method based on "Paired Seed Sequence Distance” (PSSD) to detect the Variable Number of Tandem Repeat (VNTR) mutation for TYMS.

Results: With the 121 samples validated by sanger, the consistency rate of PSSD method was 85.95% (104/121), higher than the strict matching method (78.51% (95/121)). The consistency rate of the two methods was 89.26% (108/121). We also found that the PSSD method was significantly better than the strict matching method, especially in the 4R typing.

Conclusion: Our method not only improves the detection rate and accuracy of TYMS VNTR mutations but also avoids problems caused by sequencing errors and limited sequencing length. This method provides a new solution for similar polymorphism analyses and other sequencing analyses.

Keywords: Thymidylate Synthase (TS), Next Generation Sequencing (NGS), Paired Seed Sequence Distance (PSSD), tandem repeat, polymorphism typing, cancer.

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