Detecting tyms tandem repeat polymorphism by the pssd method based on next-generation sequencing

Binsheng He, Jialiang Yang, Geng Tian, Pingping Bing, Jidong Lang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1153-1159
Number of pages7
JournalCurrent Bioinformatics
Volume15
Issue number10
DOIs
StatePublished - 2020
Externally publishedYes

Keywords

  • Cancer
  • Next Generation Sequencing (NGS)
  • Paired Seed Sequence Distance (PSSD)
  • Polymorphism typing
  • Tandem repeat
  • Thymidylate Synthase (TS)

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