NanoSTR: A Method for Detection of Target Short Tandem Repeats Based on Nanopore Sequencing Data

Abstract Background: Short tandem repeats (STRs) are widely present in the human genome. Studies have confirmed that STRs are associated with more than 30 diseases, and they have also been used in forensic identification and paternity testing. However, there are few methods for STR detection based on nanopore sequencing due to the challenges posed by the sequencing principles and the data characteristics of nanopore sequencing. Results: We developed NanoSTR for detection of target STR loci based on the length-number-rank (LNR) information of reads. NanoSTR can be used for STR detection and genotyping based on long-read data from nanopore sequencing with improved accuracy and efficiency compared with other existing methods, such as Tandem-Genotypes and TRiCoLOR. NanoSTR showed 100% concordance with the expected genotypes using error-free simulated data. Besides, NanoSTR also showed 86.36% and 73.48% concordance using the standard samples 9948 and 2800M with MinION sequencing platform, respectively. Meanwhile, the concordance with Qnome-3841 sequencing platform were 71.97% and 53.03%, respectively. Conclusions: NanoSTR showed high performance for detection of target STR markers. Although NanoSTR needs further optimization and development, it is useful as an analytical method for the detection of STR loci by nanopore sequencing. This method adds to the toolbox for nanopore-based STR analysis and expands the applications of nanopore sequencing in scientific research and clinical scenarios.