WarpSTR: Determining Tandem Repeat Lengths Using Raw Nanopore Signals

Sitarcik, J.1,2,5, Vinar, T.3, Brejova, B.3, Krampl, W.1,2,4, Budiš, J.1,2,5, Radvanszky, J.1,2,6, Lucka, M.3

Short tandem repeats (STRs) are regions of a genome containing many consecutive copies of the same short motif, possibly with small variations. Analysis of STRs has many clinical uses, but is limited by technology mainly due to STRs surpassing the used read length. Nanopore sequencing, as one of long read sequencing technologies, produces very long reads, thus offering more possibilities to study and analyze STRs. Basecalling of nanopore reads is however particularly unreliable in repeating regions, and therefore direct analysis from raw nanopore data is required.
Here we present WarpSTR, a novel method for characterizing both simple and complex tandem repeats directly from raw nanopore signals using a finite-state automaton and a search algorithm analogous to dynamic time warping. By applying this approach to determine the lengths of 241 STRs, we demonstrate that our approach decreases the mean absolute error of the STR length estimate compared to basecalling and STRique.

1Comenius University Science Park, Bratislava, Slovakia
2Geneton Ltd., Bratislava, Slovakia

3Faculty of Mathematics, Physics, and Informatics, Comenius University, Bratislava, Slovakia
4Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia
5Slovak Centre of Scientific and Technical Information, Bratislava, Slovakia
6Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia

Cite: Sitarcik, J., Vinar, T., Brejova, B., Krampl, W., Budiš, J., Radvanszky, J., Lucka, M. WarpSTR: Determining Tandem Repeat Lengths Using Raw Nanopore Signals. Bioinformatics (2023). DOI: 10.1093/bioinformatics/btad388


Mária Lucká