Lokatt: A hybrid DNA nanopore basecaller with an explicit duration hidden Markov model and a residual LSTM network

Background Basecalling long DNA sequences is a crucial step in nanopore-based DNA sequencing protocols. In recent years, the CTC-RNN model has become the leading basecalling model, supplanting preceding hidden Markov models (HMMs) that relied on pre-segmenting ion current measurements. However, the CTC-RNN model operates independently of prior biological and physical insights. Results We present a novel basecaller named Lokatt : exp l icit durati o n Mar k ov model and residu a l-LS T M ne t work. It leverages an explicit duration HMM (EDHMM) designed to model the nanopore sequencing processes. Trained on a newly generated library with methylation-free Ecoli samples and MinION R 9 . 4 . 1 chemistry, the Lokatt basecaller achieves basecalling performances with a median single read identity score of 0 . 930 , a genome coverage ratio of 99 . 750% , on par with existing state-of-the-art structure when trained on the same datasets. Conclusion Our research underlines the potential of incorporating prior knowledge into the basecalling processes, particularly through integrating HMMs and recurrent neural networks. The Lokatt basecaller showcases the efficacy of a hybrid approach, emphasizing its capacity to achieve high-quality basecalling performance while accommodating the nuances of nanopore sequencing. These outcomes pave the way for advanced basecalling methodologies, with potential implications for enhancing the accuracy and efficiency of nanopore-based DNA sequencing protocols. Supplementary information Supplementary data are available online.