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Non-B DNA play an important role in basic cellular processes and are associated with genomic instability, gene regulation, and oncogenesis. Experimental methods are low-throughput and can detect only a limited set of non-B DNA structures, while computational methods rely on non-B DNA base motifs, which are necessary but not sufficient indicators of non-B structures. Oxford Nanopore sequencing is an efficient and low-cost platform, but it is currently unknown whether nanopore reads can be used for identifying non-B structures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We build the first computational pipeline to predict non-B DNA structures from nanopore sequencing. We formalize non-B detection as a novelty detection problem and develop the GoFAE-DND, an autoencoder that uses goodness-of-fit (GoF) tests as a regularizer. A discriminative loss encourages non-B DNA to be poorly reconstructed and optimizing Gaussian GoF tests allows for the computation of P-values that indicate non-B structures. Based on whole genome nanopore sequencing of NA12878, we show that there exist significant differences between the timing of DNA translocation for non-B DNA bases compared with B-DNA. We demonstrate the efficacy of our approach through comparisons with novelty detection methods using experimental data and data synthesized from a new translocation time simulator. Experimental validations suggest that reliable detection of non-B DNA from nanopore sequencing is achievable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>Source code is available at https:\/\/github.com\/bayesomicslab\/ONT-nonb-GoFAE-DND.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btad220","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T08:16:16Z","timestamp":1688112976000},"page":"i242-i251","source":"Crossref","is-referenced-by-count":7,"title":["Deep statistical modelling of nanopore sequencing translocation times reveals latent non-B DNA structures"],"prefix":"10.1093","volume":"39","author":[{"given":"Marjan","family":"Hosseini","sequence":"first","affiliation":[{"name":"Department of Computer Science and Engineering, University of Connecticut , Storrs, CT 06269-4155, United States"}]},{"given":"Aaron","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, University of Connecticut , Storrs, CT 06269-4155, United States"}]},{"given":"William","family":"Manka","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, University of Connecticut , Storrs, CT 06269-4155, United States"}]},{"given":"Patrick G S","family":"Grady","sequence":"additional","affiliation":[{"name":"Institute for Systems Genomics and Department of Molecular and Cell Biology, University of Connecticut , Storrs, CT 06269-3003, United States"}]},{"given":"Venkata","family":"Patchigolla","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, University of Connecticut , Storrs, CT 06269-4155, United States"}]},{"given":"Jinbo","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, University of Connecticut , Storrs, CT 06269-4155, United States"}]},{"given":"Rachel J","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Institute for Systems Genomics and Department of Molecular and Cell Biology, University of Connecticut , Storrs, CT 06269-3003, United States"}]},{"given":"Zhiyi","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Statistics, University of Connecticut , Storrs, CT 06269-4120, United States"}]},{"given":"Derek","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, University of Connecticut , Storrs, CT 06269-4155, United States"}]}],"member":"286","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"2023063008150167800_btad220-B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-03402-w","article-title":"Bayesian nonparametric discovery of isoforms and individual specific quantification","volume":"9","author":"Aguiar","year":"2018","journal-title":"Nat 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