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  1. Background

    Oxford Nanopore long‐read sequencing technology addresses current limitations for DNA methylation detection that are inherent in short‐read bisulfite sequencing or methylation microarrays. A number of analytical tools, such as Nanopolish, Guppy/Tombo and DeepMod, have been developed to detect DNA methylation on Nanopore data. However, additional improvements can be made in computational efficiency, prediction accuracy, and contextual interpretation on complex genomics regions (such as repetitive regions, low GC density regions).

    Method

    In the current study, we apply Transformer architecture to detect DNA methylation on ionic signals from Oxford Nanopore sequencing data. Transformer is an algorithm that adopts self‐attention architecture in the neural networks and has been widely used in natural language processing.

    Results

    Compared to traditional deep‐learning method such as convolutional neural network (CNN) and recurrent neural network (RNN), Transformer may have specific advantages in DNA methylation detection, because the self‐attention mechanism can assist the relationship detection between bases that are far from each other and pay more attention to important bases that carry characteristic methylation‐specific signals within a specific sequence context.

    Conclusion

    We demonstrated the ability of Transformers to detect methylation on ionic signal data.

     
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    Free, publicly-accessible full text available September 1, 2024
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  3. Abstract

    It is well known that the choices of physical schemes in Regional Climate Models (RCMs) can cause considerable uncertainties in future climate projections. In this study, a factorial sensitivity analysis method has been proposed to screen out statistically significant schemes and interactions, which assists in selecting the optimized physical scheme combination from a long‐term perspective with affordable computational costs. The Regional Climate Model (RegCM) is used as an example to illustrate how the approach works. In detail, all schemes are fully tested through 120 experimental runs based on a factorial design; the contributions and statistical significance (Pvalue) of individual schemes and their interactions to temperature, precipitation, wind speed, and wind direction are then quantified. The performance of the proposed approach is then demonstrated through a case study of Canada. The results indicate that there exist considerable spatial and temporal simulated variations associated with different scheme combinations. It is also suggested that individual physical schemes have dominant influences on simulated variations, but some effects explained by their interactions are statistically significant and thus cannot be neglected. In particular, the planetary boundary layer (PBL) scheme, moisture scheme, and land surface model are found to be the dominant factors affecting the uncertainties of temperature, precipitation, and wind speed in future climate projections over Canada, respectively. Furthermore, the potential relationships between the vegetation cover conditions and the sensitivity of physical schemes are explored. The proposed approach is an attempt to analyze the sensitivity influenced by not only individual physical schemes and also their multilevel interactions.

     
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