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LeNup: learning nucleosome positioning from DNA sequences with improved convolutional neural networks.

ABSTRACT: Motivation:Nucleosome positioning plays significant roles in proper genome packing and its accessibility to execute transcription regulation. Despite a multitude of nucleosome positioning resources available on line including experimental datasets of genome-wide nucleosome occupancy profiles and computational tools to the analysis on these data, the complex language of eukaryotic Nucleosome positioning remains incompletely understood. Results:Here, we address this challenge using an approach based on a state-of-the-art machine learning method. We present a novel convolutional neural network (CNN) to understand nucleosome positioning. We combined Inception-like networks with a gating mechanism for the response of multiple patterns and long term association in DNA sequences. We developed the open-source package LeNup based on the CNN to predict nucleosome positioning in Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster as well as Saccharomyces cerevisiae genomes. We trained LeNup on four benchmark datasets. LeNup achieved greater predictive accuracy than previously published methods. Availability and implementation:LeNup is freely available as Python and Lua script source code under a BSD style license from https://github.com/biomedBit/LeNup. Contact:jhzhang@bit.edu.cn. Supplementary information:Supplementary data are available at Bioinformatics online.

SUBMITTER: Zhang J

PROVIDER: S-EPMC5946947 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe accurate identification of the exon/intron boundaries is critical for the correct annotation of genes with multiple exons. Donor and acceptor splice sites (SS) demarcate these boundaries. Therefore, deriving accurate computational models to predict the SS are useful for functional annotation of genes and genomes, and for finding alternative SS associated with different diseases. Although various models have been proposed for the in silico prediction of SS, improving their accuracy is required for reliable annotation. Moreover, models are often derived and tested using the same genome, providing no evidence of broad application, i.e. to other poorly studied genomes.ResultsWith this in mind, we developed the Splice2Deep models for SS detection. Each model is an ensemble of deep convolutional neural networks. We evaluated the performance of the models based on the ability to detect SS in Homo sapiens, Oryza sativa japonica, Arabidopsis thaliana, Drosophila melanogaster, and Caenorhabditis elegans. Results demonstrate that the models efficiently detect SS in other organisms not considered during the training of the models. Compared to the state-of-the-art tools, Splice2Deep models achieved significantly reduced average error rates of 41.97% and 28.51% for acceptor and donor SS, respectively. Moreover, the Splice2Deep cross-organism validation demonstrates that models correctly identify conserved genomic elements enabling annotation of SS in new genomes by choosing the taxonomically closest model.ConclusionsThe results of our study demonstrated that Splice2Deep both achieved a considerably reduced error rate compared to other state-of-the-art models and the ability to accurately recognize SS in other organisms for which the model was not trained, enabling annotation of poorly studied or newly sequenced genomes. Splice2Deep models are implemented in Python using Keras API; the models and the data are available at https://github.com/SomayahAlbaradei/Splice_Deep.git.

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LeNup: learning nucleosome positioning from DNA sequences with improved convolutional neural networks.

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