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Motivation Histone modifications are epigenetic markers that impact gene expression by altering the chromatin structure or recruiting histone modifiers. Their accurate identification is key to unraveling the mechanisms by which they regulate gene expression. However, the solutions for this task can be improved by exploiting multiple relationships from dataset and exploring designs of learning models, e.g. jointly learning technology. Results This paper proposes a deep learning–based multi-objective computational approach, iHMnBS, to identify which of the seven typical histone modifications a DNA sequence may choose to bind, and which parts of the DNA sequence bind to them. iHMnBS employs a customized dataset that allows the marking of modifications contained in histones that may bind to any position in the DNA sequence. iHMnBS tries to mine the information implicit in this richer data by means of deep neural networks. In comprehensive comparisons, iHMnBS outperforms a baseline method, and the probability of binding to modified histones assigned to a representative nucleotide of a DNA sequence can serve as a reference for biological experiments. Since the interaction between transcription factors (TFs) and histone modifications has an important role in gene expression, we extracted a number of sequence patterns that may bind to TFs, and explored their possible impact on disease. Availability The source code is available at https://github.com/lennylv/iHMnBS. Supplementary information Supplementary data are available at Bioinformatics online.

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A large number of inorganic and organic compounds are able to bind DNA and form complexes, among which drug-related molecules are important. Chromatin accessibility changes not only directly affect drug–DNA interactions, but they can promote or inhibit the expression of the critical genes associated with drug resistance by affecting the DNA binding capacity of TFs and transcriptional regulators. However, the biological experimental techniques for measuring it are expensive and time-consuming. In recent years, several kinds of computational methods have been proposed to identify accessible regions of the genome. Existing computational models mostly ignore the contextual information provided by the bases in gene sequences. To address these issues, we proposed a new solution called SemanticCAP. It introduces a gene language model that models the context of gene sequences and is thus able to provide an effective representation of a certain site in a gene sequence. Basically, we merged the features provided by the gene language model into our chromatin accessibility model. During the process, we designed methods called SFA and SFC to make feature fusion smoother. Compared to DeepSEA, gkm-SVM, and k-mer using public benchmarks, our model proved to have better performance, showing a 1.25% maximum improvement in auROC and a 2.41% maximum improvement in auPRC.

Nucleosome positioning is involved in diverse cellular biological processes by regulating the accessibility of DNA sequences to DNA-binding proteins and plays a vital role. Previous studies have manifested that the intrinsic preference of nucleosomes for DNA sequences may play a dominant role in nucleosome positioning. As a consequence, it is nontrivial to develop computational methods only based on DNA sequence information to accurately identify nucleosome positioning, and thus intend to verify the contribution of DNA sequences responsible for nucleosome positioning. In this work, we propose a new deep learning-based method, named DeepNup, which enables us to improve the prediction of nucleosome positioning only from DNA sequences. Specifically, we first use a hybrid feature encoding scheme that combines One-hot encoding and Trinucleotide composition encoding to encode raw DNA sequences; afterwards, we employ multiscale convolutional neural network modules that consist of two parallel convolution kernels with different sizes and gated recurrent units to effectively learn the local and global correlation feature representations; lastly, we use a fully connected layer and a sigmoid unit serving as a classifier to integrate these learned high-order feature representations and generate the final prediction outcomes. By comparing the experimental evaluation metrics on two benchmark nucleosome positioning datasets, DeepNup achieves a better performance for nucleosome positioning prediction than that of several state-of-the-art methods. These results demonstrate that DeepNup is a powerful deep learning-based tool that enables one to accurately identify potential nucleosome sequences.