Although Hi-C technology is one of the most popular tools for studying 3D genome organization, due to sequencing cost, the resolution of most Hi-C datasets are coarse and cannot be used to link distal regulatory elements to their target genes. Here we develop HiCPlus, a computational approach based on deep convolutional neural network, to infer high-resolution Hi-C interaction matrices from low-resolution Hi-C data. We demonstrate that HiCPlus can impute interaction matrices highly similar to the original ones, while only using 1/16 of the original sequencing reads. We show that the models learned from one cell type can be applied to make predictions in other cell or tissue types. Our work not only provides a computational framework to enhance Hi-C data resolution but also reveals features underlying the formation of 3D chromatin interactions.

It is necessary and essential to discovery protein function from the novel primary sequences. Wet lab experimental procedures are not only time-consuming, but also costly, so predicting protein structure and function reliably based only on amino acid sequence has significant value. TATA-binding protein (TBP) is a kind of DNA binding protein, which plays a key role in the transcription regulation. Our study proposed an automatic approach for identifying TATA-binding proteins efficiently, accurately, and conveniently. This method would guide for the special protein identification with computational intelligence strategies. Firstly, we proposed novel fingerprint features for TBP based on pseudo amino acid composition, physicochemical properties, and secondary structure. Secondly, hierarchical features dimensionality reduction strategies were employed to improve the performance furthermore. Currently, Pretata achieves 92.92% TATA-binding protein prediction accuracy, which is better than all other existing methods. The experiments demonstrate that our method could greatly improve the prediction accuracy and speed, thus allowing large-scale NGS data prediction to be practical. A web server is developed to facilitate the other researchers, which can be accessed at http://server.malab.cn/preTata/ .

Background: Protein-protein interactions (PPIs) are central to a lot of biological processes. Many algorithms and methods have been developed to predict PPIs and protein interaction networks. However, the application of most existing methods is limited since they are difficult to compute and rely on a large number of homologous proteins and interaction marks of protein partners. In this paper, we propose a novel sequence-based approach with multivariate mutual information (MMI) of protein feature representation, for predicting PPIs via Random Forest (RF). Methods: Our method constructs a 638-dimentional vector to represent each pair of proteins. First, we cluster twenty standard amino acids into seven function groups and transform protein sequences into encoding sequences. Then, we use a novel multivariate mutual information feature representation scheme, combined with normalized Moreau-Broto Autocorrelation, to extract features from protein sequence information. Finally, we feed the feature vectors into a Random Forest model to distinguish interaction pairs from non-interaction pairs. Results: To evaluate the performance of our new method, we conduct several comprehensive tests for predicting PPIs. Experiments show that our method achieves better results than other outstanding methods for sequence-based PPIs prediction. Our method is applied to the S.cerevisiae PPIs dataset, and achieves 95.01 % accuracy and 92.67 % sensitivity repectively. For the H.pylori PPIs dataset, our method achieves 87.59 % accuracy and 86.81 % sensitivity respectively. In addition, we test our method on other three important PPIs networks: the one-core network, the multiple-core network, and the crossover network. Conclusions: Compared to the Conjoint Triad method, accuracies of our method are increased by 6.25,2.06 and 18.75 %, respectively. Our proposed method is a useful tool for future proteomics studies.

Cell-penetrating peptides (CPPs) are short peptides (5–30 amino acids) that can enter almost any cell without significant damage. On account of their high delivery efficiency, CPPs are promising candidates for gene therapy and cancer treatment. Accordingly, techniques that correctly predict CPPs are anticipated to accelerate CPP applications in future therapeutics. Recently, computational methods have been reportedly successful in predicting CPPs. Unfortunately, the predictive performance of existing methods is not satisfactory and reliable so as to accurately identify CPPs. In this study, we propose a novel computational predictor called SkipCPP-Pred to further improve the predictive performance. The novelty of the proposed predictor is that we present a sequence-based feature representation algorithm called adaptive k-skip-n-gram that sufficiently captures the intrinsic correlation information of residues. By fusing the proposed adaptive skip features with a random forest (RF) classifier, we successfully construct the prediction model of SkipCPP-Pred. The various jackknife results demonstrate that the proposed SkipCPP-Pred is 3.6% higher than state-of-the-art CPP predictors in terms of accuracy. Moreover, we construct a high-quality benchmark dataset by reducing the data redundancy and enhancing the similarity between the positive and negative classes. Using this dataset to build prediction models, we can successfully avoid the performance bias lying in existing methods and yield a promising predictive model. The proposed SkipCPP-Pred is a simple and fast sequence-based predictor featured with the adaptive k-skip-n-gram model for the improved prediction of CPPs. Currently, SkipCPP-Pred is publicly available from an online webserver ( http://server.malab.cn/SkipCPP-Pred/Index.html ).

Inferring gene regulatory networks (GRNs) based on gene expression profiles is able to provide an insight into a number of cellular phenotypes from the genomic level and reveal the essential laws underlying various life phenomena. Different from the bulk expression data, single-cell transcriptomic data embody cell-to-cell variance and diverse biological information, such as tissue characteristics, transformation of cell types, etc. Inferring GRNs based on such data offers unprecedented advantages for making a profound study of cell phenotypes, revealing gene functions and exploring potential interactions. However, the high sparsity, noise and dropout events of single-cell transcriptomic data pose new challenges for regulation identification. We develop a hybrid deep learning framework for GRN inference from single-cell transcriptomic data, DGRNS, which encodes the raw data and fuses recurrent neural network and convolutional neural network (CNN) to train a model capable of distinguishing related gene pairs from unrelated gene pairs. To overcome the limitations of such datasets, it applies sliding windows to extract valuable features while preserving the direction of regulation. DGRNS is constructed as a deep learning model containing gated recurrent unit network for exploring time-dependent information and CNN for learning spatially related information. Our comprehensive and detailed comparative analysis on the dataset of mouse hematopoietic stem cells illustrates that DGRNS outperforms state-of-the-art methods. The networks inferred by DGRNS are about 16% higher than the area under the receiver operating characteristic curve of other unsupervised methods and 10% higher than the area under the precision recall curve of other supervised methods. Experiments on human datasets show the strong robustness and excellent generalization of DGRNS. By comparing the predictions with standard network, we discover a series of novel interactions which are proved to be true in some specific cell types. Importantly, DGRNS identifies a series of regulatory relationships with high confidence and functional consistency, which have not yet been experimentally confirmed and merit further research.