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Recently, advances in neural network approaches have achieved many successes in both sentiment classification and probabilistic topic modelling. On the one hand, latent topics derived from the global context of documents could be helpful in capturing more accurate word semantics and hence could potentially improve the sentiment classification accuracy. On the other hand, the word-level attention vectors obtained during the learning of sentiment classifiers could carry word-level polarity information and can be used to guide the discovery of topics in topic modelling. This paper proposes a multi-task learning framework which jointly learns a sentiment classifier and a topic model by making the word-level latent topic distributions in the topic model to be similar to the word-level attention vectors in the classifier through mutual learning. Experimental results on the Yelp and IMDB datasets verify the superior performance of the proposed framework over strong baselines on both sentiment classification accuracy and topic modelling evaluation results including perplexity and topic coherence measures. The proposed framework also extracts more interpretable topics compared to other conventional topic models and neural topic models.

There is growing evidence for the role of DNA methylation (DNAm) quantitative trait loci (mQTLs) in the genetics of complex traits, including psychiatric disorders. However, due to extensive linkage disequilibrium (LD) of the genome, it is challenging to identify causal genetic variations that drive DNAm levels by population-based genetic association studies. This limits the utility of mQTLs for fine-mapping risk loci underlying psychiatric disorders identified by genome-wide association studies (GWAS). Here we present INTERACT, a deep learning model that integrates convolutional neural networks with transformer, to predict effects of genetic variations on DNAm levels at CpG sites in the human brain. We show that INTERACT-derived DNAm regulatory variants are not confounded by LD, are concentrated in regulatory genomic regions in the human brain, and are convergent with mQTL evidence from genetic association analysis. We further demonstrate that predicted DNAm regulatory variants are enriched for heritability of brain-related traits and improve polygenic risk prediction for schizophrenia across diverse ancestry samples. Finally, we applied predicted DNAm regulatory variants for fine-mapping schizophrenia GWAS risk loci to identify potential novel risk genes. Our study shows the power of a deep learning approach to identify functional regulatory variants that may elucidate the genetic basis of complex traits.

Due to the rapid growth of network data, the authenticity and reliability of network information have become increasingly important and have presented challenges. Most of the methods for fake review detection start with textual features and behavioral features. However, they are time-consuming and easily detected by fraudulent users. Although most of the existing neural network-based methods address the problems presented by the complex semantics of reviews, they do not account for the implicit patterns among users, reviews, and products; additionally, they do not consider the usefulness of information regarding fine-grained aspects in identifying fake reviews. In this paper, we propose an attention-based multilevel interactive neural network model with aspect constraints that mines the multilevel implicit expression mode of reviews and integrates four dimensions, namely, users, review texts, products and fine-grained aspects, into review representations. We model the relationships between users and products and use these relationships as a regularization term to redefine the model’s objective function. The experimental results from three public datasets show that the model that we propose is superior to the state-of-the-art methods; thus showing the effectiveness and portability of our model.

Recently, advances in neural network approaches have achieved many successes in both sentiment classification and probabilistic topic modelling. On the one hand, latent topics derived from the global context of documents could be helpful in capturing more accurate word semantics and hence could potentially improve the sentiment classification accuracy. On the other hand, the word-level attention vectors obtained during the learning of sentiment classifiers could carry word-level polarity information and can be used to guide the discovery of topics in topic modelling. This paper proposes a multi-task learning framework which jointly learns a sentiment classifier and a topic model by making the word-level latent topic distributions in the topic model to be similar to the word-level attention vectors in the classifier through mutual learning. Experimental results on the Yelp and IMDB datasets verify the superior performance of the proposed framework over strong baselines on both sentiment classification accuracy and topic modelling evaluation results including perplexity and topic coherence measures. The proposed framework also extracts more interpretable topics compared to other conventional topic models and neural topic models.

Motivation The prediction of transcription factor binding sites (TFBSs) is crucial for gene expression analysis. Supervised learning approaches for TFBS predictions require large amounts of labeled data. However, many TFs of certain cell types either do not have sufficient labeled data or do not have any labeled data. Results In this paper, a multi-task learning framework (called MTTFsite) is proposed to address the lack of labeled data problem by leveraging on labeled data available in cross-cell types. The proposed MTTFsite contains a shared CNN to learn common features for all cell types and a private CNN for each cell type to learn private features. The common features are aimed to help predicting TFBSs for all cell types especially those cell types that lack labeled data. MTTFsite is evaluated on 241 cell type TF pairs and compared with a baseline method without using any multi-task learning model and a fully shared multi-task model that uses only a shared CNN and do not use private CNNs. For cell types with insufficient labeled data, results show that MTTFsite performs better than the baseline method and the fully shared model on more than 89% pairs. For cell types without any labeled data, MTTFsite outperforms the baseline method and the fully shared model by more than 80 and 93% pairs, respectively. A novel gene expression prediction method (called TFChrome) using both MTTFsite and histone modification features is also presented. Results show that TFBSs predicted by MTTFsite alone can achieve good performance. When MTTFsite is combined with histone modification features, a significant 5.7% performance improvement is obtained. Availability and implementation The resource and executable code are freely available at http://hlt.hitsz.edu.cn/MTTFsite/ and http://www.hitsz-hlt.com:8080/MTTFsite/. Supplementary information Supplementary data are available at Bioinformatics online.

Most proposed methods for TF-binding site (TFBS) predictions only use low order dependencies for predictions due to the lack of efficient methods to extract higher order dependencies. In this work, we first propose a novel method to extract higher order dependencies by applying CNN on histone modification features. We then propose a novel TFBS prediction method, referred to as CNN_TF, by incorporating low order and higher order dependencies. CNN_TF is first evaluated on 13 TFs in the mES cell. Results show that using higher order dependencies outperforms low order dependencies significantly on 11 TFs. This indicates that higher order dependencies are indeed more effective for TFBS predictions than low order dependencies. Further experiments show that using both low order dependencies and higher order dependencies improves performance significantly on 12 TFs, indicating the two dependency types are complementary. To evaluate the influence of cell-types on prediction performances, CNN_TF was applied to five TFs in five cell-types of humans. Even though low order dependencies and higher order dependencies show different contributions in different cell-types, they are always complementary in predictions. When comparing to several state-of-the-art methods, CNN_TF outperforms them by at least 5.3 percent in AUPR.

Most past works for DNA-binding residue prediction did not consider the relationships between residues. In this paper, we propose a novel approach for DNA-binding residue prediction, referred to as EL_LSTM, which includes two main components. The first component is the Long Short-Term Memory (LSTM), which learns pairwise relationships between residues through a bi-gram model and then learns feature vectors for all residues. The second component is an ensemble learning based classifier introduced to tackle the data imbalance problem in binding residue predictions. We use a variant of the bagging strategy in ensemble learning to achieve balanced samples. Evaluations on PDNA-224 and DBP-123 show that adding feature relationships performs better than classifiers without feature relationships by at least 0.028 on MCC, 1.18 percent on ST and 0.012 on AUC. This indicates the usefulness of feature relationships for DNA-binding residue predictions. Evaluation on using ensemble learning indicates that the improvement can reach at least 0.021 on MCC, 1.32 percent on ST, and 0.018 on AUC compared to the use of a single LSTM classifier. Comparisons with the state-of-the-art predictors show that our proposed EL_LSTM outperforms them significantly. Further feature analysis validates the effectiveness of LSTM for the prediction of DNA-binding residues.

DNA-binding proteins are crucial for various cellular processes and hence have become an important target for both basic research and drug development. With the avalanche of protein sequences generated in the postgenomic age, it is highly desired to establish an automated method for rapidly and accurately identifying DNA-binding proteins based on their sequence information alone. Owing to the fact that all biological species have developed beginning from a very limited number of ancestral species, it is important to take into account the evolutionary information in developing such a high-throughput tool. In view of this, a new predictor was proposed by incorporating the evolutionary information into the general form of pseudo amino acid composition via the top-n-gram approach. It was observed by comparing the new predictor with the existing methods via both jackknife test and independent data-set test that the new predictor outperformed its counterparts. It is anticipated that the new predictor may become a useful vehicle for identifying DNA-binding proteins. It has not escaped our notice that the novel approach to extract evolutionary information into the formulation of statistical samples can be used to identify many other protein attributes as well.

Background Prediction of DNA-binding residue is important for understanding the protein-DNA recognition mechanism. Many computational methods have been proposed for the prediction, but most of them do not consider the relationships of evolutionary information between residues. Results In this paper, we first propose a novel residue encoding method, referred to as the Position Specific Score Matrix (PSSM) Relation Transformation (PSSM-RT), to encode residues by utilizing the relationships of evolutionary information between residues. PDNA-62 and PDNA-224 are used to evaluate PSSM-RT and two existing PSSM encoding methods by five-fold cross-validation. Performance evaluations indicate that PSSM-RT is more effective than previous methods. This validates the point that the relationship of evolutionary information between residues is indeed useful in DNA-binding residue prediction. An ensemble learning classifier (EL_PSSM-RT) is also proposed by combining ensemble learning model and PSSM-RT to better handle the imbalance between binding and non-binding residues in datasets. EL_PSSM-RT is evaluated by five-fold cross-validation using PDNA-62 and PDNA-224 as well as two independent datasets TS-72 and TS-61. Performance comparisons with existing predictors on the four datasets demonstrate that EL_PSSM-RT is the best-performing method among all the predicting methods with improvement between 0.02–0.07 for MCC, 4.18–21.47% for ST and 0.013–0.131 for AUC. Furthermore, we analyze the importance of the pair-relationships extracted by PSSM-RT and the results validates the usefulness of PSSM-RT for encoding DNA-binding residues. Conclusions We propose a novel prediction method for the prediction of DNA-binding residue with the inclusion of relationship of evolutionary information and ensemble learning. Performance evaluation shows that the relationship of evolutionary information between residues is indeed useful in DNA-binding residue prediction and ensemble learning can be used to address the data imbalance issue between binding and non-binding residues. A web service of EL_PSSM-RT (http://hlt.hitsz.edu.cn:8080/PSSM-RT_SVM/) is provided for free access to the biological research community. Electronic supplementary material The online version of this article (doi:10.1186/s12859-017-1792-8) contains supplementary material, which is available to authorized users.

The PDB id and the chain id of the protein sequences in the four datasets and the discriminant weights of the 400 pair-relationships between the target residue and its neighboring residue extracted from PSSM-RT. (DOC 141Â kb)

DNA-binding proteins are crucial for various cellular processes, such as recognition of specific nucleotide, regulation of transcription, and regulation of gene expression. Developing an effective model for identifying DNA-binding proteins is an urgent research problem. Up to now, many methods have been proposed, but most of them focus on only one classifier and cannot make full use of the large number of negative samples to improve predicting performance. This study proposed a predictor called enDNA-Prot for DNA-binding protein identification by employing the ensemble learning technique. Experiential results showed that enDNA-Prot was comparable with DNA-Prot and outperformed DNAbinder and iDNA-Prot with performance improvement in the range of 3.97–9.52% in ACC and 0.08–0.19 in MCC. Furthermore, when the benchmark dataset was expanded with negative samples, the performance of enDNA-Prot outperformed the three existing methods by 2.83–16.63% in terms of ACC and 0.02–0.16 in terms of MCC. It indicated that enDNA-Prot is an effective method for DNA-binding protein identification and expanding training dataset with negative samples can improve its performance. For the convenience of the vast majority of experimental scientists, we developed a user-friendly web-server for enDNA-Prot which is freely accessible to the public.

Protein-DNA complexes play crucial roles in gene regulation. The prediction of the residues involved in protein-DNA interactions is critical for understanding gene regulation. Although many methods have been proposed, most of them overlooked motif features. Motif features are sub sequences and are important for the recognition between a protein and DNA. In order to efficiently use motif features for the prediction of DNA-binding residues, we first apply the Convolutional Neural Network (CNN) method to capture the motif features from the sequences around the target residues. CNN modeling consists of a set of learnable motif detectors that can capture the important motif features by scanning the sequences around the target residues. Then we use a neural network classifier, referred to as CNNsite, by combining the captured motif features, sequence features and evolutionary features to predict binding residues from sequences. The datasets PDNA-62 and PDNA-224 are used to evaluate the performance of CNNsite by five-fold cross-validation. Performance evaluation shows that the motif features performs better than sequence features and evolutionary features with at least 6.73% on ST, 0.097 on MCC and 0.069 on AUC. When comparing with previously published methods, CNNsite performs better with at least 0.019 on MCC, 4.37% on ST and 0.040 on AUC. CNNsite is also evaluated on an independent dataset TS-72 and CNNsite outperforms the previous methods by at least 0.012 on AUC. The discriminant powers of the motif features of size from 2 to 6 residues show that many motif features with large discriminant power are composed by the residues that play important roles in the DNA-protein interactions. The standalone version of the CNNsite is available at http://hlt.hitsz.edu.cn:8080/CNNsite/.

Transcription factor binding sites (TFBSs) play an important role in gene expression regulation. Many computational methods for TFBS prediction need sufficient labeled data. However, many transcription factors (TFs) lack labeled data in cell types. We propose a novel method, referred to as DANN_TF, for TFBS prediction. DANN_TF consists of a feature extractor, a label predictor, and a domain classifier. The feature extractor and the domain classifier constitute an Adversarial Network, which ensures that learned features are common features across different cell types. DANN_TF is evaluated on five TFs in five cell types with a total of 25 cell-type TF pairs and compared to a baseline method which does not use Adversarial Network. For both data augmentation and cross-cell-type prediction, DANN_TF performs better than the baseline method on most cell-type TF pairs. DANN_TF is further evaluated by an additional 13 TFs in the five cell types with a total of 65 cell-type TF pairs. Results show that DANN_TF achieves significantly higher AUC than the baseline method on 96.9% pairs of the 65 cell-type TF pairs. This is a strong indication that DANN_TF can indeed learn common features for cross-cell-type TFBS prediction.

Protein-DNA interactions are involved in many fundamental biological processes essential for cellular function. Most of the existing computational approaches employed only the sequence context of the target residue for its prediction. In the present study, for each target residue, we applied both the spatial context and the sequence context to construct the feature space. Subsequently, Latent Semantic Analysis (LSA) was applied to remove the redundancies in the feature space. Finally, a predictor (PDNAsite) was developed through the integration of the support vector machines (SVM) classifier and ensemble learning. Results on the PDNA-62 and the PDNA-224 datasets demonstrate that features extracted from spatial context provide more information than those from sequence context and the combination of them gives more performance gain. An analysis of the number of binding sites in the spatial context of the target site indicates that the interactions between binding sites next to each other are important for protein-DNA recognition and their binding ability. The comparison between our proposed PDNAsite method and the existing methods indicate that PDNAsite outperforms most of the existing methods and is a useful tool for DNA-binding site identification. A web-server of our predictor (http://hlt.hitsz.edu.cn:8080/PDNAsite/) is made available for free public accessible to the biological research community.

Most DNA-binding residue prediction methods overlooked the motif features which are important for the recognition between protein and DNA. In order to efficiently use the motif features for prediction, we first propose to use Convolutional Neural Network (CNN) in deep learning to extract discriminant motif features. We then propose a neural network classifier, referred to as CNNsite, by combining the extracted motif features, sequence features and evolutionary features. The evaluation on PDNA-62, PDNA-224 and TR-265 shows that motif features perform better than sequence features and evolutionary features. The evaluation on PDNA-62, PDNA-224 and an independent data set shows that CNNsite also outperforms the previous methods. We also show that many motif features composed by the residues which play important roles in DNA-protein interactions have large discriminant powers. It indicates that CNNsite has very good ability to extract important motif features for DNA-binding residue prediction.

Playing crucial roles in various cellular processes, such as recognition of specific nucleotide sequences, regulation of transcription, and regulation of gene expression, DNA-binding proteins are essential ingredients for both eukaryotic and prokaryotic proteomes. With the avalanche of protein sequences generated in the postgenomic age, it is a critical challenge to develop automated methods for accurate and rapidly identifying DNA-binding proteins based on their sequence information alone. Here, a novel predictor, called “iDNA-Prot|dis”, was established by incorporating the amino acid distance-pair coupling information and the amino acid reduced alphabet profile into the general pseudo amino acid composition (PseAAC) vector. The former can capture the characteristics of DNA-binding proteins so as to enhance its prediction quality, while the latter can reduce the dimension of PseAAC vector so as to speed up its prediction process. It was observed by the rigorous jackknife and independent dataset tests that the new predictor outperformed the existing predictors for the same purpose. As a user-friendly web-server, iDNA-Prot|dis is accessible to the public at http://bioinformatics.hitsz.edu.cn/iDNA-Prot_dis/. Moreover, for the convenience of the vast majority of experimental scientists, a step-by-step protocol guide is provided on how to use the web-server to get their desired results without the need to follow the complicated mathematic equations that are presented in this paper just for the integrity of its developing process. It is anticipated that the iDNA-Prot|dis predictor may become a useful high throughput tool for large-scale analysis of DNA-binding proteins, or at the very least, play a complementary role to the existing predictors in this regard.

Identification of DNA-binding proteins is an important problem in biomedical research as DNA-binding proteins are crucial for various cellular processes. Currently, the machine learning methods achieve the-state-of-the-art performance with different features. A key step to improve the performance of these methods is to find a suitable representation of proteins. In this study, we proposed a feature vector composed of three kinds of sequence-based features, including overall amino acid composition, pseudo amino acid composition (PseAAC) proposed by Chou and physicochemical distance transformation. These features not only consider the sequence composition of proteins, but also incorporate the sequence-order information of amino acids in proteins. The feature vectors were fed into Support Vector Machine (SVM) for DNA-binding protein identification. The proposed method is called PseDNA-Pro. Experiments on stringent benchmark datasets and independent test datasets by using the Jackknife test showed that PseDNA-Pro can achieve an accuracy of higher than 80 %, outperforming several state-of-the-art methods, including DNAbinder, DNA-Prot, and iDNA-Prot. These results indicate that the combination of various features for DNA-binding protein prediction is a suitable approach, and the sequence-order information among residues in proteins is relative for discrimination. For practical applications, a web-server of PseDNA-Pro was established, which is available from http://bioinformatics.hitsz.edu.cn/PseDNA-Pro/.

The performances of machine learning based opinion analysis systems are always puzzled by the insufficient training opinion corpus. Such problem becomes more serious for the resource-poor languages. Thus, the cross-lingual opinion analysis (CLOA) technique, which leverages opinion resources on one (source) language to another (target) language for improving the opinion analysis on target language, attracts more research interests. Currently, the transfer learning based CLOA approach sometimes falls to over fitting on single language resource, while the performance of the co-training based CLOA approach always achieves limited improvement during bi-lingual decision. Target to these problems, in this study, we propose a mixed CLOA model, which estimates the confidence of each monolingual opinion analysis system by using their training errors through bilingual transfer self-training and co-training, respectively. By using the weighted average distances between samples and classification hyper-planes as the confidence, the opinion polarity of testing samples are classified. The evaluations on NLP&CC 2013 CLOA bakeoff dataset show that this approach achieves the best performance, which outperforms transfer learning and co-training based approaches.