A Connected Convolutional Neutral Network Protocol for Design of Two-Dimensional Materials Based on Modified Graphdiyne.

In materials science, doping plays a crucial role in manipulating the electronic properties of materials. Conventional screening via a trial-and-error strategy is challenging owing to the enormous chemical space. We proposed a connected convolutional neutral network (CCNN) for quick screening of boron nitrogen (B-N) codoped graphdiyne in terms of band gap. A paired-atomic localized matrix (PALM) descriptor was designed to describe the local chemical environment of materials with the matrix form adapted to a neutral network. An attribution analysis was conducted, and a quantitative relationship between structure and band gap is proposed, which reveals more significant influence of B-N doping at sp2 hybridized sites than at sp hybridized sites on broadening of the band gap of GDY. The accuracy and efficiency of the proposed approach implicate its potential in promoting the design of graphdiyne-based optoelectronic devices and catalysts with expected electronic properties, opening a new avenue for rational design of novel materials.

Discovery and biological evaluation of a potent small molecule CRM1 inhibitor for its selective ablation of extranodal NK/T cell lymphoma.

Background: The overactivation of NF-κB signaling is a key hallmark for the pathogenesis of extranodal natural killer/T cell lymphoma (ENKTL), a very aggressive subtype of non-Hodgkin's lymphoma yet with rather limited control strategies. Previously, we found that the dysregulated exportin-1 (also known as CRM1) is mainly responsible for tumor cells to evade apoptosis and promote tumor-associated pathways such as NF-κB signaling. Methods: Herein we reported the discovery and biological evaluation of a potent small molecule CRM1 inhibitor, LFS-1107. We validated that CRM1 is a major cellular target of LFS-1107 by biolayer interferometry assay (BLI) and the knockdown of CRM1 conferred tumor cells with resistance to LFS-1107. Results: We found that LFS-1107 can strongly suppresses the growth of ENKTL cells at low-range nanomolar concentration yet with minimal effects on human platelets and healthy peripheral blood mononuclear cells. Treatment of ENKTL cells with LFS-1107 resulted in the nuclear retention of IkBα and consequent strong suppression of NF-κB transcriptional activities, NF-κB target genes downregulation and attenuated tumor cell growth and proliferation. Furthermore, LFS-1107 exhibited potent activities when administered to immunodeficient mice engrafted with human ENKTL cells. Conclusions: Therefore, LFS-1107 holds great promise for the treatment of ENKTL and may warrant translation for use in clinical trials. Funding: Yang's laboratory was supported by the National Natural Science Foundation of China (Grant: 81874301), the Fundamental Research Funds for Central University (Grant: DUT22YG122) and the Key Research project of 'be Recruited and be in Command' in Liaoning Province (Personal Target Discovery for Metabolic Diseases).

HMNPPID-human malignant neoplasm protein-protein interaction database.

BACKGROUND: Protein-protein interaction (PPI) information extraction from biomedical literature helps unveil the molecular mechanisms of biological processes. Especially, the PPIs associated with human malignant neoplasms can unveil the biology behind these neoplasms. However, such PPI database is not currently available. RESULTS: In this work, a database of protein-protein interactions associated with 171 kinds of human malignant neoplasms named HMNPPID is constructed. In addition, a visualization program, named VisualPPI, is provided to facilitate the analysis of the PPI network for a specific neoplasm. CONCLUSIONS: HMNPPID can hopefully become an important resource for the research on PPIs of human malignant neoplasms since it provides readily available data for healthcare professionals. Thus, they do not need to dig into a large amount of biomedical literatures any more, which may accelerate the researches on the PPIs of malignant neoplasms.

Neural network-based approaches for biomedical relation classification: A review.

The explosive growth of biomedical literature has created a rich source of knowledge, such as that on protein-protein interactions (PPIs) and drug-drug interactions (DDIs), locked in unstructured free text. Biomedical relation classification aims to automatically detect and classify biomedical relations, which has great benefits for various biomedical research and applications. In the past decade, significant progress has been made in biomedical relation classification. With the advance of neural network methodology, neural network-based approaches have been applied in biomedical relation classification and achieved state-of-the-art performance for some public datasets and shared tasks. In this review, we describe the recent advancement of neural network-based approaches for classifying biomedical relations. We summarize the available corpora and introduce evaluation metrics. We present the general framework for neural network-based approaches in biomedical relation extraction and pretrained word embedding resources. We discuss neural network-based approaches, including convolutional neural networks (CNNs) and recurrent neural networks (RNNs). We conclude by describing the remaining challenges and outlining future directions.

Incorporating User Generated Content for Drug Drug Interaction Extraction Based on Full Attention Mechanism.

It is crucial for doctors to fully understand the interaction between drugs in prescriptions, especially when a patient takes multiple medications at the same time during treatment. The purpose of drug drug interaction (DDI) extraction is to automatically obtain the interaction between drugs from biomedical literature. Current state-of-the-art approaches for DDI extraction task are based on artificial intelligence and natural language processing. While such existing DDI extraction methods can provide more knowledge and enhance the performance through external resources such as biomedical databases or ontologies, due to the difficulty of updating, these external resources are delayed. In fact, user generated content (UGC) is another kind of external medical resources that can be quickly updated. We are trying to use UGC resources to provide more available information for our deep learning DDI extraction method. In this paper, we present a DDI extraction approach through a new attention mechanism called full-attention which can combine the UGC information with contextual information. We conducted a series of experiments on the DDI 2013 Evaluation dataset to evaluate our method. Experiments show improved performance compared with the state of the art and UGC-DDI model achieves a competitive F-score of 0.712.

Protein complexes identification based on go attributed network embedding.

BACKGROUND: Identifying protein complexes from protein-protein interaction (PPI) network is one of the most important tasks in proteomics. Existing computational methods try to incorporate a variety of biological evidences to enhance the quality of predicted complexes. However, it is still a challenge to integrate different types of biological information into the complexes discovery process under a unified framework. Recently, attributed network embedding methods have be proved to be remarkably effective in generating vector representations for nodes in the network. In the transformed vector space, both the topological proximity and node attributed affinity between different nodes are preserved. Therefore, such attributed network embedding methods provide us a unified framework to integrate various biological evidences into the protein complexes identification process. RESULTS: In this article, we propose a new method called GANE to predict protein complexes based on Gene Ontology (GO) attributed network embedding. Firstly, it learns the vector representation for each protein from a GO attributed PPI network. Based on the pair-wise vector representation similarity, a weighted adjacency matrix is constructed. Secondly, it uses the clique mining method to generate candidate cores. Consequently, seed cores are obtained by ranking candidate cores based on their densities on the weighted adjacency matrix and removing redundant cores. For each seed core, its attachments are the proteins with correlation score that is larger than a given threshold. The combination of a seed core and its attachment proteins is reported as a predicted protein complex by the GANE algorithm. For performance evaluation, we compared GANE with six protein complex identification methods on five yeast PPI networks. Experimental results showes that GANE performs better than the competing algorithms in terms of different evaluation metrics. CONCLUSIONS: GANE provides a framework that integrate many valuable and different biological information into the task of protein complex identification. The protein vector representation learned from our attributed PPI network can also be used in other tasks, such as PPI prediction and disease gene prediction.

An attention-based effective neural model for drug-drug interactions extraction.

BACKGROUND: Drug-drug interactions (DDIs) often bring unexpected side effects. The clinical recognition of DDIs is a crucial issue for both patient safety and healthcare cost control. However, although text-mining-based systems explore various methods to classify DDIs, the classification performance with regard to DDIs in long and complex sentences is still unsatisfactory. METHODS: In this study, we propose an effective model that classifies DDIs from the literature by combining an attention mechanism and a recurrent neural network with long short-term memory (LSTM) units. In our approach, first, a candidate-drug-oriented input attention acting on word-embedding vectors automatically learns which words are more influential for a given drug pair. Next, the inputs merging the position- and POS-embedding vectors are passed to a bidirectional LSTM layer whose outputs at the last time step represent the high-level semantic information of the whole sentence. Finally, a softmax layer performs DDI classification. RESULTS: Experimental results from the DDIExtraction 2013 corpus show that our system performs the best with respect to detection and classification (84.0% and 77.3%, respectively) compared with other state-of-the-art methods. In particular, for the Medline-2013 dataset with long and complex sentences, our F-score far exceeds those of top-ranking systems by 12.6%. CONCLUSIONS: Our approach effectively improves the performance of DDI classification tasks. Experimental analysis demonstrates that our model performs better with respect to recognizing not only close-range but also long-range patterns among words, especially for long, complex and compound sentences.

Disease named entity recognition from biomedical literature using a novel convolutional neural network.

BACKGROUND: Automatic disease named entity recognition (DNER) is of utmost importance for development of more sophisticated BioNLP tools. However, most conventional CRF based DNER systems rely on well-designed features whose selection is labor intensive and time-consuming. Though most deep learning methods can solve NER problems with little feature engineering, they employ additional CRF layer to capture the correlation information between labels in neighborhoods which makes them much complicated. METHODS: In this paper, we propose a novel multiple label convolutional neural network (MCNN) based disease NER approach. In this approach, instead of the CRF layer, a multiple label strategy (MLS) first introduced by us, is employed. First, the character-level embedding, word-level embedding and lexicon feature embedding are concatenated. Then several convolutional layers are stacked over the concatenated embedding. Finally, MLS strategy is applied to the output layer to capture the correlation information between neighboring labels. RESULTS: As shown by the experimental results, MCNN can achieve the state-of-the-art performance on both NCBI and CDR corpora. CONCLUSIONS: The proposed MCNN based disease NER method achieves the state-of-the-art performance with little feature engineering. And the experimental results show the MLS strategy's effectiveness of capturing the correlation information between labels in the neighborhood.

Drug drug interaction extraction from biomedical literature using syntax convolutional neural network.

MOTIVATION: Detecting drug-drug interaction (DDI) has become a vital part of public health safety. Therefore, using text mining techniques to extract DDIs from biomedical literature has received great attentions. However, this research is still at an early stage and its performance has much room to improve. RESULTS: In this article, we present a syntax convolutional neural network (SCNN) based DDI extraction method. In this method, a novel word embedding, syntax word embedding, is proposed to employ the syntactic information of a sentence. Then the position and part of speech features are introduced to extend the embedding of each word. Later, auto-encoder is introduced to encode the traditional bag-of-words feature (sparse 0-1 vector) as the dense real value vector. Finally, a combination of embedding-based convolutional features and traditional features are fed to the softmax classifier to extract DDIs from biomedical literature. Experimental results on the DDIExtraction 2013 corpus show that SCNN obtains a better performance (an F-score of 0.686) than other state-of-the-art methods. AVAILABILITY AND IMPLEMENTATION: The source code is available for academic use at http://202.118.75.18:8080/DDI/SCNN-DDI.zip CONTACT: yangzh@dlut.edu.cnSupplementary information: Supplementary data are available at Bioinformatics online.

A graph kernel based on context vectors for extracting drug-drug interactions.

The clinical recognition of drug-drug interactions (DDIs) is a crucial issue for both patient safety and health care cost control. Thus there is an urgent need that DDIs be extracted automatically from biomedical literature by text-mining techniques. Although the top-ranking DDIs systems explore various features of texts, these features can't yet adequately express long and complicated sentences. In this paper, we present an effective graph kernel which makes full use of different types of contexts to identify DDIs from biomedical literature. In our approach, the relations among long-range words, in addition to close-range words, are obtained by the graph representation of a parsed sentence. Context vectors of a vertex, an iterative vectorial representation of all labeled nodes adjacent and nonadjacent to it, adequately capture the direct and indirect substructures' information. Furthermore, the graph kernel considering the distance between context vectors is used to detect DDIs. Experimental results on the DDIExtraction 2013 corpus show that our system achieves the best detection and classification performance (F-score) of DDIs (81.8 and 68.4, respectively). Especially for the Medline-2013 dataset, our system outperforms the top-ranking DDIs systems by F-scores of 10.7 and 12.2 in detection and classification, respectively.

PPIExtractor: a protein interaction extraction and visualization system for biomedical literature.

Protein-protein interactions (PPIs) play a key role in various aspects of the structural and functional organization of the cell. Knowledge about them unveils the molecular mechanisms of biological processes. However, the amount of biomedical literature regarding protein interactions is increasing rapidly and it is difficult for interaction database curators to detect and curate protein interaction information manually. In this paper, we present a PPI extraction system, termed PPIExtractor, which automatically extracts PPIs from biomedical text and visualizes them. Given a Medline record dataset, PPIExtractor first applies Feature Coupling Generalization (FCG) to tag protein names in text, next uses the extended semantic similarity-based method to normalize them, then combines feature-based, convolution tree and graph kernels to extract PPIs, and finally visualizes the PPI network. Experimental evaluations show that PPIExtractor can achieve state-of-the-art performance on a DIP subset with respect to comparable evaluations.

Extracting drug-drug interaction from the biomedical literature using a stacked generalization-based approach.

Drug-drug interaction (DDI) detection is particularly important for patient safety. However, the amount of biomedical literature regarding drug interactions is increasing rapidly. Therefore, there is a need to develop an effective approach for the automatic extraction of DDI information from the biomedical literature. In this paper, we present a Stacked Generalization-based approach for automatic DDI extraction. The approach combines the feature-based, graph and tree kernels and, therefore, reduces the risk of missing important features. In addition, it introduces some domain knowledge based features (the keyword, semantic type, and DrugBank features) into the feature-based kernel, which contribute to the performance improvement. More specifically, the approach applies Stacked generalization to automatically learn the weights from the training data and assign them to three individual kernels to achieve a much better performance than each individual kernel. The experimental results show that our approach can achieve a better performance of 69.24% in F-score compared with other systems in the DDI Extraction 2011 challenge task.