MicroRNAs (miRNAs) play important roles in the occurrence and development of diseases. However, it is still challenging to identify the effective miRNA biomarkers for improving the disease diagnosis and prognosis. In this study, we proposed the miRNA data analysis method based on multi-view miRNA networks and reinforcement learning, miRMarker, to define the potential miRNA disease biomarkers. miRMarker constructs the cooperative regulation network and functional similarity network based on the expression data and known miRNA-disease relations, respectively. The cooperative regulation of miRNAs was evaluated by measuring the changes of relative expression. Natural language processing was introduced for calculating the miRNA functional similarity. Then, miRMarker integrates the multi-view miRNA networks and defines the informative miRNA modules through a reinforcement learning strategy. We compared miRMarker with eight efficient data analysis methods on nine transcriptomics datasets to show its superiority in disease sample discrimination. The comparison results suggested that miRMarker outperformed other data analysis methods in receiver operating characteristic analysis. Furthermore, the defined miRNA modules of miRMarker on colorectal cancer data not only show the excellent performance of cancer sample discrimination but also play significant roles in the cancer-related pathway disturbances. The experimental results indicate that miRMarker can build the robust miRNA interaction network by integrating the multi-view networks. Besides, exploring the miRNA interaction network using reinforcement learning favors defining the important miRNA modules. In summary, miRMarker can be a hopeful tool in biomarker identification for human diseases.

During the development of complex diseases, there is a critical transition from one status to another at a tipping point, which can be an early indicator of disease deterioration. To effectively enhance the performance of early risk identification, a novel dynamic network construction algorithm for identifying early warning signals based on a data-driven approach (EWS-DDA) was proposed. In EWS-DDA, the shrunken centroid was introduced to measure dynamic expression changes in assumed pathway reactions during the progression of complex disease for network construction and to define early warning signals by means of a data-driven approach. We applied EWS-DDA to perform a comprehensive analysis of gene expression profiles of gastric cancer (GC) from The Cancer Genome Atlas database and the Gene Expression Omnibus database. Six crucial genes were selected as potential biomarkers for the early diagnosis of GC. The experimental results of statistical analysis and biological analysis suggested that the six genes play important roles in GC occurrence and development. Then, EWS-DDA was compared with other state-of-the-art network methods to validate its performance. The theoretical analysis and comparison results suggested that EWS-DDA has great potential for a more complete presentation of disease deterioration and effective extraction of early warning information.

Different biomarker patterns, such as those of molecular biomarkers and ratio biomarkers, have their own merits in clinical applications. In this study, a novel machine learning method used in biomedical data analysis for constructing classification models by combining different biomarker patterns (CDBP)is proposed. CDBP uses relative expression reversals to measure the discriminative ability of different biomarker patterns, and selects the pattern with the higher score for classifier construction. The decision boundary of CDBP can be characterized in simple and biologically meaningful manners. The CDBP method was compared with eight state-of-the-art methods on eight gene expression datasets to test its performance. CDBP, with fewer features or ratio features, had the highest classification performance. Subsequently, CDBP was employed to extract crucial diagnostic information from a rat hepatocarcinogenesis metabolomics dataset. The potential biomarkers selected by CDBP provided better classification of hepatocellular carcinoma (HCC)and non-HCC stages than previous works in the animal model. The statistical analyses of these potential biomarkers in an independent human dataset confirmed their discriminative abilities of different liver diseases. These experimental results highlight the potential of CDBP for biomarker identification from high-dimensional biomedical datasets and demonstrate that it can be a useful tool for disease classification.

Analyzing the disease data from the view of combinatorial features may better characterize the disease phenotype. In this study, a novel method is proposed to construct feature combinations and a classification model (CFC-CM) by mining key feature relationships. CFC-CM iteratively tests for differences in the feature relationship between different groups. To do this, it uses a modified $k$k-top-scoring pair (M-$k$k-TSP) algorithm and then selects the most discriminative feature pairs in the current feature set to infer the combinatorial features and build the classification model. Compared with support vector machines, random forests, least absolute shrinkage and selection operator, elastic net, and M-$k$k-TSP, the superior performance of CFC-CM on nine public gene expression datasets validates its potential for more precise identification of complex diseases. Subsequently, CFC-CM was applied to two metabolomics datasets, it obtained accuracy rates of $88.73\pm 2.06\%$88.73±2.06% and $79.11\pm 2.70\%$79.11±2.70% in distinguishing between hepatocellular carcinoma and hepatic cirrhosis groups and between acute kidney injury (AKI) and non-AKI samples, results superior to those of the other five methods. In summary, the better results of CFC-CM show that in contrast to molecules and combinations constituted by just two features, the combinations inferred by appropriate number of features could better identify the complex diseases.

This paper presents the module-phase synchronization for a class of neural networks with weights identification and time delays. In module-phase synchronization, complex-valued node states are taken into consideration. The topology weights considered here are uncertain and the time delays are bounded. By constructing a Lyapunov-Krasovskii functional and employing adaptive feedback control, sufficient conditions for module-phase synchronization are derived. After the general synchronization theory, the synchronization with topology identification is discussed. Finally, pertinent examples are given to demonstrate the effectiveness of the obtained results.

Extracting knowledge from unstructured text is one of the most important goals of Natural Language Processing, especially in biomedical event extraction domain. In this paper, we describe a system for extracting biomedical events among biotope and bacteria from biomedical literature, using the corpus from the BioNLP'16 Shared Task on Bacteria Biotope task. The current mainstream methods for event extraction are based on shallow machine learning methods. However, these methods mainly rely on domain experience and need enormous manual efforts to select features. Therefore, we propose a novel Long Short Term Memory (LSTM) Networks framework DETBLSTM for event extraction. In our framework, a dynamic extended tree is introduced as the input instead of the original sentences, which utilizes the syntactic information. Furthermore, the POS and distance embeddings are added to enrich input information and thus the complex feature extraction can be skipped. In final, we construct a bidirectional LSTM model to extract biomedical events and achieve 57.14% F-score in the test set. Our model obtains a better F-score than all official submissions to BioNLP-ST 2016, which is 1.34% higher than the best system.

In systems biology, filtering the discriminative features from complex high-dimensional data is a crucial issue. This paper proposes a feature selection algorithm based on feature overlapping and group overlapping (FS-FOGO) to calculate the feature importance. FS-FOGO weighs feature from two aspects: overlapping degree based on the ratio of overlapping area on the effective range of each class and the overlapping degree based on the proportion of heterogeneous samples in every sample's nearest neighbors. To show the validation of FS-FOGO, it is compared with effective range based gene selection (ERGS), which calculates the feature weights based on overlapping area of the effective range, on six public biological data sets and one serum metabolomics data set about liver disease. Naive Bayes and Support Vector Machine are used as classifiers, respectively. The experiment results show that the top ranked features by FS-FOGO are more discriminative and get higher classification accuracy rates than those by ERGS in most cases. And in the metabolomics data, the top ranked metabolites by FS-FOGO could separate different liver diseases well.

In this paper, the complete synchronizations for asynchronous switched Boolean network with free Boolean sequence controllers and close-loop controllers are studied. First, the basic asynchronous switched Boolean network model is provided. With the method of semi-tensor product, the Boolean dynamics is translated into linear representation. Second, necessary and sufficient conditions for ASBN synchronization with free Boolean sequence control and close-loop control are derived, respectively. Third, some illustrative examples are provided to show the efficiency of the proposed methods.

In this paper, the synchronizations of Boolean networks with different update schemes (synchronized Boolean networks and asynchronous Boolean networks) are investigated. All nodes in Boolean network are represented in terms of semi-tensor product. First, we give the concept of inner synchronization and observe that all nodes in a Boolean network are synchronized with each other. Second, we investigate the outer synchronization between a driving Boolean network and a corresponding response Boolean network. We provide not only the concept of traditional complete synchronization, but also the anti-synchronization and get the anti-synchronization in simulation. Third, we extend the outer synchronization to asynchronous Boolean network and get the complete synchronization between an asynchronous Boolean network and a response Boolean network. Consequently, theorems for synchronization of Boolean networks and asynchronous Boolean networks are derived. Examples are provided to show the correctness of our theorems.