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Background: Advanced non-invasive neuroimaging techniques offer new approaches to study functions and structures of human brains. Whole-brain functional networks obtained from resting state functional magnetic resonance imaging has been widely used to study brain diseases like autism spectrum disorder (ASD). Autoclassification of ASD has become an important issue. Existing classification methods for ASD are based on features extracted from the whole-brain functional networks, which may be not discriminant enough for good performance. Methods: In this study, we propose a network clustering based feature selection strategy for classifying ASD. In our proposed method, we first apply symmetric non-negative matrix factorization to divide brain networks into four modules. Then we extract features from one of four modules called default mode network (DMN) and use them to train several classifiers for ASD classification. Results: The computational experiments show that our proposed method achieves better performances than those trained with features extracted from the whole brain network. Conclusion: It is a good strategy to train the classifiers for ASD based on features from the default mode subnetwork. [ABSTRACT FROM AUTHOR]

Background: Chromatin immunoprecipitation sequencing (ChIP-seq) is a technology that combines chromatin immunoprecipitation (ChIP) with next generation of sequencing technology (NGS) to analyze protein interactions with DNA. At present, most ChIP-seq analysis tools adopt the command line, which lacks user-friendly interfaces. Although some web services with graphical interfaces have been developed for ChIP-seq analysis, these sites cannot provide a comprehensive analysis of ChIP-seq from raw data to downstream analysis. Results: In this study, we develop a web service for the whole process of ChIP-Seq Analysis (CSA), which covers mapping, quality control, peak calling, and downstream analysis. In addition, CSA provides a customization function for users to define their own workflows. And the visualization of mapping, peak calling, motif finding, and pathway analysis results are also provided in CSA. For the different types of ChIP-seq datasets, CSA can provide the corresponding tool to perform the analysis. Moreover, CSA can detect differences in ChIP signals between ChIP samples and controls to identify absolute binding sites. Conclusions: The two case studies demonstrate the effectiveness of CSA, which can complete the whole procedure of ChIP-seq analysis. CSA provides a web interface for users, and implements the visualization of every analysis step. The website of CSA is available at http://CompuBio.csu.edu.cn [ABSTRACT FROM AUTHOR]

Background: A drug-drug interaction (DDI) is defined as a drug effect modified by another drug, which is very common in treating complex diseases such as cancer. Many studies have evidenced that some DDIs could be an increase or a decrease of the drug effect. However, the adverse DDIs maybe result in severe morbidity and even morality of patients, which also cause some drugs to withdraw from the market. As the multi-drug treatment becomes more and more common, identifying the potential DDIs has become the key issue in drug development and disease treatment. However, traditional biological experimental methods, including in vitro and vivo, are very time-consuming and expensive to validate new DDIs. With the development of high-throughput sequencing technology, many pharmaceutical studies and various bioinformatics data provide unprecedented opportunities to study DDIs. Result: In this study, we propose a method to predict new DDIs, namely DDIGIP, which is based on Gaussian Interaction Profile (GIP) kernel on the drug-drug interaction profiles and the Regularized Least Squares (RLS) classifier. In addition, we also use the k-nearest neighbors (KNN) to calculate the initial relational score in the presence of new drugs via the chemical, biological, phenotypic data of drugs. We compare the prediction performance of DDIGIP with other competing methods via the 5-fold cross validation, 10-cross validation and de novo drug validation. Conlusion: In 5-fold cross validation and 10-cross validation, DDRGIP method achieves the area under the ROC curve (AUC) of 0.9600 and 0.9636 which are better than state-of-the-art method (L1 Classifier ensemble method) of 0.9570 and 0.9599. Furthermore, for new drugs, the AUC value of DDIGIP in de novo drug validation reaches 0.9262 which also outperforms the other state-of-the-art method (Weighted average ensemble method) of 0.9073. Case studies and these results demonstrate that DDRGIP is an effective method to predict DDIs while being beneficial to drug development and disease treatment. [ABSTRACT FROM AUTHOR]

Background: Essential proteins are crucial for cellular life and thus, identification of essential proteins is an important topic and a challenging problem for researchers. Recently lots of computational approaches have been proposed to handle this problem. However, traditional centrality methods cannot fully represent the topological features of biological networks. In addition, identifying essential proteins is an imbalanced learning problem; but few current shallow machine learning-based methods are designed to handle the imbalanced characteristics. Results: We develop DeepEP based on a deep learning framework that uses the node2vec technique, multi-scale convolutional neural networks and a sampling technique to identify essential proteins. In DeepEP, the node2vec technique is applied to automatically learn topological and semantic features for each protein in protein-protein interaction (PPI) network. Gene expression profiles are treated as images and multi-scale convolutional neural networks are applied to extract their patterns. In addition, DeepEP uses a sampling method to alleviate the imbalanced characteristics. The sampling method samples the same number of the majority and minority samples in a training epoch, which is not biased to any class in training process. The experimental results show that DeepEP outperforms traditional centrality methods. Moreover, DeepEP is better than shallow machine learning-based methods. Detailed analyses show that the dense vectors which are generated by node2vec technique contribute a lot to the improved performance. It is clear that the node2vec technique effectively captures the topological and semantic properties of PPI network. The sampling method also improves the performance of identifying essential proteins. Conclusion: We demonstrate that DeepEP improves the prediction performance by integrating multiple deep learning techniques and a sampling method. DeepEP is more effective than existing methods. [ABSTRACT FROM AUTHOR]

Protein essentiality is fundamental to comprehend the function and evolution of genes. The prediction of protein essentiality is pivotal in identifying disease genes and potential drug targets. Since the experimental methods need many investments in time and funds, it is of great value to predict protein essentiality with high accuracy using computational methods. In this study, we present a novel feature selection named Elite Search mechanism-based Flower Pollination Algorithm (ESFPA) to determine protein essentiality. Unlike other protein essentiality prediction methods, ESFPA uses an improved swarm intelligence–based algorithm for feature selection and selects optimal features for protein essentiality prediction. The first step is to collect numerous features with the highly predictive characteristics of essentiality. The second step is to develop a feature selection strategy based on a swarm intelligence algorithm to obtain the optimal feature subset. Furthermore, an elite search mechanism is adopted to further improve the quality of feature subset. Subsequently a hybrid classifier is applied to evaluate the essentiality for each protein. Finally, the experimental results show that our method is competitive to some well-known feature selection methods. The proposed method aims to provide a new perspective for protein essentiality determination. [ABSTRACT FROM AUTHOR]

Driven by high-throughput sequencing techniques,modern genomic and clinical studies are in a strong need of integrative machine learningmodels for better use of vast volumes of heterogeneous information in the deep understanding of biological systems and the development of predictivemodels. How data frommultiple sources (calledmulti-view data) are incorporated in a learning systemis a key step for successful analysis. In this article, we provide a comprehensive review on omics and clinical data integration techniques, from amachine learning perspective, for various analyses such as prediction, clustering, dimension reduction and association.We shall show that Bayesianmodels are able to use prior information andmodelmeasurements with various distributions; tree-basedmethods can either build a tree with all features or collectivelymake a final decision based on trees learned fromeach view; kernelmethods fuse the similaritymatrices learned fromindividual views together for a final similaritymatrix or learningmodel; network-based fusionmethods are capable of inferring direct and indirect associations in a heterogeneous network;matrix factorizationmodels have potential to learn interactions among features fromdifferent views; and a range of deep neural networks can be integrated inmulti-modal learning for capturing the complexmechanism of biological systems. [ABSTRACT FROM AUTHOR]

Background: Identifying protein complexes plays an important role for understanding cellular organization and functional mechanisms. As plenty of evidences have indicated that dense sub-networks in dynamic protein-protein interaction network (DPIN) usually correspond to protein complexes, identifying protein complexes is formulated as density-based clustering. Methods: In this paper, a new approach named iOPTICS-GSO is developed, which is the improved Ordering Points to Identify the Clustering Structure (OPTICS) algorithm with Glowworm swarm optimization algorithm (GSO) to optimize the parameters in OPTICS when finding dense sub-networks. In our iOPTICS-GSO, the concept of core node is redefined and the Euclidean distance in OPTICS is replaced with the improved similarity between the nodes in the PPI network according to their interaction strength, and dense sub-networks are considered as protein complexes. Results: The experiment results have shown that our iOPTICS-GSO outperforms of algorithms such as DBSCAN, CFinder, MCODE, CMC, COACH, ClusterOne MCL and OPTICS_PSO in terms of f-measure and p-value on four DPINs, which are from the DIP, Krogan, MIPS and Gavin datasets. In addition, our predicted protein complexes have a small p-value and thus are highly likely to be true protein complexes. Conclusion: The proposed iOPTICS-GSO gains optimal clustering results by adopting GSO algorithm to optimize the parameters in OPTICS, and the result on four datasets shows superior performance. What's more, the results provided clues for biologists to verify and find new protein complexes. [ABSTRACT FROM AUTHOR]

Background: Methylation is a common modification of DNA. It has been a very important and hot topic to study the correlation between methylation and diseases in medical science. Because of the special process with bisulfite treatment, traditional mapping tools do not work well with such methylation experimental reads. Traditional aligners are not designed for mapping bisulfite-treated reads, where the un-methylated 'C's are converted to 'T's. Results: In this paper, we develop a reliable and visual tool, named VAliBS, for mapping bisulfate sequences to a genome reference. VAliBS works well even on large scale data or high noise data. By comparing with other state-of-the-art tools (BisMark, BSMAP, BS-Seeker2), VAliBS can improve the accuracy of bisulfite mapping. Moreover, VAliBS is a visual tool which makes its operations more easily and the alignment results are shown with colored marks which makes it easier to be read. VAliBS provides fast and accurate mapping of bisulfite-converted reads, and a friendly window system to visualize the detail of mapping of each read. Conclusions: VAliBS works well on both simulated data and real data. It can be useful in DNAmethylation research. VALiBS implements an X-Window user interface where the methylation positions are visual and the operations are friendly. [ABSTRACT FROM AUTHOR]

Protein-protein interactions (PPIs) participate in all important biological processes in living organisms, such as catalyzing metabolic reactions, DNA replication, DNA transcription, responding to stimuli and transporting molecules from one location to another. To reveal the function mechanisms in cells, it is important to identify PPIs that take place in the living organism. A large number of PPIs have been discovered by high-throughput experiments and computational methods. However, false-positive PPIs have been introduced too. Therefore, to obtain reliable PPIs, many computational methods have been proposed. Generally, these methods can be classified into two categories. One category includes the methods that are designed to determine new reliable PPIs. The other one is designed to assess the reliability of existing PPIs and filter out the unreliable ones. In this article, we review the two kinds of methods for detecting reliable PPIs, and then focus on evaluating the performance of some of these typical methods. Later on, we also enumerate several PPI network-based applications with taking a reliability assessment of the PPI data into consideration. Finally, we will discuss the challenges for obtaining reliable PPIs and future directions of the construction of reliable PPI networks. Our research will provide readers some guidance for choosing appropriate methods and features for obtaining reliable PPIs. [ABSTRACT FROM AUTHOR]

The control of complex nonlinear dynamical networks is an ongoing challenge in diverse contexts ranging from biology to social sciences. To explore a practical framework for controlling nonlinear dynamical networks based on meaningful physical and experimental considerations, we propose a new concept of the domain control for nonlinear dynamical networks, i.e., the control of a nonlinear network in transition from the domain of attraction of an undesired state (attractor) to the domain of attraction of a desired state. We theoretically prove the existence of a domain control. In particular, we offer an approach for identifying the driver nodes that need to be controlled and design a general form of control functions for realizing domain controllability. In addition, we demonstrate the effectiveness of our theory and approaches in three realistic disease-related networks: the epithelial-mesenchymal transition (EMT) core network, the T helper (Th) differentiation cellular network and the cancer network. Moreover, we reveal certain genes that are critical to phenotype transitions of these systems. Therefore, the approach described here not only offers a practical control scheme for nonlinear dynamical networks but also helps the development of new strategies for the prevention and treatment of complex diseases. [ABSTRACT FROM AUTHOR]

Motivation: While aiming to determine orientations and orders of fragmented contigs, scaffolding is an essential step of assembly pipelines and can make assembly results more complete. Most existing scaffolding tools adopt scaffold graph approaches. However, due to repetitive regions in genome, sequencing errors and uneven sequencing depth, constructing an accurate scaffold graph is still a challenge task. Results: In this paper, we present a novel algorithm (called BOSS), which employs paired reads for scaffolding. To construct a scaffold graph, BOSS utilizes the distribution of insert size to decide whether an edge between two vertices (contigs) should be added and how an edge should be weighed. Moreover, BOSS adopts an iterative strategy to detect spurious edges whose removal can guarantee no contradictions in the scaffold graph. Based on the scaffold graph constructed, BOSS employs a heuristic algorithm to sort vertices (contigs) and then generates scaffolds. The experimental results demonstrate that BOSS produces more satisfactory scaffolds, compared with other popular scaffolding tools on real sequencing data of four genomes. [ABSTRACT FROM AUTHOR]

Motivation: Drug repositioning, which aims to identify new indications for existing drugs, offers a promising alternative to reduce the total time and cost of traditional drug development. Many computational strategies for drug repositioning have been proposed, which are based on similarities among drugs and diseases. Current studies typically use either only drug-related properties (e.g. chemical structures) or only disease-related properties (e.g. phenotypes) to calculate drug or disease similarity, respectively, while not taking into account the influence of known drug-disease association information on the similarity measures. Results: In this article, based on the assumption that similar drugs are normally associated with similar diseases and vice versa, we propose a novel computational method named MBiRW, which utilizes some comprehensive similarity measures and Bi-Random walk (BiRW) algorithm to identify potential novel indications for a given drug. By integrating drug or disease features information with known drug-disease associations, the comprehensive similarity measures are firstly developed to calculate similarity for drugs and diseases. Then drug similarity network and disease similarity network are constructed, and they are incorporated into a heterogeneous network with known drug-disease interactions. Based on the drug-disease heterogeneous network, BiRW algorithm is adopted to predict novel potential drug-disease associations. Computational experiment results from various datasets demonstrate that the proposed approach has reliable prediction performance and outperforms several recent computational drug repositioning approaches. Moreover, case studies of five selected drugs further confirm the superior performance of our method to discover potential indications for drugs practically. [ABSTRACT FROM AUTHOR]

Background: Essential proteins play an indispensable role in the cellular survival and development. There have been a series of biological experimental methods for finding essential proteins; however they are time-consuming, expensive and inefficient. In order to overcome the shortcomings of biological experimental methods, many computational methods have been proposed to predict essential proteins. The computational methods can be roughly divided into two categories, the topology-based methods and the sequence-based ones. The former use the topological features of protein-protein interaction (PPI) networks while the latter use the sequence features of proteins to predict essential proteins. Nevertheless, it is still challenging to improve the prediction accuracy of the computational methods. Results: Comparing with nonessential proteins, essential proteins appear more frequently in certain subcellular locations and their evolution more conservative. By integrating the information of subcellular localization, orthologous proteins and PPI networks, we propose a novel essential protein prediction method, named SON, in this study. The experimental results on S.cerevisiae data show that the prediction accuracy of SON clearly exceeds that of nine competing methods: DC, BC, IC, CC, SC, EC, NC, PeC and ION. Conclusions: We demonstrate that, by integrating the information of subcellular localization, orthologous proteins with PPI networks, the accuracy of predicting essential proteins can be improved. Our proposed method SON is effective for predicting essential proteins. [ABSTRACT FROM AUTHOR]

Background: Protein complexes play an important role in biological processes. Recent developments in experiments have resulted in the publication of many high-quality, large-scale protein-protein interaction (PPI) datasets, which provide abundant data for computational approaches to the prediction of protein complexes. However, the precision of protein complex prediction still needs to be improved due to the incompletion and noise in PPI networks. Results: There exist complex and diverse relationships among proteins after integrating multiple sources of biological information. Considering that the influences of different types of interactions are not the same weight for protein complex prediction, we construct a multi-relationship protein interaction network (MPIN) by integrating PPI network topology with gene ontology annotation information. Then, we design a novel algorithm named MINE (identifying protein complexes based on Multi-relationship protein Interaction NEtwork) to predict protein complexes with high cohesion and low coupling from MPIN. Conclusions: The experiments on yeast data show that MINE outperforms the current methods in terms of both accuracy and statistical significance. [ABSTRACT FROM AUTHOR]

Detecting protein complexes is crucial to understand principles of cellular organization. Plenty evidences have indicated that sub-graphs with high density in protein-protein interaction (PPI) network, especially dynamic PPI network (DPIN), usually correspond to protein complexes. As a well-known density-based clustering algorithm, Density-Based Spatial Clustering of Applications with Noise (DBSCAN) has been used in many areas due to its simplicity and the ability to detect clusters of different sizes and shapes. However, one of its limitations is that the performance of DBSCAN depends on two specified parameters e and MinPts, where e represents the maximum radius of a neighborhood from an observing point while MinPts means the minimum number of data points contained in such a neighborhood. In this article, we develop a new method named as P-DBSCAN to detect protein complexes in DPIN by using Pigeon-Inspired Optimization (PIO) Algorithm to optimize the parameters e and MinPts in DBSCAN. The experiments on DIP and MIPS datasets show that P-DBSCAN outperforms the state-of-the-art methods for protein complex detection in terms of several criteria such as precision, recall and f-measure. [ABSTRACT FROM AUTHOR]

Motivation: Advances of next generation sequencing technologies and availability of short read data enable the detection of structural variations (SVs). Deletions, an important type of SVs, have been suggested in association with genetic diseases. There are three types of deletions: blunt deletions, deletions with microhomologies and deletions with microsinsertions. The last two types are very common in the human genome, but they pose difficulty for the detection. Furthermore, finding deletions from sequencing data remains challenging. It is highly appealing to develop sensitive and accurate methods to detect deletions from sequencing data, especially deletions with microhomology and deletions with microinsertion. Results: We present a novel method called Sprites (SPlit Read re-alIgnment To dEtect Structural variants) which finds deletions from sequencing data. It aligns a whole soft-clipping read rather than its clipped part to the target sequence, a segment of the reference which is determined by spanning reads, in order to find the longest prefix or suffix of the read that has a match in the target sequence. This alignment aims to solve the problem of deletions with microhomologies and deletions with microinsertions. Using both simulated and real data we show that Sprites performs better on detecting deletions compared with other current methods in terms of F-score. [ABSTRACT FROM AUTHOR]

Many systems of interests in practices can be represented as complex networks. For biological systems, biomolecules do not perform their functions alone but interact with each other to form so-called biomolecular networks. A system is said to be controllable if it can be steered from any initial state to any other final state in finite time. The network controllability has become essential to study the dynamics of the networks and understand the importance of individual nodes in the networks. Some interesting biological phenomena have been discovered in terms of the structural controllability of biomolecular networks. Most of current studies investigate the structural controllability of networks in notion of the minimum driver node sets (MDSs). In this study, the authors analyse the network structural controllability in notion of the minimum steering node sets (MSSs). They first develop a graphtheoretic algorithm to identify the MSS for a given network and then apply it to several biomolecular networks. Application results show that biomolecules identified in the MSSs play essential roles in corresponding biological processes. Furthermore, the application results indicate that the MSSs can reflect the network dynamics and node importance in controlling the networks better than the MDSs. [ABSTRACT FROM AUTHOR]

Background: Integrating multiple data sources is indispensable in improving disease gene identification. It is not only due to the fact that disease genes associated with similar genetic diseases tend to lie close with each other in various biological networks, but also due to the fact that gene-disease associations are complex. Although various algorithms have been proposed to identify disease genes, their prediction performances and the computational time still should be further improved. Results: In this study, we propose a fast and high performance multiple data integration algorithm for identifying human disease genes. A posterior probability of each candidate gene associated with individual diseases is calculated by using a Bayesian analysis method and a binary logistic regression model. Two prior probability estimation strategies and two feature vector construction methods are developed to test the performance of the proposed algorithm. Conclusions: The proposed algorithm is not only generated predictions with high AUC scores, but also runs very fast. When only a single PPI network is employed, the AUC score is 0.769 by using F2 as feature vectors. The average running time for each leave-one-out experiment is only around 1.5 seconds. When three biological networks are integrated, the AUC score using F3 as feature vectors increases to 0.830, and the average running time for each leave-one-out experiment takes only about 12.54 seconds. It is better than many existing algorithms. [ABSTRACT FROM AUTHOR]

Motivation: In genome assembly, the primary issue is how to determine upstream and downstream sequence regions of sequence seeds for constructing long contigs or scaffolds. When extending one sequence seed, repetitive regions in the genome always cause multiple feasible extension candidates which increase the difficulty of genome assembly. The universally accepted solution is choosing one based on read overlaps and paired-end (mate-pair) reads. However, this solution faces difficulties with regard to some complex repetitive regions. In addition, sequencing errors may produce false repetitive regions and uneven sequencing depth leads some sequence regions to have too few or too many reads. All the aforementioned problems prohibit existing assemblers from getting satisfactory assembly results. Results: In this article, we develop an algorithm, called extract paths for genome assembly (EPGA), which extracts paths from De Bruijn graph for genome assembly. EPGA uses a new score function to evaluate extension candidates based on the distributions of reads and insert size. The distribution of reads can solve problems caused by sequencing errors and short repetitive regions. Through assessing the variation of the distribution of insert size, EPGA can solve problems introduced by some complex repetitive regions. For solving uneven sequencing depth, EPGA uses relative mapping to evaluate extension candidates. On real datasets, we compare the performance of EPGA and other popular assemblers. The experimental results demonstrate that EPGA can effectively obtain longer and more accurate contigs and scaffolds. [ABSTRACT FROM AUTHOR]