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Motivation Longer reads produced by PacBio or Oxford Nanopore sequencers could more frequently span the breakpoints of structural variations (SVs) than shorter reads. Therefore, existing long-read mapping methods often generate wrong alignments and variant calls. Compared to deletions and insertions, inversion events are more difficult to be detected since the anchors in inversion regions are nonlinear to those in SV-free regions. To address this issue, this study presents a novel long-read mapping algorithm (named as invMap). Results For each long noisy read, invMap first locates the aligned region with a specifically designed scoring method for chaining, then checks the remaining anchors in the aligned region to discover potential inversions. We benchmark invMap on simulated datasets across different genomes and sequencing coverages, experimental results demonstrate that invMap is more accurate to locate aligned regions and call SVs for inversions than the competing methods. The real human genome sequencing dataset of NA12878 illustrates that invMap can effectively find more candidate variant calls for inversions than the competing methods. Availability and implementation The invMap software is available at https://github.com/zhang134/invMap.git. [ABSTRACT FROM AUTHOR]

Motivation Emerging studies indicate that circular RNAs (circRNAs) are widely involved in the progression of human diseases. Due to its special structure which is stable, circRNAs are promising diagnostic and prognostic biomarkers for diseases. However, the experimental verification of circRNA–disease associations is expensive and limited to small-scale. Effective computational methods for predicting potential circRNA–disease associations are regarded as a matter of urgency. Although several models have been proposed, over-reliance on known associations and the absence of characteristics of biological functions make precise predictions are still challenging. Results In this study, we propose a method for predicting CircRNA–disease associations based on sequence and ontology representations, named CDASOR, with convolutional and recurrent neural networks. For sequences of circRNAs, we encode them with continuous k -mers, get low-dimensional vectors of k -mers, extract their local feature vectors with 1D CNN and learn their long-term dependencies with bi-directional long short-term memory. For diseases, we serialize disease ontology into sentences containing the hierarchy of ontology, obtain low-dimensional vectors for disease ontology terms and get terms' dependencies. Furthermore, we get association patterns of circRNAs and diseases from known circRNA–disease associations with neural networks. After the above steps, we get circRNAs' and diseases' high-level representations, which are informative to improve the prediction. The experimental results show that CDASOR provides an accurate prediction. Importing the characteristics of biological functions, CDASOR achieves impressive predictions in the de novo test. In addition, 6 of the top-10 predicted results are verified by the published literature in the case studies. Availability and implementation The code and data of CDASOR are freely available at https://github.com/BioinformaticsCSU/CDASOR. [ABSTRACT FROM AUTHOR]

Motivation Evidence has shown that microRNAs, one type of small biomolecule, regulate the expression level of genes and play an important role in the development or treatment of diseases. Drugs, as important chemical compounds, can interact with microRNAs and change their functions. The experimental identification of microRNA–drug interactions is time-consuming and expensive. Therefore, it is appealing to develop effective computational approaches for predicting microRNA–drug interactions. Results In this study, a matrix factorization-based method, called the microRNA–drug interaction prediction approach (MDIPA), is proposed for predicting unknown interactions among microRNAs and drugs. Specifically, MDIPA utilizes experimentally validated interactions between drugs and microRNAs, drug similarity and microRNA similarity to predict undiscovered interactions. A path-based microRNA similarity matrix is constructed, while the structural information of drugs is used to establish a drug similarity matrix. To evaluate its performance, our MDIPA is compared with four state-of-the-art prediction methods with an independent dataset and cross-validation. The results of both evaluation methods confirm the superior performance of MDIPA over other methods. Finally, the results of molecular docking in a case study with breast cancer confirm the efficacy of our approach. In conclusion, MDIPA can be effective in predicting potential microRNA–drug interactions. Availability and implementation All code and data are freely available from https://github.com/AliJam82/MDIPA. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Protein–protein interactions (PPIs) play important roles in many biological processes. Conventional biological experiments for identifying PPI sites are costly and time-consuming. Thus, many computational approaches have been proposed to predict PPI sites. Existing computational methods usually use local contextual features to predict PPI sites. Actually, global features of protein sequences are critical for PPI site prediction. Results A new end-to-end deep learning framework, named DeepPPISP, through combining local contextual and global sequence features, is proposed for PPI site prediction. For local contextual features, we use a sliding window to capture features of neighbors of a target amino acid as in previous studies. For global sequence features, a text convolutional neural network is applied to extract features from the whole protein sequence. Then the local contextual and global sequence features are combined to predict PPI sites. By integrating local contextual and global sequence features, DeepPPISP achieves the state-of-the-art performance, which is better than the other competing methods. In order to investigate if global sequence features are helpful in our deep learning model, we remove or change some components in DeepPPISP. Detailed analyses show that global sequence features play important roles in DeepPPISP. Availability and implementation The DeepPPISP web server is available at http://bioinformatics.csu.edu.cn/PPISP/. The source code can be obtained from https://github.com/CSUBioGroup/DeepPPISP. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

The molecular interactions in a cell are varying with time and surrounded environmental cues. The construction and analysis of dynamic molecular networks can elucidate dynamic cellular mechanisms of different biological functions and provide a chance to understand complex diseases at the systems level. Here, we develop DyNetViewer, a Cytoscape application that provides a range of functionalities for the construction, analysis and visualization of dynamic protein--protein interaction networks. The current version of DyNetViewer consists of four different dynamic network construction methods, twelve topological variation analysis methods and four clustering algorithms. Moreover, visualization of different topological variation of nodes and clusters over time enables users to quickly identify themost variations across many network states. [ABSTRACT FROM AUTHOR]

Motivation Many studies have shown that microRNAs (miRNAs) play a key role in human diseases. Meanwhile, traditional experimental methods for miRNA–disease association identification are extremely costly, time-consuming and challenging. Therefore, many computational methods have been developed to predict potential associations between miRNAs and diseases. However, those methods mainly predict the existence of miRNA–disease associations, and they cannot predict the deep-level miRNA–disease association types. Results In this study, we propose a new end-to-end deep learning method (called PDMDA) to predict deep-level miRNA–disease associations with graph neural networks (GNNs) and miRNA sequence features. Based on the sequence and structural features of miRNAs, PDMDA extracts the miRNA feature representations by a fully connected network (FCN). The disease feature representations are extracted from the disease–gene network and gene–gene interaction network by GNN model. Finally, a multilayer with three fully connected layers and a softmax layer is designed to predict the final miRNA–disease association scores based on the concatenated feature representations of miRNAs and diseases. Note that PDMDA does not take the miRNA–disease association matrix as input to compute the Gaussian interaction profile similarity. We conduct three experiments based on six association type samples (including circulations, epigenetics, target, genetics, known association of which their types are unknown and unknown association samples). We conduct fivefold cross-validation validation to assess the prediction performance of PDMDA. The area under the receiver operating characteristic curve scores is used as metric. The experiment results show that PDMDA can accurately predict the deep-level miRNA–disease associations. Availability and implementation Data and source codes are available at https://github.com/27167199/PDMDA. [ABSTRACT FROM AUTHOR]

Motivation High resolution annotation of gene functions is a central goal in functional genomics. A single gene may produce multiple isoforms with different functions through alternative splicing. Conventional approaches, however, consider a gene as a single entity without differentiating these functionally different isoforms. Towards understanding gene functions at higher resolution, recent efforts have focused on predicting the functions of isoforms. However, the performance of existing methods is far from satisfactory mainly because of the lack of isoform-level functional annotation. Results We present IsoResolve, a novel approach for isoform function prediction, which leverages the information from gene function prediction models with domain adaptation (DA). IsoResolve treats gene-level and isoform-level features as source and target domains, respectively. It uses DA to project the two domains into a latent variable space in such a way that the latent variables from the two domains have similar distribution, which enables the gene domain information to be leveraged for isoform function prediction. We systematically evaluated the performance of IsoResolve in predicting functions. Compared with five state-of-the-art methods, IsoResolve achieved significantly better performance. IsoResolve was further validated by case studies of genes with isoform-level functional annotation. Availability and implementation IsoResolve is freely available at https://github.com/genemine/IsoResolve. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Computationally predicting disease genes helps scientists optimize the in-depth experimental validation and accelerates the identification of real disease-associated genes. Modern high-throughput technologies have generated a vast amount of omics data, and integrating them is expected to improve the accuracy of computational prediction. As an integrative model, multimodal deep belief net (DBN) can capture cross-modality features from heterogeneous datasets to model a complex system. Studies have shown its power in image classification and tumor subtype prediction. However, multimodal DBN has not been used in predicting disease–gene associations. Results In this study, we propose a method to predict disease–gene associations by multimodal DBN (dgMDL). Specifically, latent representations of protein-protein interaction networks and gene ontology terms are first learned by two DBNs independently. Then, a joint DBN is used to learn cross-modality representations from the two sub-models by taking the concatenation of their obtained latent representations as the multimodal input. Finally, disease–gene associations are predicted with the learned cross-modality representations. The proposed method is compared with two state-of-the-art algorithms in terms of 5-fold cross-validation on a set of curated disease–gene associations. dgMDL achieves an AUC of 0.969 which is superior to the competing algorithms. Further analysis of the top-10 unknown disease–gene pairs also demonstrates the ability of dgMDL in predicting new disease–gene associations. Availability and implementation Prediction results and a reference implementation of dgMDL in Python is available on https://github.com/luoping1004/dgMDL. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation The development of single-cell RNA-sequencing (scRNA-seq) provides a new perspective to study biological problems at the single-cell level. One of the key issues in scRNA-seq analysis is to resolve the heterogeneity and diversity of cells, which is to cluster the cells into several groups. However, many existing clustering methods are designed to analyze bulk RNA-seq data, it is urgent to develop the new scRNA-seq clustering methods. Moreover, the high noise in scRNA-seq data also brings a lot of challenges to computational methods. Results In this study, we propose a novel scRNA-seq cell type detection method based on similarity learning, called SinNLRR. The method is motivated by the self-expression of the cells with the same group. Specifically, we impose the non-negative and low rank structure on the similarity matrix. We apply alternating direction method of multipliers to solve the optimization problem and propose an adaptive penalty selection method to avoid the sensitivity to the parameters. The learned similarity matrix could be incorporated with spectral clustering, t-distributed stochastic neighbor embedding for visualization and Laplace score for prioritizing gene markers. In contrast to other scRNA-seq clustering methods, our method achieves more robust and accurate results on different datasets. Availability and implementation Our MATLAB implementation of SinNLRR is available at, https://github.com/zrq0123/SinNLRR. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Reconstructing gene regulatory networks (GRNs) based on gene expression profiles is still an enormous challenge in systems biology. Random forest-based methods have been proved a kind of efficient methods to evaluate the importance of gene regulations. Nevertheless, the accuracy of traditional methods can be further improved. With time-series gene expression data, exploiting inherent time information and high order time lag are promising strategies to improve the power and accuracy of GRNs inference. Results In this study, we propose a scalable, flexible approach called BiXGBoost to reconstruct GRNs. BiXGBoost is a bidirectional-based method by considering both candidate regulatory genes and target genes for a specific gene. Moreover, BiXGBoost utilizes time information efficiently and integrates XGBoost to evaluate the feature importance. Randomization and regularization are also applied in BiXGBoost to address the over-fitting problem. The results on DREAM4 and Escherichia coli datasets show the good performance of BiXGBoost on different scale of networks. Availability and implementation Our Python implementation of BiXGBoost is available at https://github.com/zrq0123/BiXGBoost. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Scaffolding is an essential step during the de novo sequence assembly process to infer the direction and order relationships between the contigs and make the sequence assembly results more continuous and complete. However, scaffolding still faces the challenges of repetitive regions in genome, sequencing errors and uneven sequencing depth. Moreover, the accuracy of scaffolding greatly depends on the quality of contigs. Generally, the existing scaffolding methods construct a scaffold graph, and then optimize the graph by deleting spurious edges. Nevertheless, due to the wrong joints between contigs, some correct edges connecting contigs may be deleted. Results In this study, we present a novel scaffolding method SCOP, which is the first method to classify the contigs and utilize the vertices and edges to optimize the scaffold graph. Specially, SCOP employs alignment features and GC-content of paired reads to evaluate the quality of contigs (vertices), and divide the contigs into three types (True, Uncertain and Misassembled), and then optimizes the scaffold graph based on the classification of contigs together with the alignment of edges. The experiment results on the datasets of GAGE-A and GAGE-B demonstrate that SCOP performs better than 12 other competing scaffolders. Availability and implementation SCOP is publicly available for download at https://github.com/bioinfomaticsCSU/SCOP. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play pivotal roles in various biological processes. Mutations and dysregulations of lncRNAs are implicated in miscellaneous human diseases. Predicting lncRNA–disease associations is beneficial to disease diagnosis as well as treatment. Although many computational methods have been developed, precisely identifying lncRNA–disease associations, especially for novel lncRNAs, remains challenging. Results In this study, we propose a method (named SIMCLDA) for predicting potential lncRNA–disease associations based on inductive matrix completion. We compute Gaussian interaction profile kernel of lncRNAs from known lncRNA–disease interactions and functional similarity of diseases based on disease–gene and gene–gene onotology associations. Then, we extract primary feature vectors from Gaussian interaction profile kernel of lncRNAs and functional similarity of diseases by principal component analysis, respectively. For a new lncRNA, we calculate the interaction profile according to the interaction profiles of its neighbors. At last, we complete the association matrix based on the inductive matrix completion framework using the primary feature vectors from the constructed feature matrices. Computational results show that SIMCLDA can effectively predict lncRNA–disease associations with higher accuracy compared with previous methods. Furthermore, case studies show that SIMCLDA can effectively predict candidate lncRNAs for renal cancer, gastric cancer and prostate cancer. Availability and implementation https://github.com//bioinfomaticsCSU/SIMCLDA Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Studying the controllability of biomolecular networks can result in profound knowledge about molecular biological systems. However, there is no comprehensive and easy-to-use platform for analyzing controllability of biomolecular networks although various algorithms for analyzing complex network controllability have been proposed recently. In this application note, we develop the CytoCtrlAnalyser which is a Cytoscape app to provide a comprehensive platform for analyzing controllability of biomolecular networks. Nine algorithms have been integrated in CytoCtrlAnalyser. With network topologies and customized control settings imported into CytoCtrlAnalyser, users can identify the steering nodes which should be actuated by input control signals for achieving different control objectives as well as investigate the importance of nodes from different perspectives in the controllability of networks. CytoCtrlAnalyser offers a tool for many promising applications, such as identification of potential drug targets or biologically important nodes in biomolecular networks. [ABSTRACT FROM AUTHOR]

Summary The recent advance in genome engineering technologies based on CRISPR/Cas9 system is enabling people to systematically understand genomic functions. A short RNA string (the CRISPR guide RNA) can guide the Cas9 endonuclease to specific locations in complex genomes to cut DNA double-strands. The CRISPR guide RNA is essential for gene editing systems. Recently, the GuideScan software is developed to design CRISPR guide RNA libraries, which can be used for genome editing of coding and non-coding genomic regions effectively. However, GuideScan is a serial program and computationally expensive for designing CRISPR guide RNA libraries from large genomes. Here, we present an efficient guide RNA library designing tool (MultiGuideScan) by implementing multiple processes of GuideScan. MultiGuideScan speeds up the guide RNA library designing about 9–12 times on a 32-process mode comparing to GuideScan. MultiGuideScan makes it possible to design guide RNA libraries from large genomes. Availability and implementation: MultiGuideScan is available at GitHub https://github.com/bioinfomaticsCSU/MultiGuideScan. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]