ALBERT

Beschreibung: Aspect sentiment classification is an important research topic in natural language processing and computational linguistics, assisting in automatically review analysis and emotional tendency judgement. Different from extant methods that focus on text sequence representations, this paper presents a network framework to learn representation from concurrence-words relation graph (LRCWG), so as to improve the Macro-F1 and accuracy. The LRCWG first employs the multi-head attention mechanism to capture the sentiment representation from the sentences which can learn the importance of text sequence representation. And then, it leverages the priori sentiment dictionary information to construct the concurrence relations of sentiment words with Graph Convolution Network (GCN). This assists in that the learnt context representation can keep both the semantics integrity and the features of sentiment concurrence-words relations. The designed algorithm is experimentally evaluated with all the five benchmark datasets and demonstrated that the proposed aspect sentiment classification can significantly improve the prediction performance of learning task.

Beschreibung: Non-negative matrix factorization (NMF) is a powerful tool for data science researchers, and it has been successfully applied to data mining and machine learning community, due to its advantages such as simple form, good interpretability and less storage space. In this paper, we give a detailed survey on existing NMF methods, including a comprehensive analysis of their design principles, characteristics and drawbacks. In addition, we also discuss various variants of NMF methods and analyse properties and applications of these variants. Finally, we evaluate the performance of nine NMF methods through numerical experiments, and the results show that NMF methods perform well in clustering tasks.

Beschreibung: The task of question generation (QG) aims to create valid questions and correlated answers from the given text. Despite the neural QG approaches have achieved promising results, they are typically developed for languages with rich annotated training data. Because of the high annotation cost, it is difficult to deploy to other low-resource languages. Besides, different samples have their own characteristics on the aspects of text contextual structure, question type and correlations. Without capturing these diversified characteristics, the traditional one-size-fits-all model is hard to generate the best results. To address this problem, we study the task of cross-lingual QG from an adaptive learning perspective. Concretely, we first build a basic QG model on a multilingual space using the labelled data. In this way, we can transfer the supervision from the high-resource language to the language lacking labelled data. We then design a task-specific meta-learner to optimize the basic QG model. Each sample and its similar instances are viewed as a pseudo-QG task. The asking patterns and logical forms contained in the similar samples can be used as a guide to fine-tune the model fitly and produce the optimal results accordingly. Considering that each sample contains the text, question and answer, with unknown semantic correlations among them, we propose a context-dependent retriever to measure the similarity of such structured inputs. Experimental results on three languages of three typical data sets show the effectiveness of our approach.

Beschreibung: Motivation Personalized medicine aims at providing patient-tailored therapeutics based on multi-type data toward improved treatment outcomes. Chronotherapy that consists in adapting drug administration to the patient’s circadian rhythms may be improved by such approach. Recent clinical studies demonstrated large variability in patients’ circadian coordination and optimal drug timing. Consequently, new eHealth platforms allow the monitoring of circadian biomarkers in individual patients through wearable technologies (rest-activity, body temperature), blood or salivary samples (melatonin, cortisol) and daily questionnaires (food intake, symptoms). A current clinical challenge involves designing a methodology predicting from circadian biomarkers the patient peripheral circadian clocks and associated optimal drug timing. The mammalian circadian timing system being largely conserved between mouse and humans yet with phase opposition, the study was developed using available mouse datasets. Results We investigated at the molecular scale the influence of systemic regulators (e.g. temperature, hormones) on peripheral clocks, through a model learning approach involving systems biology models based on ordinary differential equations. Using as prior knowledge our existing circadian clock model, we derived an approximation for the action of systemic regulators on the expression of three core-clock genes: Bmal1, Per2 and Rev-Erbα. These time profiles were then fitted with a population of models, based on linear regression. Best models involved a modulation of either Bmal1 or Per2 transcription most likely by temperature or nutrient exposure cycles. This agreed with biological knowledge on temperature-dependent control of Per2 transcription. The strengths of systemic regulations were found to be significantly different according to mouse sex and genetic background. Availability and implementation https://gitlab.inria.fr/julmarti/model-learning-mb21eccb. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Since graph learning could preserve the structure information of the samples to improve the learning ability, it has been widely applied in both shallow learning and deep learning. However, the current graph learning methods still suffer from the issues such as outlier influence and model robustness. In this paper, we propose a new dynamic graph neural network (DGCN) method to conduct semi-supervised classification on multi-view data by jointly conducting the graph learning and the classification task in a unified framework. Specifically, our method investigates three strategies to improve the quality of the graph before feeding it into the GCN model: (i) employing robust statistics to consider the sample importance for reducing the outlier influence, i.e. assigning every sample with soft weights so that the important samples are with large weights and outliers are with small or even zero weights; (ii) learning the common representation across all views to improve the quality of the graph for every view; and (iii) learning the complementary information from all initial graphs on multi-view data to further improve the learning of the graph for every view. As a result, each of the strategies could improve the robustness of the DGCN model. Moreover, they are complementary for reducing outlier influence from different aspects, i.e. the sample importance reduces the weights of the outliers, both the common representation and the complementary information improve the quality of the graph for every view. Experimental result on real data sets demonstrates the effectiveness of our method, compared to the comparison methods, in terms of multi-class classification performance.

Beschreibung: Motivation Genomic DNA replicates according to a reproducible spatiotemporal program, with some loci replicating early in S phase while others replicate late. Despite being a central cellular process, DNA replication timing studies have been limited in scale due to technical challenges. Results We present TIGER (Timing Inferred from Genome Replication), a computational approach for extracting DNA replication timing information from whole genome sequence data obtained from proliferating cell samples. The presence of replicating cells in a biological specimen leads to non-uniform representation of genomic DNA that depends on the timing of replication of different genomic loci. Replication dynamics can hence be observed in genome sequence data by analyzing DNA copy number along chromosomes while accounting for other sources of sequence coverage variation. TIGER is applicable to any species with a contiguous genome assembly and rivals the quality of experimental measurements of DNA replication timing. It provides a straightforward approach for measuring replication timing and can readily be applied at scale. Availability and implementation TIGER is available at https://github.com/TheKorenLab/TIGER. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Spectral clustering is widely applied in real applications, as it utilizes a graph matrix to consider the similarity relationship of subjects. The quality of graph structure is usually important to the robustness of the clustering task. However, existing spectral clustering methods consider either the local structure or the global structure, which can not provide comprehensive information for clustering tasks. Moreover, previous clustering methods only consider the simple similarity relationship, which may not output the optimal clustering performance. To solve these problems, we propose a novel clustering method considering both the local structure and the global structure for conducting nonlinear clustering. Specifically, our proposed method simultaneously considers (i) preserving the local structure and the global structure of subjects to provide comprehensive information for clustering tasks, (ii) exploring the nonlinear similarity relationship to capture the complex and inherent correlation of subjects and (iii) embedding dimensionality reduction techniques and a low-rank constraint in the framework of adaptive graph learning to reduce clustering biases. These constraints are considered in a unified optimization framework to result in one-step clustering. Experimental results on real data sets demonstrate that our method achieved competitive clustering performance in comparison with state-of-the-art clustering methods.

Beschreibung: Laplacian support vector machine (LapSVM) is an extremely popular classification method and relies on a small number of labels and a Laplacian regularization to complete the training of the support vector machine (SVM). However, the training of SVM model and Laplacian matrix construction are usually two independent process. Therefore, In this paper, we propose a new adaptive LapSVM method to realize semi-supervised learning with a primal solution. Specifically, the hinge loss of unlabelled data is considered to maximize the distance between unlabelled samples from different classes and the process of dealing with labelled data are similar to other LapSVM methods. Besides, the proposed method embeds the Laplacian matrix acquisition into the SVM training process to improve the effectiveness of Laplacian matrix and the accuracy of new SVM model. Moreover, a novel optimization algorithm considering primal solver is proposed to our adaptive LapSVM model. Experimental results showed that our method outperformed all comparison methods in terms of different evaluation metrics on both real datasets and synthetic datasets.

Beschreibung: Recently, significant breakthroughs have been achieved in the field of object detection. However, existing methods mostly focus on the generic object detection task. Performance degradation can be unavoidable when applying the existing methods to some specific situations directly, e.g. a low-light environment. To address this issue, we propose a single-shot real-time object Detector based on Low-light image Enhancement, namely LEDet. LEDet adapts itself to the low-light detection task in three aspects. First, a low-light enhancement module is introduced as the image preprocessor, producing the augmented inputs from the low-light images. Second, two modules, i.e. low-light and enhanced features fusion module and the scale-aware channel attention dilated convolution module are designed. These two modules aim at learning robust and discriminative features from objects of various sizes hidden in the darkness. In experiments, we validate the effectiveness of each part of our LEDet model via several ablation studies. We also compare LEDet with various methods on the Exclusively Dark dataset, showing that our model achieves the state-of-the-art performance on the balance between speed and accuracy.

Beschreibung: Privacy protection is one of the key concerns of users in recommender system-based consumer markets. Popular recommendation frameworks such as collaborative filtering (CF) suffer from several privacy issues. Federated learning has emerged as an optimistic approach for collaborative and privacy-preserved learning. Users in a federated learning environment train a local model on a self-maintained item log and collaboratively train a global model by exchanging model parameters instead of personalized preferences. In this research, we proposed a federated learning-based privacy-preserving CF model for context-aware recommender systems that work with a user-defined collaboration protocol to ensure users’ privacy. Instead of crawling users’ personal information into a central server, the whole data are divided into two disjoint parts, i.e. user data and sharable item information. The inbuilt power of federated architecture ensures the users’ privacy concerns while providing considerably accurate recommendations. We evaluated the performance of the proposed algorithm with two publicly available datasets through both the prediction and ranking perspectives. Despite the federated cost and lack of open collaboration, the overall performance achieved through the proposed technique is comparable with popular recommendation models and satisfactory while providing significant privacy guarantees.

Beschreibung: Since the first report of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, over 100 million people have been infected by COVID-19, millions of whom have died. In the latest year, a large number of omics data have sprung up and helped researchers broadly study the sequence, chemical structure and function of SARS-CoV-2, as well as molecular abnormal mechanisms of COVID-19 patients. Though some successes have been achieved in these areas, it is necessary to analyze and mine omics data for comprehensively understanding SARS-CoV-2 and COVID-19. Hence, we reviewed the current advantages and limitations of the integration of omics data herein. Firstly, we sorted out the sequence resources and database resources of SARS-CoV-2, including protein chemical structure, potential drug information and research literature resources. Next, we collected omics data of the COVID-19 hosts, including genomics, transcriptomics, microbiology and potential drug information data. And subsequently, based on the integration of omics data, we summarized the existing data analysis methods and the related research results of COVID-19 multi-omics data in recent years. Finally, we put forward SARS-CoV-2 (COVID-19) multi-omics data integration research direction and gave a case study to mine deeper for the disease mechanisms of COVID-19.

Beschreibung: Summary Eukaryotic gene expression requires coordination among hundreds of transcriptional regulators. To characterize a specific transcriptional regulator, identifying how it shares genomic-binding profiles with others can generate important insights into its action. As genomic data such as ChIP-Seq are being rapidly generated from individual labs, there is a demand for timely integration and analysis of these new data. We have developed an R package, GPSmatch (Genomic-binding Profile Similarity match), for calculating the Jaccard index to compare ChIP-Seq peaks from one experiment to the peaks of other ChIP-Seq experiments stored in a user-supplied customizable database. GPSmatch also evaluates the statistical significance of the calculated Jaccard index using a nonparametric Monte Carlo procedure. We show that GPSmatch is suitable for identifying transcriptional regulators that share similar genomic-binding profiles, which may unravel potential mechanistic actions of gene regulation. Availability The software is freely available at https://github.com/Bao-Lab/GPSmatch.

Beschreibung: Summary Whole genome assembly (WGA) of bacterial genomes with short reads is a quite common task as DNA sequencing has become cheaper with the advances of its technology. The process of assembling a genome has no absolute golden standard and it requires to perform a sequence of steps each of which can involve combinations of many different tools. However, the quality of the final assembly is always strongly related to the quality of the input data. With this in mind we built WGA-LP, a package that connects state-of-the-art programs for microbial analysis and novel scripts to check and improve the quality of both samples and resulting assemblies. WGA-LP, with its conservative decontamination approach, has shown to be capable of creating high quality assemblies even in the case of contaminated reads. Availability and implementation WGA-LP is available on GitHub (https://github.com/redsnic/WGA-LP) and Docker Hub (https://hub.docker.com/r/redsnic/wgalp). The web app for node visualization is hosted by shinyapps.io (https://redsnic.shinyapps.io/ContigCoverageVisualizer/). Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation Reverse engineering of gene regulatory networks (GRNs) has long been an attractive research topic in system biology. Computational prediction of gene regulatory interactions has remained a challenging problem due to the complexity of gene expression and scarce information resources. The high-throughput spatial gene expression data, like in situ hybridization images that exhibit temporal and spatial expression patterns, has provided abundant and reliable information for the inference of GRNs. However, computational tools for analyzing the spatial gene expression data are highly underdeveloped. Results In this study, we develop a new method for identifying gene regulatory interactions from gene expression images, called ConGRI. The method is featured by a contrastive learning scheme and deep Siamese convolutional neural network architecture, which automatically learns high-level feature embeddings for the expression images and then feeds the embeddings to an artificial neural network to determine whether or not the interaction exists. We apply the method to a Drosophila embryogenesis dataset and identify GRNs of eye development and mesoderm development. Experimental results show that ConGRI outperforms previous traditional and deep learning methods by a large margin, which achieves accuracies of 76.7% and 68.7% for the GRNs of early eye development and mesoderm development, respectively. It also reveals some master regulators for Drosophila eye development. Availabilityand implementation https://github.com/lugimzheng/ConGRI. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Summary Non-coding RNAs are often neglected during genome annotation due to their difficulty of detection relative to protein coding genes. FindNonCoding takes a pattern mining approach to capture the essential sequence motifs and hairpin loops representing a non-coding RNA family and quickly identify matches in genomes. FindNonCoding was designed for ease of use and accurately finds non-coding RNAs with a low false discovery rate. Availability and implementation FindNonCoding is implemented within the DECIPHER package (v2.19.3) for R (v4.1) available from Bioconductor. Pre-trained models of common non-coding RNA families are included for bacteria, archaea and eukarya. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: This paper plans to develop the optimal brain tumor classification model with diverse intelligent methods. The main phases of the proposed model are ‘(a) image pre-processing, (b) skull stripping, (c) tumor segmentation, (d) feature extraction and (e) classification’. At first, pre-processing of the image is performed by converting the image from red green blue to gray followed by median filtering. Further, skull stripping is done for removing the extra-meningeal tissue from the head image, which is done by Otsu thresholding. As the main contribution, the tumor segmentation is done by the optimized threshold-based tumor segmentation using multi-objective randomly updated beetle swarm and multi-verse optimization (RBS-MVO). The objective constraints considered for the segmentation of the tumor is entropy and variance. Next, the feature extraction techniques like gray level co-occurrence matrix, local binary pattern and gray-level run length matrix is accomplished to extract the set of features. The classification side uses the combination of neural network (NN) and deep learning model called convolutional neural network (CNN) for tumor classification. The extracted features are subjected to NN, and the segmented image is taken as input to CNN. In addition, the weight function of NN and hidden neurons of CNN is optimized by the RBS-MVO.

Beschreibung: The side effects of drugs present growing concern attention in the healthcare system. Accurately identifying the side effects of drugs is very important for drug development and risk assessment. Some computational models have been developed to predict the potential side effects of drugs and provided satisfactory performance. However, most existing methods can only predict whether side effects will occur and cannot determine the frequency of side effects. Although a few existing methods can predict the frequency of drug side effects, they strongly depend on the known drug-side effect relationships. Therefore, they cannot be applied to new drugs without known side effect frequency information. In this paper, we develop a novel similarity-based deep learning method, named SDPred, for determining the frequencies of drug side effects. Compared with the existing state-of-the-art models, SDPred integrates rich features and can be applied to predict the side effect frequencies of new drugs without any known drug-side effect association or frequency information. To our knowledge, this is the first work that can predict the side effect frequencies of new drugs in the population. The comparison results indicate that SDPred is much superior to all previously reported models. In addition, some case studies also demonstrate the effectiveness of our proposed method in practical applications. The SDPred software and data are freely available at https://github.com/zhc940702/SDPred, https://zenodo.org/record/5112573 and https://hub.docker.com/r/zhc940702/sdpred.

Beschreibung: Electroless plating in microfluidic channels is a novel technology at the micrometer scale. As the microchannel depth varies with the flow of the chemicals, care must be taken for the channel not to run dry. Owing to the deposited chemical species the physical domain of the flow changes with time, leading to a free boundary problem. As the motion of the free boundary is small it is modelled by a transpiration approximation. With this simplification, the mathematical model consists of a Navier–Stokes flow and an equation for the concentration of the plating chemical coupled by nonstandard and nonlinear boundary conditions. Existence and uniqueness are proved for the concentration equation, assuming that the flow is given. Numerical analysis is carried out and justifies the proposed numerical schemes and the nonlinear algorithms. The numerical study is performed, in the two-dimensional case, with the finite element method and an implicit Euler time scheme for the coupled problem with the Navier–Stokes flow and the nonlinear concentration equation.

Beschreibung: This paper is concerned with the numerical solution of the Maxwell–Schrödinger system under the temporal gauge, which describes light–matter interactions. We first propose a semidiscrete finite element scheme for the system and establish stability estimates for the finite element solution. Due to the lack of control over its divergence we cannot get $extbf{H}^{1}$  $a ;priori$ estimates for the vector potential, making it difficult to obtain error estimates by usual techniques. We apply an exhaustion argument to overcome this difficulty and derive error estimates for the finite element approximation. An energy-conserving time-stepping scheme is proposed to solve the semidiscrete system.

Beschreibung: Summary We present the LipidQuant 1.0 tool for automated data processing workflows in lipidomic quantitation based on lipid class separation coupled with high-resolution mass spectrometry. Lipid class separation workflows, such as hydrophilic interaction liquid chromatography or supercritical fluid chromatography, should be preferred in lipidomic quantitation due to the coionization of lipid class internal standards with analytes from the same class. The individual steps in the LipidQuant workflow are explained, including lipid identification, quantitation, isotopic correction and reporting results. We show the application of LipidQuant data processing to a small cohort of human serum samples. Availability and implementation The LipidQuant 1.0 is freely available at Zenodo https://doi.org/10.5281/zenodo.5151201 and https://holcapek.upce.cz/lipidquant.php. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation Immune cells are important components of the immune system and are crucial for disease initiation, progression, prognosis, and survival. Although several computational methods have been designed for predicting the abundance of immune cells, very few tools are applicable to mouse. Given that mouse is the most widely used animal model in biomedical research, there is an urgent need to develop a precise algorithm for predicting mouse immune cells. Results We developed a tool named ImmuCellAI-mouse (Immune Cell Abundance Identifier for mouse), for estimating the abundance of 36 immune cell (sub)types from gene expression data in a hierarchical strategy of three layers. Reference expression profile and robust marker gene sets of immune cell types were curated. The abundance of cells in three layers was predicted separately by calculating the ssGSEA enrichment score of the expression deviation profile per cell type. Benchmark results showed high accuracy of ImmuCellAI-mouse in predicting most immune cell types, with correlation coefficients between predicted value and real cell proportion of most cell types being larger than 0.8. We applied ImmuCellAI-mouse to a mouse breast tumor dataset and revealed the dynamic change of immune cell infiltration during treatment, which is consistent with the findings of the original study but with more details. We also constructed an online server for ImmuCellAI-mouse, on which users can upload expression matrices for analysis. ImmuCellAI-mouse will be a useful tool for studying the immune microenvironment, cancer immunology, and immunotherapy in mouse models, providing an indispensable supplement for human disease studies. Availability Software is available at http://bioinfo.life.hust.edu.cn/ImmuCellAI-mouse/ Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: We evidence English teacher and student perspectives on the learning of pre-university mathematics ‘A Level’ courses through the pandemic period to July 2021. Data are drawn from a 2017–21 classroom-close study of enactment of such courses in 13 fairly representative centres, using an institutional ethnographic approach. The pandemic picture was generally one of the significant and sustained negative impacts, though over the course of the study, respondents reported progress in addressing early limitations in the harnessing of digital platforms for learning. A small number of participating students reported home-based study beneficial for their mathematics learning, and a bigger group identified some wider benefits that partly offset the challenges. Most participating 16–18-year-old students, though, reported finding remote learning of mathematics both demanding and limiting. Pandemic constraints impacted most strongly on opportunities to engage with newer emphases within A Level courses: problem solving, reasoning, modelling, statistics and mechanics. Receiving academics reported that mathematical preparedness, and confidence, for mathematics-intense university courses has also been widely affected, with a bigger range of preparedness and confidence than usual. The study draws attention to the importance of studying subject-specific impact and drawing on student as well as teacher perceptions. It exposes a range of consequences of the cancellation of examinations and a need to develop and share effective pedagogies for working remotely with pre-university students.

Beschreibung: Motivation Deciphering nucleosome–nucleosome interactions is an important step toward mesoscale description of chromatin organization but computational tools to perform such analyses are not publicly available. Results We developed iNucs, a user-friendly and efficient Python-based bioinformatics tool to compute and visualize nucleosome-resolved interactions using standard pairs format input generated from pairtools. Availabilityand implementation https://github.com/Karimi-Lab/inucs/. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Mobile edge computing (MEC) is a key feature of next-generation heterogeneous networks aimed at providing a variety of services for different applications by performing related processing tasks closer to the user equipment. In this research, we investigated on connection management approaches in multi-access edge computing systems. This paper presents joint radio resource allocation and MEC optimization in a multi-layer NOMA HetNet in order to maximize system’s energy efficiency. The continues carrier allocation and handoff decision variables, in addition to the interference incorporated in the goal function, modifies the primary optimization problem to a mixed integer nonlinear programming. Network selection is done statically based on the Analytic Hierarchy Process, and station selection is done dynamically based on the Data Envelope Analysis method. Also, an effective feedback mechanism has been designed in collaboration with the server resource manager to solve a global optimization problem in order to load balancing and meet the users quality of service constraints simultaneously. To reduce the computational complexity and to achieve a locally optimal solution, we applied variable relaxation and majorization minimization approach in which offloading decision and multi-part Markov noise analysis have been developed to model users’ preferences without the need for explicit information from the users. Based on the simulations, the proposed approach not only results in a significant increase of system’s energy efficiency but also enhances the system throughput in multiple-source scenarios.

Beschreibung: Summary Recent efforts to identify novel bacterial structured noncoding RNA (ncRNA) motifs through searching long, GC-rich intergenic regions (IGRs) have revealed several new classes, including the recently validated HMP-PP riboswitch. The DIMPL (Discovery of Intergenic Motifs PipeLine) discovery pipeline described herein enables rapid extraction and selection of bacterial IGRs that are enriched for structured ncRNAs. Moreover, DIMPL automates the subsequent computational steps necessary for their functional identification. Availability and implementation The DIMPL pipeline is freely available as a Docker image with an accompanying set of Jupyter notebooks. Full instructions for download and use are available at https://github.com/breakerlab/dimpl. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: We prove quartic convergence of cubic spline interpolation for curves into Riemannian manifolds as the grid size of the interpolation grid tends to zero. In contrast to cubic spline interpolation in Euclidean space, where this result is classical, the interpolation operator is no longer linear. Still, concepts from the linear setting may be generalized to the Riemannian case, where we try to use intrinsic Riemannian formulations and avoid charts as much as possible.

Beschreibung: Motivation Genetic variations of expression quantitative trait loci (eQTLs) play a critical role in influencing complex traits and diseases development. Two main factors that affect the statistical power of detecting eQTLs are: (i) relatively small size of samples available, and (ii) heavy burden of multiple testing due to a very large number of variants to be tested. The later issue is particularly severe when one tries to identify trans-eQTLs that are far away from the genes they influence. If one can exploit co-expressed genes jointly in eQTL-mapping, effective sample size can be increased. Furthermore, using the structure of the gene regulatory network (GRN) may help to identify trans-eQTLs without increasing multiple testing burden. Results In this article, we use the structure equation model (SEM) to model both GRN and effect of eQTLs on gene expression, and then develop a novel algorithm, named sparse SEM for eQTL mapping (SSEMQ), to conduct joint eQTL mapping and GRN inference. The SEM can exploit co-expressed genes jointly in eQTL mapping and also use GRN to determine trans-eQTLs. Computer simulations demonstrate that our SSEMQ significantly outperforms nine existing eQTL mapping methods. SSEMQ is further used to analyze two real datasets of human breast and whole blood tissues, yielding a number of cis- and trans-eQTLs. Availability and implementation R package ssemQr is available at https://github.com/Ivis4ml/ssemQr.git. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation Alignment-free (AF) distance/similarity functions are a key tool for sequence analysis. Experimental studies on real datasets abound and, to some extent, there are also studies regarding their control of false positive rate (Type I error). However, assessment of their power, i.e., their ability to identify true similarity, has been limited to some members of the D2 family. The corresponding experimental studies have concentrated on short sequences, a scenario no longer adequate for current applications, where sequence lengths may vary considerably. Such a State of the Art is methodologically problematic, since information regarding a key feature such as power is either missing or limited. Results By concentrating on a representative set of word-frequency based AF functions, we perform the first coherent and uniform evaluation of the power, involving also Type I error for completeness. Two Alternative models of important genomic features (CIS Regulatory Modules and Horizontal Gene Transfer), a wide range of sequence lengths from a few thousand to millions, and different values of k have been used. As a result, we provide a characterization of those AF functions that is novel and informative. Indeed, we identify weak and strong points of each function considered, which may be used as a guide to choose one for analysis tasks. Remarkably, of the fifteen functions that we have considered, only four stand out, with small differences between small and short sequence length scenarios. Finally, in order to encourage the use of our methodology for validation of future AF functions, the Big Data platform supporting it is public. Availability The software is available at: https://github.com/pipp8/power_statistics Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation Inference of Identity-by-descent (IBD) sharing along the genome between pairs of individuals has important uses. But all existing inference methods are based on genotypes, which is not ideal for low-depth Next Generation Sequencing (NGS) data from which genotypes can only be called with high uncertainty. Results We present a new probabilistic software tool, LocalNgsRelate, for inferring IBD sharing along the genome between pairs of individuals from low-depth NGS data. Its inference is based on genotype likelihoods instead of genotypes, and thereby it takes the uncertainty of the genotype calling into account. Using real data from the 1000 Genomes project, we show that LocalNgsRelate provides more accurate IBD inference for low-depth NGS data than two state-of-the-art genotype based methods, Albrechtsen et al. (2009) and hap-IBD. We also show that the method works well for NGS data down to a depth of 2X. Availability LocalNgsRelate is freely available at https://github.com/idamoltke/LocalNgsRelate Supplementary Data Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation DNA Methylation plays a key role in a variety of biological processes. Recently, Nanopore long-read sequencing has enabled direct detection of these modifications. As a consequence, a range of computational methods have been developed to exploit Nanopore data for methylation detection. However, current approaches rely on a human-defined threshold to detect the methylation status of a genomic position and are not optimized to detect sites methylated at low frequency. Furthermore, most methods employ either the Nanopore signals or the basecalling errors as the model input and do not take advantage of their combination. Results Here we present DeepMP, a convolutional neural network (CNN)-based model that takes information from Nanopore signals and basecalling errors to detect whether a given motif in a read is methylated or not. Besides, DeepMP introduces a threshold-free position modification calling model sensitive to sites methylated at low frequency across cells. We comprehensively benchmarked DeepMP against state-of-the-art methods on E. coli, human and pUC19 datasets. DeepMP outperforms current approaches at read-based and position-based methylation detection across sites methylated at different frequencies in the three datasets. Availability DeepMP is implemented and freely available under MIT license at https://github.com/pepebonet/DeepMP Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation Coiled-coil is composed of two or more helices that are wound around each other. It widely exists in proteins and has been discovered to play a variety of critical roles in biology processes. Generally, there are three types of structural features in coiled-coil: coiled-coil domain (CCD), oligomeric state, and register. However, most of the existing computational tools only focus on one of them. Results Here, we describe a new deep learning model, CoCoPRED, which is based on convolutional layers, bidirectional long short-term memory, and attention mechanism. It has three networks, i.e., CCD network, oligomeric state network, and register network, corresponding to the three types of structural features in coiled-coil. This means CoCoPRED has the ability of fulfilling comprehensive prediction for coiled-coil proteins. Through the 5-fold cross-validation experiment, we demonstrate that CoCoPRED can achieve better performance than the state-of-the-art models on both CCD prediction and oligomeric state prediction. Further analysis suggests the CCD prediction may be a performance indicator of the oligomeric state prediction in CoCoPRED. The attention heads in CoCoPRED indicate that registers a, b, and e are more crucial for the oligomeric state prediction. Availability CoCoPRED is available at http://www.csbio.sjtu.edu.cn/bioinf/CoCoPRED. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation Adverse Outcome Pathways (AOPs) are a conceptual framework developed to support the use of alternative toxicology approaches in the risk assessment. AOPs are structured linear organizations of existing knowledge illustrating causal pathways from the initial molecular perturbation triggered by various stressors, through key events (KEs) at different levels of biology, to the ultimate health or ecotoxicological adverse outcome. Results Artificial intelligence can be used to systematically explore available toxicological data that can be parsed in the scientific literature. Recently a tool called AOP-helpFinder was developed to identify associations between stressors and KEs supporting thus documentation of AOPs. To facilitate the utilization of this advanced bioinformatics tool by the scientific and the regulatory community, a webserver was created. The proposed AOP-helpFinder webserver uses better performing version of the tool which reduces the need for manual curation of the obtained results. As an example, the server was successfully applied to explore relationships of a set of endocrine disruptors with metabolic-related events. The AOP-helpFinder webserver assists in a rapid evaluation of existing knowledge stored in the PubMed database, a global resource of scientific information, to build AOPs and Adverse Outcome Networks (AONs) supporting the chemical risk assessment. Availability and implementation AOP-helpFinder is available at http://aop-helpfinder.u-paris-sciences.fr/index.php

Beschreibung: Motivation Differential network inference is a fundamental and challenging problem to reveal gene interactions and regulation relationships under different conditions. Many algorithms have been developed for this problem; however, they do not consider the differences between the importance of genes, which may not fit the real-world situation. Different genes have different mutation probabilities, and the vital genes associated with basic life activities have less fault tolerance to mutation. Equally treating all genes may bias the results of differential network inference. Thus, it is necessary to consider the importance of genes in the models of differential network inference. Results Based on the Gaussian graphical model with adaptive gene importance regularization, we develop a novel importance-penalized joint graphical Lasso method, IPJGL, for differential network inference. The presented method is validated by the simulation experiments as well as the real datasets. Furthermore, to precisely evaluate the results of differential network inference, we propose a new metric named APC2 for the differential levels of gene pairs. We apply IPJGL to analyze the TCGA colorectal and breast cancer datasets and find some candidate cancer genes with significant survival analysis results, including SOST for colorectal cancer and RBBP8 for breast cancer. We also conduct further analysis based on the interactions in the Reactome database and confirm the utility of our method. Availability R source code of importance-penalized joint graphical lasso is freely available at https://github.com/Wu-Lab/IPJGL. Supplementary information Supplementary materials are available at Bioinformatics online.

Beschreibung: Motivation Identifying proteins that interact with drugs plays an important role in the initial period of developing drugs, which helps to reduce the development cost and time. Recent methods for predicting drug–protein interactions mainly focus on exploiting various data about drugs and proteins. These methods failed to completely learn and integrate the attribute information of a pair of drug and protein nodes and their attribute distribution. Results We present a new prediction method, GVDTI, to encode multiple pairwise representations, including attention-enhanced topological representation, attribute representation and attribute distribution. First, a framework based on graph convolutional autoencoder is constructed to learn attention-enhanced topological embedding that integrates the topology structure of a drug–protein network for each drug and protein nodes. The topological embeddings of each drug and each protein are then combined and fused by multi-layer convolution neural networks to obtain the pairwise topological representation, which reveals the hidden topological relationships between drug and protein nodes. The proposed attribute-wise attention mechanism learns and adjusts the importance of individual attribute in each topological embedding of drug and protein nodes. Secondly, a tri-layer heterogeneous network composed of drug, protein and disease nodes is created to associate the similarities, interactions and associations across the heterogeneous nodes. The attribute distribution of the drug–protein node pair is encoded by a variational autoencoder. The pairwise attribute representation is learned via a multi-layer convolutional neural network to deeply integrate the attributes of drug and protein nodes. Finally, the three pairwise representations are fused by convolutional and fully connected neural networks for drug–protein interaction prediction. The experimental results show that GVDTI outperformed other seven state-of-the-art methods in comparison. The improved recall rates indicate that GVDTI retrieved more actual drug–protein interactions in the top ranked candidates than conventional methods. Case studies on five drugs further confirm GVDTI’s ability in discovering the potential candidate drug-related proteins. Contact zhang@hlju.edu.cn  Supplementary information: Supplementary data are available at Briefings in Bioinformatics online.

Beschreibung: Summary We present several recent improvements to minimap2, a versatile pairwise aligner for nucleotide sequences. Now minimap2 v2.22 can more accurately map long reads to highly repetitive regions and align through insertions or deletions up to 100 kb by default, addressing major weakness in minimap2 v2.18 or earlier. Availability and implementation https://github.com/lh3/minimap2.

Beschreibung: Motivation Over the past decades, vast amounts of genome sequencing data have been produced, requiring an enormous level of storage capacity. The time and resources needed to store and transfer such data cause bottlenecks in genome sequencing analysis. To resolve this issue, various compression techniques have been proposed to reduce the size of original FASTQ raw sequencing data, but these remain suboptimal. Long-read sequencing has become dominant in genomics, whereas most existing compression methods focus on short-read sequencing only. Results We designed a compression algorithm based on read reordering using a novel scoring model for reducing FASTQ file size with no information loss. We integrated all data processing steps into a software package called FastqCLS and provided it as a Docker image for ease of installation and execution to help users easily install and run. We compared our method with existing major FASTQ compression tools using benchmark datasets. We also included new long-read sequencing data in this validation. As a result, FastqCLS outperformed in terms of compression ratios for storing long-read sequencing data. Availability and implementation FastqCLS can be downloaded from https://github.com/krlucete/FastqCLS. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Summary Studying biological systems generally relies on computational modeling and simulation, e.g., model-driven discovery and hypothesis testing. Progress in standardization efforts led to the development of interrelated file formats to exchange and reuse models in systems biology, such as SBML, the Simulation Experiment Description Markup Language (SED-ML) or the Open Modeling EXchange format. Conducting simulation experiments based on these formats requires efficient and reusable implementations to make them accessible to the broader scientific community and to ensure the reproducibility of the results. The Systems Biology Simulation Core Library (SBSCL) provides interpreters and solvers for these standards as a versatile open-source API in JavaTM. The library simulates even complex bio-models and supports deterministic Ordinary Differential Equations; Stochastic Differential Equations; constraint-based analyses; recent SBML and SED-ML versions; exchange of results, and visualization of in silico experiments; open modeling exchange formats (COMBINE archives); hierarchically structured models; and compatibility with standard testing systems, including the Systems Biology Test Suite and published models from the BioModels and BiGG databases. Availability and implementation SBSCL is freely available at https://draeger-lab.github.io/SBSCL/ and via Maven Central. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: The amount of data generated is increasing day by day due to the development in remote sensors, and thus it needs concern to increase the accuracy in the classification of the big data. Many classification methods are in practice; however, they limit due to many reasons like its nature for data loss, time complexity, efficiency and accuracy. This paper proposes an effective and optimal data classification approach using the proposed Ant Cat Swarm Optimization-enabled Deep Recurrent Neural Network (ACSO-enabled Deep RNN) by Map Reduce framework, which is the incorporation of Ant Lion Optimization approach and the Cat Swarm Optimization technique. To process feature selection and big data classification, Map Reduce framework is used. The feature selection is performed using Pearson correlation-based Black hole entropy fuzzy clustering. The classification in reducer part is performed using Deep RNN that is trained using a developed ACSO scheme. It classifies the big data based on the reduced dimension features to produce a satisfactory result. The proposed ACSO-based Deep RNN showed improved results with maximal specificity of 0.884, highest accuracy of 0.893, maximal sensitivity of 0.900 and the maximum threat score of 0.827 based on the Cleveland dataset.

Beschreibung: Nowadays, Apache Hadoop and Apache Spark are two of the most prominent distributed solutions for processing big data applications on the market. Since in many cases these frameworks are adopted to support business critical activities, it is often important to predict with fair confidence the execution time of submitted applications, for instance when service-level agreements are established with end-users. In this work, we propose and validate a hybrid approach for the performance prediction of big data applications running on clouds, which exploits both analytical modeling and machine learning (ML) techniques and it is able to achieve a good accuracy without too many time consuming and costly experiments on a real setup. The experimental results show how the proposed approach attains improvement in accuracy, number of experiments to be run on the operational system and cost over applying ML techniques without any support from analytical models. Moreover, we compare our approach with Ernest, an ML-based technique proposed in the literature by the Spark inventors. Experiments show that Ernest can accurately estimate the performance in interpolating scenarios while it fails to predict the performance when configurations with increasing number of cores are considered. Finally, a comparison with a similar hybrid approach proposed in the literature demonstrates how our approach significantly reduce prediction errors especially when few experiments on the real system are performed.

Beschreibung: Motivation The adoption of current single-cell DNA methylation sequencing protocols is hindered by incomplete coverage, outlining the need for effective imputation techniques. The task of imputing single-cell (methylation) data requires models to build an understanding of underlying biological processes. Results We adapt the transformer neural network architecture to operate on methylation matrices through combining axial attention with sliding window self-attention. The obtained CpG Transformer displays state-of-the-art performances on a wide range of scBS-seq and scRRBS-seq datasets. Furthermore, we demonstrate the interpretability of CpG Transformer and illustrate its rapid transfer learning properties, allowing practitioners to train models on new datasets with a limited computational and time budget. Availability and Implementation CpG Transformer is freely available at https://github.com/gdewael/cpg-transformer. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation With the advancement of sequencing technologies, genomic data sets are constantly being expanded by high volumes of different data types. One recently introduced data type in genomic science is genomic signals, which are usually short-read coverage measurements over the genome. To understand and evaluate the results of such studies, one needs to understand and analyze the characteristics of the input data. Results SigTools is an R-based genomic signals visualization package developed with two objectives: 1) to facilitate genomic signals exploration in order to uncover insights for later model training, refinement, and development by including distribution and autocorrelation plots. 2) to enable genomic signals interpretation by including correlation, and aggregation plots. In addition, our corresponding web application, SigTools-Shiny, extends the accessibility scope of these modules to people who are more comfortable working with graphical user interfaces instead of command-line tools. Availability SigTools source code, installation guide, and manual is freely available on http://github.com/shohre73.

Beschreibung: Motivation Discover is an algorithm developed to identify mutually exclusive genomic events. Its main contribution is a statistical analysis based on the Poisson-Binomial (PB) distribution to take into account the mutation rate of genes and samples. Discover is very effective for identifying mutually exclusive mutations at the expense of speed in large datasets: the Poisson-Binomial is computationally costly to estimate, and checking all the potential mutually exclusive alterations requires millions of tests. Results We have implemented a new version of the package called Rediscover that implements exact and approximate computations of the PB. Rediscover exact implementation is slightly faster than Discover for large and medium-sized datasets. The approximation is 100 to 1,000 times faster for them making it possible to get results in less than a minute with a standard desktop. The memory footprint is also smaller in Rediscover. The new package is available at CRAN and provides some functions to integrate its usage with other R packages such as maftools and TCGAbiolinks. Availability Rediscover is available at CRAN (https://cran.r-project.org/web/packages/Rediscover/index.html). Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation Deep learning approaches have empowered single-cell omics data analysis in many ways and generated new insights from complex cellular systems. As there is an increasing need for single cell omics data to be integrated across sources, types, and features of data, the challenges of integrating single-cell omics data are rising. Here, we present an unsupervised deep learning algorithm that learns discriminative representations for single-cell data via maximizing mutual information, SMILE (Single-cell Mutual Information Learning). Results Using a unique cell-pairing design, SMILE successfully integrates multi-source single-cell transcriptome data, removing batch effects and projecting similar cell types, even from different tissues, into the shared space. SMILE can also integrate data from two or more modalities, such as joint profiling technologies using single-cell ATAC-seq, RNA-seq, DNA methylation, Hi-C, and ChIP data. When paired cells are known, SMILE can integrate data with unmatched feature, such as genes for RNA-seq and genome wide peaks for ATAC-seq. Integrated representations learned from joint profiling technologies can then be used as a framework for comparing independent single source data. Supplementary information Supplementary data are available at Bioinformatics online. The source code of SMILE including analyses of key results in the study can be found at: https://github.com/rpmccordlab/SMILE.

Beschreibung: Summary Large scale pre-trained language models (PLMs) have advanced state-of-the-art (SOTA) performance on various biomedical text mining tasks. The power of such PLMs can be combined with the advantages of deep generative models. These are examples of these combinations. However, they are trained only on general domain text, and biomedical models are still missing. In this work, we describe BioVAE, the first large scale pre-trained latent variable language model for the biomedical domain, which uses the OPTIMUS framework to train on large volumes of biomedical text. The model shows SOTA performance on several biomedical text mining tasks when compared to existing publicly available biomedical PLMs. Additionally, our model can generate more accurate biomedical sentences than the original OPTIMUS output. Availability Our source code and pre-trained models are freely available: https://github.com/aistairc/BioVAE Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation As one of the most important post-translational modifications (PTMs), protein lysine crotonylation (Kcr) has attracted wide attention, which involves in important physiological activities, such as cell differentiation and metabolism. However, experimental methods are expensive and time-consuming for Kcr identification. Instead, computational methods can predict Kcr sites in silico with high efficiency and low cost. Results In this study, we proposed a novel predictor, BERT-Kcr, for protein Kcr sites prediction, which was developed by using a transfer learning method with pre-trained bidirectional encoder representations from transformers (BERT) models. These models were originally used for natural language processing (NLP) tasks, such as sentence classification. Here, we transferred each amino acid into a word as the input information to the pre-trained BERT model. The features encoded by BERT were extracted and then fed to a BiLSTM network to build our final model. Compared with the models built by other machine learning and deep learning classifiers, BERT-Kcr achieved the best performance with AUROC of 0.983 for 10-fold cross-validation. Further evaluation on the independent test set indicates that BERT-Kcr outperforms the state-of-the-art model Deep-Kcr with an improvement of about 5% for AUROC. The results of our experiment indicate that the direct use of sequence information and advanced pre-trained models of natural language processing could be an effective way for identifying post-translational modification sites of proteins. Availability The BERT-Kcr model is publicly available on http://zhulab.org.cn/BERT-Kcr_models/. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation Knowing the number and the exact locations of multiple change points in genomic sequences serves several biological needs. The cumulative segmented algorithm (cumSeg) has been recently proposed as a computationally efficient approach for multiple change-points detection, which is based on a simple transformation of data and provides results quite robust to model mis-specifications. However, the errors are also accumulated in the transformed model so that heteroscedasticity and serial correlation will show up, and thus the variations of the estimated change points will be quite different, while the locations of the change points should be of the same importance in the original genomic sequences. Results In this study, we develop two new change-points detection procedures in the framework of cumulative segmented regression. Simulations reveal that the proposed methods not only improve the efficiency of each change point estimator substantially but also provide the estimators with similar variations for all the change points. By applying these proposed algorithms to Coriel and SNP genotyping data, we illustrate their performance on detecting copy number variations. Supplementary information The proposed algorithms are implemented in R program and are available at Bioinformatics online.

Beschreibung: As our understanding of the microbiome has expanded, so has the recognition of its critical role in human health and disease, thereby emphasizing the importance of testing whether microbes are associated with environmental factors or clinical outcomes. However, many of the fundamental challenges that concern microbiome surveys arise from statistical and experimental design issues, such as the sparse and overdispersed nature of microbiome count data and the complex correlation structure among samples. For example, in the human microbiome project (HMP) dataset, the repeated observations across time points (level 1) are nested within body sites (level 2), which are further nested within subjects (level 3). Therefore, there is a great need for the development of specialized and sophisticated statistical tests. In this paper, we propose multilevel zero-inflated negative-binomial models for association analysis in microbiome surveys. We develop a variational approximation method for maximum likelihood estimation and inference. It uses optimization, rather than sampling, to approximate the log-likelihood and compute parameter estimates, provides a robust estimate of the covariance of parameter estimates and constructs a Wald-type test statistic for association testing. We evaluate and demonstrate the performance of our method using extensive simulation studies and an application to the HMP dataset. We have developed an R package MZINBVA to implement the proposed method, which is available from the GitHub repository https://github.com/liudoubletian/MZINBVA.

Beschreibung: The tremendous progress of single-cell sequencing technology has given researchers the opportunity to study cell development and differentiation processes at single-cell resolution. Assay of Transposase-Accessible Chromatin by deep sequencing (ATAC-seq) was proposed for genome-wide analysis of chromatin accessibility. Due to technical limitations or other reasons, dropout events are almost a common occurrence for extremely sparse single-cell ATAC-seq data, leading to confusion in downstream analysis (such as clustering). Although considerable progress has been made in the estimation of scRNA-seq data, there is currently no specific method for the inference of dropout events in single-cell ATAC-seq data. In this paper, we select several state-of-the-art scRNA-seq imputation methods (including MAGIC, SAVER, scImpute, deepImpute, PRIME, bayNorm and knn-smoothing) in recent years to infer dropout peaks in scATAC-seq data, and perform a systematic evaluation of these methods through several downstream analyses. Specifically, we benchmarked these methods in terms of correlation with meta-cell, clustering, subpopulations distance analysis, imputation performance for corruption datasets, identification of TF motifs and computation time. The experimental results indicated that most of the imputed peaks increased the correlation with the reference meta-cell, while the performance of different methods on different datasets varied greatly in different downstream analyses, thus should be used with caution. In general, MAGIC performed better than the other methods most consistently across all assessments. Our source code is freely available at https://github.com/yueyueliu/scATAC-master.

Beschreibung: Motivation Genome-wide association studies (GWAS) summary statistics have popularized and accelerated genetic research. However, a lack of standardization of the file formats used has proven problematic when running secondary analysis tools or performing meta-analysis studies. Results To address this issue, we have developed MungeSumstats, a Bioconductor R package for the standardization and quality control of GWAS summary statistics. MungeSumstats can handle the most common summary statistic formats, including variant call format (VCF) producing a reformatted, standardized, tabular summary statistic file, VCF or R native data object. Availability and implementation MungeSumstats is available on Bioconductor (v 3.13) and can also be found on Github at: https://neurogenomics.github.io/MungeSumstats. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: The 2019/20 Level 4 mathematics cohort at the Nottingham Trent University sat a full set of mid-year assessments in January 2020 under completely normal circumstances. However, the Covid-19 lockdown meant that their end of year assessments, along with all of their teaching and learning from March 2020 onwards, moved fully online. This has given us a unique opportunity to understand how the same cohort perform in contrasting situations. In this study we consider the issue of attainment gaps and find that the attainment gap closed in this cohort for black and minority ethnic students but that students from a lower socio-economic background may have been put at a disadvantage by the move to online teaching, learning and assessment. We use a linear mixed effect models approach to present statistical evidence to support these two claims as well as investigating the specific aspects of the move online, which may have caused these results.

Beschreibung: Target identification of small molecules is an important and still changeling work in the area of drug discovery, especially for botanical drug development. Indistinct understanding of the relationships of ligand–protein interactions is one of the main obstacles for drug repurposing and identification of off-targets. In this study, we collected 9063 crystal structures of ligand-binding proteins released from January, 1995 to April, 2021 in PDB bank, and split the complexes into 5133 interaction pairs of ligand atoms and protein fragments (covalently linked three heavy atoms) with interatomic distance ≤5 Å. The interaction pairs were grouped into ligand atoms with the same SYBYL atom type surrounding each type of protein fragment, which were further clustered via Bayesian Gaussian Mixture Model (BGMM). Gaussian distributions with ligand atoms ≥20 were identified as significant interaction patterns. Reliability of the significant interaction patterns was validated by comparing the difference of number of significant interaction patterns between the docked poses with higher and lower similarity to the native crystal structures. Fifty-one candidate targets of brucine, strychnine and icajine involved in Semen Strychni (Mǎ Qián Zǐ) and eight candidate targets of astragaloside-IV, formononetin and calycosin-7-glucoside involved in Astragalus (Huáng Qí) were predicted by the significant interaction patterns, in combination with docking, which were consistent with the therapeutic effects of Semen Strychni and Astragalus for cancer and chronic pain. The new strategy in this study improves the accuracy of target identification for small molecules, which will facilitate discovery of botanical drugs.

Beschreibung: This paper proposed a novel precise point set registration method based on feature fusion for three-dimensional data. Firstly, for the prominent foreground with dense and continuous cluster structure, we propose an automatic extraction method combining the principal component analysis projection and density-based clustering method. Secondly, for point sets containing noises, we introduce correntropy measurement into registration to weaken their influence. Thirdly, for the precise registration of uneven distribution of points in the same point set, we propose a feature fusion based algorithm which is distribution specific, using point-to-point measurement for densely distributed foreground and point-to-plane measurement for sparsely distributed background, in case that only one measurement method is used for the whole point set the registration gets trapped into local extremum. Finally, we give the optimization algorithm of the proposed method. We conduct experiments on real orthodontics scenes to verify the effectiveness of our proposed feature extraction method and registration algorithm, and experimental results demonstrate that both the proposed solutions are proper for their respective tasks than other existing methods.

Beschreibung: Point vortex systems that include vortices with constant coordinate functions are largely unexplored, even though they have reasonable physical interpretations in the geophysical context. Here, we investigate the dynamical aspects of the restricted three-vortex problem when one of the point vortices is assumed to be fixed at a location in the plane. The motion of the passive tracer is explored from a rotating frame of reference within which the free vortex with non-zero circulation remains stationary. By using basic dynamical system theory, it is shown that the vortex motion is always bounded, and any configuration of the three vortices must go through at least one collinear state. The present analysis reveals that any non-relative equilibrium solution of the vortex system either has periodic inter-vortex distances or it will asymptotically converge to a relative equilibrium configuration. The initial conditions required for different types of motion are explained in detail by exploiting the Hamiltonian structure of the problem. The underlying effects of a fixed vortex on the motion of vortices are also explored.

Beschreibung: Motivation Tumour heterogeneity is being increasingly recognized as an important characteristic of cancer and as a determinant of prognosis and treatment outcome. Emerging spatial transcriptomics data hold the potential to further our understanding of tumour heterogeneity and its implications. However, existing statistical tools are not sufficiently powerful to capture heterogeneity in the complex setting of spatial molecular biology. Results We provide a statistical solution, the HeTerogeneity Average index (HTA), specifically designed to handle the multivariate nature of spatial transcriptomics. We prove that HTA has an approximately normal distribution, therefore lending itself to efficient statistical assessment and inference. We first demonstrate that HTA accurately reflects the level of heterogeneity in simulated data. We then use HTA to analyze heterogeneity in two cancer spatial transcriptomics datasets: spatial RNA sequencing by 10x Genomics and spatial transcriptomics inferred from H&E. Finally, we demonstrate that HTA also applies to 3D spatial data using brain MRI. In spatial RNA sequencing, we use a known combination of molecular traits to assert that HTA aligns with the expected outcome for this combination. We also show that HTA captures immune-cell infiltration at multiple resolutions. In digital pathology, we show how HTA can be used in survival analysis and demonstrate that high levels of heterogeneity may be linked to poor survival. In brain MRI, we show that HTA differentiates between normal ageing, Alzheimer’s disease and two tumours. HTA also extends beyond molecular biology and medical imaging, and can be applied to many domains, including GIS. Availability and implementation Python package and source code are available at: https://github.com/alonalj/hta. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation Constraint-based modeling approaches allow the estimation of maximal in vivo enzyme catalytic rates that can serve as proxies for enzyme turnover numbers. Yet, genome-scale flux profiling remains a challenge in deploying these approaches to catalogue proxies for enzyme catalytic rates across organisms. Results Here, we formulate a constraint-based approach, termed NIDLE-flux, to estimate fluxes at a genome-scale level by using the principle of efficient usage of expressed enzymes. Using proteomics data from Escherichia coli, we show that the fluxes estimated by NIDLE-flux and the existing approaches are in excellent qualitative agreement (Pearson correlation 〉 0.9). We also find that the maximal in vivo catalytic rates estimated by NIDLE-flux exhibits a Pearson correlation of 0.74 with in vitro enzyme turnover numbers. However, NIDLE-flux results in a 1.4-fold increase in the size of the estimated maximal in vivo catalytic rates in comparison to the contenders. Integration of the maximum in vivo catalytic rates with publically available proteomics and metabolomics data provide a better match to fluxes estimated by NIDLE-flux. Therefore, NIDLE-flux facilitates more effective usage of proteomics data to estimate proxies for kcatomes. Availability and implementation https://github.com/Rudan-X/NIDLE-flux-code. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Clustering is a widely used technique in data mining applications and various pattern recognition applications, in which data objects are divided into groups. K-means algorithm is one of the most classical clustering algorithms. In this algorithm, the initial clustering centers are randomly selected, this results in unstable clustering results. To solve this problem, an optimized algorithm to select the initial centers is proposed. In the proposed algorithm, dispersion degree is defined, which is based on entropy. In the algorithm, all the objects are firstly grouped into a big cluster, and the object that has the maximum dispersion degree and the object that has the minimum dispersion degree are selected as the initial clustering centers from the initial big cluster. And then other objects in the biggest cluster are partitioned to the initial clusters to which the objects are nearest. The partition process will be repeated until the cluster number is equal to the specified value k. Finally, the partitioned k clusters and their cluster centers are applied to k-means algorithm as initial clusters and centers. Several experiments are conducted on real data sets to evaluate the proposed algorithm. The proposed algorithm is compared with traditional k-means algorithm and max-min distance clustering algorithm, and experimental results show that the improved k-means algorithm is stable in selecting initial clustering, because it can select unique initial clustering centers. The optimized algorithm’s effectiveness and feasibility are also verified by experiments, and the algorithm can reduce the times of iterations and has more stable clustering results and higher accuracy.

Beschreibung: Summary We describe improvements to BAli-Phy, a Markov chain Monte Carlo (MCMC) program that jointly estimates phylogeny, alignment and other parameters from unaligned sequence data. Version 3 is substantially faster for large trees, and implements covarion models, additional codon models and other new models. It implements ancestral state reconstruction, allows prior selection for all model parameters, and can also analyze multiple genes simultaneously. Availability and implementation Software is available for download at http://www.bali-phy.org. C++ source code is freely available on Github under the GPL2 License. Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: Motivation Even within well-studied organisms, many genes lack useful functional annotations. One way to generate such functional information is to infer biological relationships between genes/proteins, using a network of gene coexpression data that includes functional annotations. However, the lack of trustworthy functional annotations can impede the validation of such networks. Hence, there is a need for a principled method to construct gene coexpression networks that capture biological information and are structurally stable even in the absence of functional information. Results We introduce the concept of signed distance correlation as a measure of dependency between two variables, and apply it to generate gene coexpression networks. Distance correlation offers a more intuitive approach to network construction than commonly used methods, such as Pearson correlation and mutual information. We propose a framework to generate self-consistent networks using signed distance correlation purely from gene expression data, with no additional information. We analyse data from three different organisms to illustrate how networks generated with our method are more stable and capture more biological information compared to networks obtained from Pearson correlation or mutual information. Availability and implementation Code is available online (https://github.com/javier-pardodiaz/sdcorGCN). Supplementary information Supplementary data are available at Bioinformatics online.

Beschreibung: This paper considers the problem of semi-parametric proportional hazards model fitting where observed survival times contain event times and also interval, left and right censoring times. Although this is not a new topic, many existing methods suffer from poor computational performance. In this paper, we adopt a more versatile penalized likelihood method to estimate the baseline hazard and the regression coefficients simultaneously. The baseline hazard is approximated using basis functions such as M-splines. A penalty is introduced to regularize the baseline hazard estimate and also to ease dependence of the estimates on the knots of the basis functions. We propose a Newton–MI (multiplicative iterative) algorithm to fit this model. We also present novel asymptotic properties of our estimates, allowing for the possibility that some parameters of the approximate baseline hazard may lie on the parameter space boundary. Comparisons of our method against other similar approaches are made through an intensive simulation study. Results demonstrate that our method is very stable and encounters virtually no numerical issues. A real data application involving melanoma recurrence is presented and an R package ‘survivalMPL’ implementing the method is available on R CRAN.

Beschreibung: Motivation As genomic data becomes more abundant, efficient algorithms and data structures for sequence alignment become increasingly important. The suffix array is a widely used data structure to accelerate alignment, but the binary search algorithm used to query, it requires widespread memory accesses, causing a large number of cache misses on large datasets. Results Here, we present Sapling, an algorithm for sequence alignment, which uses a learned data model to augment the suffix array and enable faster queries. We investigate different types of data models, providing an analysis of different neural network models as well as providing an open-source aligner with a compact, practical piecewise linear model. We show that Sapling outperforms both an optimized binary search approach and multiple widely used read aligners on a diverse collection of genomes, including human, bacteria and plants, speeding up the algorithm by more than a factor of two while adding

Beschreibung: Whole exome sequencing (WES) is a powerful approach for discovering sequence variants in cancer cells but its time effectiveness is limited by the complexity and issues of WES data analysis. Here we present iWhale, a customizable pipeline based on Docker and SCons, reliably detecting somatic variants by three complementary callers (MuTect2, Strelka2 and VarScan2). The results are combined to obtain a single variant call format file for each sample and variants are annotated by integrating a wide range of information extracted from several reference databases, ultimately allowing variant and gene prioritization according to different criteria. iWhale allows users to conduct a complex series of WES analyses with a powerful yet customizable and easy-to-use tool, running on most operating systems (macOs, GNU/Linux and Windows). iWhale code is freely available at https://github.com/alexcoppe/iWhale and the docker image is downloadable from https://hub.docker.com/r/alexcoppe/iwhale.