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Background The stability of protein sequence structure plays an important role in the prevention and treatment of diseases. Results In this paper, particle swarm optimization and tabu search are combined to propose a new method for protein structure prediction. The experimental results show that: for four groups of artificial protein sequences with different lengths, this method obtains the lowest potential energy value and stable structure prediction results, and the effect is obviously better than the other two comparison methods. Taking the first group of protein sequences as an example, our method improves the prediction of minimum potential energy by 127% and 7% respectively. Conclusions Therefore, the method proposed in this paper is more suitable for the prediction of protein structural stability.

BackgroundOver the past few decades, the emergence and maturation of new technologies have substantially reduced the cost of genome sequencing. As a result, the amount of genomic data that needs to be stored and transmitted has grown exponentially. For the standard sequencing data format, FASTQ, compression of the quality score is a key and difficult aspect of FASTQ file compression. Throughout the literature, we found that the majority of the current quality score compression methods do not support random access. Based on the above consideration, it is reasonable to investigate a lossless quality score compressor with a high compression rate, a fast compression and decompression speed, and support for random access.ResultsIn this paper, we propose CMIC, an adaptive and random access supported compressor for lossless compression of quality score sequences. CMIC is an acronym of the four steps (classification, mapping, indexing and compression) in the paper. Its framework consists of the following four parts: classification, mapping, indexing, and compression. The experimental results show that our compressor has good performance in terms of compression rates on all the tested datasets. The file sizes are reduced by up to 21.91% when compared with LCQS. In terms of compression speed, CMIC is better than all other compressors on most of the tested cases. In terms of random access speed, the CMIC is faster than the LCQS, which provides a random access function for compressed quality scores.ConclusionsCMIC is a compressor that is especially designed for quality score sequences, which has good performance in terms of compression rate, compression speed, decompression speed, and random access speed. The CMIC can be obtained in the following way:https://github.com/Humonex/Cmic.

Background Resolution estimation is the main evaluation criteria for the reconstruction of macromolecular 3D structure in the field of cryoelectron microscopy (cryo-EM). At present, there are many methods to evaluate the 3D resolution for reconstructed macromolecular structures from Single Particle Analysis (SPA) in cryo-EM and subtomogram averaging (SA) in electron cryotomography (cryo-ET). As global methods, they measure the resolution of the structure as a whole, but they are inaccurate in detecting subtle local changes of reconstruction. In order to detect the subtle changes of reconstruction of SPA and SA, a few local resolution methods are proposed. The mainstream local resolution evaluation methods are based on local Fourier shell correlation (FSC), which is computationally intensive. However, the existing resolution evaluation methods are based on multi-threading implementation on a single computer with very poor scalability. Results This paper proposes a new fine-grained 3D array partition method by key-value format in Spark. Our method first converts 3D images to key-value data (K-V). Then the K-V data is used for 3D array partitioning and data exchange in parallel. So Spark-based distributed parallel computing framework can solve the above scalability problem. In this distributed computing framework, all 3D local FSC tasks are simultaneously calculated across multiple nodes in a computer cluster. Through the calculation of experimental data, 3D local resolution evaluation algorithm based on Spark fine-grained 3D array partition has a magnitude change in computing speed compared with the mainstream FSC algorithm under the condition that the accuracy remains unchanged, and has better fault tolerance and scalability. Conclusions In this paper, we proposed a K-V format based fine-grained 3D array partition method in Spark to parallel calculating 3D FSC for getting a 3D local resolution density map. 3D local resolution density map evaluates the three-dimensional density maps reconstructed from single particle analysis and subtomogram averaging. Our proposed method can significantly increase the speed of the 3D local resolution evaluation, which is important for the efficient detection of subtle variations among reconstructed macromolecular structures.

Background Synthetic lethality has attracted a lot of attentions in cancer therapeutics due to its utility in identifying new anticancer drug targets. Identifying synthetic lethal (SL) interactions is the key step towards the exploration of synthetic lethality in cancer treatment. However, biological experiments are faced with many challenges when identifying synthetic lethal interactions. Thus, it is necessary to develop computational methods which could serve as useful complements to biological experiments. Results In this paper, we propose a novel graph regularized self-representative matrix factorization (GRSMF) algorithm for synthetic lethal interaction prediction. GRSMF first learns the self-representations from the known SL interactions and further integrates the functional similarities among genes derived from Gene Ontology (GO). It can then effectively predict potential SL interactions by leveraging the information provided by known SL interactions and functional annotations of genes. Extensive experiments on the synthetic lethal interaction data downloaded from SynLethDB database demonstrate the superiority of our GRSMF in predicting potential synthetic lethal interactions, compared with other competing methods. Moreover, case studies of novel interactions are conducted in this paper for further evaluating the effectiveness of GRSMF in synthetic lethal interaction prediction. Conclusions In this paper, we demonstrate that by adaptively exploiting the self-representation of original SL interaction data, and utilizing functional similarities among genes to enhance the learning of self-representation matrix, our GRSMF could predict potential SL interactions more accurately than other state-of-the-art SL interaction prediction methods.

Background RNA secondary structure prediction is an important research content in the field of biological information. Predicting RNA secondary structure with pseudoknots has been proved to be an NP-hard problem. Traditional machine learning methods can not effectively apply protein sequence information with different sequence lengths to the prediction process due to the constraint of the self model when predicting the RNA secondary structure. In addition, there is a large difference between the number of paired bases and the number of unpaired bases in the RNA sequences, which means the problem of positive and negative sample imbalance is easy to make the model fall into a local optimum. To solve the above problems, this paper proposes a variable-length dynamic bidirectional Gated Recurrent Unit(VLDB GRU) model. The model can accept sequences with different lengths through the introduction of flag vector. The model can also make full use of the base information before and after the predicted base and can avoid losing part of the information due to truncation. Introducing a weight vector to predict the RNA training set by dynamically adjusting each base loss function solves the problem of balanced sample imbalance. Results The algorithm proposed in this paper is compared with the existing algorithms on five representative subsets of the data set RNA STRAND. The experimental results show that the accuracy and Matthews correlation coefficient of the method are improved by 4.7% and 11.4%, respectively. Conclusions The flag vector introduced allows the model to effectively use the information before and after the protein sequence; the introduced weight vector solves the problem of unbalanced sample balance. Compared with other algorithms, the LVDB GRU algorithm proposed in this paper has the best detection results.

Background Ontology has attracted substantial attention from both academia and industry. Handling uncertainty reasoning is important in researching ontology. For example, when a patient is suffering from cirrhosis, the appearance of abdominal vein varices is four times more likely than the presence of bitter taste. Such medical knowledge is crucial for decision-making in various medical applications but is missing from existing medical ontologies. In this paper, we aim to discover medical knowledge probabilities from electronic medical record (EMR) texts to enrich ontologies. First, we build an ontology by identifying meaningful entity mentions from EMRs. Then, we propose a symptom-dependency-aware naïve Bayes classifier (SDNB) that is based on the assumption that there is a level of dependency among symptoms. To ensure the accuracy of the diagnostic classification, we incorporate the probability of a disease into the ontology via innovative approaches. Results We conduct a series of experiments to evaluate whether the proposed method can discover meaningful and accurate probabilities for medical knowledge. Based on over 30,000 deidentified medical records, we explore 336 abdominal diseases and 81 related symptoms. Among these 336 gastrointestinal diseases, the probabilities of 31 diseases are obtained via our method. These 31 probabilities of diseases and 189 conditional probabilities between diseases and the symptoms are added into the generated ontology. Conclusion In this paper, we propose a medical knowledge probability discovery method that is based on the analysis and extraction of EMR text data for enriching a medical ontology with probability information. The experimental results demonstrate that the proposed method can effectively identify accurate medical knowledge probability information from EMR data. In addition, the proposed method can efficiently and accurately calculate the probability of a patient suffering from a specified disease, thereby demonstrating the advantage of combining an ontology and a symptom-dependency-aware naïve Bayes classifier.

Background Although there is an enormous number of textual resources in the biomedical domain, currently, manually curated resources cover only a small part of the existing knowledge. The vast majority of these information is in unstructured form which contain nonstandard naming conventions. The task of named entity recognition, which is the identification of entity names from text, is not adequate without a standardization step. Linking each identified entity mention in text to an ontology/dictionary concept is an essential task to make sense of the identified entities. This paper presents an unsupervised approach for the linking of named entities to concepts in an ontology/dictionary. We propose an approach for the normalization of biomedical entities through an ontology/dictionary by using word embeddings to represent semantic spaces, and a syntactic parser to give higher weight to the most informative word in the named entity mentions. Results We applied the proposed method to two different normalization tasks: the normalization of bacteria biotope entities through the Onto-Biotope ontology and the normalization of adverse drug reaction entities through the Medical Dictionary for Regulatory Activities (MedDRA). The proposed method achieved a precision score of 65.9%, which is 2.9 percentage points above the state-of-the-art result on the BioNLP Shared Task 2016 Bacteria Biotope test data and a macro-averaged precision score of 68.7% on the Text Analysis Conference 2017 Adverse Drug Reaction test data. Conclusions The core contribution of this paper is a syntax-based way of combining the individual word vectors to form vectors for the named entity mentions and ontology concepts, which can then be used to measure the similarity between them. The proposed approach is unsupervised and does not require labeled data, making it easily applicable to different domains.

Background:The response of many biomedical systems can be modelled using a linear combination of damped exponential functions. The approximation parameters, based on equally spaced samples, can be obtained using Prony's method and its variants (e.g. the matrix pencil method). This paper provides a tutorial on the main polynomial Prony and matrix pencil methods and their implementation in MATLAB and analyses how they perform with synthetic and multifocal visual-evoked potential (mfVEP) signals. This paper briefly describes the theoretical basis of four polynomial Prony approximation methods: classic, least squares (LS), total least squares (TLS) and matrix pencil method (MPM). In each of these cases, implementation uses general MATLAB functions. The features of the various options are tested by approximating a set of synthetic mathematical functions and evaluating filtering performance in the Prony domain when applied to mfVEP signals to improve diagnosis of patients with multiple sclerosis (MS). Results:The code implemented does not achieve 100%-correct signal approximation and, of the methods tested, LS and MPM perform best. When filtering mfVEP records in the Prony domain, the value of the area under the receiver-operating-characteristic (ROC) curve is 0.7055 compared with 0.6538 obtained with the usual filtering method used for this type of signal (discrete Fourier transform low-pass filter with a cut-off frequency of 35 Hz). Conclusions:This paper reviews Prony's method in relation to signal filtering and approximation, provides the MATLAB code needed to implement the classic, LS, TLS and MPM methods, and tests their performance in biomedical signal filtering and function approximation. It emphasizes the importance of improving the computational methods used to implement the various methods described above., Universidad de Alcalá, Agencia Estatal de Investigación

Background Gene co-expression networks (GCNs) are not easily comparable due to their complex structure. In this paper, we propose a tool, Juxtapose, together with similarity measures that can be utilized for comparative transcriptomics between a set of organisms. While we focus on its application to comparing co-expression networks across species in evolutionary studies, Juxtapose is also generalizable to co-expression network comparisons across tissues or conditions within the same species. Methods A word embedding strategy commonly used in natural language processing was utilized in order to generate gene embeddings based on walks made throughout the GCNs. Juxtapose was evaluated based on its ability to embed the nodes of synthetic structures in the networks consistently while also generating biologically informative results. Evaluation of the techniques proposed in this research utilized RNA-seq datasets from GTEx, a multi-species experiment of prefrontal cortex samples from the Gene Expression Omnibus, as well as synthesized datasets. Biological evaluation was performed using gene set enrichment analysis and known gene relationships in literature. Results We show that Juxtapose is capable of globally aligning synthesized networks as well as identifying areas that are conserved in real gene co-expression networks without reliance on external biological information. Furthermore, output from a matching algorithm that uses cosine distance between GCN embeddings is shown to be an informative measure of similarity that reflects the amount of topological similarity between networks. Conclusions Juxtapose can be used to align GCNs without relying on known biological similarities and enables post-hoc analyses using biological parameters, such as orthology of genes, or conserved or variable pathways. Availability A development version of the software used in this paper is available at https://github.com/klovens/juxtapose

BackgroundBioimaging techniques offer a robust tool for studying molecular pathways and morphological phenotypes of cell populations subjected to various conditions. As modern high resolution 3D microscopy provides access to an ever-increasing amount of high quality images, there arises a need for their analysis in an automated, unbiased and simple way.Segmentation of structures within cell nucleus, which is the focus of this paper, presents a new layer of complexity in the form of dense packing and significant signal overlap.At the same time the available segmentation tools provide a steep learning curve for new users with limited technical background. This is especially apparent in bulk processing of image sets, which requires the use of some form of programming notation.ResultsIn this paper, we present PartSeg, a tool for segmentation and reconstruction of 3D microscopy images, optimised for the study of cell nucleus. PartSeg integrates refined versions of several state-of-the-art algorithms, including a new multi-scale approach for segmentation and quantitative analysis of 3D microscopy images.The features and user-friendly interface of PartSeg were carefully planned with biologists in mind, based on analysis of multiple use cases and difficulties encountered with other tools, to offer ergonomic interface with a minimal entry barrier. Bulk processing in an ad-hoc manner is possible without the need for programmer support. As the size of datasets of interest grows, such bulk processing solutions become essential for proper statistical analysis of results.Advanced users can use PartSeg components as a library within Python data processing and visualisation pipelines, for example within Jupyter notebooks. The tool is extensible so that new functionality and algorithms can be added by the use of plugins.For biologists the utility of PartSeg is presented in several scenarios, showing the quantitative analysis of nuclear structures.ConclusionsIn this paper, we have presented PartSeg which is a tool for precise and verifiable segmentation and reconstruction of 3D microscopy images. PartSeg is optimised for cell nucleus analysis and offers multiscale segmentation algorithms best-suited for this task. PartSeg can also be used for bulk processing of multiple images and its components can be reused in other systems or computational experiments.Contactg.bokota@cent.uw.edu.pl, a.magalska@nencki.edu.pl, d.plewczynski@cent.uw.edu.pl

Background Atrial fibrillation is a paroxysmal heart disease without any obvious symptoms for most people during the onset. The electrocardiogram (ECG) at the time other than the onset of this disease is not significantly different from that of normal people, which makes it difficult to detect and diagnose. However, if atrial fibrillation is not detected and treated early, it tends to worsen the condition and increase the possibility of stroke. In this paper, P-wave morphology parameters and heart rate variability feature parameters were simultaneously extracted from the ECG. A total of 31 parameters were used as input variables to perform the modeling of artificial intelligence ensemble learning model. Results This paper applied three artificial intelligence ensemble learning methods, namely Bagging ensemble learning method, AdaBoost ensemble learning method, and Stacking ensemble learning method. The prediction results of these three artificial intelligence ensemble learning methods were compared. As a result of the comparison, the Stacking ensemble learning method combined with various models finally obtained the best prediction effect with the accuracy of 92%, sensitivity of 88%, specificity of 96%, positive predictive value of 95.7%, negative predictive value of 88.9%, F1 score of 0.9231 and area under receiver operating characteristic curve value of 0.911. Conclusion In feature extraction, this paper combined P-wave morphology parameters and heart rate variability parameters as input parameters for model training, and validated the value of the proposed parameters combination for the improvement of the model’s predicting effect. In the calculation of the P-wave morphology parameters, the hybrid Taguchi-genetic algorithm was used to obtain more accurate Gaussian function fitting parameters. The prediction model was trained using the Stacking ensemble learning method, so that the model accuracy had better results, which can further improve the early prediction of atrial fibrillation.

Background In the development of science and technology, there are increasing evidences that there are some associations between lncRNAs and human diseases. Therefore, finding these associations between them will have a huge impact on our treatment and prevention of some diseases. However, the process of finding the associations between them is very difficult and requires a lot of time and effort. Therefore, it is particularly important to find some good methods for predicting lncRNA-disease associations (LDAs). Results In this paper, we propose a method based on dual sparse collaborative matrix factorization (DSCMF) to predict LDAs. The DSCMF method is improved on the traditional collaborative matrix factorization method. To increase the sparsity, the L2,1-norm is added in our method. At the same time, Gaussian interaction profile kernel is added to our method, which increase the network similarity between lncRNA and disease. Finally, the AUC value obtained by the experiment is used to evaluate the quality of our method, and the AUC value is obtained by the ten-fold cross-validation method. Conclusions The AUC value obtained by the DSCMF method is 0.8523. At the end of the paper, simulation experiment is carried out, and the experimental results of prostate cancer, breast cancer, ovarian cancer and colorectal cancer are analyzed in detail. The DSCMF method is expected to bring some help to lncRNA-disease associations research. The code can access the https://github.com/Ming-0113/DSCMF website.

Background Heart disease (HD) is one of the most common diseases nowadays, and an early diagnosis of such a disease is a crucial task for many health care providers to prevent their patients for such a disease and to save lives. In this paper, a comparative analysis of different classifiers was performed for the classification of the Heart Disease dataset in order to correctly classify and or predict HD cases with minimal attributes. The set contains 76 attributes including the class attribute, for 1025 patients collected from Cleveland, Hungary, Switzerland, and Long Beach, but in this paper, only a subset of 14 attributes are used, and each attribute has a given set value. The algorithms used K- Nearest Neighbor (K-NN), Naive Bayes, Decision tree J48, JRip, SVM, Adaboost, Stochastic Gradient Decent (SGD) and Decision Table (DT) classifiers to show the performance of the selected classifications algorithms to best classify, and or predict, the HD cases. Results It was shown that using different classification algorithms for the classification of the HD dataset gives very promising results in term of the classification accuracy for the K-NN (K = 1), Decision tree J48 and JRip classifiers with accuracy of classification of 99.7073, 98.0488 and 97.2683% respectively. A feature extraction method was performed using Classifier Subset Evaluator on the HD dataset, and results show enhanced performance in term of the classification accuracy for K-NN (N = 1) and Decision Table classifiers to 100 and 93.8537% respectively after using the selected features by only applying a combination of up to 4 attributes instead of 13 attributes for the predication of the HD cases. Conclusion Different classifiers were used and compared to classify the HD dataset, and we concluded the benefit of having a reliable feature selection method for HD disease prediction with using minimal number of attributes instead of having to consider all available ones.

BackgroundProtein-protein interactions(PPIs) engage in dynamic pathological and biological procedures constantly in our life. Thus, it is crucial to comprehend the PPIs thoroughly such that we are able to illuminate the disease occurrence, achieve the optimal drug-target therapeutic effect and describe the protein complex structures. However, compared to the protein sequences obtainable from various species and organisms, the number of revealed protein-protein interactions is relatively limited. To address this dilemma, lots of research endeavor have investigated in it to facilitate the discovery of novel PPIs. Among these methods, PPI prediction techniques that merely rely on protein sequence data are more widespread than other methods which require extensive biological domain knowledge.ResultsIn this paper, we propose a multi-modal deep representation learning structure by incorporating protein physicochemical features with the graph topological features from the PPI networks. Specifically, our method not only bears in mind the protein sequence information but also discerns the topological representations for each protein node in the PPI networks. In our paper, we construct a stacked auto-encoder architecture together with a continuous bag-of-words (CBOW) model based on generated metapaths to study the PPI predictions. Following by that, we utilize the supervised deep neural networks to identify the PPIs and classify the protein families. The PPI prediction accuracy for eight species ranged from 96.76% to 99.77%, which signifies that our multi-modal deep representation learning framework achieves superior performance compared to other computational methods.ConclusionTo the best of our knowledge, this is the first multi-modal deep representation learning framework for examining the PPI networks.

Background During procedures for conducting multiple sequence alignment, that is so essential to use the substitution score of pairwise alignment. To compute adaptive scores for alignment, researchers usually use Hidden Markov Model or probabilistic consistency methods such as partition function. Recent studies show that optimizing the parameters for hidden Markov model, as well as integrating hidden Markov model with partition function can raise the accuracy of alignment. The combination of partition function and optimized HMM, which could further improve the alignment’s accuracy, however, was ignored by these researches. Results A novel algorithm for MSA called ProbPFP is presented in this paper. It intergrate optimized HMM by particle swarm with partition function. The algorithm of PSO was applied to optimize HMM’s parameters. After that, the posterior probability obtained by the HMM was combined with the one obtained by partition function, and thus to calculate an integrated substitution score for alignment. In order to evaluate the effectiveness of ProbPFP, we compared it with 13 outstanding or classic MSA methods. The results demonstrate that the alignments obtained by ProbPFP got the maximum mean TC scores and mean SP scores on these two benchmark datasets: SABmark and OXBench, and it got the second highest mean TC scores and mean SP scores on the benchmark dataset BAliBASE. ProbPFP is also compared with 4 other outstanding methods, by reconstructing the phylogenetic trees for six protein families extracted from the database TreeFam, based on the alignments obtained by these 5 methods. The result indicates that the reference trees are closer to the phylogenetic trees reconstructed from the alignments obtained by ProbPFP than the other methods. Conclusions We propose a new multiple sequence alignment method combining optimized HMM and partition function in this paper. The performance validates this method could make a great improvement of the alignment’s accuracy.

Background Collective cell migration is a significant and complex phenomenon that affects many basic biological processes. The coordination between leader cell and follower cell affects the rate of collective cell migration. However, there are still very few papers on the impacts of the stimulus signal released by the leader on the follower. Tracking cell movement using 3D time-lapse microscopy images provides an unprecedented opportunity to systematically study and analyze collective cell migration. Results Recently, deep reinforcement learning algorithms have become very popular. In our paper, we also use this method to train the number of cells and control signals. By experimenting with single-follower cell and multi-follower cells, it is concluded that the number of stimulation signals is proportional to the rate of collective movement of the cells. Such research provides a more diverse approach and approach to studying biological problems. Conclusion Traditional research methods are always based on real-life scenarios, but as the number of cells grows exponentially, the research process is too time consuming. Agent-based modeling is a robust framework that approximates cells to isotropic, elastic, and sticky objects. In this paper, an agent-based modeling framework is used to establish a simulation platform for simulating collective cell migration. The goal of the platform is to build a biomimetic environment to demonstrate the importance of stimuli between the leading and following cells.

Background: Over the last years, substantial effort has been put into enhancing our arsenal in fighting epidemics from both technological and theoretical perspectives with scientists from different fields teaming up for rapid assessment of potentially urgent situations. This paper focusses on the computational aspects of infectious disease models and applies commonly available graphics processing units (GPUs) for the simulation of these models. However, fully utilizing the resources of both CPUs and GPUs requires a carefully balanced heterogeneous approach. Results: The contribution of this paper is twofold. First, an efficient GPU implementation for evaluating a small-scale ODE model; here, the basic S(usceptible)-I(nfected)-R(ecovered) model, is discussed. Second, an asynchronous particle swarm optimization (PSO) implementation is proposed where batches of particles are sent asynchronously from the host (CPU) to the GPU for evaluation. The ultimate goal is to infer model parameters that enable the model to correctly describe observed data. The particles of the PSO algorithm are candidate parameters of the model; finding the right one is a matter of optimizing the likelihood function which quantifies how well the model describes the observed data. By employing a heterogeneous approach, in which both CPU and GPU are kept busy with useful work, speedups of 10 to 12 times can be achieved on a moderate machine with a high-end consumer GPU as compared to a high-end system with 32 CPU cores. Conclusions: Utilizing GPUs for parameter inference can bring considerable increases in performance using average host systems with high-end consumer GPUs. Future studies should evaluate the benefit of using newer CPU and GPU architectures as well as applying this method to more complex epidemiological scenarios. TK acknowledges support from a Methusalem research grant from the Flemish government. NH gratefully acknowledges support from the University of Antwerp scientific chair in Evidence-Based Vaccinology, financed by a gift from Pfizer (2009-2017) and GSK (2017). This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement 682540 - TransMID) and from the Special Research Fund of Hasselt University.

Background High-throughput sequencing data are widely collected and analyzed in the study of complex diseases in quest of improving human health. Well-studied algorithms mostly deal with single data source, and cannot fully utilize the potential of these multi-omics data sources. In order to provide a holistic understanding of human health and diseases, it is necessary to integrate multiple data sources. Several algorithms have been proposed so far, however, a comprehensive comparison of data integration algorithms for classification of binary traits is currently lacking. Results In this paper, we focus on two common classes of integration algorithms, graph-based that depict relationships with subjects denoted by nodes and relationships denoted by edges, and kernel-based that can generate a classifier in feature space. Our paper provides a comprehensive comparison of their performance in terms of various measurements of classification accuracy and computation time. Seven different integration algorithms, including graph-based semi-supervised learning, graph sharpening integration, composite association network, Bayesian network, semi-definite programming-support vector machine (SDP-SVM), relevance vector machine (RVM) and Ada-boost relevance vector machine are compared and evaluated with hypertension and two cancer data sets in our study. In general, kernel-based algorithms create more complex models and require longer computation time, but they tend to perform better than graph-based algorithms. The performance of graph-based algorithms has the advantage of being faster computationally. Conclusions The empirical results demonstrate that composite association network, relevance vector machine, and Ada-boost RVM are the better performers. We provide recommendations on how to choose an appropriate algorithm for integrating data from multiple sources. Electronic supplementary material The online version of this article (doi: 10.1186/s12859-017-1982-4) contains supplementary material, which is available to authorized users.

Background Genome rearrangements are essential processes for evolution and are responsible for existing varieties of genome architectures. Many studies have been conducted to obtain an algorithm that identifies the minimum number of inversions that are necessary to transform one genome into another; this allows for genome sequence representation in polynomial time. Studies have not been conducted on the topic of rearranging a genome when it is represented as a secondary structure. Unlike sequences, the secondary structure preserves the functionality of the genome. Sequences can be different, but they all share the same structure and, therefore, the same functionality. Results This paper proposes a double cut and join for RNA secondary structures (DCJ-RNA) algorithm. This algorithm allows for the description of evolutionary scenarios that are based on secondary structures rather than sequences. The main aim of this paper is to suggest an efficient algorithm that can help researchers compare two ribonucleic acid (RNA) secondary structures based on rearrangement operations. The results, which are based on real datasets, show that the algorithm is able to count the minimum number of rearrangement operations, as well as to report an optimum scenario that can increase the similarity between the two structures. Conclusion The algorithm calculates the distance between structures and reports a scenario based on the minimum rearrangement operations required to make the given structure similar to the other. DCJ-RNA can also be used to measure the distance between the two structures. This can help identify the common functionalities between different species.

BackgroundProtein subcellular localization plays a crucial role in understanding cell function. Proteins need to be in the right place at the right time, and combine with the corresponding molecules to fulfill their functions. Furthermore, prediction of protein subcellular location not only should be a guiding role in drug design and development due to potential molecular targets but also be an essential role in genome annotation. Taking the current status of image-based protein subcellular localization as an example, there are three common drawbacks, i.e., obsolete datasets without updating label information, stereotypical feature descriptor on spatial domain or grey level, and single-function prediction algorithm’s limited capacity of handling single-label database.ResultsIn this paper, a novel human protein subcellular localization prediction model MIC_Locator is proposed. Firstly, the latest datasets are collected and collated as our benchmark dataset instead of obsolete data while training prediction model. Secondly, Fourier transformation, Riesz transformation, Log-Gabor filter and intensity coding strategy are employed to obtain frequency feature based on three components of monogenic signal with different frequency scales. Thirdly, a chained prediction model is proposed to handle multi-label instead of single-label datasets. The experiment results showed that the MIC_Locator can achieve 60.56% subset accuracy and outperform the existing majority of prediction models, and the frequency feature and intensity coding strategy can be conducive to improving the classification accuracy.ConclusionsOur results demonstrate that the frequency feature is more beneficial for improving the performance of model compared to features extracted from spatial domain, and the MIC_Locator proposed in this paper can speed up validation of protein annotation, knowledge of protein function and proteomics research.

Background Deep learning techniques have been successfully applied to bioimaging problems; however, these methods are highly data demanding. An approach to deal with the lack of data and avoid overfitting is the application of data augmentation, a technique that generates new training samples from the original dataset by applying different kinds of transformations. Several tools exist to apply data augmentation in the context of image classification, but it does not exist a similar tool for the problems of localization, detection, semantic segmentation or instance segmentation that works not only with 2 dimensional images but also with multi-dimensional images (such as stacks or videos). Results In this paper, we present a generic strategy that can be applied to automatically augment a dataset of images, or multi-dimensional images, devoted to classification, localization, detection, semantic segmentation or instance segmentation. The augmentation method presented in this paper has been implemented in the open-source package CLoDSA. To prove the benefits of using CLoDSA, we have employed this library to improve the accuracy of models for Malaria parasite classification, stomata detection, and automatic segmentation of neural structures. Conclusions CLoDSA is the first, at least up to the best of our knowledge, image augmentation library for object classification, localization, detection, semantic segmentation, and instance segmentation that works not only with 2 dimensional images but also with multi-dimensional images.

Background In the string correction problem, we are to transform one string into another using a set of prescribed edit operations. In string correction using the Damerau-Levenshtein (DL) distance, the permissible edit operations are: substitution, insertion, deletion and transposition. Several algorithms for string correction using the DL distance have been proposed. The fastest and most space efficient of these algorithms is due to Lowrance and Wagner. It computes the DL distance between strings of length m and n, respectively, in O(m n) time and O(m n) space. In this paper, we focus on the development of algorithms whose asymptotic space complexity is less and whose actual runtime and energy consumption are less than those of the algorithm of Lowrance and Wagner. Results We develop space- and cache-efficient algorithms to compute the Damerau-Levenshtein (DL) distance between two strings as well as to find a sequence of edit operations of length equal to the DL distance. Our algorithms require O(s min{m,n}+m+n) space, where s is the size of the alphabet and m and n are, respectively, the lengths of the two strings. Previously known algorithms require O(m n) space. The space- and cache-efficient algorithms of this paper are demonstrated, experimentally, to be superior to earlier algorithms for the DL distance problem on time, space, and enery metrics using three different computational platforms. Conclusion Our benchmarking shows that, our algorithms are able to handle much larger sequences than earlier algorithms due to the reduction in space requirements. On a single core, we are able to compute the DL distance and an optimal edit sequence faster than known algorithms by as much as 73.1% and 63.5%, respectively. Further, we reduce energy consumption by as much as 68.5%. Multicore versions of our algorithms achieve a speedup of 23.2 on 24 cores.

Background Fast and accurate automatic segmentation of skeletal muscle cell image is crucial for the diagnosis of muscle related diseases, which extremely reduces the labor-intensive manual annotation. Recently, several methods have been presented for automatic muscle cell segmentation. However, most methods exhibit high model complexity and time cost, and they are not adaptive to large-scale images such as whole-slide scanned specimens. Methods In this paper, we propose a novel distributed computing approach, which adopts both data and model parallel, for fast muscle cell segmentation. With a master-worker parallelism manner, the image data in the master is distributed onto multiple workers based on the Spark cloud computing platform. On each worker node, we first detect cell contours using a structured random forest (SRF) contour detector with fast parallel prediction and generate region candidates using a superpixel technique. Next, we propose a novel hierarchical tree based region selection algorithm for cell segmentation based on the conditional random field (CRF) algorithm. We divide the region selection algorithm into multiple sub-problems, which can be further parallelized using multi-core programming. Results We test the performance of the proposed method on a large-scale haematoxylin and eosin (H &E) stained skeletal muscle image dataset. Compared with the standalone implementation, the proposed method achieves more than 10 times speed improvement on very large-scale muscle images containing hundreds to thousands of cells. Meanwhile, our proposed method produces high-quality segmentation results compared with several state-of-the-art methods. Conclusions This paper presents a parallel muscle image segmentation method with both data and model parallelism on multiple machines. The parallel strategy exhibits high compatibility to our muscle segmentation framework. The proposed method achieves high-throughput effective cell segmentation on large-scale muscle images.

Background Long reads provide valuable information regarding the sequence composition of genomes. Long reads are usually very noisy which renders their alignments on the reference genome a daunting task. It may take days to process datasets enough to sequence a human genome on a single node. Hence, it is of primary importance to have an aligner which can operate on distributed clusters of computers with high performance in accuracy and speed. Results In this paper, we presented IMOS, an aligner for mapping noisy long reads to the reference genome. It can be used on a single node as well as on distributed nodes. In its single-node mode, IMOS is an Improved version of Meta-aligner (IM) enhancing both its accuracy and speed. IM is up to 6x faster than the original Meta-aligner. It is also implemented to run IM and Minimap2 on Apache Spark for deploying on a cluster of nodes. Moreover, multi-node IMOS is faster than SparkBWA while executing both IM (1.5x) and Minimap2 (25x). Conclusion In this paper, we purposed an architecture for mapping long reads to a reference. Due to its implementation, IMOS speed can increase almost linearly with respect to the number of nodes in a cluster. Also, it is a multi-platform application able to operate on Linux, Windows, and macOS.

Background Recently, Pereira Zanetti, Biller and Meidanis have proposed a new definition of a rearrangement distance between genomes. In this formulation, each genome is represented as a matrix, and the distance d is the rank distance between these matrices. Although defined in terms of matrices, the rank distance is equal to the minimum total weight of a series of weighted operations that leads from one genome to the other, including inversions, translocations, transpositions, and others. The computational complexity of the median-of-three problem according to this distance is currently unknown. The genome matrices are a special kind of permutation matrices, which we study in this paper. In their paper, the authors provide an \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$O\left (n^{3}\right)$\end{document}On3 algorithm for determining three candidate medians, prove the tight approximation ratio \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\frac {4}{3}$\end{document}43, and provide a sufficient condition for their candidates to be true medians. They also conduct some experiments that suggest that their method is accurate on simulated and real data. Results In this paper, we extend their results and provide the following: Three invariants characterizing the problem of finding the median of 3 matricesA sufficient condition for uniqueness of medians that can be checked in O(n)A faster, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$O\left (n^{2}\right)$\end{document}On2 algorithm for determining the median under this conditionA new heuristic algorithm for this problem based on compressed sensingA \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$O\left (n^{4}\right)$\end{document}On4 algorithm that exactly solves the problem when the inputs are orthogonal matrices, a class that includes both permutations and genomes as special cases. Conclusions Our work provides the first proof that, with respect to the rank distance, the problem of finding the median of 3 genomes, as well as the median of 3 permutations, is exactly solvable in polynomial time, a result which should be contrasted with its NP-hardness for the DCJ (double cut-and-join) distance and most other families of genome rearrangement operations. This result, backed by our experimental tests, indicates that the rank distance is a viable alternative to the DCJ distance widely used in genome comparisons. Electronic supplementary material The online version of this article (10.1186/s12859-018-2131-4) contains supplementary material, which is available to authorized users.

Background Drug repositioning is the process of identifying new uses for existing drugs. Computational drug repositioning methods can reduce the time, costs and risks of drug development by automating the analysis of the relationships in pharmacology networks. Pharmacology networks are large and heterogeneous. Clustering drugs into small groups can simplify large pharmacology networks, these subgroups can also be used as a starting point for repositioning drugs. In this paper, we propose a two-tiered drug-centric unsupervised clustering approach for drug repositioning, integrating heterogeneous drug data profiles: drug-chemical, drug-disease, drug-gene, drug-protein and drug-side effect relationships. Results The proposed drug repositioning approach is threefold; (i) clustering drugs based on their homogeneous profiles using the Growing Self Organizing Map (GSOM); (ii) clustering drugs based on drug-drug relation matrices based on the previous step, considering three state-of-the-art graph clustering methods; and (iii) inferring drug repositioning candidates and assigning a confidence value for each identified candidate. In this paper, we compare our two-tiered clustering approach against two existing heterogeneous data integration approaches with reference to the Anatomical Therapeutic Chemical (ATC) classification, using GSOM. Our approach yields Normalized Mutual Information (NMI) and Standardized Mutual Information (SMI) of 0.66 and 36.11, respectively, while the two existing methods yield NMI of 0.60 and 0.64 and SMI of 22.26 and 33.59. Moreover, the two existing approaches failed to produce useful cluster separations when using graph clustering algorithms while our approach is able to identify useful clusters for drug repositioning. Furthermore, we provide clinical evidence for four predicted results (Chlorthalidone, Indomethacin, Metformin and Thioridazine) to support that our proposed approach can be reliably used to infer ATC code and drug repositioning. Conclusion The proposed two-tiered unsupervised clustering approach is suitable for drug clustering and enables heterogeneous data integration. It also enables identifying reliable repositioning drug candidates with reference to ATC therapeutic classification. The repositioning drug candidates identified consistently by multiple clustering algorithms and with high confidence have a higher possibility of being effective repositioning candidates. Electronic supplementary material The online version of this article (10.1186/s12859-018-2123-4) contains supplementary material, which is available to authorized users.

Background The primary goal of pathway analysis using transcriptome data is to find significantly perturbed pathways. However, pathway analysis is not always successful in identifying pathways that are truly relevant to the context under study. A major reason for this difficulty is that a single gene is involved in multiple pathways. In the KEGG pathway database, there are 146 genes, each of which is involved in more than 20 pathways. Thus activation of even a single gene will result in activation of many pathways. This complex relationship often makes the pathway analysis very difficult. While we need much more powerful pathway analysis methods, a readily available alternative way is to incorporate the literature information. Results In this study, we propose a novel approach for prioritizing pathways by combining results from both pathway analysis tools and literature information. The basic idea is as follows. Whenever there are enough articles that provide evidence on which pathways are relevant to the context, we can be assured that the pathways are indeed related to the context, which is termed as relevance in this paper. However, if there are few or no articles reported, then we should rely on the results from the pathway analysis tools, which is termed as significance in this paper. We realized this concept as an algorithm by introducing Context Score and Impact Score and then combining the two into a single score. Our method ranked truly relevant pathways significantly higher than existing pathway analysis tools in experiments with two data sets. Conclusions Our novel framework was implemented as ContextTRAP by utilizing two existing tools, TRAP and BEST. ContextTRAP will be a useful tool for the pathway based analysis of gene expression data since the user can specify the context of the biological experiment in a set of keywords. The web version of ContextTRAP is available at http://biohealth.snu.ac.kr/software/contextTRAP. Electronic supplementary material The online version of this article (doi:10.1186/s12859-016-1335-8) contains supplementary material, which is available to authorized users.

Background Mass spectrometry (MS) is producing high volumes of data supporting oncological sciences, especially for translational research. Most of related elaborations can be carried out by combining existing tools at different levels, but little is currently available for the automation of the fundamental steps. For the analysis of MALDI/TOF spectra, a number of pre-processing steps are required, including joining of isotopic abundances for a given molecular species, normalization of signals against an internal standard, background noise removal, averaging multiple spectra from the same sample, and aligning spectra from different samples. In this paper, we present Geena 2, a public software tool for the automated execution of these pre-processing steps for MALDI/TOF spectra. Results Geena 2 has been developed in a Linux-Apache-MySQL-PHP web development environment, with scripts in PHP and Perl. Input and output are managed as simple formats that can be consumed by any database system and spreadsheet software. Input data may also be stored in a MySQL database. Processing methods are based on original heuristic algorithms which are introduced in the paper. Three simple and intuitive web interfaces are available: the Standard Search Interface, which allows a complete control over all parameters, the Bright Search Interface, which leaves to the user the possibility to tune parameters for alignment of spectra, and the Quick Search Interface, which limits the number of parameters to a minimum by using default values for the majority of parameters. Geena 2 has been utilized, in conjunction with a statistical analysis tool, in three published experimental works: a proteomic study on the effects of long-term cryopreservation on the low molecular weight fraction of serum proteome, and two retrospective serum proteomic studies, one on the risk of developing breat cancer in patients affected by gross cystic disease of the breast (GCDB) and the other for the identification of a predictor of breast cancer mortality following breast cancer surgery, whose results were validated by ELISA, a completely alternative method. Conclusions Geena 2 is a public tool for the automated pre-processing of MS data originated by MALDI/TOF instruments, with a simple and intuitive web interface. It is now under active development for the inclusion of further filtering options and for the adoption of standard formats for MS spectra. Electronic supplementary material The online version of this article (doi:10.1186/s12859-016-0911-2) contains supplementary material, which is available to authorized users.

Background In highly parallel next-generation sequencing (NGS) techniques millions to billions of short reads are produced from a genomic sequence in a single run. Due to the limitation of the NGS technologies, there could be errors in the reads. The error rate of the reads can be reduced with trimming and by correcting the erroneous bases of the reads. It helps to achieve high quality data and the computational complexity of many biological applications will be greatly reduced if the reads are first corrected. We have developed a novel error correction algorithm called EC and compared it with four other state-of-the-art algorithms using both real and simulated sequencing reads. Results We have done extensive and rigorous experiments that reveal that EC is indeed an effective, scalable, and efficient error correction tool. Real reads that we have employed in our performance evaluation are Illumina-generated short reads of various lengths. Six experimental datasets we have utilized are taken from sequence and read archive (SRA) at NCBI. The simulated reads are obtained by picking substrings from random positions of reference genomes. To introduce errors, some of the bases of the simulated reads are changed to other bases with some probabilities. Conclusions Error correction is a vital problem in biology especially for NGS data. In this paper we present a novel algorithm, called Error Corrector (EC), for correcting substitution errors in biological sequencing reads. We plan to investigate the possibility of employing the techniques introduced in this research paper to handle insertion and deletion errors also. Software availability The implementation is freely available for non-commercial purposes. It can be downloaded from: http://engr.uconn.edu/~rajasek/EC.zip.

Background Recently, the Bayesian method becomes more popular for analyzing high dimensional gene expression data as it allows us to borrow information across different genes and provides powerful estimators for evaluating gene expression levels. It is crucial to develop a simple but efficient gene selection algorithm for detecting differentially expressed (DE) genes based on the Bayesian estimators. Results In this paper, by extending the two-criterion idea of Chen et al. (Chen M-H, Ibrahim JG, Chi Y-Y. A new class of mixture models for differential gene expression in DNA microarray data. J Stat Plan Inference. 2008;138:387–404), we propose two new gene selection algorithms for general Bayesian models and name these new methods as the confident difference criterion methods. One is based on the standardized differences between two mean expression values among genes; the other adds the differences between two variances to it. The proposed confident difference criterion methods first evaluate the posterior probability of a gene having different gene expressions between competitive samples and then declare a gene to be DE if the posterior probability is large. The theoretical connection between the proposed first method based on the means and the Bayes factor approach proposed by Yu et al. (Yu F, Chen M-H, Kuo L. Detecting differentially expressed genes using alibrated Bayes factors. Statistica Sinica. 2008;18:783–802) is established under the normal-normal-model with equal variances between two samples. The empirical performance of the proposed methods is examined and compared to those of several existing methods via several simulations. The results from these simulation studies show that the proposed confident difference criterion methods outperform the existing methods when comparing gene expressions across different conditions for both microarray studies and sequence-based high-throughput studies. A real dataset is used to further demonstrate the proposed methodology. In the real data application, the confident difference criterion methods successfully identified more clinically important DE genes than the other methods. Conclusion The confident difference criterion method proposed in this paper provides a new efficient approach for both microarray studies and sequence-based high-throughput studies to identify differentially expressed genes. Electronic supplementary material The online version of this article (doi:10.1186/s12859-015-0664-3) contains supplementary material, which is available to authorized users.

Background Alkaline earth metal ions are important protein binding ligands in human body, and it is of great significance to predict their binding residues. Results In this paper, Mg2+ and Ca2+ ligands are taken as the research objects. Based on the characteristic parameters of protein sequences, amino acids, physicochemical characteristics of amino acids and predicted structural information, deep neural network algorithm is used to predict the binding sites of proteins. By optimizing the hyper-parameters of the deep learning algorithm, the prediction results by the fivefold cross-validation are better than those of the Ionseq method. In addition, to further verify the performance of the proposed model, the undersampling data processing method is adopted, and the prediction results on independent test are better than those obtained by the support vector machine algorithm. Conclusions An efficient method for predicting Mg2+ and Ca2+ ligand binding sites was presented.

Background Identifying protein complexes from protein–protein interaction (PPI) networks is a crucial task, and many related algorithms have been developed to solve this issue. These algorithms usually consider a node’s direct neighbors and ignore resource allocation and second-order neighbors. The effective use of such information is crucial to protein complex detection.Results To overcome this deficiency, this paper proposes a new protein complex identification method based on node-local topological properties and gene expression information on a new weighted PPI network, named NLPGE-WPN (joint node-local topological properties and gene expression information on weighted PPI network). First, based on the resource allocation of the PPI network and gene expression, a new weight metric is designed to describe the interaction between proteins. Second, our method constructs a series of dense complex cores based on density and network diameter constraints; the final complexes are recognized by expanding the second-order neighbor nodes of core complexes. Experimental results demonstrate that this algorithm has improved the performances of precision and f-measure, which is more valid in identifying protein complexes．Conclusions This identification method is simple and can accurately identify more complexes by integrating node-local properties and gene expression on PPI weighted networks.

Background At present, the bioinformatics research on the relationship between aging-related diseases and genes is mainly through the establishment of a machine learning multi-label model to classify each gene. Most of the existing methods for predicting pathogenic genes mainly rely on specific types of gene features, or directly encode multiple features with different dimensions, use the same encoder to concatenate and predict the final results, which will be subject to many limitations in the applicability of the algorithm. Possible shortcomings of the above include: incomplete coverage of gene features by a single type of biomics data, overfitting of small dimensional datasets by a single encoder, or underfitting of larger dimensional datasets. Methods We use the known gene disease association data and gene descriptors, such as gene ontology terms (GO), protein interaction data (PPI), PathDIP, Kyoto Encyclopedia of genes and genomes Genes (KEGG), etc, as input for deep learning to predict the association between genes and diseases. Our innovation is to use Mashup algorithm to reduce the dimensionality of PPI, GO and other large biological networks, and add new pathway data in KEGG database, and then combine a variety of biological information sources through modular Deep Neural Network (DNN) to predict the genes related to aging diseases. Result and conclusion The results show that our algorithm is more effective than the standard neural network algorithm (the Area Under the ROC curve from 0.8795 to 0.9153), gradient enhanced tree classifier and logistic regression classifier. In this paper, we firstly use DNN to learn the similar genes associated with the known diseases from the complex multi-dimensional feature space, and then provide the evidence that the assumed genes are associated with a certain disease.

Background The aim of the present paper is to construct an emulator of a complex biological system simulator using a machine learning approach. More specifically, the simulator is a patient-specific model that integrates metabolic, nutritional, and lifestyle data to predict the metabolic and inflammatory processes underlying the development of type-2 diabetes in absence of familiarity. Given the very high incidence of type-2 diabetes, the implementation of this predictive model on mobile devices could provide a useful instrument to assess the risk of the disease for aware individuals. The high computational cost of the developed model, being a mixture of agent-based and ordinary differential equations and providing a dynamic multivariate output, makes the simulator executable only on powerful workstations but not on mobile devices. Hence the need to implement an emulator with a reduced computational cost that can be executed on mobile devices to provide real-time self-monitoring. Results Similarly to our previous work, we propose an emulator based on a machine learning algorithm but here we consider a different approach which turn out to have better performances, indeed in terms of root mean square error we have an improvement of two order magnitude. We tested the proposed emulator on samples containing different number of simulated trajectories, and it turned out that the fitted trajectories are able to predict with high accuracy the entire dynamics of the simulator output variables. We apply the emulator to control the level of inflammation while leveraging on the nutritional input. Conclusion The proposed emulator can be implemented and executed on mobile health devices to perform quick-and-easy self-monitoring assessments.

Background With the rapid development of various advanced biotechnologies, researchers in related fields have realized that microRNAs (miRNAs) play critical roles in many serious human diseases. However, experimental identification of new miRNA–disease associations (MDAs) is expensive and time-consuming. Practitioners have shown growing interest in methods for predicting potential MDAs. In recent years, an increasing number of computational methods for predicting novel MDAs have been developed, making a huge contribution to the research of human diseases and saving considerable time. In this paper, we proposed an efficient computational method, named bipartite graph-based collaborative matrix factorization (BGCMF), which is highly advantageous for predicting novel MDAs. Results By combining two improved recommendation methods, a new model for predicting MDAs is generated. Based on the idea that some new miRNAs and diseases do not have any associations, we adopt the bipartite graph based on the collaborative matrix factorization method to complete the prediction. The BGCMF achieves a desirable result, with AUC of up to 0.9514 ± (0.0007) in the five-fold cross-validation experiments. Conclusions Five-fold cross-validation is used to evaluate the capabilities of our method. Simulation experiments are implemented to predict new MDAs. More importantly, the AUC value of our method is higher than those of some state-of-the-art methods. Finally, many associations between new miRNAs and new diseases are successfully predicted by performing simulation experiments, indicating that BGCMF is a useful method to predict more potential miRNAs with roles in various diseases.

Background Host population structure is a key determinant of pathogen and infectious disease transmission patterns. Pathogen phylogenetic trees are useful tools to reveal the population structure underlying an epidemic. Determining whether a population is structured or not is useful in informing the type of phylogenetic methods to be used in a given study. We employ tree statistics derived from phylogenetic trees and machine learning classification techniques to reveal an underlying population structure. Results In this paper, we simulate phylogenetic trees from both structured and non-structured host populations. We compute eight statistics for the simulated trees, which are: the number of cherries; Sackin, Colless and total cophenetic indices; ladder length; maximum depth; maximum width, and width-to-depth ratio. Based on the estimated tree statistics, we classify the simulated trees as from either a non-structured or a structured population using the decision tree (DT), K-nearest neighbor (KNN) and support vector machine (SVM). We incorporate the basic reproductive number ($$R_0$$ R 0 ) in our tree simulation procedure. Sensitivity analysis is done to investigate whether the classifiers are robust to different choice of model parameters and to size of trees. Cross-validated results for area under the curve (AUC) for receiver operating characteristic (ROC) curves yield mean values of over 0.9 for most of the classification models. Conclusions Our classification procedure distinguishes well between trees from structured and non-structured populations using the classifiers, the two-sample Kolmogorov-Smirnov, Cucconi and Podgor-Gastwirth tests and the box plots. SVM models were more robust to changes in model parameters and tree size compared to KNN and DT classifiers. Our classification procedure was applied to real -world data and the structured population was revealed with high accuracy of $$92.3\%$$ 92.3 % using SVM-polynomial classifier.

Background In the process of designing drugs and proteins, it is crucial to recognize hot regions in protein–protein interactions. Each hot region of protein–protein interaction is composed of at least three hot spots, which play an important role in binding. However, it takes time and labor force to identify hot spots through biological experiments. If predictive models based on machine learning methods can be trained, the drug design process can be effectively accelerated. Results The results show that different machine learning algorithms perform similarly, as evaluating using the F-measure. The main differences between these methods are recall and precision. Since the key attribute of hot regions is that they are packed tightly, we used the cluster algorithm to predict hot regions. By combining Gaussian Naïve Bayes and DBSCAN, the F-measure of hot region prediction can reach 0.809. Conclusions In this paper, different machine learning models such as Gaussian Naïve Bayes, SVM, Xgboost, Random Forest, and Artificial Neural Network are used to predict hot spots. The experiment results show that the combination of hot spot classification algorithm with higher recall rate and clustering algorithm with higher precision can effectively improve the accuracy of hot region prediction.

Background Accurate annotation of protein function is the key to understanding life at the molecular level and has great implications for biomedicine and pharmaceuticals. The rapid developments of high-throughput technologies have generated huge amounts of protein–protein interaction (PPI) data, which prompts the emergence of computational methods to determine protein function. Plagued by errors and noises hidden in PPI data, these computational methods have undertaken to focus on the prediction of functions by integrating the topology of protein interaction networks and multi-source biological data. Despite effective improvement of these computational methods, it is still challenging to build a suitable network model for integrating multiplex biological data. Results In this paper, we constructed a heterogeneous biological network by initially integrating original protein interaction networks, protein-domain association data and protein complexes. To prove the effectiveness of the heterogeneous biological network, we applied the propagation algorithm on this network, and proposed a novel iterative model, named Propagate on Heterogeneous Biological Networks (PHN) to score and rank functions in descending order from all functional partners, Finally, we picked out top L of these predicted functions as candidates to annotate the target protein. Our comprehensive experimental results demonstrated that PHN outperformed seven other competing approaches using cross-validation. Experimental results indicated that PHN performs significantly better than competing methods and improves the Area Under the Receiver-Operating Curve (AUROC) in Biological Process (BP), Molecular Function (MF) and Cellular Components (CC) by no less than 33%, 15% and 28%, respectively. Conclusions We demonstrated that integrating multi-source data into a heterogeneous biological network can preserve the complex relationship among multiplex biological data and improve the prediction accuracy of protein function by getting rid of the constraints of errors in PPI networks effectively. PHN, our proposed method, is effective for protein function prediction.

Background In recent years, huge improvements have been made in the context of sequencing genomic data under what is called Next Generation Sequencing (NGS). However, the DNA reads generated by current NGS platforms are not free of errors, which can affect the quality of downstream analysis. Although error correction can be performed as a preprocessing step to overcome this issue, it usually requires long computational times to analyze those large datasets generated nowadays through NGS. Therefore, new software capable of scaling out on a cluster of nodes with high performance is of great importance. Results In this paper, we present SparkEC, a parallel tool capable of fixing those errors produced during the sequencing process. For this purpose, the algorithms proposed by the CloudEC tool, which is already proved to perform accurate corrections, have been analyzed and optimized to improve their performance by relying on the Apache Spark framework together with the introduction of other enhancements such as the usage of memory-efficient data structures and the avoidance of any input preprocessing. The experimental results have shown significant improvements in the computational times of SparkEC when compared to CloudEC for all the representative datasets and scenarios under evaluation, providing an average and maximum speedups of 4.9$$\times$$ × and 11.9$$\times$$ × , respectively, over its counterpart. Conclusion As error correction can take excessive computational time, SparkEC provides a scalable solution for correcting large datasets. Due to its distributed implementation, SparkEC speed can increase with respect to the number of nodes in a cluster. Furthermore, the software is freely available under GPLv3 license and is compatible with different operating systems (Linux, Windows and macOS).

Background There is a widening gap between the throughput of massive parallel sequencing machines and the ability to analyze these sequencing data. Traditional assembly methods requiring long execution time and large amount of memory on a single workstation limit their use on these massive data. Results This paper presents a highly scalable assembler named as SWAP-Assembler for processing massive sequencing data using thousands of cores, where SWAP is an acronym for Small World Asynchronous Parallel model. In the paper, a mathematical description of multi-step bi-directed graph (MSG) is provided to resolve the computational interdependence on merging edges, and a highly scalable computational framework for SWAP is developed to automatically preform the parallel computation of all operations. Graph cleaning and contig extension are also included for generating contigs with high quality. Experimental results show that SWAP-Assembler scales up to 2048 cores on Yanhuang dataset using only 26 minutes, which is better than several other parallel assemblers, such as ABySS, Ray, and PASHA. Results also show that SWAP-Assembler can generate high quality contigs with good N50 size and low error rate, especially it generated the longest N50 contig sizes for Fish and Yanhuang datasets. Conclusions In this paper, we presented a highly scalable and efficient genome assembly software, SWAP-Assembler. Compared with several other assemblers, it showed very good performance in terms of scalability and contig quality. This software is available at: https://sourceforge.net/projects/swapassembler

Acquiring genomes at single-cell resolution has many applications such as in the study of microbiota. However, deep sequencing and assembly of all of millions of cells in a sample is prohibitively costly. A property that can come to rescue is that deep sequencing of every cell should not be necessary to capture all distinct genomes, as the majority of cells are biological replicates. Biologically important samples are often sparse in that sense. In this paper, we propose an adaptive compressed method, also known as distilled sensing, to capture all distinct genomes in a sparse microbial community with reduced sequencing effort. As opposed to group testing in which the number of distinct events is often constant and sparsity is equivalent to rarity of an event, sparsity in our case means scarcity of distinct events in comparison to the data size. Previously, we introduced the problem and proposed a distilled sensing solution based on the breadth first search strategy. We simulated the whole process which constrained our ability to study the behavior of the algorithm for the entire ensemble due to its computational intensity. In this paper, we modify our previous breadth first search strategy and introduce the depth first search strategy. Instead of simulating the entire process, which is intractable for a large number of experiments, we provide a dynamic programming algorithm to analyze the behavior of the method for the entire ensemble. The ensemble analysis algorithm recursively calculates the probability of capturing every distinct genome and also the expected total sequenced nucleotides for a given population profile. Our results suggest that the expected total sequenced nucleotides grows proportional to log of the number of cells and proportional linearly with the number of distinct genomes. The probability of missing a genome depends on its abundance and the ratio of its size over the maximum genome size in the sample. The modified resource allocation method accommodates a parameter to control that probability. The squeezambler 2.0 C++ source code is available at http://sourceforge.net/projects/hyda/ . The ensemble analysis MATLAB code is available at http://sourceforge.net/projects/distilled-sequencing/ .

Background This paper exploits recent developments in topological data analysis to present a pipeline for clustering based on Mapper, an algorithm that reduces complex data into a one-dimensional graph. Results We present a pipeline to identify and summarise clusters based on statistically significant topological features from a point cloud using Mapper. Conclusions Key strengths of this pipeline include the integration of prior knowledge to inform the clustering process and the selection of optimal clusters; the use of the bootstrap to restrict the search to robust topological features; the use of machine learning to inspect clusters; and the ability to incorporate mixed data types. Our pipeline can be downloaded under the GNU GPLv3 license at https://github.com/kcl-bhi/mapper-pipeline.

Background Deciphering proportions of constitutional cell types in tumor tissues is a crucial step for the analysis of tumor heterogeneity and the prediction of response to immunotherapy. In the process of measuring cell population proportions, traditional experimental methods have been greatly hampered by the cost and extensive dropout events. At present, the public availability of large amounts of DNA methylation data makes it possible to use computational methods to predict proportions. Results In this paper, we proposed PRMeth, a method to deconvolve tumor mixtures using partially available DNA methylation data. By adopting an iteratively optimized non-negative matrix factorization framework, PRMeth took DNA methylation profiles of a portion of the cell types in the tissue mixtures (including blood and solid tumors) as input to estimate the proportions of all cell types as well as the methylation profiles of unknown cell types simultaneously. We compared PRMeth with five different methods through three benchmark datasets and the results show that PRMeth could infer the proportions of all cell types and recover the methylation profiles of unknown cell types effectively. Then, applying PRMeth to four types of tumors from The Cancer Genome Atlas (TCGA) database, we found that the immune cell proportions estimated by PRMeth were largely consistent with previous studies and met biological significance. Conclusions Our method can circumvent the difficulty of obtaining complete DNA methylation reference data and obtain satisfactory deconvolution accuracy, which will be conducive to exploring the new directions of cancer immunotherapy. PRMeth is implemented in R and is freely available from GitHub (https://github.com/hedingqin/PRMeth).

Background Essential proteins are indispensable to the development and survival of cells. The identification of essential proteins not only is helpful for the understanding of the minimal requirements for cell survival, but also has practical significance in disease diagnosis, drug design and medical treatment. With the rapidly amassing of protein–protein interaction (PPI) data, computationally identifying essential proteins from protein–protein interaction networks (PINs) becomes more and more popular. Up to now, a number of various approaches for essential protein identification based on PINs have been developed. Results In this paper, we propose a new and effective approach called iMEPP to identify essential proteins from PINs by fusing multiple types of biological data and applying the influence maximization mechanism to the PINs. Concretely, we first integrate PPI data, gene expression data and Gene Ontology to construct weighted PINs, to alleviate the impact of high false-positives in the raw PPI data. Then, we define the influence scores of nodes in PINs with both orthological data and PIN topological information. Finally, we develop an influence discount algorithm to identify essential proteins based on the influence maximization mechanism. Conclusions We applied our method to identifying essential proteins from saccharomyces cerevisiae PIN. Experiments show that our iMEPP method outperforms the existing methods, which validates its effectiveness and advantage.

Background The discovery of critical biomarkers is significant for clinical diagnosis, drug research and development. Researchers usually obtain biomarkers from microarray data, which comes from the dimensional curse. Feature selection in machine learning is usually used to solve this problem. However, most methods do not fully consider feature dependence, especially the real pathway relationship of genes. Results Experimental results show that the proposed method is superior to classical algorithms and advanced methods in feature number and accuracy, and the selected features have more significance. Method This paper proposes a feature selection method based on a graph neural network. The proposed method uses the actual dependencies between features and the Pearson correlation coefficient to construct graph-structured data. The information dissemination and aggregation operations based on graph neural network are applied to fuse node information on graph structured data. The redundant features are clustered by the spectral clustering method. Then, the feature ranking aggregation model using eight feature evaluation methods acts on each clustering sub-cluster for different feature selection. Conclusion The proposed method can effectively remove redundant features. The algorithm’s output has high stability and classification accuracy, which can potentially select potential biomarkers.

Background Building biological networks with a certain function is a challenge in systems biology. For the functionality of small (less than ten nodes) biological networks, most methods are implemented by exhausting all possible network topological spaces. This exhaustive approach is difficult to scale to large-scale biological networks. And regulatory relationships are complex and often nonlinear or non-monotonic, which makes inference using linear models challenging. Results In this paper, we propose a multi-layer perceptron-based differential equation method, which operates by training a fully connected neural network (NN) to simulate the transcription rate of genes in traditional differential equations. We verify whether the regulatory network constructed by the NN method can continue to achieve the expected biological function by verifying the degree of overlap between the regulatory network discovered by NN and the regulatory network constructed by the Hill function. And we validate our approach by adapting to noise signals, regulator knockout, and constructing large-scale gene regulatory networks using link-knockout techniques. We apply a real dataset (the mesoderm inducer Xenopus Brachyury expression) to construct the core topology of the gene regulatory network and find that Xbra is only strongly expressed at moderate levels of activin signaling. Conclusion We have demonstrated from the results that this method has the ability to identify the underlying network topology and functional mechanisms, and can also be applied to larger and more complex gene network topologies.

Background Taxonomic assignment is a key step in the identification of human viral pathogens. Current tools for taxonomic assignment from sequencing reads based on alignment or alignment-free k-mer approaches may not perform optimally in cases where the sequences diverge significantly from the reference sequences. Furthermore, many tools may not incorporate the genomic coverage of assigned reads as part of overall likelihood of a correct taxonomic assignment for a sample. Results In this paper, we describe the development of a pipeline that incorporates a multi-task learning model based on convolutional neural network (MT-CNN) and a Bayesian ranking approach to identify and rank the most likely human virus from sequence reads. For taxonomic assignment of reads, the MT-CNN model outperformed Kraken 2, Centrifuge, and Bowtie 2 on reads generated from simulated divergent HIV-1 genomes and was more sensitive in identifying SARS as the closest relation in four RNA sequencing datasets for SARS-CoV-2 virus. For genomic region assignment of assigned reads, the MT-CNN model performed competitively compared with Bowtie 2 and the region assignments were used for estimation of genomic coverage that was incorporated into a naïve Bayesian network together with the proportion of taxonomic assignments to rank the likelihood of candidate human viruses from sequence data. Conclusions We have developed a pipeline that combines a novel MT-CNN model that is able to identify viruses with divergent sequences together with assignment of the genomic region, with a Bayesian approach to ranking of taxonomic assignments by taking into account both the number of assigned reads and genomic coverage. The pipeline is available at GitHub via https://github.com/MaHaoran627/CNN_Virus.

Background The rapid development of single-cell RNA sequencing (scRNA-seq) enables the exploration of cell heterogeneity, which is usually done by scRNA-seq data clustering. The essence of scRNA-seq data clustering is to group cells by measuring the similarities among genes/transcripts of cells. And the selection of features for cell similarity evaluation is of great importance, which will significantly impact clustering effectiveness and efficiency. Results In this paper, we propose a novel method called CaFew to select genes based on cluster-aware feature weighting. By optimizing the clustering objective function, CaFew obtains a feature weight matrix, which is further used for feature selection. The genes have large weights in at least one cluster or the genes whose weights vary greatly in different clusters are selected. Experiments on 8 real scRNA-seq datasets show that CaFew can obviously improve the clustering performance of existing scRNA-seq data clustering methods. Particularly, the combination of CaFew with SC3 achieves the state-of-art performance. Furthermore, CaFew also benefits the visualization of scRNA-seq data. Conclusion CaFew is an effective scRNA-seq data clustering method due to its gene selection mechanism based on cluster-aware feature weighting, and it is a useful tool for scRNA-seq data analysis.

Background With the continuous maturity of sequencing technology, different laboratories or different sequencing platforms have generated a large amount of single-cell transcriptome sequencing data for the same or different tissues. Due to batch effects and high dimensions of scRNA data, downstream analysis often faces challenges. Although a number of algorithms and tools have been proposed for removing batch effects, the current mainstream algorithms have faced the problem of data overcorrection when the cell type composition varies greatly between batches. Results In this paper, we propose a novel method named SSBER by utilizing biological prior knowledge to guide the correction, aiming to solve the problem of poor batch-effect correction when the cell type composition differs greatly between batches. Conclusions SSBER effectively solves the above problems and outperforms other algorithms when the cell type structure among batches or distribution of cell population varies considerably, or some similar cell types exist across batches.

Background Some proposed methods for identifying essential proteins have better results by using biological information. Gene expression data is generally used to identify essential proteins. However, gene expression data is prone to fluctuations, which may affect the accuracy of essential protein identification. Therefore, we propose an essential protein identification method based on gene expression and the PPI network data to calculate the similarity of "active" and "inactive" state of gene expression in a cluster of the PPI network. Our experiments show that the method can improve the accuracy in predicting essential proteins. Results In this paper, we propose a new measure named JDC, which is based on the PPI network data and gene expression data. The JDC method offers a dynamic threshold method to binarize gene expression data. After that, it combines the degree centrality and Jaccard similarity index to calculate the JDC score for each protein in the PPI network. We benchmark the JDC method on four organisms respectively, and evaluate our method by using ROC analysis, modular analysis, jackknife analysis, overlapping analysis, top analysis, and accuracy analysis. The results show that the performance of JDC is better than DC, IC, EC, SC, BC, CC, NC, PeC, and WDC. We compare JDC with both NF-PIN and TS-PIN methods, which predict essential proteins through active PPI networks constructed from dynamic gene expression. Conclusions We demonstrate that the new centrality measure, JDC, is more efficient than state-of-the-art prediction methods with same input. The main ideas behind JDC are as follows: (1) Essential proteins are generally densely connected clusters in the PPI network. (2) Binarizing gene expression data can screen out fluctuations in gene expression profiles. (3) The essentiality of the protein depends on the similarity of "active" and "inactive" state of gene expression in a cluster of the PPI network.