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Background Free and open access to primary biodiversity data is essential for informed decision-making to achieve conservation of biodiversity and sustainable development. However, primary biodiversity data are neither easily accessible nor discoverable. Among several impediments, one is a lack of incentives to data publishers for publishing of their data resources. One such mechanism currently lacking is recognition through conventional scholarly publication of enriched metadata, which should ensure rapid discovery of 'fit-for-use' biodiversity data resources. Discussion We review the state of the art of data discovery options and the mechanisms in place for incentivizing data publishers efforts towards easy, efficient and enhanced publishing, dissemination, sharing and re-use of biodiversity data. We propose the establishment of the 'biodiversity data paper' as one possible mechanism to offer scholarly recognition for efforts and investment by data publishers in authoring rich metadata and publishing them as citable academic papers. While detailing the benefits to data publishers, we describe the objectives, work flow and outcomes of the pilot project commissioned by the Global Biodiversity Information Facility in collaboration with scholarly publishers and pioneered by Pensoft Publishers through its journals Zookeys, PhytoKeys, MycoKeys, BioRisk, NeoBiota, Nature Conservation and the forthcoming Biodiversity Data Journal. We then debate further enhancements of the data paper beyond the pilot project and attempt to forecast the future uptake of data papers as an incentivization mechanism by the stakeholder communities. Conclusions We believe that in addition to recognition for those involved in the data publishing enterprise, data papers will also expedite publishing of fit-for-use biodiversity data resources. However, uptake and establishment of the data paper as a potential mechanism of scholarly recognition requires a high degree of commitment and investment by the cross-sectional stakeholder communities.

Motivation: Enzyme catalysis is involved in numerous biological processes and the disruption of enzymatic activity has been implicated in human disease. Despite this, various aspects of catalytic reactions are not completely understood, such as the mechanics of reaction chemistry and the geometry of catalytic residues within active sites. As a result, the computational prediction of catalytic residues has the potential to identify novel catalytic pockets, aid in the design of more efficient enzymes and also predict the molecular basis of disease. Results: We propose a new kernel-based algorithm for the prediction of catalytic residues based on protein sequence, structure and evolutionary information. The method relies upon explicit modeling of similarity between residue-centered neighborhoods in protein structures. We present evidence that this algorithm evaluates favorably against established approaches, and also provides insights into the relative importance of the geometry, physicochemical properties and evolutionary conservation of catalytic residue activity. The new algorithm was used to identify known mutations associated with inherited disease whose molecular mechanism might be predicted to operate specifically though the loss or gain of catalytic residues. It should, therefore, provide a viable approach to identifying the molecular basis of disease in which the loss or gain of function is not caused solely by the disruption of protein stability. Our analysis suggests that both mechanisms are actively involved in human inherited disease. Availability and Implementation: Source code for the structural kernel is available at www.informatics.indiana.edu/predrag/ Contact: predrag@indiana.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Backgrounds It has been observed that high levels of enhancer of zeste homolog 2 (EZH2) expression are associated with unsatisfactory prognoses and can be found in a wide range of malignancies. However, the effects of EZH2 on Lung Adenocarcinoma (LUAD) remain elusive. Through the integration of bioinformatic analyses, the present paper sought to ascertain the effects of EZH2 in LUAD. Methods The TIMER and UALCAN databases were applied to analyze mRNA and protein expression data for EZH2 in LUAD. The result of immunohistochemistry was obtained from the HPA database, and the survival curve was drawn according to the library provided by the HPA database. The LinkedOmics database was utilized to investigate the co-expressed genes and signal transduction pathways with EZH2. Up- and down-regulated genes from The Linked Omics database were introduced to the CMap database to predict potential drug targets for LUAD using the CMap database. The association between EZH2 and cancer-infiltrating immunocytes was studied through TIMER and TISIDB. In addition, this paper explores the relationship between EZH2 mRNA expression and NSCLC OS using the Kaplan–Meier plotter database to further validate and complement the research. Furthermore, the correlation between EZH2 expression and EGFR genes, KRAS genes, BRAF genes, and smoking from the Cancer Genome Atlas (TCGA) database is analyzed. Results In contrast to paracancer specimens, the mRNA and protein levels of EZH2 were higher in LUAD tissues. Significantly, high levels of EZH2 were associated with unsatisfactory prognoses in LUAD patients. Additionally, the coexpressed genes of EZH2 were predominantly associated with numerous cell growth-associated pathways, including the cell cycle, DNA replication, RNA transport, and the p53 signaling pathway, according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The results of TCGA database revealed that the expression of EZH2 was lower in normal tissues than in lung cancer tissues (p p r = 0.3129, p Conclusions Highly expressed EZH2 is a predictor of a suboptimal prognosis in LUAD and may serve as a prognostic marker and target gene for LUAD. The underlying cause may be associated with the synergistic effect of KRAS, immune cell infiltration, and metabolic processes.

Background Automatic literature based discovery attempts to uncover new knowledge by connecting existing facts: information extracted from existing publications in the form of $$A \rightarrow B$$ A → B and $$B \rightarrow C$$ B → C relations can be simply connected to deduce $$A \rightarrow C$$ A → C . However, using this approach, the quantity of proposed connections is often too vast to be useful. It can be reduced by using subject$$\rightarrow$$ → (predicate)$$\rightarrow$$ → object triples as the $$A \rightarrow B$$ A → B relations, but too many proposed connections remain for manual verification. Results Based on the hypothesis that only a small number of subject–predicate–object triples extracted from a publication represent the paper’s novel contribution(s), we explore using BERT embeddings to identify these before literature based discovery is performed utilizing only these, important, triples. While the method exploits the availability of full texts of publications in the CORD-19 dataset—making use of the fact that a novel contribution is likely to be mentioned in both an abstract and the body of a paper—to build a training set, the resulting tool can be applied to papers with only abstracts available. Candidate hidden knowledge pairs generated from unfiltered triples and those built from important triples only are compared using a variety of timeslicing gold standards. Conclusions The quantity of proposed knowledge pairs is reduced by a factor of $$10^3$$ 10 3 , and we show that when the gold standard is designed to avoid rewarding background knowledge, the precision obtained increases up to a factor of 10. We argue that the gold standard needs to be carefully considered, and release as yet undiscovered candidate knowledge pairs based on important triples alongside this work.

Background In the global effort to discover biomarkers for cancer prognosis, prediction tools have become essential resources. TCR (T cell receptor) repertoires contain important features that differentiate healthy controls from cancer patients or differentiate outcomes for patients being treated with different drugs. Considering, tools that can easily and quickly generate and identify important features out of TCR repertoire data and build accurate classifiers to predict future outcomes are essential. Results This paper introduces GENTLE (GENerator of T cell receptor repertoire features for machine LEarning): an open-source, user-friendly web-application tool that allows TCR repertoire researchers to discover important features; to create classifier models and evaluate them with metrics; and to quickly generate visualizations for data interpretations. We performed a case study with repertoires of TRegs (regulatory T cells) and TConvs (conventional T cells) from healthy controls versus patients with breast cancer. We showed that diversity features were able to distinguish between the groups. Moreover, the classifiers built with these features could correctly classify samples (‘Healthy’ or ‘Breast Cancer’)from the TRegs repertoire when trained with the TConvs repertoire, and from the TConvs repertoire when trained with the TRegs repertoire. Conclusion The paper walks through installing and using GENTLE and presents a case study and results to demonstrate the application’s utility. GENTLE is geared towards any researcher working with TCR repertoire data and aims to discover predictive features from these data and build accurate classifiers. GENTLE is available on https://github.com/dhiego22/gentle and https://share.streamlit.io/dhiego22/gentle/main/gentle.py.

Background Glaucoma can cause irreversible blindness to people’s eyesight. Since there are no symptoms in its early stage, it is particularly important to accurately segment the optic disc (OD) and optic cup (OC) from fundus medical images for the screening and prevention of glaucoma. In recent years, the mainstream method of OD and OC segmentation is convolution neural network (CNN). However, most existing CNN methods segment OD and OC separately and ignore the a priori information that OC is always contained inside the OD region, which makes the segmentation accuracy of most methods not high enough. Methods This paper proposes a new encoder–decoder segmentation structure, called RSAP-Net, for joint segmentation of OD and OC. We first designed an efficient U-shaped segmentation network as the backbone. Considering the spatial overlap relationship between OD and OC, a new Residual spatial attention path is proposed to connect the encoder–decoder to retain more characteristic information. In order to further improve the segmentation performance, a pre-processing method called MSRCR-PT (Multi-Scale Retinex Colour Recovery and Polar Transformation) has been devised. It incorporates a multi-scale Retinex colour recovery algorithm and a polar coordinate transformation, which can help RSAP-Net to produce more refined boundaries of the optic disc and the optic cup. Results The experimental results show that our method achieves excellent segmentation performance on the Drishti-GS1 standard dataset. In the OD and OC segmentation effects, the F1 scores are 0.9752 and 0.9012, respectively. The BLE are 6.33 pixels and 11.97 pixels, respectively. Conclusions This paper presents a new framework for the joint segmentation of optic discs and optic cups, called RSAP-Net. The framework mainly consists of a U-shaped segmentation skeleton and a residual space attention path module. The design of a pre-processing method called MSRCR-PT for the OD/OC segmentation task can improve segmentation performance. The method was evaluated on the publicly available Drishti-GS1 standard dataset and proved to be effective.

Background Assessing the reproducibility of measurements is an important first step for improving the reliability of downstream analyses of high-throughput metabolomics experiments. We define a metabolite to be reproducible when it demonstrates consistency across replicate experiments. Similarly, metabolites which are not consistent across replicates can be labeled as irreproducible. In this work, we introduce and evaluate the use (Ma)ximum (R)ank (R)eproducibility (MaRR) to examine reproducibility in mass spectrometry-based metabolomics experiments. We examine reproducibility across technical or biological samples in three different mass spectrometry metabolomics (MS-Metabolomics) data sets. Results We apply MaRR, a nonparametric approach that detects the change from reproducible to irreproducible signals using a maximal rank statistic. The advantage of using MaRR over model-based methods that it does not make parametric assumptions on the underlying distributions or dependence structures of reproducible metabolites. Using three MS Metabolomics data sets generated in the multi-center Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) study, we applied the MaRR procedure after data processing to explore reproducibility across technical or biological samples. Under realistic settings of MS-Metabolomics data, the MaRR procedure effectively controls the False Discovery Rate (FDR) when there was a gradual reduction in correlation between replicate pairs for less highly ranked signals. Simulation studies also show that the MaRR procedure tends to have high power for detecting reproducible metabolites in most situations except for smaller values of proportion of reproducible metabolites. Bias (i.e., the difference between the estimated and the true value of reproducible signal proportions) values for simulations are also close to zero. The results reported from the real data show a higher level of reproducibility for technical replicates compared to biological replicates across all the three different datasets. In summary, we demonstrate that the MaRR procedure application can be adapted to various experimental designs, and that the nonparametric approach performs consistently well. Conclusions This research was motivated by reproducibility, which has proven to be a major obstacle in the use of genomic findings to advance clinical practice. In this paper, we developed a data-driven approach to assess the reproducibility of MS-Metabolomics data sets. The methods described in this paper are implemented in the open-source R package marr, which is freely available from Bioconductor at http://bioconductor.org/packages/marr.

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 Breast cancer is currently one of the cancers with a higher mortality rate in the world. The biological research on anti-breast cancer drugs focuses on the activity of estrogen receptors alpha (ER$$\alpha$$ α ), the pharmacokinetic properties and the safety of the compounds, which, however, is an expensive and time-consuming process. Developments of deep learning bring potential to efficiently facilitate the candidate drug selection against breast cancer. Methods In this paper, we propose an Anti-Breast Cancer Drug selection method utilizing Gated Graph Neural Networks (ABCD-GGNN) to topologically enhance the molecular representation of candidate drugs. By constructing atom-level graphs through atomic descriptors for each distinct compound, ABCD-GGNN can topologically learn both the implicit structure and substructure characteristics of a candidate drug and then integrate the representation with explicit discrete molecular descriptors to generate a molecule-level representation. As a result, the representation of ABCD-GGNN can inductively predict the ER$$\alpha$$ α , the pharmacokinetic properties and the safety of each candidate drug. Finally, we design a ranking operator whose inputs are the predicted properties so as to statistically select the appropriate drugs against breast cancer. Results Extensive experiments conducted on our collected anti-breast cancer candidate drug dataset demonstrate that our proposed method outperform all the other representative methods in the tasks of predicting ER$$\alpha$$ α , and the pharmacokinetic properties and safety of the compounds. Extended result analysis demonstrates the efficiency and biological rationality of the operator we design to calculate the candidate drug ranking from the predicted properties. Conclusion In this paper, we propose the ABCD-GGNN representation method to efficiently integrate the topological structure and substructure features of the molecules with the discrete molecular descriptors. With a ranking operator applied, the predicted properties efficiently facilitate the candidate drug selection against breast cancer.

Background Nerve discharge is the carrier of information transmission, which can reveal the basic rules of various nerve activities. Recognition of the nerve discharge rhythm is the key to correctly understand the dynamic behavior of the nervous system. The previous methods for the nerve discharge recognition almost depended on the traditional statistical features, and the nonlinear dynamical features of the discharge activity. The artificial extraction and the empirical judgment of the features were required for the recognition. Thus, these methods suffered from subjective factors and were not conducive to the identification of a large number of discharge rhythms. Results The ability of automatic feature extraction along with the development of the neural network has been greatly improved. In this paper, an effective discharge rhythm classification model based on sparse auto-encoder was proposed. The sparse auto-encoder was used to construct the feature learning network. The simulated discharge data from the Chay model and its variants were taken as the input of the network, and the fused features, including the network learning features, covariance and approximate entropy of nerve discharge, were classified by Softmax. The results showed that the accuracy of the classification on the testing data was 87.5%, which could provide more accurate classification results. Compared with other methods for the identification of nerve discharge types, this method could extract the characteristics of nerve discharge rhythm automatically without artificial design, and show a higher accuracy. Conclusions The sparse auto-encoder, even neural network has not been used to classify the basic nerve discharge from neither biological experiment data nor model simulation data. The automatic classification method of nerve discharge rhythm based on the sparse auto-encoder in this paper reduced the subjectivity and misjudgment of the artificial feature extraction, saved the time for the comparison with the traditional method, and improved the intelligence of the classification of discharge types. It could further help us to recognize and identify the nerve discharge activities in a new way.

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 In silico experiments, with the aid of computer simulation, speed up the process of in vitro or in vivo experiments. Cancer therapy design is often based on signalling pathway. MicroRNAs (miRNA) are small non-coding RNA molecules. In several kinds of diseases, including cancer, hepatitis and cardiovascular diseases, they are often deregulated, acting as oncogenes or tumor suppressors. miRNA therapeutics is based on two main kinds of molecules injection: miRNA mimics, which consists of injection of molecules that mimic the targeted miRNA, and antagomiR, which consists of injection of molecules inhibiting the targeted miRNA. Nowadays, the research is focused on miRNA therapeutics. This paper addresses cancer related signalling pathways to investigate miRNA therapeutics. Results In order to prove our approach, we present two different case studies: non-small cell lung cancer and melanoma. KEGG signalling pathways are modelled by a digital circuit. A logic value of 1 is linked to the expression of the corresponding gene. A logic value of 0 is linked to the absence (not expressed) gene. All possible relationships provided by a signalling pathway are modelled by logic gates. Mutations, derived according to the literature, are introduced and modelled as well. The modelling approach and analysis are widely discussed within the paper. MiRNA therapeutics is investigated by the digital circuit analysis. The most effective miRNA and combination of miRNAs, in terms of reduction of pathogenic conditions, are obtained. A discussion of obtained results in comparison with literature data is provided. Results are confirmed by existing data. Conclusions The proposed study is based on drug discovery and miRNA therapeutics and uses a digital circuit simulation of a cancer pathway. Using this simulation, the most effective combination of drugs and miRNAs for mutated cancer therapy design are obtained and these results were validated by the literature. The proposed modelling and analysis approach can be applied to each human disease, starting from the corresponding signalling pathway.

Background Ancestry estimation of skulls is under a wide range of applications in forensic science, anthropology, and facial reconstruction. This study aims to avoid defects in traditional skull ancestry estimation methods, such as time-consuming and labor-intensive manual calibration of feature points, and subjective results. Results This paper uses the skull depth image as input, based on AlexNet, introduces the Wide module and SE-block to improve the network, designs and proposes ANINet, and realizes the ancestry classification. Such a unified model architecture of ANINet overcomes the subjectivity of manually calibrating feature points, of which the accuracy and efficiency are improved. We use depth projection to obtain the local depth image and the global depth image of the skull, take the skull depth image as the object, use global, local, and local + global methods respectively to experiment on the 95 cases of Han skull and 110 cases of Uyghur skull data sets, and perform cross-validation. The experimental results show that the accuracies of the three methods for skull ancestry estimation reached 98.21%, 98.04% and 99.03%, respectively. Compared with the classic networks AlexNet, Vgg-16, GoogLenet, ResNet-50, DenseNet-121, and SqueezeNet, the network proposed in this paper has the advantages of high accuracy and small parameters; compared with state-of-the-art methods, the method in this paper has a higher learning rate and better ability to estimate. Conclusions In summary, skull depth images have an excellent performance in estimation, and ANINet is an effective approach for skull ancestry estimation.

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 Lung cancer is one of the cancers with the highest mortality rate in China. With the rapid development of high-throughput sequencing technology and the research and application of deep learning methods in recent years, deep neural networks based on gene expression have become a hot research direction in lung cancer diagnosis in recent years, which provide an effective way of early diagnosis for lung cancer. Thus, building a deep neural network model is of great significance for the early diagnosis of lung cancer. However, the main challenges in mining gene expression datasets are the curse of dimensionality and imbalanced data. The existing methods proposed by some researchers can’t address the problems of high-dimensionality and imbalanced data, because of the overwhelming number of variables measured (genes) versus the small number of samples, which result in poor performance in early diagnosis for lung cancer. Method Given the disadvantages of gene expression data sets with small datasets, high-dimensionality and imbalanced data, this paper proposes a gene selection method based on KL divergence, which selects some genes with higher KL divergence as model features. Then build a deep neural network model using Focal Loss as loss function, at the same time, we use k-fold cross validation method to verify and select the best model, we set the value of k is five in this paper. Result The deep learning model method based on KL divergence gene selection proposed in this paper has an AUC of 0.99 on the validation set. The generalization performance of model is high. Conclusion The deep neural network model based on KL divergence gene selection proposed in this paper is proved to be an accurate and effective method for lung cancer prediction.

Background: the study of drug-target interactions (DTIs) affinity plays an important role in safety assessment and pharmacology. Currently, quantitative structure-activity relationship (QSAR) and molecular docking (MD) are most common methods in research of DTIs affinity. However, they often built for a specific target or several targets and most QSAR and MD were based either only on structure of drug molecules or on structure of targets with low accuracy and small scope of application. How to construct quantitative prediction models with high accuracy with wide applicability remains a challenge. To this end, this paper screened molecular descriptors based on molecular vibrations and took molecule-target as a whole system to construct prediction model with high accuracy-wide applicability based on Kd and EC50, and to provide reference for quantifying affinity of DTIs.Methods: Through parametric characterization based on molecular vibrations and protein sequences, taking molecule-target as whole system and feature selection of drug molecule-target, we constructed feature datasets of DTIs quantified by Kd and EC50, respectively. Then, prediction models were constructed using above datasets and SVM, RF and ANN. In addition, optimal models were selected for application evaluation and comprehensive comparison.Results: Under ten-fold cross-validation, evaluation parameters based on RF for EC50 dataset are as follows: R2 (RF) of training and test sets are 0.9611, 0.9641; MSE (RF) of training and test sets are 0.0891, 0.0817. Evaluation parameters based on RF for Kd dataset are as follows: R2 (RF) of training and test sets are 0.9425, 0.9485; MSE (RF) of training and test sets are 0.1208, 0.1191. After comprehensive comparison, the results showed that RF model in this paper is optimal model. In application evaluation of RF model, the errors of most prediction results were in range of 1.5-2.0.Conclusion: Through screening molecular descriptors based on molecular vibrations and taking molecule-target as whole system, we obtained optimal model based on RF with more accurate-widely applicable, which indicated that selection of molecular descriptors associated with molecular vibrations and the use of molecular-target as whole system are reliable methods for improving performance of model. It can provide reference for quantifying affinity of DTIs.

BackgroundThe adverse reactions that are caused by drugs are potentially life-threatening problems. Comprehensive knowledge of adverse drug reactions (ADRs) can reduce their detrimental impacts on patients. Detecting ADRs through clinical trials takes a large number of experiments and a long period of time. With the growing amount of unstructured textual data, such as biomedical literature and electronic records, detecting ADRs in the available unstructured data has important implications for ADR research. Most of the neural network-based methods typically focus on the simple semantic information of sentence sequences; however, the relationship of the two entities depends on more complex semantic information.MethodsIn this paper, we propose multihop self-attention mechanism (MSAM) model that aims to learn the multi-aspect semantic information for the ADR detection task. first, the contextual information of the sentence is captured by using the bidirectional long short-term memory (Bi-LSTM) model. Then, via applying the multiple steps of an attention mechanism, multiple semantic representations of a sentence are generated. Each attention step obtains a different attention distribution focusing on the different segments of the sentence. Meanwhile, our model locates and enhances various keywords from the multiple representations of a sentence.ResultsOur model was evaluated by using two ADR corpora. It is shown that the method has a stable generalization ability. Via extensive experiments, our model achieved F-measure of 0.853, 0.799 and 0.851 for ADR detection for TwiMed-PubMed, TwiMed-Twitter, and ADE, respectively. The experimental results showed that our model significantly outperforms other compared models for ADR detection.ConclusionsIn this paper, we propose a modification of multihop self-attention mechanism (MSAM) model for an ADR detection task. The proposed method significantly improved the learning of the complex semantic information of sentences.

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: Automatic extraction of chemical-disease relations (CDR) from unstructured text is of essential importance for disease treatment and drug development. Meanwhile, biomedical experts have built many highly-structured knowledge bases (KBs), which contain prior knowledge about chemicals and diseases. Prior knowledge provides strong support for CDR extraction. How to make full use of it is worth studying. Results: This paper proposes a novel model called "Knowledge-guided Convolutional Networks (KCN)" to leverage prior knowledge for CDR extraction. The proposed model first learns knowledge representations including entity embeddings and relation embeddings from KBs. Then, entity embeddings are used to control the propagation of context features towards a chemical-disease pair with gated convolutions. After that, relation embeddings are employed to further capture the weighted context features by a shared attention pooling. Finally, the weighted context features containing additional knowledge information are used for CDR extraction. Experiments on the BioCreative V CDR dataset show that the proposed KCN achieves 71.28% F1-score, which outperforms most of the state-of-the-art systems. Conclusions: This paper proposes a novel CDR extraction model KCN to make full use of prior knowledge. Experimental results demonstrate that KCN could effectively integrate prior knowledge and contexts for the performance improvement., Published on BMC Bioinformatics, 16 pages, 5 figures

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.

The XVth Annual MidSouth Computational Biology and Bioinformatics Society (MCBIOS XV) conference was held in Starkville, MS from March 29–31, 2018 at Mississippi State University (MSU) within the Mill Conference Center. MSU had previously hosted the conference (MCBIOS VI) in 2009. The theme of MCBIOS XV was “Genomics and Big Data”. The co-chairs and conference hosts were Drs. Bindu Nanduri, Andy Perkins, and Daniel G. Peterson from MSU. The program was co-chaired by Dr. Shraddha Thakkar from the National Center for Toxicological Research (NCTR) within the US Food and Drug Administration (FDA), Dr. Mary Yang, from University of Arkansas at Little Rock (UALR) and Dr. Prashanti Manda from University of North Carolina at Greensboro. The conference was attended by 183 registered participants, of these, 73 registered participants were in the professional category, while 13 were postdoctoral fellows and 97 were student participants. A total of 157 abstracts were submitted for MCBIOS XV, including 65 oral presentations and 92 poster presentations at the meeting. There were nine breakout sessions conducted during the meeting. Each breakout session included a presentation by a featured speaker, a renowned scientist in the topic of that session, followed by four additional presentations in that area. Dr. Cesar M. Compadre, from University of Arkansas for Medical Sciences served as the finance coordinator for the conference. Dr. Ping Gong, at the US Army Engineer Research and Development Center, Vicksburg served as the coordinator of Young Scientist Research Excellence Award. Dr. George Popescu from the Institute of Genomics, Biocomputing and Biotechnology (IGBB) of MSU served as the poster session coordinator, and Dr. William S. Sanders from The Jackson Laboratory served as the workshop coordinator. For 2019–20, Dr. Weida Tong, Director of Division of Bioinformatics and Biostatics from NCTR/FDA was chosen as the President-Elect and Dr. Ramin Homayouni from University of Memphis as the President. Keynote speakers for MCBIOS 2018 Keynote Session I: “Next-Gen Data Science”, Russ Wolfinger, Ph.D., Director of Scientific Discovery and Genomics, JMP Life Sciences, SAS Institute, Cary, NC Keynote Session II: “Real World Data and Precision Medicine: Treatment Selection and Dose Optimization Strategies”, Lawrence J. Lesko Ph.D., F.C.P., University of Florida, Orlando, FL Keynote Session III: “No-Boundary Thinking: Defining Problems So Their Solutions Matter”, Steve Jennings, Ph.D., UALR Keynote Session IV: “Informatics Tools for Big Biologicals and Small Drug Molecules”, William J Welsh, Ph.D., Norman H. Edelman Professor in Bioinformatics, Rutgers University, New Brunswick, NJ Keynote Session V: “A decade of MAQC effort and its contribution to our understanding of high-throughput genomics technologies”, Weida Tong, Ph.D., Director, Division of Bioinformatics and Biostatistics, NCTR/FDA The conference program included three workshops: Workshop I: “Advanced Data Analytics using JMP Genomics”, Wenjun Bao, Ph.D., JMP Life Sciences, SAS Institute, Cary, NC. Workshop II: “Career Development Workshop for Young Scientist”, Inimary Toby, Ph.D., University of Dallas, Dallas, TX. Workshop III: “MCBIOS and No-Boundary Thinking Joint Bioinformatics Research workshop”. Session chair - Steve Jennings, Ph.D., UALR. Presentations: “Encoding biomedical knowledge using hetnets”, Daniel Himmelstein, Ph.D., University of Pennsylvania, Philadelphia, PN. “Microbial interactions and microbe-host interactions”, Hongmei Jiang Ph.D., Northwestern University, Evanston, IL. “Evolution as a metaphor for No Boundary Thinking”, Scott M. Williams, Ph.D., Case Western Reserve University, Cleveland, Ohio. Panel Discussion: Joan Peckham, Ph.D., University of Rhode Island Xiuzhen Huang, Ph.D., Arkansas State University Scott M. Williams, Ph.D., Case Western Reserve University Hongmei Jiang, Ph.D., Northwestern University Daniel Himmelstein, Ph.D., University of Pennsylvania In addition to the workshops, MCBIOS provided assistance to students in preparing their resume. A one-on-one resume clinic was conducted by Gladys Awosemo, HRP, Baylor Scott and White Health, TX. Breakout Session I: Plant Omics I. Session Chair – Sorina C. Popescu, Ph.D., Assistant Professor, MSU. Featured speaker: Marilyn Warburton, Ph.D., United States Department of Agriculture, Agriculture Research Services, MS, “A pathway-based method to interpret GWAS results”. Breakout Session II: Next generation tools for environment and health research. Session Chair and featured speaker: Natalia Reyero, Ph.D., US Army Engineer Research and Development Center, Vicksburg MS, “Next Generation Tools for Environmental Research”. Breakout Session III: Drug Discovery and Precision Medicine. Session Chair and featured speaker: Robert J. Doerksen, Ph.D., University of Mississippi (UM), Oxford, MS, “Protein structure-based virtual screening: deep learning for precision medicine”. Breakout Session IV: Breakout Session IV: Plant Omics II. Session Chair – Sorina C. Popescu, Ph.D., MSU. Featured Speaker: Tessa Burch-Smith, Ph.D., University of Tennessee, Knoxville, TN, “Focused ion beam-scanning electron microscopy for three-dimensional modelling of cellular ultrastructure”. Breakout Session V: Transcriptomics and Genome Sequencing. Session Chair and featured speaker: Brian Counterman, Ph.D., MSU, “Patternize: an R package for color pattern variation”. Breakout Session VI: Big Data and Risk Assessment. Session Chair – Minjun Chen, Ph.D., NCTR/FDA. Featured Speaker: William Mattes, Ph.D., NCTR/FDA, “Systems Biology and Big Data: Little Mitochondria as a Big Example”. Breakout Session VII: Genomics and Proteomics application. Session Chair - Zhichao Liu, Ph.D., NCTR/FDA. Featured Speaker: Rakesh Kaundal, Ph.D., Utah State University, Logan, UT, “Complete genome sequence of Pythium brassicum P1, an oomycete root pathogen: insights into its host specificity to Brassicaceae”. Breakout Session VIII: Genomics and Infectious Disease. Session Chair and Featured speaker: Stephen Pruett, Ph.D., MSU, “Machine Learning Analysis of the Relationship between Changes in Immunological Parameters and Changes in Resistance to Listeria monocytogenes: A New Approach for Risk Assessment and Systems Immunology”. Breakout Session IX: MCBIOS Group Projects. Shraddha Thakkar, Ph.D., NCTR/FDA. William Sanders, Ph.D., IT Research Cyberinfrastructure, The Jackson Laboratory, Bar Harbor, ME. Best Paper Award, MCBIOS 2018: Phillip Berg et al., “Evaluation of Linear Models and Missing Value Imputation for the Analysis of Peptide-Centric Proteomics” [1]. Best Paper Runner-up, MCBIOS 2018: Bohu Pan et al., “Similarities and differences between variants called with human reference genome HG19 or HG38” [2]. This was the 2nd year for “MCBIOS Young Scientist Excellence Award” awards to recognize students and postdoctoral fellows that exhibit scientific excellence in the field of Bioinformatics. Student and postdoctoral fellows went through a rigorous award application process with both internal and external judges. The top five candidates were selected to present during the opening session on March 29th. To compete, applicants submitted an extended abstract with a description of the innovation of their research and their specific contribution to the work presented, from which the quality and impact of the research was judged. Initiative in expanding their skills and bringing multidisciplinary talent to their project was an important consideration for selection for an oral presentation, and the quality of the presentation during the plenary session was the primary consideration for award. Additional evaluation criteria included creativity, dedication and multidisciplinary contribution. This award was supported by the FDA grant to MCBIOS (5R13FD005931–03) and JMP Life Sciences. MCBIOS young scientist excellence award 2018 Post-doctoral winners First Place: Sundar Thangapandian, Ph.D., University of Illinois Urbana-Champaign, Urbana, IL. “Quantitative Target-specific Toxicity Prediction Model (QTTPM): A Novel Computational Toxicology Approach Integrating Molecular Dynamics Simulation and Machine Learning”. Second Place: Brian Walker, Ph.D., UALR. “Synthesis of xanthine derivatives for the inhibition of PARG”. Third Place: Darshan Mehta, Ph.D., NCTR/FDA. “Mining pharmacogenomic information from drug labeling using FDALabel database for advancing precision medicine”.

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 Addiction to drugs and alcohol constitutes one of the significant factors underlying the decline in life expectancy in the US. Several context-specific reasons influence drug use and recovery. In particular emotional distress, physical pain, relationships, and self-development efforts are known to be some of the factors associated with addiction recovery. Unfortunately, many of these factors are not directly observable and quantifying, and assessing their impact can be difficult. Based on social media posts of users engaged in substance use and recovery on the forum Reddit, we employed two psycholinguistic tools, Linguistic Inquiry and Word Count and Empath and activities of substance users on various Reddit sub-forums to analyze behavior underlining addiction recovery and relapse. We then employed a statistical analysis technique called structural equation modeling to assess the effects of these latent factors on recovery and relapse. Results We found that both emotional distress and physical pain significantly influence addiction recovery behavior. Self-development activities and social relationships of the substance users were also found to enable recovery. Furthermore, within the context of self-development activities, those that were related to influencing the mental and physical well-being of substance users were found to be positively associated with addiction recovery. We also determined that lack of social activities and physical exercise can enable a relapse. Moreover, geography, especially life in rural areas, appears to have a greater correlation with addiction relapse. Conclusions The paper describes how observable variables can be extracted from social media and then be used to model important latent constructs that impact addiction recovery and relapse. We also report factors that impact self-induced addiction recovery and relapse. To the best of our knowledge, this paper represents the first use of structural equation modeling of social media data with the goal of analyzing factors influencing addiction recovery.

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 Permutation testing is often considered the “gold standard” for multi-test significance analysis, as it is an exact test requiring few assumptions about the distribution being computed. However, it can be computationally very expensive, particularly in its naive form in which the full analysis pipeline is re-run after permuting the phenotype labels. This can become intractable in multi-locus genome-wide association studies (GWAS), in which the number of potential interactions to be tested is combinatorially large. Results In this paper, we develop an approach for permutation testing in multi-locus GWAS, specifically focusing on SNP–SNP-phenotype interactions using multivariable measures that can be computed from frequency count tables, such as those based in Information Theory. We find that the computational bottleneck in this process is the construction of the count tables themselves, and that this step can be eliminated at each iteration of the permutation testing by transforming the count tables directly. This leads to a speed-up by a factor of over 103 for a typical permutation test compared to the naive approach. Additionally, this approach is insensitive to the number of samples making it suitable for datasets with large number of samples. Conclusions The proliferation of large-scale datasets with genotype data for hundreds of thousands of individuals enables new and more powerful approaches for the detection of multi-locus genotype-phenotype interactions. Our approach significantly improves the computational tractability of permutation testing for these studies. Moreover, our approach is insensitive to the large number of samples in these modern datasets. The code for performing these computations and replicating the figures in this paper is freely available at https://github.com/kunert/permute-counts.

The 16th Annual Meeting of the Bioinformatics Italian Society was held in Palermo, Italy, on June 26-28, 2019. More than 80 scientific contributions were presented, including 4 keynote lectures, 31 oral communications and 49 posters. Also, three workshops were organised before and during the meeting. Full papers from some of the works presented in Palermo were submitted for this Supplement of BMC Bioinformatics. Here, we provide an overview of meeting aims and scope. We also shortly introduce selected papers that have been accepted for publication in this Supplement, for a complete presentation of the outcomes of the meeting.

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.

Background Melanoma is one of the most aggressive types of cancer that has become a world-class problem. According to the World Health Organization estimates, 132,000 cases of the disease and 66,000 deaths from malignant melanoma and other forms of skin cancer are reported annually worldwide (https://apps.who.int/gho/data/?theme=main) and those numbers continue to grow. In our opinion, due to the increasing incidence of the disease, it is necessary to find new, easy to use and sensitive methods for the early diagnosis of melanoma in a large number of people around the world. Over the last decade, neural networks show highly sensitive, specific, and accurate results. Objective This study presents a review of PubMed papers including requests «melanoma neural network» and «melanoma neural network dermatoscopy». We review recent researches and discuss their opportunities acceptable in clinical practice. Methods We searched the PubMed database for systematic reviews and original research papers on the requests «melanoma neural network» and «melanoma neural network dermatoscopy» published in English. Only papers that reported results, progress and outcomes are included in this review. Results We found 11 papers that match our requests that observed convolutional and deep-learning neural networks combined with fuzzy clustering or World Cup Optimization algorithms in analyzing dermatoscopic images. All of them require an ABCD (asymmetry, border, color, and differential structures) algorithm and its derivates (in combination with ABCD algorithm or separately). Also, they require a large dataset of dermatoscopic images and optimized estimation parameters to provide high specificity, accuracy and sensitivity. Conclusions According to the analyzed papers, neural networks show higher specificity, accuracy and sensitivity than dermatologists. Neural networks are able to evaluate features that might be unavailable to the naked human eye. Despite that, we need more datasets to confirm those statements. Nowadays machine learning becomes a helpful tool in early diagnosing skin diseases, especially melanoma.

Background The main research topic in this paper is how to compare multiple biological experiments using transcriptome data, where each experiment is measured and designed to compare control and treated samples. Comparison of multiple biological experiments is usually performed in terms of the number of DEGs in an arbitrary combination of biological experiments. This process is usually facilitated with Venn diagram but there are several issues when Venn diagram is used to compare and analyze multiple experiments in terms of DEGs. First, current Venn diagram tools do not provide systematic analysis to prioritize genes. Because that current tools generally do not fully focus to prioritize genes, genes that are located in the segments in the Venn diagram (especially, intersection) is usually difficult to rank. Second, elucidating the phenotypic difference only with the lists of DEGs and expression values is challenging when the experimental designs have the combination of treatments. Experiment designs that aim to find the synergistic effect of the combination of treatments are very difficult to find without an informative system. Results We introduce Venn-diaNet, a Venn diagram based analysis framework that uses network propagation upon protein-protein interaction network to prioritizes genes from experiments that have multiple DEG lists. We suggest that the two issues can be effectively handled by ranking or prioritizing genes with segments of a Venn diagram. The user can easily compare multiple DEG lists with gene rankings, which is easy to understand and also can be coupled with additional analysis for their purposes. Our system provides a web-based interface to select seed genes in any of areas in a Venn diagram and then perform network propagation analysis to measure the influence of the selected seed genes in terms of ranked list of DEGs. Conclusions We suggest that our system can logically guide to select seed genes without additional prior knowledge that makes us free from the seed selection of network propagation issues. We showed that Venn-diaNet can reproduce the research findings reported in the original papers that have experiments that compare two, three and eight experiments. Venn-diaNet is freely available at: http://biohealth.snu.ac.kr/software/venndianet

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.