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Motivation Biomedical entity linking (BEL) is the task of grounding entity mentions to a knowledge base (KB). It plays a vital role in information extraction pipelines for the life sciences literature. We review recent work in the field and find that, as the task is absent from existing benchmarks for biomedical text mining, different studies adopt different experimental setups making comparisons based on published numbers problematic. Furthermore, neural systems are tested primarily on instances linked to the broad coverage KB UMLS, leaving their performance to more specialized ones, e.g. genes or variants, understudied. Results We therefore developed BELB, a biomedical entity linking benchmark, providing access in a unified format to 11 corpora linked to 7 KBs and spanning six entity types: gene, disease, chemical, species, cell line, and variant. BELB greatly reduces preprocessing overhead in testing BEL systems on multiple corpora offering a standardized testbed for reproducible experiments. Using BELB, we perform an extensive evaluation of six rule-based entity-specific systems and three recent neural approaches leveraging pre-trained language models. Our results reveal a mixed picture showing that neural approaches fail to perform consistently across entity types, highlighting the need of further studies towards entity-agnostic models. Availability and implementation The source code of BELB is available at: https://github.com/sg-wbi/belb. The code to reproduce our experiments can be found at: https://github.com/sg-wbi/belb-exp. [ABSTRACT FROM AUTHOR]

Motivation The recognition of mentions of species names in text is a critically important task for biomedical text mining. While deep learning-based methods have made great advances in many named entity recognition tasks, results for species name recognition remain poor. We hypothesize that this is primarily due to the lack of appropriate corpora. Results We introduce the S1000 corpus, a comprehensive manual re-annotation and extension of the S800 corpus. We demonstrate that S1000 makes highly accurate recognition of species names possible (F -score =93.1%), both for deep learning and dictionary-based methods. Availability and implementation All resources introduced in this study are available under open licenses from https://jensenlab.org/resources/s1000/. The webpage contains links to a Zenodo project and three GitHub repositories associated with the study. [ABSTRACT FROM AUTHOR]

Motivation Large-scale prediction of drug–target affinity (DTA) plays an important role in drug discovery. In recent years, machine learning algorithms have made great progress in DTA prediction by utilizing sequence or structural information of both drugs and proteins. However, sequence-based algorithms ignore the structural information of molecules and proteins, while graph-based algorithms are insufficient in feature extraction and information interaction. Results In this article, we propose NHGNN-DTA, a node-adaptive hybrid neural network for interpretable DTA prediction. It can adaptively acquire feature representations of drugs and proteins and allow information to interact at the graph level, effectively combining the advantages of both sequence-based and graph-based approaches. Experimental results have shown that NHGNN-DTA achieved new state-of-the-art performance. It achieved the mean squared error (MSE) of 0.196 on the Davis dataset (below 0.2 for the first time) and 0.124 on the KIBA dataset (3% improvement). Meanwhile, in the case of cold start scenario, NHGNN-DTA proved to be more robust and more effective with unseen inputs than baseline methods. Furthermore, the multi-head self-attention mechanism endows the model with interpretability, providing new exploratory insights for drug discovery. The case study on Omicron variants of SARS-CoV-2 illustrates the efficient utilization of drug repurposing in COVID-19. Availability and implementation The source code and data are available at https://github.com/hehh77/NHGNN-DTA. [ABSTRACT FROM AUTHOR]

Motivation Biomedical named entity recognition (BioNER) seeks to automatically recognize biomedical entities in natural language text, serving as a necessary foundation for downstream text mining tasks and applications such as information extraction and question answering. Manually labeling training data for the BioNER task is costly, however, due to the significant domain expertise required for accurate annotation. The resulting data scarcity causes current BioNER approaches to be prone to overfitting, to suffer from limited generalizability, and to address a single entity type at a time (e.g. gene or disease). Results We therefore propose a novel all-in-one (AIO) scheme that uses external data from existing annotated resources to enhance the accuracy and stability of BioNER models. We further present AIONER, a general-purpose BioNER tool based on cutting-edge deep learning and our AIO schema. We evaluate AIONER on 14 BioNER benchmark tasks and show that AIONER is effective, robust, and compares favorably to other state-of-the-art approaches such as multi-task learning. We further demonstrate the practical utility of AIONER in three independent tasks to recognize entity types not previously seen in training data, as well as the advantages of AIONER over existing methods for processing biomedical text at a large scale (e.g. the entire PubMed data). Availability and implementation The source code, trained models and data for AIONER are freely available at https://github.com/ncbi/AIONER. [ABSTRACT FROM AUTHOR]

Motivation Machine learning (ML) methods are motivated by the need to automate information extraction from large datasets in order to support human users in data-driven tasks. This is an attractive approach for integrative joint analysis of vast amounts of omics data produced in next generation sequencing and other -omics assays. A systematic assessment of the current literature can help to identify key trends and potential gaps in methodology and applications. We surveyed the literature on ML multi-omic data integration and quantitatively explored the goals, techniques and data involved in this field. We were particularly interested in examining how researchers use ML to deal with the volume and complexity of these datasets. Results Our main finding is that the methods used are those that address the challenges of datasets with few samples and many features. Dimensionality reduction methods are used to reduce the feature count alongside models that can also appropriately handle relatively few samples. Popular techniques include autoencoders, random forests and support vector machines. We also found that the field is heavily influenced by the use of The Cancer Genome Atlas dataset, which is accessible and contains many diverse experiments. Availability and implementation All data and processing scripts are available at this GitLab repository: https://gitlab.com/polavieja%5flab/ml%5fmulti-omics%5freview/ or in Zenodo: https://doi.org/10.5281/zenodo.7361807. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Most of the conventional deep neural network-based methods for drug–drug interaction (DDI) extraction consider only context information around drug mentions in the text. However, human experts use heterogeneous background knowledge about drugs to comprehend pharmaceutical papers and extract relationships between drugs. Therefore, we propose a novel method that simultaneously considers various heterogeneous information for DDI extraction from the literature. Results We first construct drug representations by conducting the link prediction task on a heterogeneous pharmaceutical knowledge graph (KG) dataset. We then effectively combine the text information of input sentences in the corpus and the information on drugs in the heterogeneous KG (HKG) dataset. Finally, we evaluate our DDI extraction method on the DDIExtraction-2013 shared task dataset. In the experiment, integrating heterogeneous drug information significantly improves the DDI extraction performance, and we achieved an F-score of 85.40%, which results in state-of-the-art performance. We evaluated our method on the DrugProt dataset and improved the performance significantly, achieving an F-score of 77.9%. Further analysis showed that each type of node in the HKG contributes to the performance improvement of DDI extraction, indicating the importance of considering multiple pieces of information. Availability and implementation Our code is available at https://github.com/tticoin/HKG-DDIE.git [ABSTRACT FROM AUTHOR]

Motivation In modern translational research, the development of biomarkers heavily relies on use of omics technologies, but implementations with basic data mining algorithms frequently lead to false positives. Non-dominated Sorting Genetic Algorithm II (NSGA2) is an extremely effective algorithm for biomarker discovery but has been rarely evaluated against large-scale datasets. The exploration of the feature search space is the key to NSGA2 success but in specific cases NSGA2 expresses a shallow exploration of the space of possible feature combinations, possibly leading to models with low predictive performances. Results We propose two improved NSGA2 algorithms for finding subsets of biomarkers exhibiting different trade-offs between accuracy and feature number. The performances are investigated on gene expression data of breast cancer patients. The results are compared with NSGA2 and LASSO. The benchmarking dataset includes internal and external validation sets. The results show that the proposed algorithms generate a better approximation of the optimal trade-offs between accuracy and set size. Moreover, validation and test accuracies are better than those provided by NSGA2 and LASSO. Remarkably, the GA-based methods provide biomarkers that achieve a very high prediction accuracy (>80%) with a small number of features (<10), representing a valid alternative to known biomarker models, such as Pam50 and MammaPrint. Availability and implementation The software is publicly available on GitHub at github.com/UEFBiomedicalInformaticsLab/BIODAI/tree/main/MOO. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

MotivationA heterogeneous network topology possessing abundant interactions between biomedical entities has yet to be utilized in similarity-based methods for predicting drug-target associations based on the array of varying features of drugs and their targets. Deep learning reveals features of vertices of a large network that can be adapted in accommodating the similarity-based solutions to provide a flexible method of drug-target prediction.ResultsWe propose a similarity-based drug-target prediction method that enhances existing association discovery methods by using a topology-based similarity measure. DeepWalk, a deep learning method, is adopted in this study to calculate the similarities within Linked Tripartite Network (LTN), a heterogeneous network generated from biomedical linked datasets. This proposed method shows promising results for drug-target association prediction: 98.96% AUC ROC score with a 10-fold cross-validation and 99.25% AUC ROC score with a Monte Carlo cross-validation with LTN. By utilizing DeepWalk, we demonstrate that: (i) this method outperforms other existing topology-based similarity computation methods, (ii) the performance is better for tripartite than with bipartite networks and (iii) the measure of similarity using network topology outperforms the ones derived from chemical structure (drugs) or genomic sequence (targets). Our proposed methodology proves to be capable of providing a promising solution for drug-target prediction based on topological similarity with a heterogeneous network, and may be readily re-purposed and adapted in the existing of similarity-based methodologies.Availability and implementationThe proposed method has been developed in JAVA and it is available, along with the data at the following URL: https://github.com/zongnansu1982/drug-target-prediction .Contactnazong@ucsd.edu.Supplementary informationSupplementary data are available at Bioinformatics online.

Motivation Chemical cross-linking combined with mass spectrometry (CXMS) is now a well-established method for profiling existing protein–protein interactions (PPIs) with partially known structures. It is expected to map the results of CXMS with existing structure databases to study the protein dynamic profile in the structure analysis. However, currently available structure-based analysis software suffers from the difficulty of achieving large-scale analysis. Besides, it is infeasible for structure analysis and data mining on a large scale, since of lacking global measurement of dynamic structure mapping results. Results ComMap (protein complex structure mapping) is a software designed to perform large-scale structure-based mapping by integrating CXMS data with existing structures. It allows complete the distance calculation of PPIs with existing structures in batch within minutes and provides scores for different PPI-structure pairs of testable hypothetical structural dynamism via a global view. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation DNA methylation plays an important role in epigenetic modification, the occurrence, and the development of diseases. Therefore, identification of DNA methylation sites is critical for better understanding and revealing their functional mechanisms. To date, several machine learning and deep learning methods have been developed for the prediction of different DNA methylation types. However, they still highly rely on manual features, which can largely limit the high-latent information extraction. Moreover, most of them are designed for one specific DNA methylation type, and therefore cannot predict multiple methylation sites in multiple species simultaneously. In this study, we propose iDNA-ABT, an advanced deep learning model that utilizes adaptive embedding based on Bidirectional Encoder Representations from Transformers (BERT) together with transductive information maximization (TIM). Results Benchmark results show that our proposed iDNA-ABT can automatically and adaptively learn the distinguishing features of biological sequences from multiple species, and thus perform significantly better than the state-of-the-art methods in predicting three different DNA methylation types. In addition, TIM loss is proven to be effective in dichotomous tasks via the comparison experiment. Furthermore, we verify that our features have strong adaptability and robustness to different species through comparison of adaptive embedding and six handcrafted feature encodings. Importantly, our model shows great generalization ability in different species, demonstrating that our model can adaptively capture the cross-species differences and improve the predictive performance. For the convenient use of our method, we further established an online webserver as the implementation of the proposed iDNA-ABT. Availability and implementation Our proposed iDNA-ABT and data are freely accessible via http://server.wei-group.net/iDNA%5fABT and our source codes are available for downloading in the GitHub repository (https://github.com/YUYING07/iDNA%5fABT). Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation For network-assisted analysis, which has become a popular method of data mining, network construction is a crucial task. Network construction relies on the accurate quantification of direct associations among variables. The existence of multiscale associations among variables presents several quantification challenges, especially when quantifying nonlinear direct interactions. Results In this study, the multiscale part mutual information (MPMI), based on part mutual information (PMI) and nonlinear partial association (NPA), was developed for effectively quantifying nonlinear direct associations among variables in networks with multiscale associations. First, we defined the MPMI in theory and derived its five important properties. Second, an experiment in a three-node network was carried out to numerically estimate its quantification ability under two cases of strong associations. Third, experiments of the MPMI and comparisons with the PMI, NPA and conditional mutual information were performed on simulated datasets and on datasets from DREAM challenge project. Finally, the MPMI was applied to real datasets of glioblastoma and lung adenocarcinoma to validate its effectiveness. Results showed that the MPMI is an effective alternative measure for quantifying nonlinear direct associations in networks, especially those with multiscale associations. Availability and implementation The source code of MPMI is available online at https://github.com/CDMB-lab/MPMI. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Synthetic lethality (SL) is a promising gold mine for the discovery of anti-cancer drug targets. Wet-lab screening of SL pairs is afflicted with high cost, batch-effect, and off-target problems. Current computational methods for SL prediction include gene knock-out simulation, knowledge-based data mining and machine learning methods. Most of the existing methods tend to assume that SL pairs are independent of each other, without taking into account the shared biological mechanisms underlying the SL pairs. Although several methods have incorporated genomic and proteomic data to aid SL prediction, these methods involve manual feature engineering that heavily relies on domain knowledge. Results Here, we propose a novel graph neural network (GNN)-based model, named KG4SL, by incorporating knowledge graph (KG) message-passing into SL prediction. The KG was constructed using 11 kinds of entities including genes, compounds, diseases, biological processes and 24 kinds of relationships that could be pertinent to SL. The integration of KG can help harness the independence issue and circumvent manual feature engineering by conducting message-passing on the KG. Our model outperformed all the state-of-the-art baselines in area under the curve, area under precision-recall curve and F1. Extensive experiments, including the comparison of our model with an unsupervised TransE model, a vanilla graph convolutional network model, and their combination, demonstrated the significant impact of incorporating KG into GNN for SL prediction. Availability and implementation : KG4SL is freely available at https://github.com/JieZheng-ShanghaiTech/KG4SL. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation: The wealth of data resources on human phenotypes, risk factors, molecular traits and therapeutic interventions presents new opportunities for population health sciences. These opportunities are paralleled by a growing need for data integration, curation and mining to increase research efficiency, reduce mis-inference and ensure reproducible research. Results: We developed EpiGraphDB (https://epigraphdb.org/), a graph database containing an array of different biomedical and epidemiological relationships and an analytical platform to support their use in human population health data science. In addition, we present three case studies that illustrate the value of this platform. The first uses EpiGraphDB to evaluate potential pleiotropic relationships, addressing mis-inference in systematic causal analysis. In the second case study, we illustrate how protein–protein interaction data offer opportunities to identify new drug targets. The final case study integrates causal inference using Mendelian randomization with relationships mined from the biomedical literature to 'triangulate' evidence from different sources. Availability and implementation: The EpiGraphDB platform is openly available at https://epigraphdb.org. Code for replicating case study results is available at https://github.com/MRCIEU/epigraphdb as Jupyter notebooks using the API, and https://mrcieu.github.io/epigraphdb-r using the R package. Supplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Summary MeRIPseqPipe is an integrated and automatic pipeline that can provide users a friendly solution to perform in-depth mining of MeRIP-seq data. It integrates many functional analysis modules, range from basic processing to downstream analysis. All the processes are embedded in Nextflow with Docker support, which ensures high reproducibility and scalability of the analysis. MeRIPseqPipe is particularly suitable for analyzing a large number of samples at once with a simple command. The final output directory is structured based on each step and tool. And visualization reports containing various tables and plots are provided as HTML files. Availability and implementation MeRIPseqPipe is freely available at https://github.com/canceromics/MeRIPseqPipe. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation The development of deep, bidirectional transformers such as Bidirectional Encoder Representations from Transformers (BERT) led to an outperformance of several Natural Language Processing (NLP) benchmarks. Especially in radiology, large amounts of free-text data are generated in daily clinical workflow. These report texts could be of particular use for the generation of labels in machine learning, especially for image classification. However, as report texts are mostly unstructured, advanced NLP methods are needed to enable accurate text classification. While neural networks can be used for this purpose, they must first be trained on large amounts of manually labelled data to achieve good results. In contrast, BERT models can be pre-trained on unlabelled data and then only require fine tuning on a small amount of manually labelled data to achieve even better results. Results Using BERT to identify the most important findings in intensive care chest radiograph reports, we achieve areas under the receiver operation characteristics curve of 0.98 for congestion, 0.97 for effusion, 0.97 for consolidation and 0.99 for pneumothorax, surpassing the accuracy of previous approaches with comparatively little annotation effort. Our approach could therefore help to improve information extraction from free-text medical reports. Availability   and implementation We make the source code for fine-tuning the BERT-models freely available at https://github.com/fast-raidiology/bert-for-radiology. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Searching the Longest Common Subsequences of many sequences is called a Multiple Longest Common Subsequence (MLCS) problem which is a very fundamental and challenging problem in many fields of data mining. The existing algorithms cannot be applicable to problems with long and large-scale sequences due to their huge time and space consumption. To efficiently handle large-scale MLCS problems, a Path Recorder Directed Acyclic Graph (PRDAG) model and a novel Path Recorder Algorithm (PRA) are proposed. Results In PRDAG, we transform the MLCS problem into searching the longest path from the Directed Acyclic Graph (DAG), where each longest path in DAG corresponds to an MLCS. To tackle the problem efficiently, we eliminate all redundant and repeated nodes during the construction of DAG, and for each node, we only maintain the longest paths from the source node to it but ignore all non-longest paths. As a result, the size of the DAG becomes very small, and the memory space and search time will be greatly saved. Empirical experiments have been performed on a standard benchmark set of both DNA sequences and protein sequences. The experimental results demonstrate that our model and algorithm outperform the related leading algorithms, especially for large-scale MLCS problems. Availability and implementation This program code is written by the first author and can be available at https://www.ncbi.nlm.nih.gov/nuccore and https://blog.csdn.net/wswguilin. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Biomedical literature is growing at a rate that outpaces our ability to harness the knowledge contained therein. To mine valuable inferences from the large volume of literature, many researchers use information extraction algorithms to harvest information in biomedical texts. Information extraction is usually accomplished via a combination of manual expert curation and computational methods. Advances in computational methods usually depend on the time-consuming generation of gold standards by a limited number of expert curators. Citizen science is public participation in scientific research. We previously found that citizen scientists are willing and capable of performing named entity recognition of disease mentions in biomedical abstracts, but did not know if this was true with relationship extraction (RE). Results In this article, we introduce the Relationship Extraction Module of the web-based application Mark2Cure (M2C) and demonstrate that citizen scientists can perform RE. We confirm the importance of accurate named entity recognition on user performance of RE and identify design issues that impacted data quality. We find that the data generated by citizen scientists can be used to identify relationship types not currently available in the M2C Relationship Extraction Module. We compare the citizen science-generated data with algorithm-mined data and identify ways in which the two approaches may complement one another. We also discuss opportunities for future improvement of this system, as well as the potential synergies between citizen science, manual biocuration and natural language processing. Availability and implementation Mark2Cure platform: https://mark2cure.org ; Mark2Cure source code: https://github.com/sulab/mark2cure ; and data and analysis code for this article: https://github.com/gtsueng/M2C%5frel%5fnb. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Association studies based on SNP arrays and Next Generation Sequencing technologies have enabled the discovery of thousands of genetic loci related to human diseases. Nevertheless, their biological interpretation is still elusive, and their medical applications limited. Recently, various tools have been developed to help bridging the gap between genomes and phenomes. To our knowledge, however none of these tools allows users to retrieve the phenotype-wide list of genetic variants that may be linked to a given disease or to visually explore the joint genetic architecture of different pathologies. Results We present the Genome-Phenome Explorer (GePhEx), a web-tool easing the visual exploration of phenotypic relationships supported by genetic evidences. GePhEx is primarily based on the thorough analysis of linkage disequilibrium between disease-associated variants and also considers relationships based on genes, pathways or drug-targets, leveraging on publicly available variant-disease associations to detect potential relationships between diseases. We demonstrate that GePhEx does retrieve well-known relationships as well as novel ones, and that, thus, it might help shedding light on the patho-physiological mechanisms underlying complex diseases. To this end, we investigate the potential relationship between schizophrenia and lung cancer, first detected using GePhEx and provide further evidence supporting a functional link between them. Availability and implementation GePhEx is available at: https://gephex.ega-archive.org/. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Biomedical event extraction is fundamental for information extraction in molecular biology and biomedical research. The detected events form the central basis for comprehensive biomedical knowledge fusion, facilitating the digestion of massive information influx from the literature. Limited by the event context, the existing event detection models are mostly applicable for a single task. A general and scalable computational model is desiderated for biomedical knowledge management. Results We consider and propose a bottom-up detection framework to identify the events from recognized arguments. To capture the relations between the arguments, we trained a bidirectional long short-term memory network to model their context embedding. Leveraging the compositional attributes, we further derived the candidate samples for training event classifiers. We built our models on the datasets from BioNLP Shared Task for evaluations. Our method achieved the average F -scores of 0.81 and 0.92 on BioNLPST-BGI and BioNLPST-BB datasets, respectively. Comparing with seven state-of-the-art methods, our method nearly doubled the existing F -score performance (0.92 versus 0.56) on the BioNLPST-BB dataset. Case studies were conducted to reveal the underlying reasons. Availability and implementation https://github.com/cskyan/evntextrc. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Automatic biomedical named entity recognition (BioNER) is a key task in biomedical information extraction. For some time, state-of-the-art BioNER has been dominated by machine learning methods, particularly conditional random fields (CRFs), with a recent focus on deep learning. However, recent work has suggested that the high performance of CRFs for BioNER may not generalize to corpora other than the one it was trained on. In our analysis, we find that a popular deep learning-based approach to BioNER, known as bidirectional long short-term memory network-conditional random field (BiLSTM-CRF), is correspondingly poor at generalizing. To address this, we evaluate three modifications of BiLSTM-CRF for BioNER to improve generalization: improved regularization via variational dropout, transfer learning and multi-task learning. Results We measure the effect that each strategy has when training/testing on the same corpus ('in-corpus' performance) and when training on one corpus and evaluating on another ('out-of-corpus' performance), our measure of the model's ability to generalize. We found that variational dropout improves out-of-corpus performance by an average of 4.62%, transfer learning by 6.48% and multi-task learning by 8.42%. The maximal increase we identified combines multi-task learning and variational dropout, which boosts out-of-corpus performance by 10.75%. Furthermore, we make available a new open-source tool, called Saber that implements our best BioNER models. Availability and implementation Source code for our biomedical IE tool is available at https://github.com/BaderLab/saber. Corpora and other resources used in this study are available at https://github.com/BaderLab/Towards-reliable-BioNER. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Information extraction by mining the scientific literature is key to uncovering relations between biomedical entities. Most existing approaches based on natural language processing extract relations from single sentence-level co-mentions, ignoring co-occurrence statistics over the whole corpus. Existing approaches counting entity co-occurrences ignore the textual context of each co-occurrence. Results We propose a novel corpus-wide co-occurrence scoring approach to relation extraction that takes the textual context of each co-mention into account. Our method, called CoCoScore, scores the certainty of stating an association for each sentence that co-mentions two entities. CoCoScore is trained using distant supervision based on a gold-standard set of associations between entities of interest. Instead of requiring a manually annotated training corpus, co-mentions are labeled as positives/negatives according to their presence/absence in the gold standard. We show that CoCoScore outperforms previous approaches in identifying human disease–gene and tissue–gene associations as well as in identifying physical and functional protein–protein associations in different species. CoCoScore is a versatile text mining tool to uncover pairwise associations via co-occurrence mining, within and beyond biomedical applications. Availability and implementation CoCoScore is available at: https://github.com/JungeAlexander/cocoscore. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation An important goal of cancer genomics initiatives is to provide the research community with the resources for the unbiased query of cancer mechanisms. Several excellent web platforms have been developed to enable the visual analyses of molecular alterations in cancers from these datasets. However, there are few tools to allow the researchers to mine these resources for mechanisms of cancer processes and their functional interactions in an intuitive unbiased manner. Results To address this need, we developed SEMA, a web platform for building and testing of models of cancer mechanisms from large multidimensional cancer genomics datasets. Unlike the existing tools for the analyses and query of these resources, SEMA is explicitly designed to enable exploratory and confirmatory analyses of complex cancer mechanisms through a suite of intuitive visual and statistical functionalities. Here, we present a case study of the functional mechanisms of TP53 -mediated tumor suppression in various cancers, using SEMA, and identify its role in the regulation of cell cycle progression, DNA repair and signal transduction in different cancers. SEMA is a first-in-its-class web application designed to allow visual data mining and hypothesis testing from the multidimensional cancer datasets. The web application, an extensive tutorial and several video screencasts with case studies are freely available for academic use at https://sema.research.cchmc.org/. Availability and implementation SEMA is freely available at https://sema.research.cchmc.org. The web site also contains a detailed Tutorial (also in Supplementary Information), and a link to the YouTube channel for video screencasts of analyses, including the analyses presented here. The Shiny and JavaScript source codes have been deposited to GitHub: https://github.com/msolmazm/sema. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation We proposed a wiSDOM (w eb-based i nclusionary analysis S uite for D isease- O riented M etagenomics) R Shiny application which comprises six functional modules: (i) initial visualization of sampling effort and distribution of dominant bacterial taxa among groups or individual samples at different taxonomic levels; (ii) statistical and visual analysis of α diversity; (iii) analysis of similarity (ANOSIM) of β diversity on UniFrac, Bray-Curtis, Horn-Morisita or Jaccard distance and visualizations; (iv) microbial biomarker discovery between two or more groups with various statistical and machine learning approaches; (v) assessment of the clinical validity of selected biomarkers by creating the interactive receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC) for binary classifiers; and lastly (vi) functional prediction of metagenomes with PICRUSt or Tax4Fun. Results The performance of wiSDOM has been evaluated in several of our previous studies for exploring microbial biomarkers and their clinical validity as well as assessing the alterations in bacterial diversity and functionality. The wiSDOM can be customized and visualized as per users' needs and specifications, allowing researchers without programming background to conduct comprehensive data mining and illustration using an intuitive browser-based interface. Availability and implementation The browser-based R Shiny interface can be accessible via (https://lun-ching.shinyapps.io/wisdom/) and freely available at (https://github.com/lunching/wiSDOM). Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Summary Named entity recognition (NER) is an important step in biomedical information extraction pipelines. Tools for NER should be easy to use, cover multiple entity types, be highly accurate and be robust toward variations in text genre and style. We present HunFlair , a NER tagger fulfilling these requirements. HunFlair is integrated into the widely used NLP framework Flair , recognizes five biomedical entity types, reaches or overcomes state-of-the-art performance on a wide set of evaluation corpora, and is trained in a cross-corpus setting to avoid corpus-specific bias. Technically, it uses a character-level language model pretrained on roughly 24 million biomedical abstracts and three million full texts. It outperforms other off-the-shelf biomedical NER tools with an average gain of 7.26 pp over the next best tool in a cross-corpus setting and achieves on-par results with state-of-the-art research prototypes in in-corpus experiments. HunFlair can be installed with a single command and is applied with only four lines of code. Furthermore, it is accompanied by harmonized versions of 23 biomedical NER corpora. Availability and implementation HunFlair ist freely available through the Flair NLP framework (https://github.com/flairNLP/flair) under an MIT license and is compatible with all major operating systems. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Numerous experimental and computational studies in the biomedical literature have provided considerable amounts of data on diverse RNA–RNA interactions (RRIs). However, few text mining systems for RRIs information extraction are available. Results RNA Interactome Scoper (RIscoper) represents the first tool for full-scale RNA interactome scanning and was developed for extracting RRIs from the literature based on the N-gram model. Notably, a reliable RRI corpus was integrated in RIscoper, and more than 13 300 manually curated sentences with RRI information were recruited. RIscoper allows users to upload full texts or abstracts, and provides an online search tool that is connected with PubMed (PMID and keyword input), and these capabilities are useful for biologists. RIscoper has a strong performance (90.4% precision and 93.9% recall), integrates natural language processing techniques and has a reliable RRI corpus. Availability and implementation The standalone software and web server of RIscoper are freely available at www.rna-society.org/riscoper/. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Single-cell RNA sequencing allows us to simultaneously profile the transcriptomes of thousands of cells and to indulge in exploring cell diversity, development and discovery of new molecular mechanisms. Analysis of scRNA data involves a combination of non-trivial steps from statistics, data visualization, bioinformatics and machine learning. Training molecular biologists in single-cell data analysis and empowering them to review and analyze their data can be challenging, both because of the complexity of the methods and the steep learning curve. Results We propose a workshop-style training in single-cell data analytics that relies on an explorative data analysis toolbox and a hands-on teaching style. The training relies on scOrange, a newly developed extension of a data mining framework that features workflow design through visual programming and interactive visualizations. Workshops with scOrange can proceed much faster than similar training methods that rely on computer programming and analysis through scripting in R or Python, allowing the trainer to cover more ground in the same time-frame. We here review the design principles of the scOrange toolbox that support such workshops and propose a syllabus for the course. We also provide examples of data analysis workflows that instructors can use during the training. Availability and implementation scOrange is an open-source software. The software, documentation and an emerging set of educational videos are available at http://singlecell.biolab.si. [ABSTRACT FROM AUTHOR]

Motivation The datasets generated by DNA methylation analyses are getting bigger. With the release of the HumanMethylationEPIC micro-array and datasets containing thousands of samples, analyses of these large datasets using R are becoming impractical due to large memory requirements. As a result there is an increasing need for computationally efficient methodologies to perform meaningful analysis on high dimensional data. Results Here we introduce the bigmelon R package, which provides a memory efficient workflow that enables users to perform the complex, large scale analyses required in epigenome wide association studies (EWAS) without the need for large RAM. Building on top of the CoreArray Genomic Data Structure file format and libraries packaged in the gdsfmt package, we provide a practical workflow that facilitates the reading-in, preprocessing, quality control and statistical analysis of DNA methylation data. We demonstrate the capabilities of the bigmelon package using a large dataset consisting of 1193 human blood samples from the Understanding Society: UK Household Longitudinal Study, assayed on the EPIC micro-array platform. Availability and implementation The bigmelon package is available on Bioconductor (http://bioconductor.org/packages/bigmelon/). The Understanding Society dataset is available at https://www.understandingsociety.ac.uk/about/health/data upon request. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Inference of gene regulatory networks (GRNs) from perturbation data can give detailed mechanistic insights of a biological system. Many inference methods exist, but the resulting GRN is generally sensitive to the choice of method-specific parameters. Even though the inferred GRN is optimal given the parameters, many links may be wrong or missing if the data is not informative. To make GRN inference reliable, a method is needed to estimate the support of each predicted link as the method parameters are varied. Results To achieve this we have developed a method called nested bootstrapping, which applies a bootstrapping protocol to GRN inference, and by repeated bootstrap runs assesses the stability of the estimated support values. To translate bootstrap support values to false discovery rates we run the same pipeline with shuffled data as input. This provides a general method to control the false discovery rate of GRN inference that can be applied to any setting of inference parameters, noise level, or data properties. We evaluated nested bootstrapping on a simulated dataset spanning a range of such properties, using the LASSO, Least Squares, RNI, GENIE3 and CLR inference methods. An improved inference accuracy was observed in almost all situations. Nested bootstrapping was incorporated into the GeneSPIDER package, which was also used for generating the simulated networks and data, as well as running and analyzing the inferences. Availability and implementation https://bitbucket.org/sonnhammergrni/genespider/src/NB/%2B Methods/NestBoot.m [ABSTRACT FROM AUTHOR]

Motivation Computational biologists face many challenges related to data size, and they need to manage complicated analyses often including multiple stages and multiple tools, all of which must be deployed to modern infrastructures. To address these challenges and maintain reproducibility of results, researchers need (i) a reliable way to run processing stages in any computational environment, (ii) a well-defined way to orchestrate those processing stages and (iii) a data management layer that tracks data as it moves through the processing pipeline. Results Pachyderm is an open-source workflow system and data management framework that fulfils these needs by creating a data pipelining and data versioning layer on top of projects from the container ecosystem, having Kubernetes as the backbone for container orchestration. We adapted Pachyderm and demonstrated its attractive properties in bioinformatics. A Helm Chart was created so that researchers can use Pachyderm in multiple scenarios. The Pachyderm File System was extended to support block storage. A wrapper for initiating Pachyderm on cloud-agnostic virtual infrastructures was created. The benefits of Pachyderm are illustrated via a large metabolomics workflow, demonstrating that Pachyderm enables efficient and sustainable data science workflows while maintaining reproducibility and scalability. Availability and implementation Pachyderm is available from https://github.com/pachyderm/pachyderm. The Pachyderm Helm Chart is available from https://github.com/kubernetes/charts/tree/master/stable/pachyderm. Pachyderm is available out-of-the-box from the PhenoMeNal VRE (https://github.com/phnmnl/KubeNow-plugin) and general Kubernetes environments instantiated via KubeNow. The code of the workflow used for the analysis is available on GitHub (https://github.com/pharmbio/LC-MS-Pachyderm). Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Summary More than 150 peptide therapeutics are globally in clinical development. Many enzymatic barriers should be crossed by a successful drug to be prosperous in such a process. Therefore, the new peptide drugs must be designed preventing the potential protease cleavage to make the compound less susceptible to protease reaction. We present a new data analysis tool developed in WebMetabase, an approach that stores the information from liquid chromatography mass spectrometry-based experimental data or from external sources such as the MEROPS database. The tool is a chemically aware system where each peptide substrate is presented as a sequence of structural blocks (SBs) connected by amide bonds and not being limited to the natural amino acids. Each SB is characterized by its pharmacophoric and physicochemical properties including a similarity score that describes likelihood between a SB and each one of the other SBs in the database. This methodology can be used to perform a frequency analysis to discover the most frequent cleavage sites for similar amide bonds, defined based on the similarity of the SB that participate in such a bond within the experimentally derived and/or public database. Availability and implementation http://webmetabase.com:8182/WebMetabaseBioinformatics/ Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Complex diseases such as cancers often involve multiple types of genomic and/or epigenomic abnormalities. Rapid accumulation of multiple types of omics data demands methods for integrating the multidimensional data in order to elucidate complex relationships among different types of genomic and epigenomic abnormalities. Results In the present study, we propose a tightly integrated approach based on tensor decomposition. Multiple types of data, including mRNA, methylation, copy number variations and somatic mutations, are merged into a high-order tensor which is used to develop predictive models for overall survival. The weight tensors of the models are constrained using CANDECOMP/PARAFAC (CP) tensor decomposition and learned using support tensor machine regression (STR) and ridge tensor regression (RTR). The results demonstrate that the tensor decomposition based approaches can achieve better performance than the models based individual data type and the concatenation approach. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Recognition of biomedical named entities in the textual literature is a highly challenging research topic with great interest, playing as the prerequisite for extracting huge amount of high-valued biomedical knowledge deposited in unstructured text and transforming them into well-structured formats. Long Short-Term Memory (LSTM) networks have recently been employed in various biomedical named entity recognition (NER) models with great success. They, however, often did not take advantages of all useful linguistic information and still have many aspects to be further improved for better performance. Results We propose D3NER, a novel biomedical named entity recognition (NER) model using conditional random fields and bidirectional long short-term memory improved with fine-tuned embeddings of various linguistic information. D3NER is thoroughly compared with seven very recent state-of-the-art NER models, of which two are even joint models with named entity normalization (NEN), which was proven to bring performance improvements to NER. Experimental results on benchmark datasets, i.e. the BioCreative V Chemical Disease Relation (BC5 CDR), the NCBI Disease and the FSU-PRGE gene/protein corpus, demonstrate the out-performance and stability of D3NER over all compared models for chemical, gene/protein NER and over all models (without NEN jointed, as D3NER) for disease NER, in almost all cases. On the BC5 CDR corpus, D3NER achieves F 1   of   93.14   and   84.68 % for the chemical and disease NER, respectively; while on the NCBI Disease corpus, its F 1 for the disease NER is 84.41%. Its F 1 for the gene/protein NER on FSU-PRGE is 87.62%. Availability and implementation Data and source code are available at: https://github.com/aidantee/D3NER. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Summary The rapid progresses of high-throughput sequencing technology-based omics and mass spectrometry-based proteomics, such as data-independent acquisition and its penetration to clinical studies have generated increasing number of proteomic datasets containing hundreds to thousands of samples. To analyze these quantitative proteomic datasets and other omics (e.g. transcriptomics and metabolomics) datasets more efficiently and conveniently, we present a web server-based software tool ProteomeExpert implemented in Docker, which offers various analysis tools for experimental design, data mining, interpretation and visualization of quantitative proteomic datasets. ProteomeExpert can be deployed on an operating system with Docker installed or with R language environment. Availability and implementation The Docker image of ProteomeExpert is freely available from https://hub.docker.com/r/lifeinfo/proteomeexpert. The source code of ProteomeExpert is also openly accessible at http://www.github.com/guomics-lab/ProteomeExpert/. In addition, a demo server is provided at https://proteomic.shinyapps.io/peserver/. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Summary Recent whole-brain mapping projects are collecting increasingly larger sets of high-resolution brain images using a variety of imaging, labeling and sample preparation techniques. Both mining and analysis of these data require reliable and robust cross-modal registration tools. We recently developed the mBrainAligner, a pipeline for performing cross-modal registration of the whole mouse brain. However, using this tool requires scripting or command-line skills to assemble and configure the different modules of mBrainAligner for accommodating different registration requirements and platform settings. In this application note, we present mBrainAligner-Web, a web server with a user-friendly interface that allows to configure and run mBrainAligner locally or remotely across platforms. Availability and implementation mBrainAligner-Web is available at http://mbrainaligner.ahu.edu.cn/ with source code at https://github.com/reaneyli/mBrainAligner-web. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]