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ABSTRACT Clinical decisions are often guided by clinical prediction models or diagnostic tests. Decision curve analysis (DCA) combines classical assessment of predictive performance with the consequences of using these strategies for clinical decision‐making. In DCA, the best decision strategy is the one that maximizes the net benefit: the net number of true positives (or negatives) provided by a given strategy. Here, we employ Bayesian approaches to DCA, addressing four fundamental concerns when evaluating clinical decision strategies: (i) which strategies are clinically useful, (ii) what is the best available decision strategy, (iii) which of two competing strategies is better, and (iv) what is the expected net benefit loss associated with the current level of uncertainty. While often consistent with frequentist point estimates, fully Bayesian DCA allows for an intuitive probabilistic interpretation framework and the incorporation of prior evidence. We evaluate the methods using simulation and provide a comprehensive case study. Software implementation is available in the bayesDCA R package. Ultimately, the Bayesian DCA workflow may help clinicians and health policymakers adopt better‐informed decisions. [ABSTRACT FROM AUTHOR]

We present the new R package instrument to perform Bayesian estimation of person explanatory multidimensional item response theory. The package implements an exploratory multidimensional item response theory model and a higher-order multidimensional item response theory model, a type of confirmatory multidimensional item response theory. Explanation of person parameters is accomplished by fixed and random effect linear regression models. Estimation is carried out using Hamiltonian Monte Carlo in Stan. In this article, we provide a detailed description of the models; we use the instrument package to demonstrate fitting explanatory item response models with fixed and random effects (i.e., mixed modeling) of person parameters in R; and, we perform a simulation study to evaluate the performance of our implementation of the models. [ABSTRACT FROM AUTHOR]

The increasing online availability of biodiversity data and advances in ecological modeling have led to a proliferation of open‐source modeling tools. In particular, R packages for species distribution modeling continue to multiply without guidance on how they can be employed together, resulting in high fidelity of researchers to one or several packages. Here, we assess the wide variety of software for species distribution models (SDMs) and highlight how packages can work together to diversify and expand analyses in each step of a modeling workflow. We also introduce the new R package ‘sdmverse' to catalog metadata for packages, cluster them based on their methodological functions, and visualize their relationships. To demonstrate how pluralism of software use helps improve SDM workflows, we provide three extensive and fully documented analyses that utilize tools for modeling and visualization from multiple packages, then score these tutorials according to recent methodological standards. We end by identifying gaps in the capabilities of current tools and highlighting outstanding challenges in the development of software for SDMs. [ABSTRACT FROM AUTHOR]

Hybrid zones, where genetically distinct groups of organisms meet and interbreed, offer valuable insights into the nature of species and speciation. Here, we present a new R package, bgchm, for population genomic analyses of hybrid zones. This R package extends and updates the existing bgc software and combines Bayesian analyses of hierarchical genomic clines with Bayesian methods for estimating hybrid indexes, interpopulation ancestry proportions, and geographic clines. Compared to existing software, bgchm offers enhanced efficiency through Hamiltonian Monte Carlo sampling and the ability to work with genotype likelihoods combined with a hierarchical Bayesian approach, enabling inference for diverse types of genetic data sets. The package also facilitates the quantification of introgression patterns across genomes, which is crucial for understanding reproductive isolation and speciation genetics. We first describe the models underlying bgchm and then provide an overview of the R package and illustrate its use through the analysis of simulated and empirical data sets. We show that bgchm generates accurate estimates of model parameters under a variety of conditions, especially when the genetic loci analyzed are highly ancestry informative. This includes relatively robust estimates of genome‐wide variability in clines, which has not been the focus of previous models and methods. We also illustrate how both selection and genetic drift contribute to variability in introgression among loci and how additional information can be used to help distinguish these contributions. We conclude by describing the promises and limitations of bgchm, comparing bgchm to other software for genomic cline analyses, and identifying areas for fruitful future development. [ABSTRACT FROM AUTHOR]

The mixed model for repeated measures (MMRM) analysis is sometimes used as a primary statistical analysis for a longitudinal randomized clinical trial. When the MMRM analysis is implemented in ordinary statistical software, the standard error of the treatment effect is estimated by assuming orthogonality between the fixed effects and covariance parameters, based on the characteristics of the normal distribution. However, orthogonality does not hold unless the normality assumption of the error distribution holds, and/or the missing data are derived from the missing completely at random structure. Therefore, assuming orthogonality in the MMRM analysis is not preferable. However, without the assumption of orthogonality, the small-sample bias in the standard error of the treatment effect is significant. Nonetheless, there is no method to improve small-sample performance. Furthermore, there is no software that can easily implement inferences on treatment effects without assuming orthogonality. Hence, we propose two small-sample adjustment methods inflating standard errors that are reasonable in ideal situations and achieve empirical conservatism even in general situations. We also provide an R package to implement these inference processes. The simulation results show that one of the proposed small-sample adjustment methods performs particularly well in terms of underestimation bias of standard errors; consequently, the proposed method is recommended. When using the MMRM analysis, our proposed method is recommended if the sample size is not large and between-group heteroscedasticity is expected. [ABSTRACT FROM AUTHOR]

Background and objective: The primary cilium is a small protrusion found on most mammalian cells. It acts as a cellular antenna, being involved in various cell signaling pathways. The length of the primary cilium affects its function. To study the impact of physical or chemical stimuli on cilia, their lengths must be determined easily and reproducibly. Methods: We have developed and evaluated an open-source R package called detectCilia to detect and measure primary cilia automatically. As a case study to demonstrate the capability of our tool, we compared the influence of 4 different cell culture media compositions on the lengths of primary cilia in human chondrocytes. These media compositions include (1) insulin-transferrin-selenium (ITS); (2) ITS and dexamethasone (Dexa); (3) ITS, Dexa, insulin-like growth factor 1 (IGF-1), and transforming growth factor beta 1 (TGF-β1); and (4) fetal bovine serum (FBS). Results: The assessment of detectCilia included a comparison with 2 similar tools: ACDC (Automated Cilia Detection in Cells) and CiliaQ. Several differences and advantages of our package make it a valuable addition to these tools. In the case study, we have observed variations in the ciliary lengths associated with using different media compositions. Conclusions: We conclude that detectCilia can automatically and reproducibly detect and measure primary cilia in confocal microscopy images with low false-positive rates without requiring extensive user interaction. [ABSTRACT FROM AUTHOR]

Traditional gene set enrichment analyses are typically limited to a few ontologies and do not account for the interdependence of gene sets or terms, resulting in overcorrected p-values. To address these challenges, we introduce mulea, an R package offering comprehensive overrepresentation and functional enrichment analysis. mulea employs a progressive empirical false discovery rate (eFDR) method, specifically designed for interconnected biological data, to accurately identify significant terms within diverse ontologies. mulea expands beyond traditional tools by incorporating a wide range of ontologies, encompassing Gene Ontology, pathways, regulatory elements, genomic locations, and protein domains. This flexibility enables researchers to tailor enrichment analysis to their specific questions, such as identifying enriched transcriptional regulators in gene expression data or overrepresented protein domains in protein sets. To facilitate seamless analysis, mulea provides gene sets (in standardised GMT format) for 27 model organisms, covering 22 ontology types from 16 databases and various identifiers resulting in almost 900 files. Additionally, the muleaData ExperimentData Bioconductor package simplifies access to these pre-defined ontologies. Finally, mulea's architecture allows for easy integration of user-defined ontologies, or GMT files from external sources (e.g., MSigDB or Enrichr), expanding its applicability across diverse research areas. mulea is distributed as a CRAN R package downloadable from https://cran.r-project.org/web/packages/mulea/ and https://github.com/ELTEbioinformatics/mulea. It offers researchers a powerful and flexible toolkit for functional enrichment analysis, addressing limitations of traditional tools with its progressive eFDR and by supporting a variety of ontologies. Overall, mulea fosters the exploration of diverse biological questions across various model organisms. [ABSTRACT FROM AUTHOR]

Background/Objectives: We present hidecan, an R package for generating visualisations that summarise the results of one or more genome-wide association studies (GWAS) and differential expression analyses, as well as manually curated candidate genes, e.g., extracted from the literature. This tool is applicable to all ploidy levels; we notably provide functionalities to facilitate the visualisation of GWAS results obtained for autotetraploid organisms with the GWASpoly package. Results: We illustrate the capabilities of hidecan with examples from two autotetraploid potato datasets. Conclusions: The hidecan package is implemented in R and is publicly available on the CRAN repository and on GitHub. A description of the package, as well as a detailed tutorial, is made available alongside the package. It is also part of the VIEWpoly tool for the visualisation and exploration of results from polyploids computational tools. [ABSTRACT FROM AUTHOR]

Immunotherapy shows great promise for treating advanced cancers, but its effectiveness varies widely among different patients and cancer types. Identifying biomarkers and developing robust predictive models to discern which patients are most likely to benefit from immunotherapy is of great importance. In this context, we have developed the tumor immunotherapy gene expression R package (tigeR 1.0) to address the increasing need for effective tools to explore biomarkers and construct predictive models. tigeR encompasses four distinct yet closely interconnected modules. The Biomarker Evaluation module enables researchers to evaluate whether the biomarkers of interest are associated with immunotherapy response via built‐in or custom immunotherapy gene expression data. The Tumor Microenvironment Deconvolution module integrates 10 open‐source algorithms to obtain the proportions of different cell types within the tumor microenvironment, facilitating the investigation of the association between immune cell populations and immunotherapy response. The Prediction Model Construction module equips users with the ability to construct sophisticated prediction models using a range of built‐in machine‐learning algorithms. The Response Prediction module predicts the immunotherapy response for the patients from gene expression data using our pretrained machine learning models or public gene expression signatures. By providing these diverse functionalities, tigeR aims to simplify the process of analyzing immunotherapy gene expression data, thus making it accessible to researchers without advanced programming skills. The source code and example for the tigeR project can be accessed at http://github.com/YuLab-SMU/tigeR. Highlights: Tumor Immunotherapy Gene Expression R package (tigeR) is an effective R package to explore biomarkers and construct predictive models to predict immunotherapeutic outcomes.tigeR enables the flexibility to load built‐in or custom gene expression data with immunotherapy outcome information.tigeR encompasses four distinct yet closely interconnected modules, including the Biomarker Evaluation module, Tumor Microenvironment Deconvolution module, Prediction Model Construction module, and Response Prediction module. [ABSTRACT FROM AUTHOR]

In species distribution modelling (SDM), it is common practice to explore multiple machine learning (ML) algorithms and combine their results into ensembles. In R, many implementations of different ML algorithms are available but, as they were mostly developed independently, they often use inconsistent syntax and data structures. For this reason, repeating an analysis with multiple algorithms and combining their results can be challenging.Specialised SDM packages solve this problem by providing a simpler, unified interface by wrapping the original functions to tackle each specific requirement. However, creating and maintaining such interfaces is time‐consuming, and with this approach, the user cannot easily integrate other methods that may become available.Here, we present tidysdm, an R package that solves this problem by taking advantage of the tidymodels universe. tidymodels provide standardised grammar, data structures and modelling interfaces, and a well‐documented infrastructure to integrate new algorithms and metrics. The wide adoption of tidymodels means that most ML algorithms and metrics are already integrated, and the user can add additional ones. Moreover, because of the broad adoption of tidymodels, new statistical approaches tend to be implemented quickly, making them easily integrated into existing pipelines and analyses.tidysdm takes advantage of the tidymodels universe to provide a flexible and fully customisable pipeline to fit SDM. It includes SDM‐specific algorithms and metrics, and methods to facilitate the use of spatial data within tidymodels.Additionally, tidysdm is the first software that natively allows SDM to be performed using data from different periods, expanding the availability of SDM for scholars working in palaeontology, archaeology, palaeobiology, palaeoecology and other disciplines focussing on the past. [ABSTRACT FROM AUTHOR]

Single-cell studies in neuroscience require precise cell type classification and consistent nomenclature that allows for meaningful comparisons across diverse datasets. Current approaches often lack the ability to identify fine-grained cell types and establish standardized annotations at the cluster level, hindering comprehensive understanding of the brain's cellular composition. To facilitate data integration across multiple models and datasets, we designed BrainCellR. This pipeline provides researchers with a powerful and user-friendly tool for efficient cell type classification and nomination from single-cell transcriptomic data. While initially focused on brain studies, BrainCellR is applicable to other tissues with complex cellular compositions. BrainCellR goes beyond conventional classification approaches by incorporating a standardized nomenclature system for cell types at the cluster level. This feature enables consistent and comparable annotations across different studies, promoting data integration and providing deeper insights into the complex cellular landscape of the brain. All documents for BrainCellR, including source code, user manual and tutorials, are freely available at https://github.com/WangLab-SINH/BrainCellR.

Gastric cancer (GC) is one of the most commonly diagnosed malignancies, threatening millions of lives worldwide each year. Importantly, GC is a heterogeneous disease, posing a significant challenge to the selection of patients for more optimized therapy. Over the last decades, extensive community effort has been spent on dissecting the heterogeneity of GC, leading to the identification of distinct molecular subtypes that are clinically relevant. However, so far, no tool is publicly available for GC subtype prediction, hindering the research into GC subtype-specific biological mechanisms, the design of novel targeted agents, and potential clinical applications. To address the unmet need, we developed an R package GCclassifier for predicting GC molecular subtypes based on gene expression profiles. To facilitate the use by non-bioinformaticians, we also provide an interactive, user-friendly web server implementing the major functionalities of GCclassifier. The predictive performance of GCclassifier was demonstrated using case studies on multiple independent datasets.

Abstract Traditional gene set enrichment analyses are typically limited to a few ontologies and do not account for the interdependence of gene sets or terms, resulting in overcorrected p-values. To address these challenges, we introduce mulea, an R package offering comprehensive overrepresentation and functional enrichment analysis. mulea employs a progressive empirical false discovery rate (eFDR) method, specifically designed for interconnected biological data, to accurately identify significant terms within diverse ontologies. mulea expands beyond traditional tools by incorporating a wide range of ontologies, encompassing Gene Ontology, pathways, regulatory elements, genomic locations, and protein domains. This flexibility enables researchers to tailor enrichment analysis to their specific questions, such as identifying enriched transcriptional regulators in gene expression data or overrepresented protein domains in protein sets. To facilitate seamless analysis, mulea provides gene sets (in standardised GMT format) for 27 model organisms, covering 22 ontology types from 16 databases and various identifiers resulting in almost 900 files. Additionally, the muleaData ExperimentData Bioconductor package simplifies access to these pre-defined ontologies. Finally, mulea's architecture allows for easy integration of user-defined ontologies, or GMT files from external sources (e.g., MSigDB or Enrichr), expanding its applicability across diverse research areas. mulea is distributed as a CRAN R package downloadable from https://cran.r-project.org/web/packages/mulea/ and https://github.com/ELTEbioinformatics/mulea . It offers researchers a powerful and flexible toolkit for functional enrichment analysis, addressing limitations of traditional tools with its progressive eFDR and by supporting a variety of ontologies. Overall, mulea fosters the exploration of diverse biological questions across various model organisms.

Abstract In species distribution modelling (SDM), it is common practice to explore multiple machine learning (ML) algorithms and combine their results into ensembles. In R, many implementations of different ML algorithms are available but, as they were mostly developed independently, they often use inconsistent syntax and data structures. For this reason, repeating an analysis with multiple algorithms and combining their results can be challenging. Specialised SDM packages solve this problem by providing a simpler, unified interface by wrapping the original functions to tackle each specific requirement. However, creating and maintaining such interfaces is time‐consuming, and with this approach, the user cannot easily integrate other methods that may become available. Here, we present tidysdm, an R package that solves this problem by taking advantage of the tidymodels universe. tidymodels provide standardised grammar, data structures and modelling interfaces, and a well‐documented infrastructure to integrate new algorithms and metrics. The wide adoption of tidymodels means that most ML algorithms and metrics are already integrated, and the user can add additional ones. Moreover, because of the broad adoption of tidymodels, new statistical approaches tend to be implemented quickly, making them easily integrated into existing pipelines and analyses. tidysdm takes advantage of the tidymodels universe to provide a flexible and fully customisable pipeline to fit SDM. It includes SDM‐specific algorithms and metrics, and methods to facilitate the use of spatial data within tidymodels. Additionally, tidysdm is the first software that natively allows SDM to be performed using data from different periods, expanding the availability of SDM for scholars working in palaeontology, archaeology, palaeobiology, palaeoecology and other disciplines focussing on the past.

Abstract Background Bio-ontologies are keys in structuring complex biological information for effective data integration and knowledge representation. Semantic similarity analysis on bio-ontologies quantitatively assesses the degree of similarity between biological concepts based on the semantics encoded in ontologies. It plays an important role in structured and meaningful interpretations and integration of complex data from multiple biological domains. Results We present simona, a novel R package for semantic similarity analysis on general bio-ontologies. Simona implements infrastructures for ontology analysis by offering efficient data structures, fast ontology traversal methods, and elegant visualizations. Moreover, it provides a robust toolbox supporting over 70 methods for semantic similarity analysis. With simona, we conducted a benchmark against current semantic similarity methods. The results demonstrate methods are clustered based on their mathematical methodologies, thus guiding researchers in the selection of appropriate methods. Additionally, we explored annotation-based versus topology-based methods, revealing that semantic similarities solely based on ontology topology can efficiently reveal semantic similarity structures, facilitating analysis on less-studied organisms and other ontologies. Conclusions Simona offers a versatile interface and efficient implementation for processing, visualization, and semantic similarity analysis on bio-ontologies. We believe that simona will serve as a robust tool for uncovering relationships and enhancing the interoperability of biological knowledge systems.

Background: The opioid crisis remains a significant public health challenge in North America, highlighted by the substantial need for tools to analyze and understand opioid potency and prescription patterns. Methods: The OralOpioids package automates the retrieval, processing, and analysis of opioid data from Health Canada’s Drug Product Database (DPD) and the U.S. Food and Drug Administration’s (FDA) National Drug Code (NDC) database. It includes functions such as load_Opioid_Table, which integrates country-specific data processing and Morphine Equivalent Dose (MED) calculations, providing a comprehensive dataset for analysis. The package facilitates a comprehensive examination of opioid prescriptions, allowing researchers to identify high-risk opioids and patterns that could inform policy and healthcare practices. Results: The integration of MED calculations with Canadian and U.S. data provides a robust tool for assessing opioid potency and prescribing practices. The OralOpioids R package is an essential tool for public health researchers, enabling a detailed analysis of North American opioid prescriptions. Conclusions: By providing easy access to opioid potency data and supporting cross-national studies, the package plays a critical role in addressing the opioid crisis. It suggests a model for similar tools that could be adapted for global use, enhancing our capacity to manage and mitigate opioid misuse effectively.

Abstract The inability to correctly account for unmeasured confounding can lead to bias in parameter estimates, invalid uncertainty assessments, and erroneous conclusions. Sensitivity analysis is an approach to investigate the impact of unmeasured confounding in observational studies. However, the adoption of this approach has been slow given the lack of accessible software. An extensive review of available R packages to account for unmeasured confounding list deterministic sensitivity analysis methods, but no R packages were listed for probabilistic sensitivity analysis. The R package unmconf implements the first available package for probabilistic sensitivity analysis through a Bayesian unmeasured confounding model. The package allows for normal, binary, Poisson, or gamma responses, accounting for one or two unmeasured confounders from the normal or binomial distribution. The goal of unmconf is to implement a user friendly package that performs Bayesian modeling in the presence of unmeasured confounders, with simple commands on the front end while performing more intensive computation on the back end. We investigate the applicability of this package through novel simulation studies. The results indicate that credible intervals will have near nominal coverage probability and smaller bias when modeling the unmeasured confounder(s) for varying levels of internal/external validation data across various combinations of response-unmeasured confounder distributional families.

Abstract Background Although aggregate data (AD) from randomised clinical trials (RCTs) are used in the majority of network meta-analyses (NMAs), other study designs (e.g., cohort studies and other non-randomised studies, NRS) can be informative about relative treatment effects. The individual participant data (IPD) of the study, when available, are preferred to AD for adjusting for important participant characteristics and to better handle heterogeneity and inconsistency in the network. Results We developed the R package crossnma to perform cross-format (IPD and AD) and cross-design (RCT and NRS) NMA and network meta-regression (NMR). The models are implemented as Bayesian three-level hierarchical models using Just Another Gibbs Sampler (JAGS) software within the R environment. The R package crossnma includes functions to automatically create the JAGS model, reformat the data (based on user input), assess convergence and summarize the results. We demonstrate the workflow within crossnma by using a network of six trials comparing four treatments. Conclusions The R package crossnma enables the user to perform NMA and NMR with different data types in a Bayesian framework and facilitates the inclusion of all types of evidence recognising differences in risk of bias.

Abstract Background A major stream of research on symptom checkers aims at evaluating the technology’s predictive accuracy, but apart from general trends, the results are marked by high variability. Several authors suggest that this variability might in part be due to different assessment methods and a lack of standardization. To improve the reliability of symptom checker evaluation studies, several approaches have been suggested, including standardizing input procedures, the generation of test vignettes, and the assignment of gold standard solutions for these vignettes. Recently, we suggested a third approach––test-theoretic metrics for standardized performance reporting–– to allow systematic and comprehensive comparisons of symptom checker performance. However, calculating these metrics is time-consuming and error prone, which could hamper the use and effectiveness of these metrics. Results We developed the R package symptomcheckR as an open-source software to assist researchers in calculating standard metrics to evaluate symptom checker performance individually and comparatively and produce publication-ready figures. These metrics include accuracy (by triage level), safety of advice (i.e., rate of correctly or overtriaged cases), comprehensiveness (i.e., how many cases could be entered or were assessed), inclination to overtriage (i.e., how risk-averse a symptom checker is) and a capability comparison score (i.e., a score correcting for case difficulty and comprehensiveness that enables a fair and reliable comparison of different symptom checkers). Each metric can be obtained using a single command and visualized with another command. For the analysis of individual or the comparison of multiple symptom checkers, single commands can be used to produce a comprehensive performance profile that complements the standard focus on accuracy with additional metrics that reveal strengths and weaknesses of symptom checkers. Conclusions Our package supports ongoing efforts to improve the quality of vignette-based symptom checker evaluation studies by means of standardized methods. Specifically, with our package, adhering to reporting standards and metrics becomes easier, simple, and time efficient. Ultimately, this may help users gain a more systematic understanding of the strengths and limitations of symptom checkers for different use cases (e.g., all-purpose symptom checkers for general medicine versus symptom checkers that aim at improving triage in emergency departments), which can improve patient safety and resource allocation.

Abstract Background Inbreeding and relationship coefficients are essential for conservation and breeding programs. Whether dealing with a small conserved population or a large commercial population, monitoring the inbreeding rate and designing mating plans that minimize the inbreeding rate and maximize the effective population size is important. Free, open-source, and efficient software may greatly contribute to conservation and breeding programs and help students and researchers. Efficient methods exist for calculating inbreeding coefficients. Therefore, an efficient way of calculating the numerator relationship coefficients is via the inbreeding coefficients. i.e., the relationship coefficient between parents is twice the inbreeding coefficient of their progeny. A dummy progeny is introduced where no progeny exists for a pair of individuals. Calculating inbreeding coefficients is very fast, and finding whether a pair of individuals has a progeny and picking one from multiple progenies is computationally more demanding. Therefore, the R package introduces a dummy progeny for any pair of individuals whose relationship coefficient is of interest, whether they have a progeny or not. Results Runtime and peak memory usage were benchmarked for calculating relationship coefficients between two sets of 250 and 800 animals (200,000 dummy progenies) from a pedigree of 2,721,252 animals. The program performed efficiently (200,000 relationship coefficients, which involved calculating 2,721,252 + 200,000 inbreeding coefficients) within 3:45 (mm:ss). Providing the inbreeding coefficients (for real animals), the runtime was reduced to 1:08. Furthermore, providing the diagonal elements of D in $$\textbf{A} = \textbf{TDT}^{\prime }$$ A = TDT ′ (d), the runtime was reduced to 54s. All the analyses were performed on a machine with a total memory size of 1 GB. Conclusions The R package FnR is free and open-source software with implications in conservation and breeding programs. It proved to be time and memory efficient for large populations and many dummy progenies. Calculation of inbreeding coefficients can be resumed for new animals in the pedigree. Thus, saving the latest inbreeding coefficient estimates is recommended. Calculation of d coefficients (from scratch) was very fast, and there was limited value in storing those for future use.

Abstract Background Decision analytic models and meta-analyses often rely on survival probabilities that are digitized from published Kaplan–Meier (KM) curves. However, manually extracting these probabilities from KM curves is time-consuming, expensive, and error-prone. We developed an efficient and accurate algorithm that automates extraction of survival probabilities from KM curves. Methods The automated digitization algorithm processes images from a JPG or PNG format, converts them in their hue, saturation, and lightness scale and uses optical character recognition to detect axis location and labels. It also uses a k-medoids clustering algorithm to separate multiple overlapping curves on the same figure. To validate performance, we generated survival plots form random time-to-event data from a sample size of 25, 50, 150, and 250, 1000 individuals split into 1,2, or 3 treatment arms. We assumed an exponential distribution and applied random censoring. We compared automated digitization and manual digitization performed by well-trained researchers. We calculated the root mean squared error (RMSE) at 100-time points for both methods. The algorithm’s performance was also evaluated by Bland–Altman analysis for the agreement between automated and manual digitization on a real-world set of published KM curves. Results The automated digitizer accurately identified survival probabilities over time in the simulated KM curves. The average RMSE for automated digitization was 0.012, while manual digitization had an average RMSE of 0.014. Its performance was negatively correlated with the number of curves in a figure and the presence of censoring markers. In real-world scenarios, automated digitization and manual digitization showed very close agreement. Conclusions The algorithm streamlines the digitization process and requires minimal user input. It effectively digitized KM curves in simulated and real-world scenarios, demonstrating accuracy comparable to conventional manual digitization. The algorithm has been developed as an open-source R package and as a Shiny application and is available on GitHub: https://github.com/Pechli-Lab/SurvdigitizeR and https://pechlilab.shinyapps.io/SurvdigitizeR/ .

Background: Bio-ontologies are keys in structuring complex biological information for effective data integration and knowledge representation. Semantic similarity analysis on bio-ontologies quantitatively assesses the degree of similarity between biological concepts based on the semantics encoded in ontologies. It plays an important role in structured and meaningful interpretations and integration of complex data from multiple biological domains. Results: We present simona, a novel R package for semantic similarity analysis on general bio-ontologies. Simona implements infrastructures for ontology analysis by offering efficient data structures, fast ontology traversal methods, and elegant visualizations. Moreover, it provides a robust toolbox supporting over 70 methods for semantic similarity analysis. With simona, we conducted a benchmark against current semantic similarity methods. The results demonstrate methods are clustered based on their mathematical methodologies, thus guiding researchers in the selection of appropriate methods. Additionally, we explored annotation-based versus topology-based methods, revealing that semantic similarities solely based on ontology topology can efficiently reveal semantic similarity structures, facilitating analysis on less-studied organisms and other ontologies. Conclusions: Simona offers a versatile interface and efficient implementation for processing, visualization, and semantic similarity analysis on bio-ontologies. We believe that simona will serve as a robust tool for uncovering relationships and enhancing the interoperability of biological knowledge systems. [ABSTRACT FROM AUTHOR]

As plant research generates an ever-growing volume of spatial quantitative data, the need for decentralized and user-friendly visualization tools to explore large and complex datasets becomes crucial. Existing resources, such as the Plant eFP (electronic Fluorescent Pictograph) viewer, have played a pivotal role on the communication of gene expression data across many plant species. However, although widely used by the plant research community, the Plant eFP viewer lacks open and user-friendly tools for the creation of customized expression maps independently. Plant biologists with less coding experience can often encounter challenges when attempting to explore ways to communicate their own spatial quantitative data. We present 'ggPlantmap' an open-source R package designed to address this challenge by providing an easy and user-friendly method for the creation of ggplot representative maps from plant images. ggPlantmap is built in R, one of the most used languages in biology, to empower plant scientists to create and customize eFP-like viewers tailored to their experimental data. Here, we provide an overview of the package and tutorials that are accessible even to users with minimal R programming experience. We hope that ggPlantmap can assist the plant science community, fostering innovation, and improving our understanding of plant development and function. [ABSTRACT FROM AUTHOR]

The inability to correctly account for unmeasured confounding can lead to bias in parameter estimates, invalid uncertainty assessments, and erroneous conclusions. Sensitivity analysis is an approach to investigate the impact of unmeasured confounding in observational studies. However, the adoption of this approach has been slow given the lack of accessible software. An extensive review of available R packages to account for unmeasured confounding list deterministic sensitivity analysis methods, but no R packages were listed for probabilistic sensitivity analysis. The R package unmconf implements the first available package for probabilistic sensitivity analysis through a Bayesian unmeasured confounding model. The package allows for normal, binary, Poisson, or gamma responses, accounting for one or two unmeasured confounders from the normal or binomial distribution. The goal of unmconf is to implement a user friendly package that performs Bayesian modeling in the presence of unmeasured confounders, with simple commands on the front end while performing more intensive computation on the back end. We investigate the applicability of this package through novel simulation studies. The results indicate that credible intervals will have near nominal coverage probability and smaller bias when modeling the unmeasured confounder(s) for varying levels of internal/external validation data across various combinations of response-unmeasured confounder distributional families. [ABSTRACT FROM AUTHOR]

Background: The opioid crisis remains a significant public health challenge in North America, highlighted by the substantial need for tools to analyze and understand opioid potency and prescription patterns. Methods: The OralOpioids package automates the retrieval, processing, and analysis of opioid data from Health Canada's Drug Product Database (DPD) and the U.S. Food and Drug Administration's (FDA) National Drug Code (NDC) database. It includes functions such as load_Opioid_Table, which integrates country-specific data processing and Morphine Equivalent Dose (MED) calculations, providing a comprehensive dataset for analysis. The package facilitates a comprehensive examination of opioid prescriptions, allowing researchers to identify high-risk opioids and patterns that could inform policy and healthcare practices. Results: The integration of MED calculations with Canadian and U.S. data provides a robust tool for assessing opioid potency and prescribing practices. The OralOpioids R package is an essential tool for public health researchers, enabling a detailed analysis of North American opioid prescriptions. Conclusions: By providing easy access to opioid potency data and supporting cross-national studies, the package plays a critical role in addressing the opioid crisis. It suggests a model for similar tools that could be adapted for global use, enhancing our capacity to manage and mitigate opioid misuse effectively. [ABSTRACT FROM AUTHOR]

RNA sequencing (RNA-seq) has become a standard method for profiling gene expression, yet genomic DNA (gDNA) contamination carried over to the sequencing library poses a significant challenge to data integrity. Detecting and correcting this contamination is vital for accurate downstream analyses. Particularly, when RNA samples are scarce and invaluable, it becomes essential not only to identify but also to correct gDNA contamination to maximize the data's utility. However, existing tools capable of correcting gDNA contamination are limited and lack thorough evaluation. To fill the gap, we developed CleanUpRNAseq, which offers a comprehensive set of functionalities for identifying and correcting gDNA-contaminated RNA-seq data. Our package offers three correction methods for unstranded RNA-seq data and a dedicated approach for stranded data. Through rigorous validation on published RNA-seq datasets with known levels of gDNA contamination and real-world RNA-seq data, we demonstrate CleanUpRNAseq's efficacy in detecting and correcting detrimental levels of gDNA contamination across diverse library protocols. CleanUpRNAseq thus serves as a valuable tool for post-alignment quality assessment of RNA-seq data and should be integrated into routine workflows for RNA-seq data analysis. Its incorporation into OneStopRNAseq should significantly bolster the accuracy of gene expression quantification and differential expression analysis of RNA-seq data. [ABSTRACT FROM AUTHOR]

Exploration of toxicological mechanisms is imperative for the assessment of potential adverse reactions to chemicals and pharmaceutical agents, the engineering of safer compounds, and the preservation of public health. It forms the foundation of drug development and disease treatment. High-throughput proteomics and transcriptomics can accurately capture the body's response to toxins and have become key tools for revealing complex toxicological mechanisms. Recently, a vast amount of omics data related to toxicological mechanisms have been accumulated. However, analyzing and utilizing these data remains a major challenge for researchers, especially as there is a lack of a knowledge-based analysis system to identify relevant biological pathways associated with toxicity from the data and to establish connections between omics data and existing toxicological knowledge. To address this, we have developed ToxDAR, a workflow-oriented R package for preprocessing and analyzing toxicological multi-omics data. ToxDAR integrates packages like NormExpression, DESeq2, and igraph, and utilizes R functions such as prcomp and phyper. It supports data preparation, quality control, differential expression analysis, functional analysis, and network analysis. ToxDAR's architecture also includes a knowledge graph with five major categories of mechanism-related biological entities and details fifteen types of interactions among them, providing comprehensive knowledge annotation for omics data analysis results. As a case study, we used ToxDAR to analyze a transcriptomic dataset on the toxicology of triphenyl phosphate (TPP). The results indicate that TPP may impair thyroid function by activating thyroid hormone receptor β (THRB), impacting pathways related to programmed cell death and inflammation. As a workflow-oriented data analysis tool, ToxDAR is expected to be crucial for understanding toxic mechanisms from omics data, discovering new therapeutic targets, and evaluating chemical safety. [ABSTRACT FROM AUTHOR]

Key Biodiversity Areas (KBAs) represent the largest global network of sites critical to the persistence of biodiversity, which have been identified against standardised quantitative criteria. Sites that hold very high biodiversity value or potential are given specific attention on site‐based conservation targets of the Kunming‐Montreal Global Biodiversity Framework (GBF), and KBAs are already used in indicators for the GBF and the Sustainable Development Goals. However, most of the species that trigger KBA status are birds and to maximise benefits for biodiversity under the actions taken to fulfil the GBF, countries need to update their KBAs to represent important sites across multiple taxa. Here we introduce KBAscope, an R package to identify potential KBAs using multiple taxonomic groups. KBAscope provides flexible, user‐friendly functions to edit species data (population, range maps, area of occupancy, area of habitat and localities); apply KBA criteria; and generate outputs to support the delineation and validation of KBAs. The details of the analysis – such as the spatial units tested or the KBA criteria applied – can be decided according to the scope of the analysis. We demonstrate the functionality of KBAscope by using it to identify potential KBAs in Greece based on multiple terrestrial taxonomic groups and four sizes of grid cells (4 km2, 25 km2, 100 km2, 225 km2). [ABSTRACT FROM AUTHOR]

This paper presents the ARDL package for the statistical language R, demonstrating its main functionalities in a step by step guide. Some of its main advantages over other related R packages are the intuitive API, and the fact that includes many important features missing from other packages that are essential for an in depth analysis. Additionally, it is designed in such a way that it can be combined with other packages for post regression diagnostics and tests. These characteristics are shown through an example, where we showcase part of the application demonstrated in the seminal work of Pesaran et al. (J Appl Econom 16:289–326, 2001). [ABSTRACT FROM AUTHOR]

We use Bayesian model selection paradigms, such as group least absolute shrinkage and selection operator priors, to facilitate generalized additive model selection. Our approach allows for the effects of continuous predictors to be categorized as either zero, linear or non-linear. Employment of carefully tailored auxiliary variables results in Gibbsian Markov chain Monte Carlo schemes for practical implementation of the approach. In addition, mean field variational algorithms with closed form updates are obtained. Whilst not as accurate, this fast variational option enhances scalability to very large data sets. A package in the R language aids use in practice. [ABSTRACT FROM AUTHOR]

Background: Although aggregate data (AD) from randomised clinical trials (RCTs) are used in the majority of network meta-analyses (NMAs), other study designs (e.g., cohort studies and other non-randomised studies, NRS) can be informative about relative treatment effects. The individual participant data (IPD) of the study, when available, are preferred to AD for adjusting for important participant characteristics and to better handle heterogeneity and inconsistency in the network. Results: We developed the R package crossnma to perform cross-format (IPD and AD) and cross-design (RCT and NRS) NMA and network meta-regression (NMR). The models are implemented as Bayesian three-level hierarchical models using Just Another Gibbs Sampler (JAGS) software within the R environment. The R package crossnma includes functions to automatically create the JAGS model, reformat the data (based on user input), assess convergence and summarize the results. We demonstrate the workflow within crossnma by using a network of six trials comparing four treatments. Conclusions: The R package crossnma enables the user to perform NMA and NMR with different data types in a Bayesian framework and facilitates the inclusion of all types of evidence recognising differences in risk of bias. [ABSTRACT FROM AUTHOR]

Background: A major stream of research on symptom checkers aims at evaluating the technology's predictive accuracy, but apart from general trends, the results are marked by high variability. Several authors suggest that this variability might in part be due to different assessment methods and a lack of standardization. To improve the reliability of symptom checker evaluation studies, several approaches have been suggested, including standardizing input procedures, the generation of test vignettes, and the assignment of gold standard solutions for these vignettes. Recently, we suggested a third approach––test-theoretic metrics for standardized performance reporting–– to allow systematic and comprehensive comparisons of symptom checker performance. However, calculating these metrics is time-consuming and error prone, which could hamper the use and effectiveness of these metrics. Results: We developed the R package symptomcheckR as an open-source software to assist researchers in calculating standard metrics to evaluate symptom checker performance individually and comparatively and produce publication-ready figures. These metrics include accuracy (by triage level), safety of advice (i.e., rate of correctly or overtriaged cases), comprehensiveness (i.e., how many cases could be entered or were assessed), inclination to overtriage (i.e., how risk-averse a symptom checker is) and a capability comparison score (i.e., a score correcting for case difficulty and comprehensiveness that enables a fair and reliable comparison of different symptom checkers). Each metric can be obtained using a single command and visualized with another command. For the analysis of individual or the comparison of multiple symptom checkers, single commands can be used to produce a comprehensive performance profile that complements the standard focus on accuracy with additional metrics that reveal strengths and weaknesses of symptom checkers. Conclusions: Our package supports ongoing efforts to improve the quality of vignette-based symptom checker evaluation studies by means of standardized methods. Specifically, with our package, adhering to reporting standards and metrics becomes easier, simple, and time efficient. Ultimately, this may help users gain a more systematic understanding of the strengths and limitations of symptom checkers for different use cases (e.g., all-purpose symptom checkers for general medicine versus symptom checkers that aim at improving triage in emergency departments), which can improve patient safety and resource allocation. [ABSTRACT FROM AUTHOR]

Background: Decision analytic models and meta-analyses often rely on survival probabilities that are digitized from published Kaplan–Meier (KM) curves. However, manually extracting these probabilities from KM curves is time-consuming, expensive, and error-prone. We developed an efficient and accurate algorithm that automates extraction of survival probabilities from KM curves. Methods: The automated digitization algorithm processes images from a JPG or PNG format, converts them in their hue, saturation, and lightness scale and uses optical character recognition to detect axis location and labels. It also uses a k-medoids clustering algorithm to separate multiple overlapping curves on the same figure. To validate performance, we generated survival plots form random time-to-event data from a sample size of 25, 50, 150, and 250, 1000 individuals split into 1,2, or 3 treatment arms. We assumed an exponential distribution and applied random censoring. We compared automated digitization and manual digitization performed by well-trained researchers. We calculated the root mean squared error (RMSE) at 100-time points for both methods. The algorithm's performance was also evaluated by Bland–Altman analysis for the agreement between automated and manual digitization on a real-world set of published KM curves. Results: The automated digitizer accurately identified survival probabilities over time in the simulated KM curves. The average RMSE for automated digitization was 0.012, while manual digitization had an average RMSE of 0.014. Its performance was negatively correlated with the number of curves in a figure and the presence of censoring markers. In real-world scenarios, automated digitization and manual digitization showed very close agreement. Conclusions: The algorithm streamlines the digitization process and requires minimal user input. It effectively digitized KM curves in simulated and real-world scenarios, demonstrating accuracy comparable to conventional manual digitization. The algorithm has been developed as an open-source R package and as a Shiny application and is available on GitHub: https://github.com/Pechli-Lab/SurvdigitizeR and https://pechlilab.shinyapps.io/SurvdigitizeR/. [ABSTRACT FROM AUTHOR]

Bibliographic databases have long been a cornerstone of scientometrics research, and new information sources have prompted several comparative studies between them. Such studies often employ document-level matching procedures to identify overlaps in the corpus of each database and assess their coverage. However, despite being increasingly relevant in comparative studies, such a type of analysis still lacks an open-source tool to automate it. To fill this gap, we have developed an R package called biblioverlap, which implements a hybrid matching approach using a unique identifier and a selection of ubiquitous bibliographic fields to establish document co-occurrence. It supports data analysis from a broad range of secondary sources and can be used for comparing databases and assessing document overlap in virtually any bibliographic dataset, which can be insightful for various research questions. This paper presents the biblioverlap tool, details the matching procedure's implementation, and uses an example dataset containing records from the Federal University of Rio de Janeiro to illustrate the package's built-in functionality. [ABSTRACT FROM AUTHOR]

The analysis of photosynthetic traits has become an integral part of plant (eco-)physiology. Many of these characteristics are not directly measured, but calculated from combinations of several, more direct, measurements. The calculations of such derived variables are based on underlying physical models and may use additional constants or assumed values. Commercially available gas-exchange instruments typically report such derived variables, but the available implementations use different definitions and assumptions. Moreover, no software is currently available to allow a fully scripted and reproducible workflow that includes importing data, pre-processing and recalculating derived quantities. The R package gasanalyzer aims to address these issues by providing methods to import data from different instruments, by translating photosynthetic variables to a standardized nomenclature, and by optionally recalculating derived quantities using standardized equations. In addition, the package facilitates performing sensitivity analyses on variables or assumptions used in the calculations to allow researchers to better assess the robustness of the results. The use of the package and how to perform sensitivity analyses are demonstrated using three different examples. [ABSTRACT FROM AUTHOR]

Estimating sample size and statistical power is an essential part of a good epidemiological study design. Closed-form formulas exist for simple hypothesis tests but not for advanced statistical methods designed for exposure mixture studies. Estimating power with Monte Carlo simulations is flexible and applicable to these methods. However, it is not straightforward to code a simulation for non-experienced programmers and is often hard for a researcher to manually specify multivariate associations among exposure mixtures to set up a simulation. To simplify this process, we present the R package mpower for power analysis of observational studies of environmental exposure mixtures involving recently developed mixtures analysis methods. The components within mpower are also versatile enough to accommodate any mixtures methods that will be developed in future. The package allows users to simulate realistic exposure data and mixed-typed covariates based on public dataset such as the National Health and Nutrition Examination Survey or other existing dataset from prior studies. Users can generate power curves to assess the trade-offs between sample size, effect size, and power of a design. This paper presents tutorials and examples of power analysis using mpower. [ABSTRACT FROM AUTHOR]

The goal of the Length and Information Optimization Criterion (LIC) is to handle datasets containing redundant information, identify and select the most informative subsets, and ensure that a large portion of the information from the dataset is retained. The proposed R package, called LIC, is specifically designed for optimal subset selection in distributed redundant data. It achieves this by minimizing the length of the final interval estimator while maximizing the amount of information retained from the selected data subset. This functionality is highly useful across various fields such as economics, industry, and medicine. For example, in studies involving the prediction of nitrogen oxide emissions from gas turbines, self-noise of airfoils under stochastic wind conditions, and real estate valuation predictions, LIC can be used to explore the performance of random distributed block methods in parallel computing environments.

ABSTRACT Hybrid zones, where genetically distinct groups of organisms meet and interbreed, offer valuable insights into the nature of species and speciation. Here, we present a new R package, bgchm, for population genomic analyses of hybrid zones. This R package extends and updates the existing bgc software and combines Bayesian analyses of hierarchical genomic clines with Bayesian methods for estimating hybrid indexes, interpopulation ancestry proportions, and geographic clines. Compared to existing software, bgchm offers enhanced efficiency through Hamiltonian Monte Carlo sampling and the ability to work with genotype likelihoods combined with a hierarchical Bayesian approach, enabling inference for diverse types of genetic data sets. The package also facilitates the quantification of introgression patterns across genomes, which is crucial for understanding reproductive isolation and speciation genetics. We first describe the models underlying bgchm and then provide an overview of the R package and illustrate its use through the analysis of simulated and empirical data sets. We show that bgchm generates accurate estimates of model parameters under a variety of conditions, especially when the genetic loci analyzed are highly ancestry informative. This includes relatively robust estimates of genome‐wide variability in clines, which has not been the focus of previous models and methods. We also illustrate how both selection and genetic drift contribute to variability in introgression among loci and how additional information can be used to help distinguish these contributions. We conclude by describing the promises and limitations of bgchm, comparing bgchm to other software for genomic cline analyses, and identifying areas for fruitful future development.

Background Binary diagnostic tests are commonly used in medicine to answer a question about a patient’s clinical status, most commonly, do they or do they not have some disease. Recent advances in statistical methodologies for performing inferential statistics to compare commonly used test metrics for two diagnostic tests have not yet been implemented in a statistical package. Methods Up-to-date statistical methods to compare the test metrics achieved by two binary diagnostic tests are implemented in the new R package testCompareR. The output and efficiency of testCompareR is compared to the only other available package which performs this function, DTComPair, as well as an open-source program, compbdt, using a motivating example. Results testCompareR achieves similar results to DTComPair using statistical methods with improved coverage and asymptotic performance. Further, testCompareR is faster than the currently available package and requires fewer pre-processing steps in order to produce accurate results. Conclusions testCompareR provides a new tool to compare the test metrics for two binary diagnostic tests compared with the gold standard. This tool allows flexible inputs, which minimises the need for data pre-processing, and operates in very few steps, so that it is easy to use even for those less experienced with R. testCompareR achieves results comparable to those computed by DTComPair, using optimised statistical methods and with improved computational efficiency.

Trait databases have proliferated over the past decades, facilitating research on the ecology, evolution, and conservation of taxa across the Tree of Life. Typically, teams of independent researchers build these databases, and each must develop their own workflow and output structure. This divests research hours from downstream tasks such as trait-based analysis and interpretation and the resultant datasets are often difficult to integrate due to disparate database structures. Here we introduce the {traits.build} R-package, which offers a generalised workflow for building trait databases. {traits.build} contains bespoke functions for propagating metadata files, extensive tutorials, and sample configuration files, allowing researchers to efficiently build a new trait database using open-source tools. In addition, the {traits.build} output structure is fully documented by a data model, ensuring the meaning of each variable and semantic relationship between variables is transparent and consistent. The data standard links to terms in previously published data standards, drawing strongly on DarwinCore and the Ecological Trait-data Standard, but also includes the ability to fully map location and context properties absent from these vocabularies. It is the first published database-building workflow that adheres to the Extensible Observation Ontology. Simultaneously developing a generalised workflow and publishing a data standard for the workflow provides {traits.build} users a straightforward pathway to build a new trait database that achieves the FAIR principles. The meaning of all variables in a {traits.build} database are already documented, allowing further integration with either other {traits.build} databases or indeed any other database with a documented data model. This follows the vision of the Open Traits Network to build trait databases whose data can be easily integrated for further analysis.

Background Binary diagnostic tests are commonly used in medicine to answer a question about a patient’s clinical status, most commonly, do they or do they not have some disease. Recent advances in statistical methodologies for performing inferential statistics to compare commonly used test metrics for two diagnostic tests have not yet been implemented in a robust statistical package. Methods Up-to-date statistical methods to compare the test metrics achieved by two binary diagnostic tests are implemented in the new R package testCompareR. The output and efficiency of testCompareR is compared to the only other available package which performs this function, DTComPair, as well as an open-source program, compbdt, using a motivating example. Results testCompareR achieves similar results to DTComPair using statistical methods with improved coverage and asymptotic performance. Further, testCompareR is faster than the currently available package and requires fewer pre-processing steps in order to produce accurate results. Conclusions testCompareR provides a new tool to compare the test metrics for two binary diagnostic tests compared with the gold standard. This tool allows flexible inputs, which minimises the need for data pre-processing, and operates in very few steps, so that it is easy to use even for those less experienced with R. testCompareR achieves results comparable to those computed by DTComPair, using optimised statistical methods and with improved computational efficiency.

Abstract Immunotherapy shows great promise for treating advanced cancers, but its effectiveness varies widely among different patients and cancer types. Identifying biomarkers and developing robust predictive models to discern which patients are most likely to benefit from immunotherapy is of great importance. In this context, we have developed the tumor immunotherapy gene expression R package (tigeR 1.0) to address the increasing need for effective tools to explore biomarkers and construct predictive models. tigeR encompasses four distinct yet closely interconnected modules. The Biomarker Evaluation module enables researchers to evaluate whether the biomarkers of interest are associated with immunotherapy response via built‐in or custom immunotherapy gene expression data. The Tumor Microenvironment Deconvolution module integrates 10 open‐source algorithms to obtain the proportions of different cell types within the tumor microenvironment, facilitating the investigation of the association between immune cell populations and immunotherapy response. The Prediction Model Construction module equips users with the ability to construct sophisticated prediction models using a range of built‐in machine‐learning algorithms. The Response Prediction module predicts the immunotherapy response for the patients from gene expression data using our pretrained machine learning models or public gene expression signatures. By providing these diverse functionalities, tigeR aims to simplify the process of analyzing immunotherapy gene expression data, thus making it accessible to researchers without advanced programming skills. The source code and example for the tigeR project can be accessed at http://github.com/YuLab-SMU/tigeR.

Abstract Background The functional coupling between alternative pre-mRNA splicing (AS) and the mRNA quality control mechanism called nonsense-mediated decay (NMD) can modulate transcript abundance. Previous studies have identified several examples of such a regulation in developing neurons. However, the systems-level effects of AS-NMD in this context are poorly understood. Results We developed an R package, factR2, which offers a comprehensive suite of AS-NMD analysis functions. Using this tool, we conducted a longitudinal analysis of gene expression in pluripotent stem cells undergoing induced neuronal differentiation. Our analysis uncovers hundreds of AS-NMD events with significant potential to regulate gene expression. Notably, this regulation is significantly overrepresented in specific functional groups of developmentally downregulated genes. Particularly strong association with gene downregulation is detected for alternative cassette exons stimulating NMD upon their inclusion into mature mRNA. By combining bioinformatic analyses with CRISPR/Cas9 genome editing and other experimental approaches we show that NMD-stimulating cassette exons regulated by the RNA-binding protein PTBP1 dampen the expression of their genes in developing neurons. We also provided evidence that the inclusion of NMD-stimulating cassette exons into mature mRNAs is temporally coordinated with NMD-independent gene repression mechanisms. Conclusions Our study provides an accessible workflow for the discovery and prioritization of AS-NMD targets. It further argues that the AS-NMD pathway plays a widespread role in developing neurons by facilitating the downregulation of functionally related non-neuronal genes.

Abstract Ecological and ecosystem monitoring is rapidly shifting towards using environmental DNA (eDNA) data, particularly in aquatic systems. This approach enables a combined coverage of biodiversity across all major organismal groups and the assessment of ecological indices. Yet, most current approaches are not exploiting the full potential of eDNA data, largely interpreting results in a localized perspective. In riverine networks, by explicitly modelling hydrological transport and associated DNA decay, hydrology‐based models enable upscaling eDNA‐based diversity information, providing spatially integrated inference. To capitalize on these unprecedented biodiversity data and translate it into space‐filling biodiversity projections, a streamlined implementation is needed. Here, we introduce the eDITH R‐package, implementing the eDITH model to project biodiversity across riverine networks with minimal prior information. eDITH couples a species distribution model relating a local taxon's eDNA shedding rate in streamwater to environmental covariates, a mass balance expressing the eDNA concentration at a river's cross‐section as a weighted sum of upstream contributions, and an observational model accounting for uncertainties in eDNA measurements. By leveraging on spatially replicated eDNA measurements and minimal hydro‐morphological data, eDITH enables disentangling the various upstream eDNA sources, and produces space‐filling maps of a taxon's spatial distribution at any chosen resolution. eDITH is applicable to both eDNA concentration and metabarcoding data, and to any taxon whose DNA can be retrieved in streamwater. The eDITH package provides user‐friendly functions for single‐run execution and fitting of eDITH to eDNA data with both Bayesian methods (via the BayesianTools package) and non‐linear optimization. An interface to the DHARMa package allows model validation via posterior predictive checks. Necessary preliminary steps such as watershed delineation and hydrological characterization are implemented via the rivnet package. We illustrate eDITH's workflow and functionalities with two case studies from published fish eDNA data. The eDITH package provides a user‐friendly implementation of eDITH, specifically intended for ecologists and conservation biologists. It can be used without previous modelling knowledge but also allows customization for experienced users. Ultimately, eDITH allows upscaling eDNA biodiversity data for any river globally, transforming how state and change in biodiversity in riverine systems can be tracked at high resolution in a highly versatile manner.

Purpose: Information from the Pittsburgh Sleep Quality Index (PSQI) and Athlete Sleep Behavior Questionnaire (ASBQ) provide the ability to identify the sleep disturbances experienced by athletes and their associated athlete-specific challenges that cause these disturbances. However, determining the appropriate support strategy to optimize the sleep habits and characteristics of large groups of athletes can be time-consuming and resource-intensive. The purpose of this study was to characterize the sleep profiles of elite athletes to optimize sleep-support strategies and present a novel R package, AthSlpBehaviouR, to aid practitioners with athlete sleep monitoring and support efforts. Methods: PSQI and ASBQ data were collected from a cohort of 412 elite athletes across 27 sports through an electronic survey. A k-means cluster analysis was employed to characterize the unique sleep-characteristic typologies based on PSQI and ASBQ component scores. Results: Three unique clusters were identified and qualitatively labeled based on the z scores of the PSQI components and ASBQ components: cluster 1, "high-priority; poor overall sleep characteristics + behavioral-focused support"; cluster 2, "medium-priority, sleep disturbances + routine/environment-focused support"; and cluster 3, "low-priority; acceptable sleep characteristics + general support." Conclusions: The findings of this study highlight the practical utility of an unsupervised learning approach to perform clustering on questionnaire data to inform athlete sleep-support recommendations. Practitioners can consider using the AthSlpBehaviouR package to adopt a similar approach in athlete sleep screening and support provision. [ABSTRACT FROM AUTHOR]

Street view imagery (SVI) is an increasingly important data source for urban analytics and environmental researchers studying the visual quality of the built environment. Compared to remote sensing imagery, SVI can provide a different plane of perspective at ground level and better determine the interplay between urban physical settings and socio-ecological factors that enhance well-being and sustainability. Mapillary, a platform for volunteered street view imagery, has emerged as a promising alternative to Google Street View, offering greater accessibility. Nonetheless, the utility of this open-source database can be limited by the current Mapillary Application Programming Interface (API), which only partially meets the needs of urban analytics research. To address this, we introduce ''streetscape,'' an R package designed to provide user-friendly functions for collecting and analyzing street view imagery data from Mapillary. In addition, the package supports the generation of surveys for the qualitative study of urban landscapes.

Proteomics offers a robust method for quantifying proteins and elucidating their roles in cellular functions, surpassing the insights provided by transcriptomics. The Clinical Proteomic Tumor Analysis Consortium database, enriched with comprehensive cancer proteomics data including phosphorylation and ubiquitination profiles, alongside transcriptomics data from the Genomic Data Commons, allow for integrative molecular studies of cancer. The ProteoCancer Analysis Suite (PCAS), our newly developed R package and Shinyapp, leverages these resources to facilitate in-depth analyses of proteomics, phosphoproteomics, and transcriptomics, enhancing our understanding of the tumor microenvironment through features like immune infiltration and drug sensitivity analysis. This tool aids in identifying critical signaling pathways and therapeutic targets, particularly through its detailed phosphoproteomic analysis. To demonstrate the functionality of the PCAS, we conducted an analysis of GAPDH across multiple cancer types, revealing a significant upregulation of protein levels, which is consistent with its important biological and clinical significance in tumors, as indicated in our prior research. Further experiments were used to validate the findings performed using the tool. In conclusion, the PCAS is a powerful and valuable tool for conducting comprehensive proteomic analyses, significantly enhancing our ability to uncover oncogenic mechanisms and identify potential therapeutic targets in cancer research. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has used bibliometric methods to analyze the research progress and knowledge structure in this field. Our research is dedicated to systematically exploring the global trends and focal points in scientific research on pain comorbidity with bipolar disorder from 2003 to 2023, with the goal of contributing to the field. Methods: Relevant publications in this field were retrieved from the Web of Science core collection database (WOSSCC). And we used VOSviewer, CiteSpace, and the R package "Bibliometrix" for bibliometric analysis. Results: A total of 485 publications (including 360 articles and 125 reviews) from 66 countries, 1019 institutions, were included in this study. Univ Toront and Kings Coll London are the leading research institutions in this field. J Affect Disorders contributed the largest number of articles, and is the most co-cited journal. Of the 2,537 scholars who participated in the study, Stubbs B, Vancampfort D, and Abdin E had the largest number of articles. Stubbs B is the most co-cited author. "chronic pain," "neuropathic pain," "psychological pain" are the keywords in the research. Conclusion: This is the first bibliometric analysis of pain-related bipolar disorder. There is growing interest in the area of pain and comorbid bipolar disorder. Focusing on different types of pain in bipolar disorder and emphasizing pain management in bipolar disorder are research hotspots and future trends. The study of pain related bipolar disorder still has significant potential for development, and we look forward to more high-quality research in the future. [ABSTRACT FROM AUTHOR]

This article describes the R package CorrToolBox, which is designed for modeling the correlation transitions under specified distributional assumptions within the realm of discretization in the context of the latency and threshold concepts. The practical utility and functionality of the package are demonstrated by several illustrative examples. In addition, the package's feasibility and performance are evaluated via simulation studies using synthetic mixed data with a range of marginal distributions. [ABSTRACT FROM AUTHOR]

The growth and fertility rates of past populations can be estimated by analyzing the age-at-death distribution of skeletal samples. The procedure involves regressing growth or fertility rate on the age-at-death ratio, which is a proxy that captures the number of skeletons in two broad age-at-death categories (e.g., D5+/D20+). Galeta and Pankowská (2023, doi: 10.1371/journal.pone.0286580) recently developed a new prediction algorithm. They proposed to estimate growth and fertility rates using a unique prediction formula for each skeletal sample. Each formula is based on a unique reference set of simulated skeletal samples that match the size of the target real skeletal sample. The simulated skeletal samples are generated from populations with similar mortality levels to those assumed in the time period represented by the target skeletal sample. A correct setting of the sample size and the level of mortality increases the accuracy of the estimate. The approach, however, is computationally intensive because it involves generating many simulated reference skeletal samples. In this paper, we present the demrat package, written in the R programming language, which automates the simulation. The functions of the package provide a complete workflow from a real skeletal sample to the prediction of demographic rates. In addition, we offer a web application that allows non-R users to deploy predictions using the demrat package with a user-friendly, point-and-click graphical interface. Although the demrat package allows for estimating demographic rates for a single skeletal sample, we recommend predicting demographic rates in a larger set of skeletal samples and producing smoothed general demographic trends over large areas and/or long periods of time. [ABSTRACT FROM AUTHOR]