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The M5 competition uncertainty track aims for probabilistic forecasting of sales of thousands of Walmart retail goods. We show that the M5 competition data faces strong overdispersion and sporadic demand, especially zero demand. We discuss resulting modeling issues concerning adequate probabilistic forecasting of such count data processes. Unfortunately, the majority of popular prediction methods used in the M5 competition (e.g. lightgbm and xgboost GBMs) fails to address the data characteristics due to the considered objective functions. The distributional forecasting provides a suitable modeling approach for to the overcome those problems. The GAMLSS framework allows flexible probabilistic forecasting using low dimensional distributions. We illustrate, how the GAMLSS approach can be applied for the M5 competition data by modeling the location and scale parameter of various distributions, e.g. the negative binomial distribution. Finally, we discuss software packages for distributional modeling and their drawback, like the R package gamlss with its package extensions, and (deep) distributional forecasting libraries such as TensorFlow Probability.

Recently, numerous bio-optical algorithms have been proposed to estimate chlorophyll-a (Chla) concentration in global surface waters. The surge of algorithms is mainly due to the heterogeneity of waters, especially in inland systems. To reduce redundant modeling work for inland waters and to enhance the usability of algorithms, it is urgent to evaluate the published algorithms for similar optical water types. However, approaches of the algorithm assessment in previous studies vary in error metrics usage or relative comparison, leading to the current lack of a standard or consensus in the community. Thus, we proposed a round-robin scoring method based on optically fuzzy clustering for algorithm assessment. An improved scoring approach (namely the sort-based method) was employed to aggregate the metrics of candidate algorithms. We generate a new set of optical water types using 1702 in situ samples, showing an improvement on our previous work [Bi et al. (2019)]. Then, an integrated Chla result was produced by blending the estimations of optimal algorithms weighted by the membership values, which showed better performance than that of any single algorithm. The blending framework presents more flexible and expandable than previous studies. We aim to illustrate the importance of assessment which considers key properties of algorithms (i.e., Accuracy, Precision, and Effectiveness) and to advocate more in-depth research on certain water types under the fuzzy clustering-based estimation framework (such as clean inland waters with low Chla). This article is accompanied by the open-source R package FCMm for implementation of the proposed method.

There are two potential directions of forecast combination: combining for adaptation and combining for improvement. The former direction targets the performance of the best forecaster, while the latter attempts to combine forecasts to improve on the best forecaster. It is often useful to infer which goal is more appropriate so that a suitable combination method may be used. This paper proposes an AI-AFTER approach that can not only determine the appropriate goal of forecast combination but also intelligently combine the forecasts to automatically achieve the proper goal. As a result of this approach, the combined forecasts from AI-AFTER perform well universally in both adaptation and improvement scenarios. The proposed forecasting approach is implemented in our R package AIafter , which is available at https://github.com/weiqian1/AIafter .

In computational and applied statistics, it is of great interest to get fast and accurate calculation for the distributions of the quadratic forms of Gaussian random variables. This paper presents a novel approximation strategy that contains two developments. First, we propose a faster numerical procedure in computing the moments of the quadratic forms. Second, we establish a general moment-matching framework for distribution approximation, which covers existing approximation methods for the distributions of the quadratic forms of Gaussian variables. Under this framework, a novel moment-ratio method (MR) is proposed to match the ratio of skewness and kurtosis based on the gamma distribution. Our extensive simulations show that 1) MR is almost as accurate as the exact distribution calculation and is much more efficient; 2) comparing with existing approximation methods, MR significantly improves the accuracy of approximating far right tail probabilities. The proposed method has wide applications. For example, it is a better choice than existing methods for facilitating hypothesis testing in big data analysis, where efficient and accurate calculation of very small $p$-values is desired. An R package Qapprox that implements related methods is available on CRAN.

Statistical phylogenetic methods are the foundation for a wide range of evolutionary and epidemiological studies. However, as these methods grow increasingly complex, users often encounter significant challenges with summarizing, visualizing, and communicating their key results.We presentRevGadgets, anRpackage for creating publication-quality figures from the results of a large variety of phylogenetic analyses performed inRevBayes(and other phylogenetic software packages).We demonstrate how to useRevGadgetsthrough a set of vignettes that cover the most common use cases that researchers will encounter.RevGadgetsis an open-source, extensible package that will continue to evolve in parallel withRevBayes, helping researchers to make sense of and communicate the results of a diverse array of analyses.[Bayesian phylogenetics, data visualization, R, RevBayes]

Objectives Non-syndromic cleft lip with or without cleft palate (NSCL ± P) is one of the most common birth malformations. Currently, numerous susceptibility SNPs have been reported by GWA studies, however, the replications of them among NSCL ± P from Han Chinese were very limited. Design In this study, we selected 16 SNPs around 1q32.2 based on the published GWA studies and replicated them among 302 trios with NSCL ± P from Han Chinese Population. The genotypic data was analyzed with FBAT, PLINK and R package. Setting The study was conducted in a tertiary medical center. Patients, participants 302 patients with CL ± P and their parents. Main outcome measures To ascertain the genetic variants in 1q32.2 in patients with CL ± P in Han Chinese Population. Interventions Blood samples were collected. Results We found T allele ( Z = 4.26, p = 0.00002) and T/T homozygotes ( Z = 4.4, p = 0.000011) at rs12063989 was significantly over-transmitted among non-syndromic cleft lip with or without cleft palate (NSCL ± P). Conclusions We found rs12063989 exhibited significant association with the occurrence of NSCL ± P, which would provide new evidence for the future study in the etiology of NSCL ± P.

Most common methods for automatic text analysis in communication science ignore syntactic information, focusing on the occurrence and co-occurrence of individual words, and sometimes n-grams. This is remarkably effective for some purposes, but poses a limitation for fine-grained analyses into semantic relations such as who does what to whom and according to what source. One tested, effective method for moving beyond this bag-of-words assumption is to use a rule-based approach for labeling and extracting syntactic patterns in dependency trees. Although this method can be used for a variety of purposes, its application is hindered by the lack of dedicated and accessible tools. In this paper we introduce the rsyntax R package, which is designed to make working with dependency trees easier and more intuitive for R users, and provides a framework for combining multiple rules for reliably extracting useful semantic relations.

BackgroundMetabolomic biomarkers offer potential for objective and reliable food intake assessment, and there is growing interest in using biomarkers in place of or with traditional self-reported approaches. Ongoing research suggests that multiple biomarkers are associated with single foods, offering great sensitivity and specificity. However, currently there is a dearth of methods to model the relationship between multiple biomarkers and single food intake measurements.ResultsHere, we introduce multiMarker, a web-based application based on the homonymous R package, that enables one to infer the relationship between food intake and two or more metabolomic biomarkers. Furthermore, multiMarker allows prediction of food intake from biomarker data alone. multiMarker differs from previous approaches by providing distributions of predicted intakes, directly accounting for uncertainty in food intake quantification. Usage of both the R package and the web application is demonstrated using real data concerning three biomarkers for orange intake. Further, example data is pre-loaded in the web application to enable users to examine multiMarker’s functionality.ConclusionThe proposed software advance the field of Food Intake Biomarkers providing researchers with a novel tool to perform continuous food intake quantification, and to assess its associated uncertainty, from multiple biomarkers. To facilitate widespread use of the framework, multiMarker has been implemented as an R package and a Shiny web application.

This article provides a step-by-step guide for the analysis of experiments using Bayesian methods, using the BANOVA R package. We provide two worked examples. First, we reanalyze data from research by Romano and Balliet, which examined reciprocity and conformity as alternative mechanisms for cooperation between partners. The study has a between-subjects design and Poisson dependent variable, and we use Bayesian floodlight analysis to explore the interaction between reciprocity/conformity and two continuous covariates. Second, we reanalyze data from a study by Perfecto, Donnelly, and Critcher, who investigated whether mental simulation could be the psychological mechanism that explains how people make volume judgments of three-dimensional objects. The study has a mixed between- and within-subjects design with a Normal dependent variable, and we use Bayesian simple effects to explore the interactions between mental simulation and the shape and orientation of cups. The applications demonstrate the versatility of BANOVA (Bayesian Analysis of Variance) in analyzing a wide range of experimental designs and reveal that the results of the Bayesian analyses differ to some degree from those of the original studies.

Gene expression-based subtypes of colorectal cancer have clinical relevance, but the representativeness of primary tumors and the consensus molecular subtypes (CMS) for metastatic cancers is not well known. We investigated the metastatic heterogeneity of CMS. The best approach to subtype translation was delineated by comparisons of transcriptomic profiles from 317 primary tumors and 295 liver metastases, including multi-metastatic samples from 45 patients and 14 primary-metastasis sets. Associations were validated in an external data set (n = 618). Projection of metastases onto principal components of primary tumors showed that metastases were depleted of CMS1-immune/CMS3-metabolic signals, enriched for CMS4-mesenchymal/stromal signals, and heavily influenced by the microenvironment. The tailored CMS classifier (available in an updated version of the R package CMScaller) therefore implemented an approach to regress out the liver tissue background. The majority of classified metastases were either CMS2 or CMS4. Nonetheless, subtype switching and inter-metastatic CMS heterogeneity were frequent and increased with sampling intensity. Poor-prognostic value of CMS1/3 metastases was consistent in the context of intra-patient tumor heterogeneity.

Configural Frequency Analysis (CFA) is a useful statistical method for the analysis of multiway contingency tables and an appropriate tool for person-oriented or person-centered methods. In complex contingency tables, patterns or configurations are analyzed by comparing observed cell frequencies with expected frequencies. Significant differences between observed and expected frequencies lead to the emergence of Types and Antitypes. Types are patterns or configurations which are significantly more often observed than the expected frequencies; Antitypes represent configurations which are observed less frequently than expected. The R-package confreq is an easy-to-use software for conducting CFAs; another useful shareware to run CFAs was developed by Alexander von Eye. Here, CFA is presented based on the log-linear modeling approach. CFA may be used together with interval level variables which can be added as covariates into the design matrix. In this article, a real data example and the use of confreq are presented. In sum, the use of a covariate may bring the estimated cell frequencies closer to the observed cell frequencies. In those cases, the number of Types or Antitypes may decrease. However, in rare cases, the Type-Antitype pattern can change with new emerging Types or Antitypes.

Motivation Polygenic scores (PGS) aim to genetically predict complex traits at an individual level. PGS are typically trained on genome-wide association summary statistics and require an independent test dataset to tune parameters. More recent methods allow parameters to be tuned on the training data, removing the need for independent test data, but approaches are computationally intensive. Based on fine-mapping principles, we present RápidoPGS, a flexible and fast method to compute PGS requiring summary-level Genome-wide association studies (GWAS) datasets only, with little computational requirements and no test data required for parameter tuning. Results We show that RápidoPGS performs slightly less well than two out of three other widely used PGS methods (LDpred2, PRScs and SBayesR) for case–control datasets, with median r2 difference: -0.0092, -0.0042 and 0.0064, respectively, but up to 17 000-fold faster with reduced computational requirements. RápidoPGS is implemented in R and can work with user-supplied summary statistics or download them from the GWAS catalog. Availability and implementation Our method is available with a GPL license as an R package from CRAN and GitHub. Supplementary information Supplementary data are available at Bioinformatics online.

For the cancer clinical trials with immunotherapy and molecularly targeted therapy, time-to-event endpoint is often a desired endpoint. In this paper, we present an event-driven approach for Bayesian one-stage and two-stage single-arm phase II trial designs. Two versions of Bayesian one-stage designs were proposed with executable algorithms and meanwhile, we also develop theoretical relationships between the frequentist and Bayesian designs. These findings help investigators who want to design a trial using Bayesian approach have an explicit understanding of how the frequentist properties can be achieved. Moreover, the proposed Bayesian designs using the exact posterior distributions accommodate the single-arm phase II trials with small sample sizes. We also proposed an optimal two-stage approach, which can be regarded as an extension of Simon's two-stage design with the time-to-event endpoint. Comprehensive simulations were conducted to explore the frequentist properties of the proposed Bayesian designs and an R package BayesDesign can be assessed via R CRAN for convenient use of the proposed methods.

Background When applying secondary analysis on published survival data, it is critical to obtain each patient’s raw data, because the individual patient data (IPD) approach has been considered as the gold standard of data analysis. However, researchers often lack access to IPD. We aim to propose a straightforward and robust approach to obtain IPD from published survival curves with a user-friendly software platform. Results Improving upon existing methods, we propose an easy-to-use, two-stage approach to reconstruct IPD from published Kaplan-Meier (K-M) curves. Stage 1 extracts raw data coordinates and Stage 2 reconstructs IPD using the proposed method. To facilitate the use of the proposed method, we developed the R package IPDfromKM and an accompanying web-based Shiny application. Both the R package and Shiny application have an “all-in-one” feature such that users can use them to extract raw data coordinates from published K-M curves, reconstruct IPD from the extracted data coordinates, visualize the reconstructed IPD, assess the accuracy of the reconstruction, and perform secondary analysis on the basis of the reconstructed IPD. We illustrate the use of the R package and the Shiny application with K-M curves from published studies. Extensive simulations and real-world data applications demonstrate that the proposed method has high accuracy and great reliability in estimating the number of events, number of patients at risk, survival probabilities, median survival times, and hazard ratios. Conclusions IPDfromKM has great flexibility and accuracy to reconstruct IPD from published K-M curves with different shapes. We believe that the R package and the Shiny application will greatly facilitate the potential use of quality IPD and advance the use of secondary data to facilitate informed decision making in medical research.

Background Network-based analysis of gene expression through co-expression networks can be used to investigate modular relationships occurring between genes performing different biological functions. An extended description of each of the network modules is therefore a critical step to understand the underlying processes contributing to a disease or a phenotype. Biological integration, topology study and conditions comparison (e.g. wild vs mutant) are the main methods to do so, but to date no tool combines them all into a single pipeline. Results Here we present GWENA, a new R package that integrates gene co-expression network construction and whole characterization of the detected modules through gene set enrichment, phenotypic association, hub genes detection, topological metric computation, and differential co-expression. To demonstrate its performance, we applied GWENA on two skeletal muscle datasets from young and old patients of GTEx study. Remarkably, we prioritized a gene whose involvement was unknown in the muscle development and growth. Moreover, new insights on the variations in patterns of co-expression were identified. The known phenomena of connectivity loss associated with aging was found coupled to a global reorganization of the relationships leading to expression of known aging related functions. Conclusion GWENA is an R package available through Bioconductor (https://bioconductor.org/packages/release/bioc/html/GWENA.html) that has been developed to perform extended analysis of gene co-expression networks. Thanks to biological and topological information as well as differential co-expression, the package helps to dissect the role of genes relationships in diseases conditions or targeted phenotypes. GWENA goes beyond existing packages that perform co-expression analysis by including new tools to fully characterize modules, such as differential co-expression, additional enrichment databases, and network visualization.

Motivation Marker genes, defined as genes that are expressed primarily in a single-cell type, can be identified from the single-cell transcriptome; however, such data are not always available for the many uses of marker genes, such as deconvolution of bulk tissue. Marker genes for a cell type, however, are highly correlated in bulk data, because their expression levels depend primarily on the proportion of that cell type in the samples. Therefore, when many tissue samples are analyzed, it is possible to identify these marker genes from the correlation pattern. Results To capitalize on this pattern, we develop a new algorithm to detect marker genes by combining published information about likely marker genes with bulk transcriptome data in the form of a semi-supervised algorithm. The algorithm then exploits the correlation structure of the bulk data to refine the published marker genes by adding or removing genes from the list. Availability and implementation We implement this method as an R package markerpen, hosted on CRAN (https://CRAN.R-project.org/package=markerpen). Supplementary information Supplementary data are available at Bioinformatics online.

SummarySpiral layout has two major advantages for data visualization. First, it is able to visualize data with long axes, which greatly improves the resolution of visualization. Second, it is efficient for time series data to reveal periodic patterns. Here we present the R package spiralize that provides a general solution for visualizing data on spirals. spiralize implements numerous graphics functions so that self-defined high-level graphics can be easily implemented by users. The flexibility and power of spiralize are demonstrated by five examples from real-world datasets.Availability and implementationThe spiralize package and documentations are freely available at the Comprehensive R Archive Network (CRAN) https://CRAN.R-project.org/package=spiralize.Contactz.gu@dkfz.de or d.huebschmann@dkfz.deSupplementary informationSupplementary data are available at Bioinformatics online.

Summary Multiplex immunofluorescence (mIF) staining combined with quantitative digital image analysis is a novel and increasingly used technique that allows for the characterization of the tumor immune microenvironment (TIME). Generally, mIF data is used to examine the abundance of immune cells in the TIME; however, this does not capture spatial patterns of immune cells throughout the TIME, a metric increasingly recognized as important for prognosis. To address this gap, we developed an R package spatialTIME that enables spatial analysis of mIF data, as well as the iTIME web application that provides a robust but simplified user interface for describing both abundance and spatial architecture of the TIME. The spatialTIME package calculates univariate and bivariate spatial statistics (e.g. Ripley’s K, Besag’s L, Macron’s M and G or nearest neighbor distance) and creates publication quality plots for spatial organization of the cells in each tissue sample. The iTIME web application allows users to statistically compare the abundance measures with patient clinical features along with visualization of the TIME for one tissue sample at a time. Availability and implementation spatialTIME is implemented in R and can be downloaded from GitHub (https://github.com/FridleyLab/spatialTIME) or CRAN. An extensive vignette for using spatialTIME can also be found at https://cran.r-project.org/web/packages/spatialTIME/index.html. iTIME is implemented within a R Shiny application and can be accessed online (http://itime.moffitt.org/), with code available on GitHub (https://github.com/FridleyLab/iTIME). Supplementary information Supplementary data are available at Bioinformatics online.

Objectives Data mining can complement traditional hypothesis-based approaches in characterizing unhealthy work exposures. We used it to derive a hypothesis-free characterization of working hour patterns in shift work and their associations with sickness absence (SA). Methods In this prospective cohort study, complete payroll-based work hours and SA dates were extracted from a shift-scheduling register from 2008 to 2019 on 6029 employees from a hospital district in Southwestern Finland. We applied permutation distribution clustering to time series of successive shift lengths, between-shift rest periods, and shift starting times to identify clusters of similar working hour patterns over time. We examined associations of clusters spanning on average 23 months with SA during the following 23 months. Results We identified eight distinct working hour patterns in shift work: (i) regular morning (M)/evening (E) work, weekends off; (ii) irregular M work; (iii) irregular M/E/night (N) work; (iv) regular M work, weekends off; (v) irregular, interrupted M/E/N work; (vi) variable M work, weekends off; (vii) quickly rotating M/E work, non-standard weeks; and (viii) slowly rotating M/E work, non-standard weeks. The associations of these eight working-hour clusters with risk of future SA varied. The cluster of irregular, interrupted M/E/N work was the strongest predictor of increased SA (days per year) with an incidence rate ratio of 1.77 (95% confidence interval 1.74–1.80) compared to regular M/E work, weekends off. Conclusions This data-mining suggests that hypothesis-free approaches can contribute to scientific understanding of healthy working hour characteristics and complement traditional hypothesis-driven approaches.

Single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) identifies regulated chromatin accessibility modules at the single-cell resolution. Robust evaluation is critical to the development of scATAC-seq pipelines, which calls for reproducible datasets for benchmarking. We hereby present the simATAC framework, an R package that generates scATAC-seq count matrices that highly resemble real scATAC-seq datasets in library size, sparsity, and chromatin accessibility signals. simATAC deploys statistical models derived from analyzing 90 real scATAC-seq cell groups. simATAC provides a robust and systematic approach to generate in silico scATAC-seq samples with known cell labels for assessing analytical pipelines. Supplementary Information The online version contains supplementary material available at (10.1186/s13059-021-02270-w).

Background An increasing number of clinical trials require biomarker-driven patient stratification, especially for revolutionary immune checkpoint blockade therapy. Due to the complicated interaction between a tumor and its microenvironment, single biomarkers, such as PDL1 protein level, tumor mutational burden (TMB), single gene mutation and expression, are far from satisfactory for response prediction or patient stratification. Recently, combinatorial biomarkers were reported to be more precise and powerful for predicting therapy response and identifying potential target populations with superior survival. However, there is a lack of dedicated tools for such combinatorial biomarker analysis. Results Here, we present dualmarker, an R package designed to facilitate the data exploration for dual biomarker combinations. Given two biomarkers, dualmarker comprehensively visualizes their association with drug response and patient survival through 14 types of plots, such as boxplots, scatterplots, ROCs, and Kaplan–Meier plots. Using logistic regression and Cox regression models, dualmarker evaluated the superiority of dual markers over single markers by comparing the data fitness of dual-marker versus single-marker models, which was utilized for de novo searching for new biomarker pairs. We demonstrated this straightforward workflow and comprehensive capability by using public biomarker data from one bladder cancer patient cohort (IMvigor210 study); we confirmed the previously reported biomarker pair TMB/TGF-beta signature and CXCL13 expression/ARID1A mutation for response and survival analyses, respectively. In addition, dualmarker de novo identified new biomarker partners, for example, in overall survival modelling, the model with combination of HMGB1 expression and ARID1A mutation had statistically better goodness-of-fit than the model with either HMGB1 or ARID1A as single marker. Conclusions The dualmarker package is an open-source tool for the visualization and identification of combinatorial dual biomarkers. It streamlines the dual marker analysis flow into user-friendly functions and can be used for data exploration and hypothesis generation. Its code is freely available at GitHub at https://github.com/maxiaopeng/dualmarker under MIT license.

Data from untargeted metabolomics studies employing nuclear magnetic resonance (NMR) spectroscopy oftentimes contain negative values. These negative values hamper data processing and analysis algorithms and prevent the use of such data in multiomics integration settings. New methods to deal with such negative values are thus an urgent need in the metabolomics community. This study presents affine transformation of negative values (ATNV), a novel algorithm for replacement of negative values in NMR data sets. ATNV was implemented in the R package mrbin, which features interactive menus for user-friendly application and is available for free for various operating systems within the free R statistical programming language. The novel algorithms were tested on a set of human urinary NMR spectra and were able to successfully identify relevant metabolites.

This paper explores how to prepare data for analyzing the Chinese texts with R language based on the theory of Welbers, particularly comparing the R package Rwordseg with jiebaR to see the results of Chinese text segmentation at the step of preprocessing. ...

Summary UCSC Xena platform provides huge amounts of processed cancer omics data from large cancer research projects (e.g. TCGA, CCLE and PCAWG) or individual research groups and enables unprecedented research opportunities. However, a graphical user interface-based tool for interactively analyzing UCSC Xena data and generating elegant plots is still lacking, especially for cancer researchers and clinicians with limited programming experience. Here, we present UCSCXenaShiny, an R Shiny package for quickly searching, downloading, exploring, analyzing and visualizing data from UCSC Xena data hubs. This tool could effectively promote the practical use of public data, and can serve as an important complement to the current Xena genomics explorer. Availability and implementation UCSCXenaShiny is an open source R package under GPLv3 license and it is freely available at https://github.com/openbiox/UCSCXenaShiny or https://cran.r-project.org/package=UCSCXenaShiny. The docker image is available at https://hub.docker.com/r/shixiangwang/ucscxenashiny. Supplementary information Supplementary data are available at Bioinformatics online.

Identification of metal-binding sites in proteins and understanding metal-coupled protein folding mechanisms are aspects of high importance for the structure-to-function relationship. Mass spectrometry (MS) has brought a powerful adjunct perspective to structural biology, obtaining from metal-to-protein stoichiometry to quaternary structure information. Currently, the different experimental and/or instrumental setups usually require the use of multiple data analysis software, and in some cases, they lack some of the main data analysis steps (MS processing, scoring, identification). Here, we present a comprehensive data analysis pipeline that addresses charge-state deconvolution, statistical scoring, and mass assignment for native MS, bottom-up, and native top-down with emphasis on metal–protein complexes. We have evaluated all of the approaches using assemblies of increasing complexity, including free and chemically labeled proteins, from low- to high-resolution MS. In all cases, the results have been compared with common software and proved how MetaOdysseus outperformed them.

The consideration of a patient's treatment preference may be essential in determining how a patient will respond to a particular treatment. While traditional clinical trials are unable to capture these effects, the two-stage randomized preference design provides an important tool for researchers seeking to understand the role of patient preferences. In addition to the treatment effect, these designs seek to estimate the role of preferences through testing of selection and preference effects. The R package preference facilitates the use of two-stage clinical trials by providing the necessary tools to design and analyze these studies. To aid in the design, functions are provided to estimate the required sample size and to estimate the study power when a sample size is fixed. In addition, analysis functions are provided to determine the significance of each effect using either raw data or summary statistics. The package is able to incorporate either an unstratified or stratified preference design. The functionality of the package is demonstrated using data from a study evaluating two management methods in women found to have an atypical Pap smear.

Precision medicine is an approach to health care in which treatment decisions are tailored to patient-level information. Statistical methods for the estimation of dynamic treatment regimes (DTRs) a...

In the past few decades, major initiatives have been launched around the world to address chemical safety testing. These efforts aim to innovate and improve the efficacy of existing methods with the long-term goal of developing new risk assessment paradigms. The transcriptomic and toxicological profiling of mammalian cells has resulted in the creation of multiple toxicogenomic datasets and corresponding tools for analysis. To enable easy access and analysis of these valuable toxicogenomic data, we have developed ToxicoDB (toxicodb.ca), a free and open cloud-based platform integrating data from large in vitro toxicogenomic studies, including gene expression profiles of primary human and rat hepatocytes treated with 231 potential toxicants. To efficiently mine these complex toxicogenomic data, ToxicoDB provides users with harmonized chemical annotations, time- and dose-dependent plots of compounds across datasets, as well as the toxicity-related pathway analysis. The data in ToxicoDB have been generated using our open-source R package, ToxicoGx (github.com/bhklab/ToxicoGx). Altogether, ToxicoDB provides a streamlined process for mining highly organized, curated, and accessible toxicogenomic data that can be ultimately applied to preclinical toxicity studies and further our understanding of adverse outcomes.

Network meta-analysis is a method to combine evidence from randomized controlled trials (RCTs) that compare a number of different interventions for a given clinical condition. Usually, this requires a connected network. A possible approach to link a disconnected network is to add evidence from nonrandomized comparisons, using propensity score or matching-adjusted indirect comparisons methods. However, nonrandomized comparisons may be associated with an unclear risk of bias. Schmitz et al. used single-arm observational studies for bridging the gap between two disconnected networks of treatments for multiple myeloma. We present a reanalysis of these data using component network meta-analysis (CNMA) models entirely based on RCTs, utilizing the fact that many of the treatments consisted of common treatment components occurring in both networks. We discuss forward and backward strategies for selecting appropriate CNMA models and compare the results to those obtained by Schmitz et al. using their matching method. CNMA models provided a good fit to the data and led to treatment rankings that were similar, though not fully equal to that obtained by Schmitz et al. We conclude that researchers encountering a disconnected network with treatments in different subnets having common components should consider a CNMA model. Such models, exclusively based on evidence from RCTs, are a promising alternative to matching approaches that require additional evidence from observational studies. CNMA models are implemented in the R package netmeta.

Coral reefs provide major nutritional inputs to humans through fish production. Yet, our capacity to adequately assess fish productivity in these and other high-diversity aquatic systems is hampered by a lack of computationally accessible methods with realistic data requirements. Standing stock biomass is often assumed to reflect biomass productivity, yet theoretical and empirical evidence question this assumption. These methodological hurdles have stymied progress in managing this critical coral reef function, potentially jeopardising the future of many small-scale tropical fisheries struggling to respond to global changes. Here, we summarise the physiological and ecological processes that lead to the production of fish biomass. We outline principles and present a robust framework for quantifying fish productivity in high-diversity ecosystems that overcomes these shortcomings by integrating readily accessible individual-level data (e.g. from visual counts) with growth trajectories and predicted mortality rates. This framework provides fisheries-independent estimates of multispecies fish productivity without the need to specify often unknown detailed trophic relationships. We delineate five simple steps and provide a critical user-friendly interface (an easy-to-use R package) to make the calculation of fish productivity a readily accessible tool for coral reef scientists and managers.

This book is written to be a practical guide to both structural equation modeling (SEM) and to using the R package lavaan (Rosseel 2012) to apply SEM. As one can read in Gana and Broc’s (2019) introduction, the book is meant to be “a didactic book presenting the basics of a technique for beginners who wish to gradually learn structural equation modeling and make use of its flexibility, opportunities, and upgrades and extenxions [sic]” (p. xi). The authors stress that they have put themselves in the shoes of the user with a limited statistical background, who should “easily find in it both a technical introduction and a practical introduction, oriented towards the use of SEM” (p. xii). Open-source software was chosen deliberately on Gana’s part, as the preface mentions his experience “teaching SEM in African universities where it was impossible to have SEM commercial software” (p. ix).

The R package catR is a useful developmental and testing platform for adaptive tests. Developers and researchers have been using catR for their assessments or research projects. However, there is a flaw in catR that can potentially cause misleading results. This article shows the flaw and provides a solution. Suggestions in using seeds for random numbers were also provided.

Despite a major increase in the range and number of software offerings now available to help researchers produce evidence syntheses, there is currently no generic tool for producing figures to display and explore the risk-of-bias assessments that routinely take place as part of systematic review. However, tools such as the R programming environment and Shiny (an R package for building interactive web apps) have made it straightforward to produce new tools to help in producing evidence syntheses. We present a new tool, robvis (Risk-Of-Bias VISualization), available as an R package and web app, which facilitates rapid production of publication-quality risk-of-bias assessment figures. We present a timeline of the tool's development and its key functionality.

Background Perfusion-weighted imaging is only scarcely used in veterinary medicine. The exact reasons are unclear. One reason might be the typically high costs of the software packages for image analysis. In addition, a great variability concerning available programs makes it hard to compare results between different studies. Moreover, these algorithms are tuned for their usage in human medicine and often difficult to adapt to veterinary studies. In order to address these issues, our aim is to deliver a free open source package for calculating quantitative perfusion parameters. We develop an “R package” calculating mean transit time, cerebral blood flow and cerebral blood volume from data obtained with freely imaging software (OsiriX Light®). We hope that the free availability, in combination with the fact that the underlying algorithm is open and adaptable, makes it easier for scientists in veterinary medicine to use, compare and adapt perfusion-weighted imaging analysis. In order to demonstrate the usage of our software package, we reviewed previously acquired perfusion-weighted images from a group of eight purpose-breed healthy beagle dogs and twelve client-owned dogs with idiopathic epilepsy. In order to obtain the data needed for our algorithm, the following steps were performed: First, regions of interest (ROI) were drawn around different, previously reported, brain regions and the middle cerebral artery. Second, a ROI enhancement curve was generated for each ROI using a freely available PlugIn. Third, the signal intensity curves were exported as a comma-separated-value file. These files constitute the input to our software package, which then calculates the PWI parameters. Results We used our software package to re-assess perfusion weighted images from two previous studies. The clinical results were similar, showing a significant increase in the mean transit time and a significant decrease in cerebral blood flow for diseased dogs. Conclusion We provide an “R package” for computing the main perfusion parameters from measurements taken with standard imaging software and describe in detail how to obtain these measurements. We hope that our contribution enables users in veterinary medicine to easily obtain perfusion parameters using standard Open Source software in a standard, adaptable and comparable way.

In randomized controlled trials of seriously ill patients, death is common and often defined as the primary endpoint. Increasingly, non-mortality outcomes such as functional outcomes are co-primary or secondary endpoints. Functional outcomes are not defined for patients who die, referred to as "truncation due to death", and among survivors, functional outcomes are often unobserved due to missed clinic visits or loss to follow-up. It is well known that if the functional outcomes "truncated due to death" or missing are handled inappropriately, treatment effect estimation can be biased. In this paper, we describe the package idem that implements a procedure for comparing treatments that is based on a composite endpoint of mortality and the functional outcome among survivors. Among survivors, the procedure incorporates a missing data imputation procedure with a sensitivity analysis strategy. A web-based graphical user interface is provided in the idem package to facilitate users conducting the proposed analysis in an interactive and user-friendly manner. We demonstrate idem using data from a recent trial of sedation interruption among mechanically ventilated patients.

We present the R package and web app statcheck to automatically detect statistical reporting inconsistencies in primary studies and meta‐analyses. Previous research has shown a high prevalence of reported p‐values that are inconsistent ‐ meaning a re‐calculated p‐value, based on the reported test statistic and degrees of freedom, does not match the author‐reported p‐value. Such inconsistencies affect the reproducibility and evidential value of published findings. The tool statcheck can help researchers to identify statistical inconsistencies so that they may correct them. In this paper, we provide an overview of the prevalence and consequences of statistical reporting inconsistencies. We also discuss the tool statcheck in more detail and give an example of how it can be used in a meta‐analysis. We end with some recommendations concerning the use of statcheck in meta‐analyses and make a case for better reporting standards of statistical results.

Evidence accumulation models are a useful tool to allow researchers to investigate the latent cognitive variables that underlie response time and response accuracy. However, applying evidence accumulation models can be difficult because they lack easily computable forms. Numerical methods are required to determine the parameters of evidence accumulation that best correspond to the fitted data. When applied to complex cognitive models, such numerical methods can require substantial computational power which can lead to infeasibly long compute times. In this paper, we provide efficient, practical software and a step-by-step guide to fit evidence accumulation models with Bayesian methods. The software, written in C++, is provided in an R package: 'ggdmc'. The software incorporates three important ingredients of Bayesian computation, (1) the likelihood functions of two common response time models, (2) the Markov chain Monte Carlo (MCMC) algorithm (3) a population-based MCMC sampling method. The software has gone through stringent checks to be hosted on the Comprehensive R Archive Network (CRAN) and is free to download. We illustrate its basic use and an example of fitting complex hierarchical Wiener diffusion models to four shooting-decision data sets.

Point data obtained from real‐time location systems (RTLSs) can be processed into animal contact networks, describing instances of interaction between tracked individuals. Proximity‐based definitions of interanimal “contact,” however, may be inadequate for describing epidemiologically and sociologically relevant interactions involving body parts or other physical spaces relatively far from tracking devices. This weakness can be overcome by using polygons, rather than points, to represent tracked individuals and defining “contact” as polygon intersections.We present novel procedures for deriving polygons from RTLS point data while maintaining distances and orientations associated with individuals' relocation events. We demonstrate the versatility of this methodology for network modeling using two contact network creation examples, wherein we use this procedure to create (a) interanimal physical contact networks and (b) a visual contact network. Additionally, in creating our networks, we establish another procedure to adjust definitions of “contact” to account for RTLS positional accuracy, ensuring all true contacts are likely captured and represented in our networks.Using the methods described herein and the associated R package we have developed, called contact, researchers can derive polygons from RTLS points. Furthermore, we show that these polygons are highly versatile for contact network creation and can be used to answer a wide variety of epidemiological, ethological, and sociological research questions.By introducing these methodologies and providing the means to easily apply them through the contact R package, we hope to vastly improve network‐model realism and researchers' ability to draw inferences from RTLS data., Point data obtained from real‐time location systems (RTLSs) are often processed into animal contact networks, describing instances of interaction between tracked individuals. Proximity‐based definitions of interanimal “contact,” however, are inadequate for describing epidemiologically and sociologically relevant interactions involving body parts or other physical spaces relatively far from tracking devices. To overcome this weakness, we present novel procedures for deriving polygons from RTLS point data while maintaining distances and orientations associated with individuals' relocation events, allowing researchers to define “contact” as polygon intersections.

With the increasing demand for air-conditioning and refrigeration and depleting fossil fuel resources, countries across the globe have been exploring sustainable alternatives to supply cooling loads. While solar cooling technology has been investigated and demonstrated in recent decades, it has not yet been able to take over traditional cooling systems due to the technical and financial constraints. Understanding the state of the art in this emerging research field is crucial in planning future research efforts. In light of this motivation, this study uses bibliometric analysis to identify hot topics, trends, and research clusters in solar cooling. A dataset of 3639 publications on solar cooling obtained from Web of Science has been analyzed using (i) the open source tool VOSviewer, (ii) the R package Bibliometrix and (iii) an in-house bibliometric tool. This analysis allowed us to determine the annual publication rate both total and segregated by country, author, journal, and research institution. With an overall increasing trend in the total number of publications, China was identified as the leading country in solar cooling research followed by the USA, and Southern European countries. Keyword analysis and time evolution of various key solar cooling technologies have shown that the focus has so far been on solar thermal cooling technology. Nonetheless, as solar photovoltaic prices drop significantly, researchers are expected to focus more closely on photovoltaic driven cooling systems in the near future as a step towards reducing fossil fuel dependence and mitigating climate change.

In this paper we present the RMCriteria package to support the decision making system in the R software environment for statistical computing and graphics. The RMCriteria is a support decision syst...