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1.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38770717

RESUMO

Drug therapy is vital in cancer treatment. Accurate analysis of drug sensitivity for specific cancers can guide healthcare professionals in prescribing drugs, leading to improved patient survival and quality of life. However, there is a lack of web-based tools that offer comprehensive visualization and analysis of pancancer drug sensitivity. We gathered cancer drug sensitivity data from publicly available databases (GEO, TCGA and GDSC) and developed a web tool called Comprehensive Pancancer Analysis of Drug Sensitivity (CPADS) using Shiny. CPADS currently includes transcriptomic data from over 29 000 samples, encompassing 44 types of cancer, 288 drugs and more than 9000 gene perturbations. It allows easy execution of various analyses related to cancer drug sensitivity. With its large sample size and diverse drug range, CPADS offers a range of analysis methods, such as differential gene expression, gene correlation, pathway analysis, drug analysis and gene perturbation analysis. Additionally, it provides several visualization approaches. CPADS significantly aids physicians and researchers in exploring primary and secondary drug resistance at both gene and pathway levels. The integration of drug resistance and gene perturbation data also presents novel perspectives for identifying pivotal genes influencing drug resistance. Access CPADS at https://smuonco.shinyapps.io/CPADS/ or https://robinl-lab.com/CPADS.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Internet , Neoplasias , Software , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Resistencia a Medicamentos Antineoplásicos/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biologia Computacional/métodos , Bases de Dados Genéticas , Transcriptoma , Perfilação da Expressão Gênica/métodos
2.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38271482

RESUMO

Recent technological advances in sequencing DNA and RNA modifications using high-throughput platforms have generated vast epigenomic and epitranscriptomic datasets whose power in transforming life science is yet fully unleashed. Currently available in silico methods have facilitated the identification, positioning and quantitative comparisons of individual modification sites. However, the essential challenge to link specific 'epi-marks' to gene expression in the particular context of cellular and biological processes is unmet. To fast-track exploration, we generated epidecodeR implemented in R, which allows biologists to quickly survey whether an epigenomic or epitranscriptomic status of their interest potentially influences gene expression responses. The evaluation is based on the cumulative distribution function and the statistical significance in differential expression of genes grouped by the number of 'epi-marks'. This tool proves useful in predicting the role of H3K9ac and H3K27ac in associated gene expression after knocking down deacetylases FAM60A and SDS3 and N6-methyl-adenosine-associated gene expression after knocking out the reader proteins. We further used epidecodeR to explore the effectiveness of demethylase FTO inhibitors and histone-associated modifications in drug abuse in animals. epidecodeR is available for downloading as an R package at https://bioconductor.riken.jp/packages/3.13/bioc/html/epidecodeR.html.


Assuntos
Epigenômica , Software , Animais , Epigenômica/métodos , Metilação de DNA , DNA/metabolismo , Epigênese Genética
3.
BMC Biol ; 22(1): 220, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39343900

RESUMO

BACKGROUND: Eukaryotic cells are highly compartmentalized by a variety of organelles that carry out specific cellular processes. The position of these organelles within the cell is elaborately regulated and vital for their function. For instance, the position of lysosomes relative to the nucleus controls their degradative capacity and is altered in pathophysiological conditions. The molecular components orchestrating the precise localization of organelles remain incompletely understood. A confounding factor in these studies is the fact that organelle positioning is surprisingly non-trivial to address e.g., perturbations that affect the localization of organelles often lead to secondary phenotypes such as changes in cell or organelle size. These phenotypes could potentially mask effects or lead to the identification of false positive hits. To uncover and test potential molecular components at scale, accurate and easy-to-use analysis tools are required that allow robust measurements of organelle positioning. RESULTS: Here, we present an analysis workflow for the faithful, robust, and quantitative analysis of organelle positioning phenotypes. Our workflow consists of an easy-to-use Fiji plugin and an R Shiny App. These tools enable users without background in image or data analysis to (1) segment single cells and nuclei and to detect organelles, (2) to measure cell size and the distance between detected organelles and the nucleus, (3) to measure intensities in the organelle channel plus one additional channel, (4) to measure radial intensity profiles of organellar markers, and (5) to plot the results in informative graphs. Using simulated data and immunofluorescent images of cells in which the function of known factors for lysosome positioning has been perturbed, we show that the workflow is robust against common problems for the accurate assessment of organelle positioning such as changes of cell shape and size, organelle size and background. CONCLUSIONS: OrgaMapper is a versatile, robust, and easy-to-use automated image analysis workflow that can be utilized in microscopy-based hypothesis testing and screens. It effectively allows for the mapping of the intracellular space and enables the discovery of novel regulators of organelle positioning.


Assuntos
Organelas , Software , Fluxo de Trabalho , Humanos , Processamento de Imagem Assistida por Computador/métodos , Núcleo Celular
4.
BMC Bioinformatics ; 25(1): 93, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438871

RESUMO

An organism's observable traits, or phenotype, result from intricate interactions among genes, proteins, metabolites and the environment. External factors, such as associated microorganisms, along with biotic and abiotic stressors, can significantly impact this complex biological system, influencing processes like growth, development and productivity. A comprehensive analysis of the entire biological system and its interactions is thus crucial to identify key components that support adaptation to stressors and to discover biomarkers applicable in breeding programs or disease diagnostics. Since the genomics era, several other 'omics' disciplines have emerged, and recent advances in high-throughput technologies have facilitated the generation of additional omics datasets. While traditionally analyzed individually, the last decade has seen an increase in multi-omics data integration and analysis strategies aimed at achieving a holistic understanding of interactions across different biological layers. Despite these advances, the analysis of multi-omics data is still challenging due to their scale, complexity, high dimensionality and multimodality. To address these challenges, a number of analytical tools and strategies have been developed, including clustering and differential equations, which require advanced knowledge in bioinformatics and statistics. Therefore, this study recognizes the need for user-friendly tools by introducing Holomics, an accessible and easy-to-use R shiny application with multi-omics functions tailored for scientists with limited bioinformatics knowledge. Holomics provides a well-defined workflow, starting with the upload and pre-filtering of single-omics data, which are then further refined by single-omics analysis focusing on key features. Subsequently, these reduced datasets are subjected to multi-omics analyses to unveil correlations between 2-n datasets. This paper concludes with a real-world case study where microbiomics, transcriptomics and metabolomics data from previous studies that elucidate factors associated with improved sugar beet storability are integrated using Holomics. The results are discussed in the context of the biological background, underscoring the importance of multi-omics insights. This example not only highlights the versatility of Holomics in handling different types of omics data, but also validates its consistency by reproducing findings from preceding single-omics studies.


Assuntos
Beta vulgaris , Multiômica , Melhoramento Vegetal , Biologia Computacional , Análise por Conglomerados
5.
BMC Bioinformatics ; 25(1): 142, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566005

RESUMO

BACKGROUND: The rapid advancement of new genomic sequencing technology has enabled the development of multi-omic single-cell sequencing assays. These assays profile multiple modalities in the same cell and can often yield new insights not revealed with a single modality. For example, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) simultaneously profiles the RNA transcriptome and the surface protein expression. The surface protein markers in CITE-Seq can be used to identify cell populations similar to the iterative filtration process in flow cytometry, also called "gating", and is an essential step for downstream analyses and data interpretation. While several packages allow users to interactively gate cells, they often do not process multi-omic sequencing datasets and may require writing redundant code to specify gate boundaries. To streamline the gating process, we developed CITEViz which allows users to interactively gate cells in Seurat-processed CITE-Seq data. CITEViz can also visualize basic quality control (QC) metrics allowing for a rapid and holistic evaluation of CITE-Seq data. RESULTS: We applied CITEViz to a peripheral blood mononuclear cell CITE-Seq dataset and gated for several major blood cell populations (CD14 monocytes, CD4 T cells, CD8 T cells, NK cells, B cells, and platelets) using canonical surface protein markers. The visualization features of CITEViz were used to investigate cellular heterogeneity in CD14 and CD16-expressing monocytes and to detect differential numbers of detected antibodies per patient donor. These results highlight the utility of CITEViz to enable the robust classification of single cell populations. CONCLUSIONS: CITEViz is an R-Shiny app that standardizes the gating workflow in CITE-Seq data for efficient classification of cell populations. Its secondary function is to generate basic feature plots and QC figures specific to multi-omic data. The user interface and internal workflow of CITEViz uniquely work together to produce an organized workflow and sensible data structures for easy data retrieval. This package leverages the strengths of biologists and computational scientists to assess and analyze multi-omic single-cell datasets. In conclusion, CITEViz streamlines the flow cytometry gating workflow in CITE-Seq data to help facilitate novel hypothesis generation.


Assuntos
Leucócitos Mononucleares , Software , Humanos , Análise de Sequência de RNA/métodos , Fluxo de Trabalho , Citometria de Fluxo , Proteínas de Membrana , Análise de Célula Única/métodos , Perfilação da Expressão Gênica/métodos
6.
Curr Issues Mol Biol ; 46(5): 4803-4814, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38785557

RESUMO

Over the last decades, the analysis of complex microbial communities by high-throughput sequencing of marker gene amplicons has become routine work for many research groups. However, the main challenges faced by scientists who want to make use of the generated sequencing datasets are the lack of expertise to select a suitable pipeline and the need for bioinformatics or programming skills to apply it. Here, we present MetaXplore, an interactive, user-friendly platform that enables the discovery and visualization of amplicon sequencing data. Currently, it provides a set of well-documented choices for downstream analysis, including alpha and beta diversity analysis, taxonomic composition, differential abundance analysis, identification of the core microbiome within a population, and biomarker analysis. These features are presented in a user-friendly format that facilitates easy customization and the generation of publication-quality graphics. MetaXplore is implemented entirely in the R language using the Shiny framework. It can be easily used locally on any system with R installed, including Windows, Mac OS, and most Linux distributions, or remotely via a web server without bioinformatic expertise. It can also be used as a framework for advanced users who can modify and expand the tool.

7.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34642739

RESUMO

Development of interactive web applications to deposit, visualize and analyze biological datasets is a major subject of bioinformatics. R is a programming language for data science, which is also one of the most popular languages used in biological data analysis and bioinformatics. However, building interactive web applications was a great challenge for R users before the Shiny package was developed by the RStudio company in 2012. By compiling R code into HTML, CSS and JavaScript code, Shiny has made it incredibly easy to build web applications for the large R community in bioinformatics and for even non-programmers. Over 470 biological web applications have been developed with R/Shiny up to now. To further promote the utilization of R/Shiny, we reviewed the development of biological web applications with R/Shiny, including eminent biological web applications built with R/Shiny, basic steps to build an R/Shiny application, commonly used R packages to build the interface and server of R/Shiny applications, deployment of R/Shiny applications in the cloud and online resources for R/Shiny.


Assuntos
Biologia Computacional , Software , Linguagens de Programação
8.
J Transl Med ; 22(1): 282, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491529

RESUMO

BACKGROUND: Oral inflammatory diseases are localized infectious diseases primarily caused by oral pathogens with the potential for serious systemic complications. However, publicly available datasets for these diseases are underutilized. To address this issue, a web tool called OralExplorer was developed. This tool integrates the available data and provides comprehensive online bioinformatic analysis. METHODS: Human oral inflammatory disease-related datasets were obtained from the GEO database and normalized using a standardized process. Transcriptome data were then subjected to differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis, and visualization. The single-cell sequencing data was visualized as cluster plot, feature plot, and heatmaps. The web platform was primarily built using Shiny. The biomarkers identified in OralExplorer were validated using local clinical samples through qPCR and IHC. RESULTS: A total of 35 human oral inflammatory disease-related datasets, covering 6 main disease types and 901 samples, were included in the study to identify potential molecular signatures of the mechanisms of oral diseases. OralExplorer consists of 5 main analysis modules (differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis and single-cell analysis), with multiple visualization options. The platform offers a simple and intuitive interface, high-quality images for visualization, and detailed analysis results tables for easy access by users. Six markers (IL1ß, SRGN, CXCR1, FGR, ARHGEF2, and PTAFR) were identified by OralExplorer. qPCR- and IHC-based experimental validation showed significantly higher levels of these genes in the periodontitis group. CONCLUSIONS: OralExplorer is a comprehensive analytical platform for oral inflammatory diseases. It allows users to interactively explore the molecular mechanisms underlying the action and regression of these diseases. It also aids dental researchers in unlocking the potential value of transcriptomics data related to oral diseases. OralExplorer can be accessed at https://smuonco.shinyapps.io/OralExplorer/  (Alternate URL: http://robinl-lab.com/OralExplorer ).


Assuntos
Biologia Computacional , Software , Humanos , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Transcriptoma/genética , Bases de Dados Factuais , Fatores de Troca de Nucleotídeo Guanina Rho
9.
J Exp Bot ; 75(8): 2266-2279, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38190348

RESUMO

In plants, C-to-U RNA editing mainly occurs in plastid and mitochondrial transcripts, which contributes to a complex transcriptional regulatory network. More evidence reveals that RNA editing plays critical roles in plant growth and development. However, accurate detection of RNA editing sites using transcriptome sequencing data alone is still challenging. In the present study, we develop PlantC2U, which is a convolutional neural network, to predict plastid C-to-U RNA editing based on the genomic sequence. PlantC2U achieves >95% sensitivity and 99% specificity, which outperforms the PREPACT tool, random forests, and support vector machines. PlantC2U not only further checks RNA editing sites from transcriptome data to reduce possible false positives, but also assesses the effect of different mutations on C-to-U RNA editing based on the flanking sequences. Moreover, we found the patterns of tissue-specific RNA editing in the mangrove plant Kandelia obovata, and observed reduced C-to-U RNA editing rates in the cold stress response of K. obovata, suggesting their potential regulatory roles in plant stress adaptation. In addition, we present RNAeditDB, available online at https://jasonxu.shinyapps.io/RNAeditDB/. Together, PlantC2U and RNAeditDB will help researchers explore the RNA editing events in plants and thus will be of broad utility for the plant research community.


Assuntos
Aprendizado Profundo , Edição de RNA , Edição de RNA/genética , Plantas/metabolismo , Plastídeos/genética , Plastídeos/metabolismo , Transcriptoma , RNA de Plantas/genética , RNA de Plantas/metabolismo
10.
Br J Clin Pharmacol ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38994750

RESUMO

AIMS: Tacrolimus, metabolized by CYP3A4 and CYP3A5 enzymes, is susceptible to drug-drug interactions (DDI). Steroids induce CYP3A genes to increase tacrolimus clearance, but the effect is variable. We hypothesized that the extent of the steroid-tacrolimus DDI differs by CYP3A4/5 genotypes. METHODS: Kidney transplant recipients (n = 2462) were classified by the number of loss of function alleles (LOF) (CYP3A5*3, *6 and *7 and CYP3A4*22) and steroid use at each tacrolimus trough in the first 6 months post-transplant. A population pharmacokinetic analysis was performed by nonlinear mixed-effect modelling (NONMEM) and stepwise covariate modelling to define significant covariates affecting tacrolimus clearance. A stochastic simulation was performed and translated into a Shiny application with the mrgsolve and Shiny packages in R. RESULTS: Steroids were associated with modestly higher (3%-11.8%) tacrolimus clearance. Patients with 0-LOF alleles receiving steroids showed the greatest increase (11.8%) in clearance compared to no steroids, whereas those with 2-LOFs had a negligible increase (2.6%) in the presence of steroids. Steroid use increased tacrolimus clearance by 5% and 10.3% in patients with 1-LOF and 3/4-LOFs, respectively. CONCLUSIONS: Steroids increase the clearance of tacrolimus but vary slightly by CYP3A genotype. This is important in individuals of African ancestry who are more likely to carry no LOF alleles, may more commonly receive steroid treatment, and will need higher tacrolimus doses.

11.
BMC Med Res Methodol ; 24(1): 147, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003440

RESUMO

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/ .


Assuntos
Algoritmos , Humanos , Estimativa de Kaplan-Meier , Análise de Sobrevida , Probabilidade
12.
BMC Med Res Methodol ; 24(1): 116, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762731

RESUMO

BACKGROUND: Extended illness-death models (a specific class of multistate models) are a useful tool to analyse situations like hospital-acquired infections, ventilation-associated pneumonia, and transfers between hospitals. The main components of these models are hazard rates and transition probabilities. Calculation of different measures and their interpretation can be challenging due to their complexity. METHODS: By assuming time-constant hazards, the complexity of these models becomes manageable and closed mathematical forms for transition probabilities can be derived. Using these forms, we created a tool in R to visualize transition probabilities via stacked probability plots. RESULTS: In this article, we present this tool and give some insights into its theoretical background. Using published examples, we give guidelines on how this tool can be used. Our goal is to provide an instrument that helps obtain a deeper understanding of a complex multistate setting. CONCLUSION: While multistate models (in particular extended illness-death models), can be highly complex, this tool can be used in studies to both understand assumptions, which have been made during planning and as a first step in analysing complex data structures. An online version of this tool can be found at https://eidm.imbi.uni-freiburg.de/ .


Assuntos
Probabilidade , Humanos , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/epidemiologia , Modelos Estatísticos , Modelos de Riscos Proporcionais , Pneumonia Associada à Ventilação Mecânica/mortalidade , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Aplicativos Móveis/estatística & dados numéricos , Algoritmos
13.
Clin Chem Lab Med ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39194010

RESUMO

OBJECTIVES: A recent challenge for clinical laboratories is the lack of clear guidelines for handling significant modifications of CE-marked assays. The modifications may involve, for example, extending measurement intervals, changing dilution procedures or using non-validated sample materials. The challenge arises due to the amended Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR), which is now poised for implementation, despite the extended transition periods. The IVDR application imposes challenges not only for diagnostic companies but also for clinical laboratories when using laboratory developed tests (LDTs), often referred to as in-house assays. In this context, a coherent and meticulously structured LDT documentation is highly beneficial. While laboratories are obliged to meet the IVDR requirements, the absence of a streamlined framework or guideline hampers the ability to gain a comprehensive overview on the requirements and possible options for their fulfilment. METHODS: To address this issue, we introduce a web based digital tool powered by an R Shiny web application. This tool facilitates a seamless implementation of IVDR requirements for LDTs across diverse laboratory environments in terms of their transparency and validity. Our approach focuses on adequate handling of significant modifications of CE-marked in vitro diagnostic medical devices (IVD). RESULTS: IVDRCheckR is an open-source tool that is easily accessible and free from system dependencies. The tool promotes a seamless process and a guide to enhance transparency, reliability, and validity of laboratory examination results based on LDTs. Additionally, the tool further provides modules for evaluating quality control data and quantitative method comparison data. CONCLUSIONS: Our Shiny web application-based platform is a digitised, user-friendly tool that simplifies the documentation for LDTs according to IVDR requirements with special emphasis on solutions for handling modifications to CE-marked assays.

14.
Arch Toxicol ; 98(3): 1015-1022, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38112716

RESUMO

The design of dose-response experiments is an important part of toxicology research. Efficient design of these experiments requires choosing optimal doses and assigning the correct number of subjects to those doses under a given criterion. Optimal design theory provides the tools to find the most efficient experimental designs in terms of cost and statistical efficiency. However, the mathematical details can be distracting and make these designs inaccessible to many toxicologists. To facilitate use of these designs, we present an easy to use web-app for finding two types of optimal designs for models commonly used in toxicology. We include tools for checking the optimality of a given design and for assessing efficiency of any user-supplied design. Using state-of-the-art nature-inspired metaheuristic algorithms, the web-app allows the user to quickly find optimal designs for estimating model parameters or the benchmark dose.


Assuntos
Algoritmos , Projetos de Pesquisa , Humanos , Relação Dose-Resposta a Droga , Benchmarking
15.
J Biopharm Stat ; : 1-12, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869267

RESUMO

Patient Reported Outcomes (PROs) are widely used in quality of life (QOL) studies, health outcomes research, and clinical trials. The importance of PRO has been advocated by health authorities. We propose this R shiny web application, PROpwr, that estimates power for two-arm clinical trials with PRO measures as endpoints using Item Response Theory (GRM: Graded Response Model) and simulations. PROpwr also supports the analysis of PRO data for convenience of estimating the effect size. There are seven function tabs in PROpwr: Frequentist Analysis, Bayesian Analysis, GRM power, T-test Power Given Sample Size, T-test Sample Size Given Power, Download, and References. PROpwr is user-friendly with point-and-click functions. PROpwr can assist researchers to analyze and calculate power and sample size for PRO endpoints in clinical trials without prior programming knowledge.

16.
Plant Dis ; 108(7): 1937-1945, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38319624

RESUMO

Research synthesis methods such as meta-analysis rely primarily on appropriate summary statistics (i.e., means and variance) of a response of interest for implementation to draw general conclusions from a body of research. A commonly encountered problem arises when a measure of variability of a response across a study is not explicitly provided in the summary statistics of primary studies. Typically, these otherwise credible studies are omitted in research synthesis, leading to potential small-study effects and loss of statistical power. We present MSE FINDR, a user-friendly Shiny R application for estimating the mean square error (i.e., within-study residual variance, [Formula: see text]) for continuous outcomes from analysis of variance (ANOVA)-type studies, with specific experimental designs and treatment structures (Latin square, completely randomized, randomized complete block, two-way factorial, and split-plot designs). MSE FINDR accomplishes this by using commonly reported information on treatment means, significance level (α), number of replicates, and post hoc mean separation tests (Fisher's least significant difference [LSD], Tukey's honest significant difference [HSD], Bonferroni, Sidák, and Scheffé). Users upload a CSV file containing the relevant information reported in the study and specify the experimental design and post hoc test that was applied in the analysis of the underlying data. MSE FINDR then proceeds to recover [Formula: see text] based on user-provided study information. The recovered within-study variance can be downloaded and exported as a CSV file. Simulations of trials with a variable number of treatments and treatment effects showed that the MSE FINDR-recovered [Formula: see text] was an accurate predictor of the actual ANOVA [Formula: see text] for one-way experimental designs when summary statistics (i.e., means, variance, and post hoc results) were available for the single factor. Similarly, [Formula: see text] recovered by the application accurately predicted the actual [Formula: see text] for two-way experimental designs when summary statistics were available for both factors and the sub-plot factor in split-plot designs, irrespective of the post hoc mean separation test. The MSE FINDR Shiny application, documentation, and an accompanying tutorial are hosted at https://garnica.shinyapps.io/MSE_FindR/ and https://github.com/vcgarnica/MSE_FindR/. With this tool, researchers can now easily estimate the within-study variance absent in published reports that nonetheless provide appropriate summary statistics, thus enabling the inclusion of such studies that would have otherwise been excluded in meta-analyses involving estimates of effect sizes based on a continuous response.


Assuntos
Software , Análise de Variância , Projetos de Pesquisa , Metanálise como Assunto
17.
Int J Mol Sci ; 25(12)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38928396

RESUMO

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.


Assuntos
Neoplasias , Proteômica , Humanos , Proteômica/métodos , Neoplasias/metabolismo , Neoplasias/genética , Microambiente Tumoral/genética , Software , Biologia Computacional/métodos , Proteoma/metabolismo
18.
Behav Res Methods ; 56(3): 1738-1769, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37231326

RESUMO

When designing a study for causal mediation analysis, it is crucial to conduct a power analysis to determine the sample size required to detect the causal mediation effects with sufficient power. However, the development of power analysis methods for causal mediation analysis has lagged far behind. To fill the knowledge gap, I proposed a simulation-based method and an easy-to-use web application ( https://xuqin.shinyapps.io/CausalMediationPowerAnalysis/ ) for power and sample size calculations for regression-based causal mediation analysis. By repeatedly drawing samples of a specific size from a population predefined with hypothesized models and parameter values, the method calculates the power to detect a causal mediation effect based on the proportion of the replications with a significant test result. The Monte Carlo confidence interval method is used for testing so that the sampling distributions of causal effect estimates are allowed to be asymmetric, and the power analysis runs faster than if the bootstrapping method is adopted. This also guarantees that the proposed power analysis tool is compatible with the widely used R package for causal mediation analysis, mediation, which is built upon the same estimation and inference method. In addition, users can determine the sample size required for achieving sufficient power based on power values calculated from a range of sample sizes. The method is applicable to a randomized or nonrandomized treatment, a mediator, and an outcome that can be either binary or continuous. I also provided sample size suggestions under various scenarios and a detailed guideline of app implementation to facilitate study designs.


Assuntos
Aplicativos Móveis , Humanos , Tamanho da Amostra , Simulação por Computador , Causalidade , Negociação
19.
Behav Res Methods ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39168920

RESUMO

Objects are commonly described based on their relations to other objects (e.g., associations, semantic similarity, etc.) or their physical features (e.g., birds have wings, feathers, etc.). However, objects can also be described in terms of their actionable properties (i.e., affordances), which reflect interactive relations between actors and objects. While several normed datasets have been developed to categorize various aspects of meaning (e.g., semantic features, cue-target associations, etc.), to date, norms for affordances have not been generated. We address this limitation by developing a set of affordance norms for 2825 concrete nouns. Using an open-response format, we computed affordance strength (AFS; i.e., the probability of an item eliciting a particular action response), affordance proportion (AFP; i.e., the proportion of participants who provided a specific action response), and affordance set size (AFSS; i.e., the total number of unique action responses) for each item. Because our stimuli overlapped with Pexman et al.'s, Behavior Research Methods, 51, 453-466, (2019) body-object interaction norms (BOI), we tested whether AFS, AFP, and AFSS were related to BOI, as objects with more perceived action properties may be viewed as being more interactive. Additionally, we tested the relationship between AFS and AFP and two separate measures of relatedness: cosine similarity (Buchanan et al., Behavior Research Methods, 51, 1849-1863, 2019a, Behavior Research Methods, 51, 1878-1888, 2019b) and forward associative strength (Nelson et al., Behavior Research Methods, Instruments, & Computers, 36(3), 402-407, 2004). All analyses, however, revealed weak relationships between affordance measures and existing semantic norms, suggesting that affordance properties reflect a separate construct.

20.
Behav Res Methods ; 56(7): 7728-7747, 2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-38961038

RESUMO

The discriminability measure d ' is widely used in psychology to estimate sensitivity independently of response bias. The conventional approach to estimate d ' involves a transformation from the hit rate and the false-alarm rate. When performance is perfect, correction methods must be applied to calculate d ' , but these corrections distort the estimate. In three simulation studies, we show that distortion in d ' estimation can arise from other properties of the experimental design (number of trials, sample size, sample variance, task difficulty) that, when combined with application of the correction method, make d ' distortion in any specific experiment design complex and can mislead statistical inference in the worst cases (Type I and Type II errors). To address this problem, we propose that researchers simulate d ' estimation to explore the impact of design choices, given anticipated or observed data. An R Shiny application is introduced that estimates d ' distortion, providing researchers the means to identify distortion and take steps to minimize its impact.


Assuntos
Simulação por Computador , Humanos , Projetos de Pesquisa , Interpretação Estatística de Dados
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