ChatGPT-Enhanced ROC Analysis (CERA): A shiny web tool for finding optimal cutoff points in biomarker analysis.

Diagnostic tests play a crucial role in establishing the presence of a specific disease in an individual. Receiver Operating Characteristic (ROC) curve analyses are essential tools that provide performance metrics for diagnostic tests. Accurate determination of the cutoff point in ROC curve analyses is the most critical aspect of the process. A variety of methods have been developed to find the optimal cutoffs. Although the R programming language provides a variety of package programs for conducting ROC curve analysis and determining the appropriate cutoffs, it typically needs coding skills and a substantial investment of time. Specifically, the necessity for data preprocessing and analysis can present a significant challenge, especially for individuals without coding experience. We have developed the CERA (ChatGPT-Enhanced ROC Analysis) tool, a user-friendly ROC curve analysis web tool using the shiny interface for faster and more effective analyses to solve this problem. CERA is not only user-friendly, but it also interacts with ChatGPT, which interprets the outputs. This allows for an interpreted report generated by R-Markdown to be presented to the user, enhancing the accessibility and understanding of the analysis results.

Genetic Network Design Automation with LOICA.

Genetic design automation (GDA) is the use of computer-aided design (CAD) in designing genetic networks. GDA tools are necessary to create more complex synthetic genetic networks in a high-throughput fashion. At the core of these tools is the abstraction of a hierarchy of standardized components. The components' input, output, and interactions must be captured and parametrized from relevant experimental data. Simulations of genetic networks should use those parameters and include the experimental context to be compared with the experimental results.This chapter introduces Logical Operators for Integrated Cell Algorithms (LOICA), a Python package used for designing, modeling, and characterizing genetic networks using a simple object-oriented design abstraction. LOICA represents different biological and experimental components as classes that interact to generate models. These models can be parametrized by direct connection to the Flapjack experimental data management platform to characterize abstracted components with experimental data. The models can be simulated using stochastic simulation algorithms or ordinary differential equations with varying noise levels. The simulated data can be managed and published using Flapjack alongside experimental data for comparison. LOICA genetic network designs can be represented as graphs and plotted as networks for visual inspection and serialized as Python objects or in the Synthetic Biology Open Language (SBOL) format for sharing and use in other designs.

Computer programmers show distinct, expertise-dependent brain responses to violations in form and meaning when reading code.

As computer programming becomes more central to the workforce, the need for better models of how it is effectively learned has become more apparent. The current study addressed this gap by recording electrophysiological brain responses as 62 Python programmers with varying skill levels read lines of code with manipulations of form (syntax) and meaning (semantics). At the group level, results showed that manipulations of form resulted in P600 effects, with syntactically invalid code generating more positive deflections in the 500-800 ms range than syntactically valid code. Meaning manipulations resulted in N400 effects, with semantically implausible code generating more negative deflections in the 300-500 ms range than semantically plausible code. Greater Python expertise within the group was associated with greater sensitivity to violations in form. These results support the notion that skilled programming, like skilled natural language learning, is associated with the incorporation of rule-based knowledge into online comprehension processes. Conversely, programmers at all skill levels showed neural sensitivity to meaning manipulations, suggesting that reliance on pre-existing semantic relationships facilitates code comprehension across skill levels.

Automated code development based on genetic programming in graphical programming language: A pilot study.

Continual technological advances associated with the recent automation revolution have tremendously increased the impact of computer technology in the industry. Software development and testing are time-consuming processes, and the current market faces a lack of specialized experts. Introducing automation to this field could, therefore, improve software engineers' common workflow and decrease the time to market. Even though many code-generating algorithms have been proposed in textual-based programming languages, to the best of the authors' knowledge, none of the studies deals with the implementation of such algorithms in graphical programming environments, especially LabVIEW. Due to this fact, the main goal of this study is to conduct a proof-of-concept for a requirement-based automated code-developing system within the graphical programming environment LabVIEW. The proposed framework was evaluated on four basic benchmark problems, encompassing a string model, a numeric model, a boolean model and a mixed-type problem model, which covers fundamental programming scenarios. In all tested cases, the algorithm demonstrated an ability to create satisfying functional and errorless solutions that met all user-defined requirements. Even though the generated programs were burdened with redundant objects and were much more complex compared to programmer-developed codes, this fact has no effect on the code's execution speed or accuracy. Based on the achieved results, we can conclude that this pilot study not only proved the feasibility and viability of the proposed concept, but also showed promising results in solving linear and binary programming tasks. Furthermore, the results revealed that with further research, this poorly explored field could become a powerful tool not only for application developers but also for non-programmers and low-skilled users.

Simplifying Multimodal Clinical Research Data Management: Introducing an Integrated and User-friendly Database Concept.

BACKGROUND: Clinical research, particularly in scientific data, grapples with the efficient management of multimodal and longitudinal clinical data. Especially in neuroscience, the volume of heterogeneous longitudinal data challenges researchers. While current research data management systems offer rich functionality, they suffer from architectural complexity that makes them difficult to install and maintain and require extensive user training. OBJECTIVES: The focus is the development and presentation of a data management approach specifically tailored for clinical researchers involved in active patient care, especially in the neuroscientific environment of German university hospitals. Our design considers the implementation of FAIR (Findable, Accessible, Interoperable, and Reusable) principles and the secure handling of sensitive data in compliance with the General Data Protection Regulation. METHODS: We introduce a streamlined database concept, featuring an intuitive graphical interface built on Hypertext Markup Language revision 5 (HTML5)/Cascading Style Sheets (CSS) technology. The system can be effortlessly deployed within local networks, that is, in Microsoft Windows 10 environments. Our design incorporates FAIR principles for effective data management. Moreover, we have streamlined data interchange through established standards like HL7 Clinical Document Architecture (CDA). To ensure data integrity, we have integrated real-time validation mechanisms that cover data type, plausibility, and Clinical Quality Language logic during data import and entry. RESULTS: We have developed and evaluated our concept with clinicians using a sample dataset of subjects who visited our memory clinic over a 3-year period and collected several multimodal clinical parameters. A notable advantage is the unified data matrix, which simplifies data aggregation, anonymization, and export. THIS STREAMLINES DATA EXCHANGE AND ENHANCES DATABASE INTEGRATION WITH PLATFORMS LIKE KONSTANZ INFORMATION MINER (KNIME): . CONCLUSION: Our approach offers a significant advancement for capturing and managing clinical research data, specifically tailored for small-scale initiatives operating within limited information technology (IT) infrastructures. It is designed for immediate, hassle-free deployment by clinicians and researchers.The database template and precompiled versions of the user interface are available at: https://github.com/stebro01/research_database_sqlite_i2b2.git.

A systematic literature review on the applications of recurrent neural networks in code clone research.

Code clones, referring to code fragments that are either similar or identical and are copied and pasted within software systems, have negative effects on both software quality and maintenance. The objective of this work is to systematically review and analyze recurrent neural network techniques used to detect code clones to shed light on the current techniques and offer valuable knowledge to the research community. Upon applying the review protocol, we have successfully identified 20 primary studies within this field from a total of 2099 studies. A deep investigation of these studies reveals that nine recurrent neural network techniques have been utilized for code clone detection, with a notable preference for LSTM techniques. These techniques have demonstrated their efficacy in detecting both syntactic and semantic clones, often utilizing abstract syntax trees for source code representation. Moreover, we observed that most studies applied evaluation metrics like F-score, precision, and recall. Additionally, these studies frequently utilized datasets extracted from open-source systems coded in Java and C programming languages. Notably, the Graph-LSTM technique exhibited superior performance. PyTorch and TensorFlow emerged as popular tools for implementing RNN models. To advance code clone detection research, further exploration of techniques like parallel LSTM, sentence-level LSTM, and Tree-Structured GRU is imperative. In addition, more research is needed to investigate the capabilities of the recurrent neural network techniques for identifying semantic clones across different programming languages and binary codes. The development of standardized benchmarks for languages like Python, Scratch, and C#, along with cross-language comparisons, is essential. Therefore, the utilization of recurrent neural network techniques for clone identification is a promising area that demands further research.

Open-source milligram-scale, four channel, automated protein purification system.

Liquid chromatography purification of multiple recombinant proteins, in parallel, could catalyze research and discovery if the processes are fast and approach the robustness of traditional, "one-protein-at-a-time" purification. Here, we report an automated, four channel chromatography platform that we have designed and validated for parallelized protein purification at milligram scales. The device can purify up to four proteins (each with its own single column), has inputs for up to eight buffers or solvents that can be directed to any of the four columns via a network of software-driven valves, and includes an automated fraction collector with ten positions for 1.5 or 5.0 mL collection tubes and four positions for 50 mL collection tubes for each column output. The control software can be accessed either via Python scripting, giving users full access to all steps of the purification process, or via a simple-to-navigate touch screen graphical user interface that does not require knowledge of the command line or any programming language. Using our instrument, we report milligram-scale, parallelized, single-column purification of a panel of mammalian cell expressed coronavirus (SARS-CoV-2, HCoV-229E, HCoV-OC43, HCoV-229E) trimeric Spike and monomeric Receptor Binding Domain (RBD) antigens, and monoclonal antibodies targeting SARS-CoV-2 Spike (S) and Influenza Hemagglutinin (HA). We include a detailed hardware build guide, and have made the controlling software open source, to allow others to build and customize their own protein purifier systems.

ReUseData: an R/Bioconductor tool for reusable and reproducible genomic data management.

BACKGROUND: The increasing volume and complexity of genomic data pose significant challenges for effective data management and reuse. Public genomic data often undergo similar preprocessing across projects, leading to redundant or inconsistent datasets and inefficient use of computing resources. This is especially pertinent for bioinformaticians engaged in multiple projects. Tools have been created to address challenges in managing and accessing curated genomic datasets, however, the practical utility of such tools becomes especially beneficial for users who seek to work with specific types of data or are technically inclined toward a particular programming language. Currently, there exists a gap in the availability of an R-specific solution for efficient data management and versatile data reuse. RESULTS: Here we present ReUseData, an R software tool that overcomes some of the limitations of existing solutions and provides a versatile and reproducible approach to effective data management within R. ReUseData facilitates the transformation of ad hoc scripts for data preprocessing into Common Workflow Language (CWL)-based data recipes, allowing for the reproducible generation of curated data files in their generic formats. The data recipes are standardized and self-contained, enabling them to be easily portable and reproducible across various computing platforms. ReUseData also streamlines the reuse of curated data files and their integration into downstream analysis tools and workflows with different frameworks. CONCLUSIONS: ReUseData provides a reliable and reproducible approach for genomic data management within the R environment to enhance the accessibility and reusability of genomic data. The package is available at Bioconductor ( https://bioconductor.org/packages/ReUseData/ ) with additional information on the project website ( https://rcwl.org/dataRecipes/ ).

cytoviewer: an R/Bioconductor package for interactive visualization and exploration of highly multiplexed imaging data.

BACKGROUND: Highly multiplexed imaging enables single-cell-resolved detection of numerous biological molecules in their spatial tissue context. Interactive visualization of multiplexed imaging data is crucial at any step of data analysis to facilitate quality control and the spatial exploration of single cell features. However, tools for interactive visualization of multiplexed imaging data are not available in the statistical programming language R. RESULTS: Here, we describe cytoviewer, an R/Bioconductor package for interactive visualization and exploration of multi-channel images and segmentation masks. The cytoviewer package supports flexible generation of image composites, allows side-by-side visualization of single channels, and facilitates the spatial visualization of single-cell data in the form of segmentation masks. As such, cytoviewer improves image and segmentation quality control, the visualization of cell phenotyping results and qualitative validation of hypothesis at any step of data analysis. The package operates on standard data classes of the Bioconductor project and therefore integrates with an extensive framework for single-cell and image analysis. The graphical user interface allows intuitive navigation and little coding experience is required to use the package. We showcase the functionality and biological application of cytoviewer by analysis of an imaging mass cytometry dataset acquired from cancer samples. CONCLUSIONS: The cytoviewer package offers a rich set of features for highly multiplexed imaging data visualization in R that seamlessly integrates with the workflow for image and single-cell data analysis. It can be installed from Bioconductor via https://www.bioconductor.org/packages/release/bioc/html/cytoviewer.html . The development version and further instructions can be found on GitHub at https://github.com/BodenmillerGroup/cytoviewer .

SimService: a lightweight library for building simulation services in Python.

SUMMARY: Integrative biological modeling requires software infrastructure to launch, interconnect, and execute simulation software components without loss of functionality. SimService is a software library that enables deploying simulations in integrated applications as memory-isolated services with interactive proxy objects in the Python programming language. SimService supports customizing the interface of proxies so that simulation developers and users alike can tailor generated simulation instances according to model, method, and integrated application. AVAILABILITY AND IMPLEMENTATION: SimService is written in Python, is freely available on GitHub under the MIT license at https://github.com/tjsego/simservice, and is available for download via the Python Package Index (package name "simservice") and conda (package name "simservice" on the conda-forge channel).

vcfpp: a C++ API for rapid processing of the variant call format.

MOTIVATION: Given the widespread use of the variant call format (VCF/BCF) coupled with continuous surge in big data, there remains a perpetual demand for fast and flexible methods to manipulate these comprehensive formats across various programming languages. RESULTS: This work presents vcfpp, a C++ API of HTSlib in a single file, providing an intuitive interface to manipulate VCF/BCF files rapidly and safely, in addition to being portable. Moreover, this work introduces the vcfppR package to demonstrate the development of a high-performance R package with vcfpp, allowing for rapid and straightforward variants analyses. AVAILABILITY AND IMPLEMENTATION: vcfpp is available from https://github.com/Zilong-Li/vcfpp under MIT license. vcfppR is available from https://cran.r-project.org/web/packages/vcfppR.

R programming environment in wildlife: Are Veterinary Sciences at the same level than other research areas?

The computing environment has revolutionized the management and analysis of data in sciences during the last decades. This study aimed to evaluate the use of R software in research articles addressing the study of wildlife worldwide, particularly focusing on the research area "Veterinary Sciences". For this purpose, a systematic review mainly performed in the Web of Science database was conducted. Out of a total of 509 articles reviewed, our results show an increasing trend of the number of publications using the R software over time, as well as a wide geographical distribution at a global scale, particularly in North America, Europe, Australia and China. Most publications were categorized in research areas related to "Biological Sciences", while a minority of them was included in "Veterinary Sciences" (5.9%; 30/509). About the species groups assessed, many articles evaluated a single species group (96.5%), being mammals (50.7%) and birds (14.8%) the most studied ones. The present study showed a high variety of R-packages used in the publications reviewed, all of them related to data analysis, the study of genetic/phylogenetic information and graphical representation. Interestingly, the common use of packages between different research areas is indicative of the high interest of using R software in scientific articles. Our study points the R software as an open-source programming language that allows to support research addressing the study of wildlife, becoming a key software for many research areas, including "Veterinary Sciences". However, an in-depth methodological description about the use of R software in publications to improve the tracking, reproducibility and transparency is encouraged.

CodonU: A Python Package for Codon Usage Analysis.

Codon Usage Analysis (CUA) has been accompanied by several web servers and independent programs written in several programming languages. Also this diversity speaks for the need of a reusable software that can be helpful in reading, manipulating and acting as a pipeline for such data and file formats. This kind of analyses use multiple tools to address the multifaceted aspects of CUA. So, we propose CodonU, a package written in Python language to integrate all aspects. It is compatible with existing file formats and can be used solely or with a group of other such packages. The proposed package incorporates various statistical measures necessary for codon usage analysis. The measures vary with nature of the sequences, viz. for nucleotide, codon adaptation index (CAI), codon bias index (CBI), tRNA adaptation index (tAI) etc. and for protein sequences Gravy score etc. Users can also perform the correspondence analysis (COA). This package also provides the liberty to generate graphics to users, and also develop phylogenetic tree. Capabilities of the proposed package were checked thoroughly on a genomic set of Staphylococcus aureus.

VSCode-Antimony: a source editor for building, analyzing, and translating antimony models.

MOTIVATION: Developing biochemical models in systems biology is a complex, knowledge-intensive activity. Some modelers (especially novices) benefit from model development tools with a graphical user interface. However, as with the development of complex software, text-based representations of models provide many benefits for advanced model development. At present, the tools for text-based model development are limited, typically just a textual editor that provides features such as copy, paste, find, and replace. Since these tools are not "model aware," they do not provide features for: (i) model building such as autocompletion of species names; (ii) model analysis such as hover messages that provide information about chemical species; and (iii) model translation to convert between model representations. We refer to these as BAT features. RESULTS: We present VSCode-Antimony, a tool for building, analyzing, and translating models written in the Antimony modeling language, a human readable representation of Systems Biology Markup Language (SBML) models. VSCode-Antimony is a source editor, a tool with language-aware features. For example, there is autocompletion of variable names to assist with model building, hover messages that aid in model analysis, and translation between XML and Antimony representations of SBML models. These features result from making VSCode-Antimony model-aware by incorporating several sophisticated capabilities: analysis of the Antimony grammar (e.g. to identify model symbols and their types); a query system for accessing knowledge sources for chemical species and reactions; and automatic conversion between different model representations (e.g. between Antimony and SBML). AVAILABILITY AND IMPLEMENTATION: VSCode-Antimony is available as an open source extension in the VSCode Marketplace https://marketplace.visualstudio.com/items?itemName=stevem.vscode-antimony. Source code can be found at https://github.com/sys-bio/vscode-antimony.

Inferring cellular and molecular processes in single-cell data with non-negative matrix factorization using Python, R and GenePattern Notebook implementations of CoGAPS.

Non-negative matrix factorization (NMF) is an unsupervised learning method well suited to high-throughput biology. However, inferring biological processes from an NMF result still requires additional post hoc statistics and annotation for interpretation of learned features. Here, we introduce a suite of computational tools that implement NMF and provide methods for accurate and clear biological interpretation and analysis. A generalized discussion of NMF covering its benefits, limitations and open questions is followed by four procedures for the Bayesian NMF algorithm Coordinated Gene Activity across Pattern Subsets (CoGAPS). Each procedure will demonstrate NMF analysis to quantify cell state transitions in a public domain single-cell RNA-sequencing dataset. The first demonstrates PyCoGAPS, our new Python implementation that enhances runtime for large datasets, and the second allows its deployment in Docker. The third procedure steps through the same single-cell NMF analysis using our R CoGAPS interface. The fourth introduces a beginner-friendly CoGAPS platform using GenePattern Notebook, aimed at users with a working conceptual knowledge of data analysis but without a basic proficiency in the R or Python programming language. We also constructed a user-facing website to serve as a central repository for information and instructional materials about CoGAPS and its application programming interfaces. The expected timing to setup the packages and conduct a test run is around 15 min, and an additional 30 min to conduct analyses on a precomputed result. The expected runtime on the user's desired dataset can vary from hours to days depending on factors such as dataset size or input parameters.

Portable BLAST-like algorithm library and its implementations for command line, Python, and R.

Basic local-alignment search tool (BLAST) is a versatile and commonly used sequence analysis tool in bioinformatics. BLAST permits fast and flexible sequence similarity searches across nucleotide and amino acid sequences, leading to diverse applications such as protein domain identification, orthology searches, and phylogenetic annotation. Most BLAST implementations are command line tools which produce output as comma-separated values files. However, a portable, modular and embeddable implementation of a BLAST-like algorithm, is still missing from our toolbox. Here we present nsearch, a command line tool and C++11 library which provides BLAST-like functionality that can easily be embedded in any application. As an example of this portability we present Blaster which leverages nsearch to provide native BLAST-like functionality for the R programming language, as well as npysearch which provides similar functionality for Python. These packages permit embedding BLAST-like functionality into larger frameworks such as Shiny or Django applications. Benchmarks show that nsearch, npysearch, and Blaster are comparable in speed and accuracy to other commonly used modern BLAST implementations such as VSEARCH and BLAST+. We envision similar implementations of nsearch for other languages commonly used in data science such as Julia to facilitate sequence similarity comparisons. Nsearch, Blaster and npysearch are free to use under the BSD 3.0 license and available on Github Conda, CRAN (Blaster) and PyPi (npysearch).

A Computational Software for Training Robust Drug-Target Affinity Prediction Models: pydebiaseddta.

Robust generalization of drug-target affinity (DTA) prediction models is a notoriously difficult problem in computational drug discovery. In this article, we present pydebiaseddta: a computational software for improving the generalizability of DTA prediction models to novel ligands and/or proteins. pydebiaseddta serves as the practical implementation of the DebiasedDTA training framework, which advocates modifying the training distribution to mitigate the effect of spurious correlations in the training data set that leads to substantially degraded performance for novel ligands and proteins. Written in Python programming language, pydebiaseddta combines a user-friendly streamlined interface with a feature-rich and highly modifiable architecture. With this article we introduce our software, showcase its main functionalities, and describe practical ways for new users to engage with it.

deltaXpress (ΔXpress): a tool for mapping differentially correlated genes using single-cell qPCR data.

BACKGROUND: High-throughput experiments provide deep insight into the molecular biology of different species, but more tools need to be developed to handle this type of data. At the transcriptomics level, quantitative Polymerase Chain Reaction technology (qPCR) can be affordably adapted to produce high-throughput results through a single-cell approach. In addition to comparative expression profiles between groups, single-cell approaches allow us to evaluate and propose new dependency relationships among markers. However, this alternative has not been explored before for large-scale qPCR-based experiments. RESULTS: Herein, we present deltaXpress (ΔXpress), a web app for analyzing data from single-cell qPCR experiments using a combination of HTML and R programming languages in a friendly environment. This application uses cycle threshold (Ct) values and categorical information for each sample as input, allowing the best pair of housekeeping genes to be chosen to normalize the expression of target genes. ΔXpress emulates a bulk analysis by observing differentially expressed genes, but in addition, it allows the discovery of pairwise genes differentially correlated when comparing two experimental conditions. Researchers can download normalized data or use subsequent modules to map differentially correlated genes, perform conventional comparisons between experimental groups, obtain additional information about their genes (gene glossary), and generate ready-to-publication images (600 dots per inch). CONCLUSIONS: ΔXpress web app is freely available to non-commercial users at https://alexismurillo.shinyapps.io/dXpress/ and can be used for different experiments in all technologies involving qPCR with at least one housekeeping region.

General, open-source vertex modeling in biological applications using Tissue Forge.

Vertex models are a widespread approach for describing the biophysics and behaviors of multicellular systems, especially of epithelial tissues. Vertex models describe a wide variety of developmental scenarios and behaviors like cell rearrangement and tissue folding. Often, these models are implemented as single-use or closed-source software, which inhibits reproducibility and decreases accessibility for researchers with limited proficiency in software development and numerical methods. We developed a physics-based vertex model methodology in Tissue Forge, an open-source, particle-based modeling and simulation environment. Our methodology describes the properties and processes of vertex model objects on the basis of vertices, which allows integration of vertex modeling with the particle-based formalism of Tissue Forge, enabling an environment for developing mixed-method models of multicellular systems. Our methodology in Tissue Forge inherits all features provided by Tissue Forge, delivering open-source, extensible vertex modeling with interactive simulation, real-time simulation visualization and model sharing in the C, C++ and Python programming languages and a Jupyter Notebook. Demonstrations show a vertex model of cell sorting and a mixed-method model of cell migration combining vertex- and particle-based models. Our methodology provides accessible vertex modeling for a broad range of scientific disciplines, and we welcome community-developed contributions to our open-source software implementation.