EMImR: a Shiny application for identifying transcriptomic and epigenomic changes

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    Editors Assessment:

    Coded and written up as part of the African Society for Bioinformatics and Computational Biology (ASBCB) Omicscodeathons, EMImR is a novel Shiny application for transcriptomic and epigenomic change identification and correlation wrapped up using a combination of Bioconductor and CRAN packages. Case studies are on publicly available GEO data corresponding to sequencing data of human blood cell samples of multiple sclerosis patients to demonstrate how the tool works. And a documentation and videos are provided. Peer review and the study highlighting the usefulness of the developed tool for analyzing transcriptomic and epigenomic data.

    This evaluation refers to version 1 of the preprint

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Abstract

Identifying differentially expressed genes associated with genetic pathologies is crucial to understanding the biological differences between healthy and diseased states and identifying potential biomarkers and therapeutic targets. However, gene expression profiles are controlled by various mechanisms, including epigenomic changes, such as DNA methylation, histone modifications, and interfering microRNA silencing. We developed a novel Shiny application for transcriptomic and epigenomic change identification and correlation using a combination of Bioconductor and CRAN packages. The developed package, named EMImR, is a user-friendly tool with an easy-to-use graphical user interface to identify differentially expressed genes, differentially methylated genes, and differentially expressed interfering microRNA. In addition, it identifies the correlation between transcriptomic and epigenomic modifications and performs the ontology analysis of genes of interest. The developed tool could be used to study the regulatory effects of epigenetic factors. The application is publicly available in the GitHub repository (https://github.com/omicscodeathon/emimr).

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  1. Editors Assessment:

    Coded and written up as part of the African Society for Bioinformatics and Computational Biology (ASBCB) Omicscodeathons, EMImR is a novel Shiny application for transcriptomic and epigenomic change identification and correlation wrapped up using a combination of Bioconductor and CRAN packages. Case studies are on publicly available GEO data corresponding to sequencing data of human blood cell samples of multiple sclerosis patients to demonstrate how the tool works. And a documentation and videos are provided. Peer review and the study highlighting the usefulness of the developed tool for analyzing transcriptomic and epigenomic data.

    This evaluation refers to version 1 of the preprint

  2. AbstractIdentifying differentially expressed genes associated with genetic pathologies is crucial to understanding the biological differences between healthy and diseased states and identifying potential biomarkers and therapeutic targets. However, gene expression profiles are controlled by various mechanisms including epigenomic changes, such as DNA methylation, histone modifications, and interfering microRNA silencing.We developed a novel Shiny application for transcriptomic and epigenomic change identification and correlation using a combination of Bioconductor and CRAN packages.The developed package, named EMImR, is a user-friendly tool with an easy-to-use graphical user interface to identify differentially expressed genes, differentially methylated genes, and differentially expressed interfering miRNA. In addition, it identifies the correlation between transcriptomic and epigenomic modifications and performs the ontology analysis of genes of interest.The developed tool could be used to study the regulatory effects of epigenetic factors. The application is publicly available in the GitHub repository (https://github.com/omicscodeathon/emimr).

    This work has been published in GigaByte Journal under a CC-BY 4.0 license (https://doi.org/10.46471/gigabyte.168), and has published the reviews under the same license.

    Reviewer 1. Haikuo Li

    Is there a clear statement of need explaining what problems the software is designed to solve and who the target audience is? No. Should be made more clear.

    Comments: The authors developed EMImR as an R toolkit and open-sourced software for analysis of bulk RNA-seq as well as epigenomic sequencing data including DNA methylation seq and non-coding RNA profiling. This work is very interesting and should be of interest to people interested in transcriptomic and epigenomic data analysis but without computational background. I have two major comments:

    1. Results presented in this manuscript were only from microarray datasets and are kind of “old” data. Although these data types and sequencing platforms are still very valuable, I don’t think they are widely used as of today, and therefore, it may be less compelling to the audience. It is suggested to validate EMImR using additional more recently published datasets.
    2. The authors studied bulk transcriptomic and epigenomic sequencing data. In fact, single-cell and spatially resolved profiling of these modalities are becoming the mainstream of biomedical research since those methods offer much better resolution and biological insights. The authors are encouraged to discuss some key references of this field (for example, PMIDs: 34062119 and 38513647 for single-cell multiomics; PMID: 40119005 for spatial multiomics sequencing), potentially as the future direction of package development. Re-review: The authors have answered my questions and added new content in the Discussion section as suggested.

    Reviewer 2. Weiming He

    Dear Editor-in-Chief, The EMImR developed by the author is a Shiny application designed for the identification of transcriptomic and epigenomic changes and data association. This program is mainly targeted at Windows UI users who do not possess extensive computational skills. Its core function is to identify the intersections between genetic and epigenetic modifications

    Review Recommendation I recommend that after making appropriate revisions to the current “Minor Revision”, the article can be accepted. However, the author needs to address the following issues.

    Major Issue The article does not provide specific information on the resource consumption (memory and time) of the program. This is crucial for new users. Although we assume that the resource consumption is minimal, users need to know the machine configuration required to run the program. Therefore, I suggest adding two columns for “Time” and “Memory” in Table 1.

    Minor Issues

    1. GitHub Page The Table of Contents on the GitHub page provides a Demonstration Video. However, due to restricted access to YouTube in some regions, it is recommended to also upload a manual in PDF format named “EMImR_manual.pdf” on GitHub. In step 4 of the Installation Guide, it states that “All dependencies will be installed automaticly”. It is advisable to add a step: if the installation fails, prompt the user about the specific error location and guide the user to install the dependent packages manually first to ensure successful installation. Currently, the command “source(‘Dependencies_emimr.R’)” does not return any error messages, which is extremely inconvenient for novice users. The author can provide the maintainer's email address so that users can seek timely solutions when encountering problems

    2. R Version The author recommends using R - 4.2.1 (2022), which was released three years ago. The current latest version is R 4.5.1. It is suggested that the author test the program with the latest version to ensure its adaptability to future developments.

    3. Flowchart Suggestion It is recommended to add a flowchart to illustrate the sequential relationships among packages such as DESeq2 for differential analysis, clusterProfiler for clustering, enrichplot for plotting, and miRNA - related packages (this is optional).

    4.Function Addition Currently, the program seems to lack a button for saving PDFs, as well as functions for batch uploading, saving sessions, and one - click exporting of PDF/PNG files. It is recommended to add the “shinysaver” and “downloadHandler” functions to fulfill these requirements.

    1. Personalized Features and Upgrade Plan To attract more users, more personalized features should be added. The author can mention the future upgrade plan in the discussion section. For example, currently, DESeq2 is used for differential analysis, and in future upgrades, more methods such as PossionDis, NOIseq, and EBseq could be provided for users to choose from.

    2. Text Polishing Suggestions 6.1 Unify the usage of “down - regulated” and “downregulated”, preferably using the latter. 6.2 “R - studio version” ---》 “RStudio” 6.3 Lumian, ---》 Lumian 6.4 no login wall ---》 does not require user registration 6.5 Rewrite “genes were simultaneously differentially expressed and methylated” as “genes that were both differentially expressed and differentially methylated”. 6.6 Ensure that Latin names of species are in italics 6.7 make corresponding modifications to other sentences to improve the accuracy and professionalism of the language in the article.

    The above are my detailed review comments on this article. I hope they can provide a reference for your decision - making.