RBP-Tar – a searchable database for experimental RBP binding sites

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Identifying these binding sites is crucial for understanding the many functions of RBPs in cellular function, development and disease. Current experimental methods for identifying RBP binding sites, such as ultra-violet (UV) crosslinking and immunoprecipitation (CLIP), and especially the enhanced CLIP (eCLIP) protocol, were developed to identify authentic RBP binding sites experimentally. Methods To make this data more accessible to the scientific community, we have developed RBP-Tar (https://ncbr.muni.cz/RBP-Tar ), a web server and database that utilises eCLIP data for 167 RBPs mapped on the human genome. The web server allows researchers to easily search and retrieve binding site information by genomic location and RBP name. Use case Researchers can produce lists of all known RBP binding sites on a gene of interest, or produce lists of binding sites for one RBP on different genomic loci. Conclusions Our future goal is to continue to populate the web server with additional experimental datasets from CLIP experiments as they become available and processed, making it an increasingly valuable resource for the scientific community. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/12-755/v3", "name": "RBP-Tar – a searchable database for experimental RBP binding sites" } } ] } Home Browse RBP-Tar – a searchable database for experimental RBP binding sites ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Gresova K, Racek T, Martinek V et al. RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.12688/f1000research.131014.3 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Software Tool Article Revised RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] Katarina Gresova 1,2 , Tomas Racek 1,2 , Vlastimil Martinek 1,2 , David Cechak 1,2 , Radka Svobodova 1,2 , Panagiotis Alexiou https://orcid.org/0000-0003-3437-7482 2-4 Katarina Gresova 1,2 , Tomas Racek 1,2 , [...] Vlastimil Martinek 1,2 , David Cechak 1,2 , Radka Svobodova 1,2 , Panagiotis Alexiou https://orcid.org/0000-0003-3437-7482 2-4 PUBLISHED 25 Nov 2024 Author details Author details 1 National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czech Republic 2 Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic 3 Centre for Molecular Medicine & Biobanking, University of Malta, Msida, Malta 4 Department of Applied Biomedical science, University of Malta, Msida, Malta Katarina Gresova Roles: Data Curation, Formal Analysis, Investigation, Methodology, Software, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Tomas Racek Roles: Resources, Software, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Vlastimil Martinek Roles: Software, Writing – Original Draft Preparation, Writing – Review & Editing David Cechak Roles: Data Curation, Investigation, Methodology, Software, Writing – Original Draft Preparation, Writing – Review & Editing Radka Svobodova Roles: Project Administration, Resources, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Panagiotis Alexiou Roles: Conceptualization, Funding Acquisition, Methodology, Project Administration, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Bioinformatics gateway. Abstract Background RNA-binding proteins (RBPs) play a critical role in regulating gene expression by binding to specific sites on RNA molecules. Identifying these binding sites is crucial for understanding the many functions of RBPs in cellular function, development and disease. Current experimental methods for identifying RBP binding sites, such as ultra-violet (UV) crosslinking and immunoprecipitation (CLIP), and especially the enhanced CLIP (eCLIP) protocol, were developed to identify authentic RBP binding sites experimentally. Methods To make this data more accessible to the scientific community, we have developed RBP-Tar (https://ncbr.muni.cz/RBP-Tar ), a web server and database that utilises eCLIP data for 167 RBPs mapped on the human genome. The web server allows researchers to easily search and retrieve binding site information by genomic location and RBP name. Use case Researchers can produce lists of all known RBP binding sites on a gene of interest, or produce lists of binding sites for one RBP on different genomic loci. Conclusions Our future goal is to continue to populate the web server with additional experimental datasets from CLIP experiments as they become available and processed, making it an increasingly valuable resource for the scientific community. READ ALL READ LESS Keywords RNA Binding Proteins, CLIP, RBP, Web-server Corresponding Author(s) Panagiotis Alexiou ( [email protected] ) Close Corresponding author: Panagiotis Alexiou Competing interests: No competing interests were disclosed. Grant information: Computational resources were supplied by the project "e-Infrastruktura CZ" (e-INFRA CZ LM2018140) supported by the Ministry of Education, Youth and Sports of the Czech Republic. Computational resources were provided by the ELIXIR-CZ project (LM2018131), part of the international ELIXIR infrastructure. Core Facility Biological Data Management and Analysis of CEITEC Masaryk University, supported by ELIXIR CZ research infrastructure (MEYS Grant No: LM2018131), is gratefully acknowledged for obtaining the scientific data presented in this paper. The Horizon Europe, ERA Chair grant (BioGeMT, ID: 101086768) supplied funding for publication fees. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2024 Gresova K et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Gresova K, Racek T, Martinek V et al. RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.12688/f1000research.131014.3 ) First published: 27 Jun 2023, 12 :755 ( https://doi.org/10.12688/f1000research.131014.1 ) Latest published: 25 Nov 2024, 12 :755 ( https://doi.org/10.12688/f1000research.131014.3 ) Revised Amendments from Version 2 In this update, we have added a p-value column to provide statistical context for evaluating RNA binding protein binding sites. Additionally, we introduced filtering and sorting by p-value to enhance usability, allowing users to prioritize data based on significance. In this update, we have added a p-value column to provide statistical context for evaluating RNA binding protein binding sites. Additionally, we introduced filtering and sorting by p-value to enhance usability, allowing users to prioritize data based on significance. See the authors' detailed response to the review by Xiaoyong Pan See the authors' detailed response to the review by Clifford A Meyer READ REVIEWER RESPONSES Introduction RNA binding proteins (RBPs) are key players in a broad spectrum of RNA regulation, including all stages of the RNA lifecycle ( Gerstberger et al . 2014 ; Gebauer et al. 2021 ). Eukaryotic genomes typically encode hundreds of RBPs. For example, over 1500 human RBPs involved in the maturation, transport, stability and translation of coding and non-coding RNA were recently characterised and manually curated ( Gerstberger et al. 2014 ). Each RBP can typically target hundreds of RNAs in a complex coordinated fashion ( Hogan et al. 2008 ). The general transcriptomic locations of thousands of RNA binding sites corresponding to hundreds of RBPs have been identified using a family of experimental techniques based on RBP CrossLinking, ImmunoPrecipitation and Sequencing (CLIP-Seq) ( Chi et al. 2009 ; Licatalosi et al. 2008 ; Moore et al. 2014 ; Hafner et al. 2010 ). A thorough exploration of tens of RBPs binding characteristics in vitro has shown that RBPs can differentiate their binding sites with context preferences beyond narrowly defined binding sequence motif and secondary structure often involving complex binding configurations ( Dominguez et al. 2018 ). Among the experimental techniques available to date, the enhanced CLIP (eCLIP) protocol (Van Nostrand et al. 2016 ) is particularly important, as it significantly reduces required amplification and increases specificity in identifying authentic binding sites. This improves the efficiency and accuracy of RBP binding site identification and allows for a deeper understanding of the role of RBPs in gene regulation. The availability of a large amount of data points produced from the same experimental technique can be very beneficial for applications such as machine learning, as it allows researchers to train and test models with more confidence. Here we present RBP-Tar ( Tomáš Raček 2023 ), a centralised and searchable database of experimentally identified RBP binding sites that can significantly facilitate the study of the RBP mediated gene regulation. Using RBP-Tar, researchers can quickly and cleanly retrieve RBP binding sites constrained by both genomic location and associated RBP for hundreds of RBPs. Methods Implementation Pipeline for reproducible data download and annotation We have developed a reproducible and easy-to-use pipeline for downloading and annotating RBP eCLIP data from the ENCODE ( Luo et al . 2020 ) database. Metadata for eCLIP experiments, as well as additional files containing genomic coordinates are downloaded from the ENCODE database with the following parameters: “status= released& internal_tags=ENCORE& assay_title=eCLIP& biosample_ontology.term_name=K562& biosample_ontology.term_name=HepG2& files.file_type=bed+narrowPeak& type=Experiment files.analyses.status=released”. Following the download, information about the chromosome, start position, end position, strand and p values of reads are extracted for each RBP binding site. Binding sites are filtered by length, excluding ones shorter than 20 and longer than 100 nucleotides. As a last step, genomic sequences of binding sites are retrieved. The described pipeline is implemented as a set of python scripts and is freely available at GitHub . Using this pipeline, data for 168 RBPs on two cell lines (K562, HepG2) were downloaded. In total, 42 MB of data, representing more than 400 thousand binding sites, were thus processed. Web server Here we present RBP-Tar, a web server that can access the above-curated dataset of RBP binding sites ( https://rbp-tar.biodata.ceitec.cz/ ) and was built with Python (RRID:SCR_008394), the web development framework Flask, and a simple SQLite database (RRID:SCR_017672). The application’s source codes can be found on the project’s GitHub page, along with the requirements and instructions for the deployment if a user wants to run the application locally. The web user interface allows searching and filtering based on the start and end position of the binding site, strand, chromosome, p value and protein name. It offers the download of the filtered data based on the search done by the user. Due to the size of the dataset, the view is limited to 10,000 results. However, the whole dataset can be conveniently downloaded as a gzipped CSV (14 MB) ( https://rbp-tar.biodata.ceitec.cz/download_all ). Operation The RBP-Tar web server can take as input any of the following user-provided parameters: [Start min, Start max] denote the limits of the low genomic coordinate of the locus of interest. Similarly, [End min, End max] denote the limits of the high coordinate. [Strand] and [Chromosome] can be used to narrow down the search to only one strand and a specific chromosome and [-log10(p-value) min, -log10(p-value) max] allows for filtering based on the significance of binding sites. Using these combinations of parameters, a user can easily search for binding sites on their favourite gene, exon, or even a whole chromosome. The last parameter is [Protein name], which brings out a drop-down menu of all the RBPs in the database. If this parameter is not set, all RBPs are queried. Results are shown as a table with the [Chromosome, Start, End, Strand] genomic location of the binding site, followed by the [-log10(p-value)] p-value of the binding site, [Protein name] of the associated RBP and the [Sequence] of the binding site contains the genomic sequence of the binding site. Results can be seen online in a table format or downloaded as a CSV file with one button click. We expect most users to download the results and use them for further downstream analyses. Use cases Use case 1: all known RBP binding sites on the gene of interest The first and potentially most common use case would be the query of all known RBP binding sites on a gene of interest. For example, we can query our web server with the coordinates of the Fused in Sarcoma (FUS) gene (chr16: 31180139-31191605, +) and leave the protein field empty. After this search, all 345 known RBP binding sites on this gene are returned and can be easily downloaded in a CSV file for further analysis ( Figure 1 ). Figure 1. Extracting binding sites of all RNA-binding proteins on one locus (use case 1). In fact, the gene we used encodes the RBP FUS, which plays important roles, among others, in neurodegeneration and cancer progression. We can use the filter [Protein Name] to identify the potential self-targeting of FUS on itself. Indeed, we can thus identify 19 potential FUS self-targeting binding sites identified via eCLIP ( Figure 2 ). Of course, the biological relevance of this type of finding is left to the users, as is the further validation of high-throughput derived RBP binding sites. Figure 2. Fused in Sarcoma (FUS) self-targeting identified by filtering by gene location and protein name. Use case 2: training/testing dataset for one RBP A potential user may want to develop an RBP binding site machine learning tool that would be able to predict binding sites based on a sequence. It is important to make sure that training and testing sets for their machine learning method are not overlapping. Using our web server, they can download all binding sites for a specific RBP, for example, on chromosome 1, and use them as a training set ( Figure 3 ). Then, do the same for chromosome 2 and use it as an independent testing set, thus ensuring that the training and testing sets do not overlap. Figure 3. Extracting all binding sites of a single protein on a single chromosome (use case 2). Conclusion Recent advancements in experimental techniques, such as eCLIP, have greatly expanded our understanding of RBP binding preferences and their role in gene regulation. The development of centralised and searchable databases of experimentally identified RBP binding sites allows researchers to access and analyse the binding preferences of RBPs easily. This information can be used to identify known binding sites on genes of interest and aid in training machine-learning models for RBP binding site prediction. This paper presents RBP-Tar, a centralised web server that can retrieve RBP Target sites with location and RBP constraints. RBP-Tar has been designed to be easily accessible by non-experts. It is still confined to a single source of data, which is helpful for avoiding experimental design effects, but makes its scope limited. We plan to expand the web server with other sources of data, as well as ways for the user to be able to take into account provenance and experimental variation. Data availability Source data All data used in RBP-Tar has been downloaded from ENCODE and Ensembl projects in November 2024. RBP eCLIP metadata were downloaded from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE &assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type= bed+narrowPeak&type=Experiment&files.analyses.status=released . A list of all downloaded files containing genomic coordinates can be found here: https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt . The reference genome was downloaded from http://ftp.ensembl.org/pub/release-97/fasta/homo_sapiens/dna/Homo_sapiens.GRCh38.dna.toplevel.fa.gz Columns ‘chr’, ‘start’, ‘end’, ‘strand’ and ‘pValue’ from downloaded files containing genomic coordinates can be found here: https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/tree/main/csv . The whole dataset (curated and including sequence) can be downloaded from https://rbp-tar.biodata.ceitec.cz/ as a gzipped CSV (18 MB) ( https://rbp-tar.biodata.ceitec.cz//download_all ). Software availability RBP-Tar Software: https://rbp-tar.biodata.ceitec.cz/ Source code: https://github.com/sb-ncbr/RBP-Tar/releases/tag/v1.0.2 Archived source code at the time of publication: https://doi.org/10.5281/zenodo.14135388 ( Raček 2024 ) License: MIT eCLIP RBP Source code: https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/tree/v1.0.3 Archived source code at the time of publication: https://doi.org/10.5281/zenodo.14082502 ( Grešová & Raček 2024 ) License: Apache 2.0 References Chi SW, Zang JB, Mele A, et al. : Argonaute HITS-CLIP Decodes microRNA–mRNA Interaction Maps. Nature. 2009; 460 : 479–486. PubMed Abstract | Publisher Full Text | Free Full Text Dominguez D, Freese P, Alexis MS, et al. : Sequence, Structure, and Context Preferences of Human RNA Binding Proteins. Mol. Cell 2018; 70 (5): 854–67.e9. PubMed Abstract | Publisher Full Text | Free Full Text Gerstberger S, Hafner M, Tuschl T: A Census of Human RNA-Binding Proteins. Nat. Rev. Genet. 2014; 15 (12): 829–845. PubMed Abstract | Publisher Full Text Gebauer F, Schwarzl T, Valcárcel J, et al. : A-binding proteins in human genetic disease. Nat. Rev. Genet. 2021; 22 : 185–198. Publisher Full Text Grešová K, Raček T: “ML-Bioinfo-CEITEC/rbp_encode_eclip: v1.0.3 (v1.0.3).”2024. Publisher Full Text Hafner M, Landthaler M, Burger L, et al. : Transcriptome-Wide Identification of RNA-Binding Protein and microRNA Target Sites by PAR-CLIP. Cell. 2010; 141 (1): 129–141. PubMed Abstract | Publisher Full Text | Free Full Text Hogan DJ, Riordan DP, Gerber AP, et al. : Diverse RNA-Binding Proteins Interact with Functionally Related Sets of RNAs, Suggesting an Extensive Regulatory System. PLoS Biol. 2008; 6 (10): e255. PubMed Abstract | Publisher Full Text | Free Full Text Licatalosi DD, Mele A, Fak JJ, et al. : HITS-CLIP Yields Genome-Wide Insights into Brain Alternative RNA Processing. Nature 2008; 456 (7221): 464–469. PubMed Abstract | Publisher Full Text | Free Full Text Luo Y, Hitz BC, Gabdank I, et al. : New developments on the Encyclopedia of DNA Elements (ENCODE) data portal. Nucleic Acids Res. 2020 Jan 8; 48 (D1): D882–D889. PubMed Abstract | Publisher Full Text | Free Full Text Moore MJ, Zhang C, Gantman EC, et al. : Mapping Argonaute and Conventional RNA-Binding Protein Interactions with RNA at Single-Nucleotide Resolution Using HITS-CLIP and CIMS Analysis. Nat. Protoc. 2014; 9 (2): 263–293. Publisher Full Text Nostrand V, Eric L, Pratt GA, et al. : Robust Transcriptome-Wide Discovery of RNA-Binding Protein Binding Sites with Enhanced CLIP (eCLIP). Nat. Methods 2016; 13 (6): 508–514. PubMed Abstract | Publisher Full Text | Free Full Text Raček T: “sb-ncbr/RBP-Tar: v1.0.2 (v1.0.2).”2024. Publisher Full Text Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 27 Jun 2023 ADD YOUR COMMENT Comment Author details Author details 1 National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czech Republic 2 Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic 3 Centre for Molecular Medicine & Biobanking, University of Malta, Msida, Malta 4 Department of Applied Biomedical science, University of Malta, Msida, Malta Katarina Gresova Roles: Data Curation, Formal Analysis, Investigation, Methodology, Software, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Tomas Racek Roles: Resources, Software, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Vlastimil Martinek Roles: Software, Writing – Original Draft Preparation, Writing – Review & Editing David Cechak Roles: Data Curation, Investigation, Methodology, Software, Writing – Original Draft Preparation, Writing – Review & Editing Radka Svobodova Roles: Project Administration, Resources, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Panagiotis Alexiou Roles: Conceptualization, Funding Acquisition, Methodology, Project Administration, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information Computational resources were supplied by the project "e-Infrastruktura CZ" (e-INFRA CZ LM2018140) supported by the Ministry of Education, Youth and Sports of the Czech Republic. Computational resources were provided by the ELIXIR-CZ project (LM2018131), part of the international ELIXIR infrastructure. Core Facility Biological Data Management and Analysis of CEITEC Masaryk University, supported by ELIXIR CZ research infrastructure (MEYS Grant No: LM2018131), is gratefully acknowledged for obtaining the scientific data presented in this paper. The Horizon Europe, ERA Chair grant (BioGeMT, ID: 101086768) supplied funding for publication fees. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (3) version 3 Revised Published: 25 Nov 2024, 12:755 https://doi.org/10.12688/f1000research.131014.3 version 2 Revised Published: 12 Aug 2024, 12:755 https://doi.org/10.12688/f1000research.131014.2 version 1 Published: 27 Jun 2023, 12:755 https://doi.org/10.12688/f1000research.131014.1 Copyright © 2024 Gresova K et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Gresova K, Racek T, Martinek V et al. RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.12688/f1000research.131014.3 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 3 VERSION 3 PUBLISHED 25 Nov 2024 Revised Views 0 Cite How to cite this report: Liu ZP. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.175053.r354325 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v3#referee-response-354325 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 16 Jan 2025 Zhi-Ping Liu , Shandong University, Jinan, Shandong, China Approved VIEWS 0 https://doi.org/10.5256/f1000research.175053.r354325 In this paper, the authors present the development of RBP-Tar, a searchable database and web server dedicated to experimental RNA-binding protein (RBP) binding sites. RBP-Tar currently focuses on eCLIP data for 167 RBPs mapped on the human genome, though its ... Continue reading READ ALL In this paper, the authors present the development of RBP-Tar, a searchable database and web server dedicated to experimental RNA-binding protein (RBP) binding sites. RBP-Tar currently focuses on eCLIP data for 167 RBPs mapped on the human genome, though its scope has the potential to be expanded to include a broader range of CLIP data to enhance its utility. To address the current limitation of focusing solely on eCLIP data, the authors suggest exploring the inclusion of other CLIP data types in future updates. Additionally, to clarify the purpose and content of this paper, the authors recommend refining the title and abstract to more accurately reflect the scope and contributions of their work. Furthermore, to provide context for their work, the authors need include a discussion of existing databases similar to RBP-Tar. This section should summarize the features and specificity of RBP-Tar compared to these existing resources. If possible, a comparison of the overlapping information with these databases would be beneficial to highlight the unique aspects of RBP-Tar. For the web server component of RBP-Tar, the authors need consider incorporating submission and download options for original data and query results. These features would enhance the usability and accessibility of the server, making it a more comprehensive resource for researchers studying RNA-binding proteins. Is the rationale for developing the new software tool clearly explained? Yes Is the description of the software tool technically sound? Yes Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Yes Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Bioinformatics, Systems Biology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Liu ZP. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.175053.r354325 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v3#referee-response-354325 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Nishanth MJ. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.175053.r354315 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v3#referee-response-354315 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 16 Jan 2025 M. J. Nishanth , St Joseph’s University, Bengaluru, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.175053.r354315 The authors have developed RBP-Tar, a database and tool that can be used to identify the known target motifs of RBPs on human genes or chromosomal loci. This would be a useful tool for scientific community to identify RBP target ... Continue reading READ ALL The authors have developed RBP-Tar, a database and tool that can be used to identify the known target motifs of RBPs on human genes or chromosomal loci. This would be a useful tool for scientific community to identify RBP target motifs. Following are the technical queries/suggestions for the authors: 1. The authors state that the target motifs 100 bases are excluded from the result-list. Why are the motifs < 20 bases excluded? The rationale for this parameter needs to be given. 2. It may be beneficial to add an 'evidence' column in the result/output table. This column could have the reference of the primary study/experiment which forms the evidence for the particular target site being displayed in the result table. This would be helpful for the users if further validation of the target motifs is needed. 3. The authors could consider adding a summary of the existing software tools in the realm of RBP target motif identification and related bioinformatic analyses. They could elaborate on the utility of RBP-Tar in the context of the existing software tools, which would give a broader perspective of the usefulness of RBP-Tar. A few of the existing relevant tools that could be discussed: RBP Map (https://rbpmap.technion.ac.il/), Transite (https://transite.mit.edu/), oRNAment (https://rnabiology.ircm.qc.ca/oRNAment/), and ATtRACT (https://attract.cnic.es/). 4. The authors need to detail the statistical tests and analyses on which the p-value calculations are based. Is the rationale for developing the new software tool clearly explained? Partly Is the description of the software tool technically sound? Yes Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Yes Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Yes Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Molecular biology, gene regulation I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Nishanth MJ. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.175053.r354315 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v3#referee-response-354315 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Van Nostrand E. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.175053.r349169 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v3#referee-response-349169 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 10 Jan 2025 Eric Van Nostrand , Baylor College of Medicine, Houston, TX, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.175053.r349169 This article by Gresova et al build a searchable web tool for the ENCODE eCLIP data that profiles RNA binding protein interactions. Since this is a named review, I can specifically comment - as one other reviewer ... Continue reading READ ALL This article by Gresova et al build a searchable web tool for the ENCODE eCLIP data that profiles RNA binding protein interactions. Since this is a named review, I can specifically comment - as one other reviewer notes, some of the filtering choices here are done without really justifying why they are appropriate - i.e., why are peaks shorter than 20 or longer than 100nt excluded? That's something that should either be justified with analysis showing that it improves signal-to-noise, or not done. (In particular, the CLIP per peak caller used in ENCODE tends to err on the side of calling short peaks, so I highly suspect filtering peaks shorter than 20 is removing a significant amount of real signal) Similarly, we reported the fold-enrichment versus input because we found that to often be more informative than p-value (which is often more a function of transcript abundance rather than binding signal), but that is not reported here for an undescribed reason. Since the entire website is based off of the ENCODE eCLIP data, it seems appropriate to cite that manuscript (Van Nostrand EL, et al., 2020 - PMID 32728246 [Ref-1]) rather than the broader ENCODE overview Luo et al publication. If the idea is to make it extremely user-friendly, it seems like having an ability to copy-paste a UCSC browser-style region (e.g. "chr1:xxxx-yyyy") would make it simpler to use Is the rationale for developing the new software tool clearly explained? Partly Is the description of the software tool technically sound? Yes Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Yes Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Yes Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes References 1. Van Nostrand EL, Freese P, Pratt GA, Wang X, et al.: A large-scale binding and functional map of human RNA-binding proteins. Nature . 2020; 583 (7818): 711-719 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: eCLIP, RNA binding protein studies I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Van Nostrand E. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.175053.r349169 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v3#referee-response-349169 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Stock M. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.175053.r349176 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v3#referee-response-349176 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 09 Jan 2025 Michiel Stock , Ghent University, Ghent, Belgium Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.175053.r349176 This article presents RBP-tar, a small database with a web interface that enables users to access RNA-binding proteins in humans. Users can select regions on different chromosomes and view a list of all binding proteins. Additionally, there are various filter ... Continue reading READ ALL This article presents RBP-tar, a small database with a web interface that enables users to access RNA-binding proteins in humans. Users can select regions on different chromosomes and view a list of all binding proteins. Additionally, there are various filter options, such as filtering by protein name for self-binding. Users can also directly download a CSV file containing the entire database, which I always appreciate. The database is designed to facilitate the development of machine learning models. The short article appears to be well explained. However, I find one aspect lacking: the comparison and relationship with similar databases, such as RBP2GO or EuRBPDB. This should be addressed in a designated section. I would also like some information on how this will be maintained. Will more RBPs be added? Furthermore, I would appreciate some additional clarification regarding what the p-values refer to. minor: - "p values" => "p-values" (clarify what the p-values are for). - what is exactly the " [-log10(p-value)] p-value of the binding site"? Is the rationale for developing the new software tool clearly explained? Partly Is the description of the software tool technically sound? Yes Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Yes Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Yes Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Bioinformatics and machine learning. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Stock M. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.175053.r349176 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v3#referee-response-349176 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 2 VERSION 2 PUBLISHED 12 Aug 2024 Revised Views 0 Cite How to cite this report: Meyer CA. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.169056.r313335 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v2#referee-response-313335 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 05 Sep 2024 Clifford A Meyer , Harvard T.H. Chan School of Public Health, Dana-Farber Cancer Institute, Boston, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.169056.r313335 The revision is not satisfactory as most of the reviewers' suggestions for improving the ... Continue reading READ ALL The revision is not satisfactory as most of the reviewers' suggestions for improving the website were not implemented. We hope that these will be implemented in future versions. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Epigenetics, Chromatin analysis, Gene regulation, Single cell I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Meyer CA. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.169056.r313335 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v2#referee-response-313335 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 25 Nov 2024 Panagiotis Alexiou , Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic 25 Nov 2024 Author Response Thank you for the continued feedback on our manuscript and webserver resource. We appreciate the reviewer’s commitment to ensuring that the resource becomes more robust and user-friendly. In response to ... Continue reading Thank you for the continued feedback on our manuscript and webserver resource. We appreciate the reviewer’s commitment to ensuring that the resource becomes more robust and user-friendly. In response to the earlier suggestions, we have implemented the following improvements in our webserver, as outlined below: Inclusion of p-values: We have added a p-value column to our data, providing an additional layer of statistical context to aid users in evaluating the significance of RNA binding protein binding sites. Filtering and sorting functionality by p-value: To enhance usability, we have introduced the functionality to filter and sort binding site data based on p-values. This improvement allows users to more easily interpret and prioritize results according to their significance. We recognize that many of the enhancements suggested in previous rounds, such as expanding the dataset scope and incorporating broader quality control metrics, require a significant overhaul and are part of our longer-term development roadmap. Our current updates reflect initial, impactful steps toward addressing reviewer concerns, and we remain committed to further expanding the features and datasets in future versions. Thank you for the continued feedback on our manuscript and webserver resource. We appreciate the reviewer’s commitment to ensuring that the resource becomes more robust and user-friendly. In response to the earlier suggestions, we have implemented the following improvements in our webserver, as outlined below: Inclusion of p-values: We have added a p-value column to our data, providing an additional layer of statistical context to aid users in evaluating the significance of RNA binding protein binding sites. Filtering and sorting functionality by p-value: To enhance usability, we have introduced the functionality to filter and sort binding site data based on p-values. This improvement allows users to more easily interpret and prioritize results according to their significance. We recognize that many of the enhancements suggested in previous rounds, such as expanding the dataset scope and incorporating broader quality control metrics, require a significant overhaul and are part of our longer-term development roadmap. Our current updates reflect initial, impactful steps toward addressing reviewer concerns, and we remain committed to further expanding the features and datasets in future versions. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 25 Nov 2024 Panagiotis Alexiou , Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic 25 Nov 2024 Author Response Thank you for the continued feedback on our manuscript and webserver resource. We appreciate the reviewer’s commitment to ensuring that the resource becomes more robust and user-friendly. In response to ... Continue reading Thank you for the continued feedback on our manuscript and webserver resource. We appreciate the reviewer’s commitment to ensuring that the resource becomes more robust and user-friendly. In response to the earlier suggestions, we have implemented the following improvements in our webserver, as outlined below: Inclusion of p-values: We have added a p-value column to our data, providing an additional layer of statistical context to aid users in evaluating the significance of RNA binding protein binding sites. Filtering and sorting functionality by p-value: To enhance usability, we have introduced the functionality to filter and sort binding site data based on p-values. This improvement allows users to more easily interpret and prioritize results according to their significance. We recognize that many of the enhancements suggested in previous rounds, such as expanding the dataset scope and incorporating broader quality control metrics, require a significant overhaul and are part of our longer-term development roadmap. Our current updates reflect initial, impactful steps toward addressing reviewer concerns, and we remain committed to further expanding the features and datasets in future versions. Thank you for the continued feedback on our manuscript and webserver resource. We appreciate the reviewer’s commitment to ensuring that the resource becomes more robust and user-friendly. In response to the earlier suggestions, we have implemented the following improvements in our webserver, as outlined below: Inclusion of p-values: We have added a p-value column to our data, providing an additional layer of statistical context to aid users in evaluating the significance of RNA binding protein binding sites. Filtering and sorting functionality by p-value: To enhance usability, we have introduced the functionality to filter and sort binding site data based on p-values. This improvement allows users to more easily interpret and prioritize results according to their significance. We recognize that many of the enhancements suggested in previous rounds, such as expanding the dataset scope and incorporating broader quality control metrics, require a significant overhaul and are part of our longer-term development roadmap. Our current updates reflect initial, impactful steps toward addressing reviewer concerns, and we remain committed to further expanding the features and datasets in future versions. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Pan X. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.169056.r313334 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v2#referee-response-313334 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 23 Aug 2024 Xiaoyong Pan , Shanghai Jiao Tong University, Shanghai, Shanghai, China Approved VIEWS 0 https://doi.org/10.5256/f1000research.169056.r313334 The authors ... Continue reading READ ALL The authors addressed my comments. Competing Interests: No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Pan X. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.169056.r313334 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v2#referee-response-313334 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 27 Jun 2023 Views 0 Cite How to cite this report: Meyer CA. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.143817.r224195 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v1#referee-response-224195 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 18 Dec 2023 Clifford A Meyer , Harvard T.H. Chan School of Public Health, Dana-Farber Cancer Institute, Boston, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.143817.r224195 This paper describes a database of RNA binding protein binding sites based on 2 ENCODE cell lines. The website allows uses to search for data by querying a gene or genomic interval. The scope of the database ... Continue reading READ ALL This paper describes a database of RNA binding protein binding sites based on 2 ENCODE cell lines. The website allows uses to search for data by querying a gene or genomic interval. The scope of the database is very limited. It is not clear why the data is restricted to eCLIP data and not CLIP data in general. Although the authors make the argument that eCLIP data is of good quality, quality will vary from sample to sample and there are likely to be high quality CLIP data sets as well as low quality eCLIP ones. It appears that the processed peaks are downloaded from ENCODE, but the methods used by ENCODE to identify these peaks are not described, and statistics such as p-values, false discovery rates and enrichment relative to background are not provided. Quality controls are also not provided, so it is not possible to know if the experiment worked. As processed RBP data is downloaded from ENCODE this resource does not add much to what is already available on the ENCODE website. A resource that processed the raw read data from other data resources, such as GEO, would be more valuable. There are over 2,000 eCLIP samples and over 6,000 CLIP samples in GEO. The search features are useful, although it is hard to interpret the results. Some ranking of the results from most significant to least is needed. It would also be helpful to enable filtering based on some binding sites statistics. Overall, the resource is limited in terms of the data included and the website features. It would be helpful to include quality control metrics to let users know which samples are more informative. Is the rationale for developing the new software tool clearly explained? Yes Is the description of the software tool technically sound? Yes Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? No Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Epigenetics, Chromatin analysis, Gene regulation, Single cell I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Meyer CA. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.143817.r224195 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v1#referee-response-224195 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 12 Jul 2024 Panagiotis Alexiou , Department of Applied Biomedical science, University of Malta, Msida, Malta 12 Jul 2024 Author Response This paper describes a database of RNA binding protein binding sites based on 2 ENCODE cell lines. The website allows uses to search for data by querying a gene or ... Continue reading This paper describes a database of RNA binding protein binding sites based on 2 ENCODE cell lines. The website allows uses to search for data by querying a gene or genomic interval. The scope of the database is very limited. It is not clear why the data is restricted to eCLIP data and not CLIP data in general. Although the authors make the argument that eCLIP data is of good quality, quality will vary from sample to sample and there are likely to be high quality CLIP data sets as well as low quality eCLIP ones. We agree that the scope of the database is limited at this point and we aim to widen it in the future updates of the app. ENCODE/ENCORE has a comprehensive eCLIP experimental list, and only 3 iCLIP libraries ( https://www.encodeproject.org/encore-matrix/?type=Experiment&status=released&internal_tags=ENCORE ). We chose eCLIP to keep the experimental procedure more consistent in case of different methods introducing different biases. In a future version, we will explore using different datasets from multiple sources. It appears that the processed peaks are downloaded from ENCODE, but the methods used by ENCODE to identify these peaks are not described, and statistics such as p-values, false discovery rates and enrichment relative to background are not provided. Quality controls are also not provided, so it is not possible to know if the experiment worked. Methods used by ENCODE to identify peaks from eCLIP data are described here: https://www.encodeproject.org/eclip/ while the detailed description of data processing pipeline can be downloaded from here: https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf . This pipeline ensures that only high-quality peaks are identified. As processed RBP data is downloaded from ENCODE this resource does not add much to what is already available on the ENCODE website. A resource that processed the raw read data from other data resources, such as GEO, would be more valuable. There are over 2,000 eCLIP samples and over 6,000 CLIP samples in GEO. We agree that a resource that processed the raw read data from other data resources, such as GEO, would be more valuable, we will consider adding other data resources in the future updates of the webserver. The addition of our app to what is already available on the ENCODE website is advanced filtering of binding sites based on the genome position. This paper describes a database of RNA binding protein binding sites based on 2 ENCODE cell lines. The website allows uses to search for data by querying a gene or genomic interval. The scope of the database is very limited. It is not clear why the data is restricted to eCLIP data and not CLIP data in general. Although the authors make the argument that eCLIP data is of good quality, quality will vary from sample to sample and there are likely to be high quality CLIP data sets as well as low quality eCLIP ones. We agree that the scope of the database is limited at this point and we aim to widen it in the future updates of the app. ENCODE/ENCORE has a comprehensive eCLIP experimental list, and only 3 iCLIP libraries ( https://www.encodeproject.org/encore-matrix/?type=Experiment&status=released&internal_tags=ENCORE ). We chose eCLIP to keep the experimental procedure more consistent in case of different methods introducing different biases. In a future version, we will explore using different datasets from multiple sources. It appears that the processed peaks are downloaded from ENCODE, but the methods used by ENCODE to identify these peaks are not described, and statistics such as p-values, false discovery rates and enrichment relative to background are not provided. Quality controls are also not provided, so it is not possible to know if the experiment worked. Methods used by ENCODE to identify peaks from eCLIP data are described here: https://www.encodeproject.org/eclip/ while the detailed description of data processing pipeline can be downloaded from here: https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf . This pipeline ensures that only high-quality peaks are identified. As processed RBP data is downloaded from ENCODE this resource does not add much to what is already available on the ENCODE website. A resource that processed the raw read data from other data resources, such as GEO, would be more valuable. There are over 2,000 eCLIP samples and over 6,000 CLIP samples in GEO. We agree that a resource that processed the raw read data from other data resources, such as GEO, would be more valuable, we will consider adding other data resources in the future updates of the webserver. The addition of our app to what is already available on the ENCODE website is advanced filtering of binding sites based on the genome position. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 12 Jul 2024 Panagiotis Alexiou , Department of Applied Biomedical science, University of Malta, Msida, Malta 12 Jul 2024 Author Response This paper describes a database of RNA binding protein binding sites based on 2 ENCODE cell lines. The website allows uses to search for data by querying a gene or ... Continue reading This paper describes a database of RNA binding protein binding sites based on 2 ENCODE cell lines. The website allows uses to search for data by querying a gene or genomic interval. The scope of the database is very limited. It is not clear why the data is restricted to eCLIP data and not CLIP data in general. Although the authors make the argument that eCLIP data is of good quality, quality will vary from sample to sample and there are likely to be high quality CLIP data sets as well as low quality eCLIP ones. We agree that the scope of the database is limited at this point and we aim to widen it in the future updates of the app. ENCODE/ENCORE has a comprehensive eCLIP experimental list, and only 3 iCLIP libraries ( https://www.encodeproject.org/encore-matrix/?type=Experiment&status=released&internal_tags=ENCORE ). We chose eCLIP to keep the experimental procedure more consistent in case of different methods introducing different biases. In a future version, we will explore using different datasets from multiple sources. It appears that the processed peaks are downloaded from ENCODE, but the methods used by ENCODE to identify these peaks are not described, and statistics such as p-values, false discovery rates and enrichment relative to background are not provided. Quality controls are also not provided, so it is not possible to know if the experiment worked. Methods used by ENCODE to identify peaks from eCLIP data are described here: https://www.encodeproject.org/eclip/ while the detailed description of data processing pipeline can be downloaded from here: https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf . This pipeline ensures that only high-quality peaks are identified. As processed RBP data is downloaded from ENCODE this resource does not add much to what is already available on the ENCODE website. A resource that processed the raw read data from other data resources, such as GEO, would be more valuable. There are over 2,000 eCLIP samples and over 6,000 CLIP samples in GEO. We agree that a resource that processed the raw read data from other data resources, such as GEO, would be more valuable, we will consider adding other data resources in the future updates of the webserver. The addition of our app to what is already available on the ENCODE website is advanced filtering of binding sites based on the genome position. This paper describes a database of RNA binding protein binding sites based on 2 ENCODE cell lines. The website allows uses to search for data by querying a gene or genomic interval. The scope of the database is very limited. It is not clear why the data is restricted to eCLIP data and not CLIP data in general. Although the authors make the argument that eCLIP data is of good quality, quality will vary from sample to sample and there are likely to be high quality CLIP data sets as well as low quality eCLIP ones. We agree that the scope of the database is limited at this point and we aim to widen it in the future updates of the app. ENCODE/ENCORE has a comprehensive eCLIP experimental list, and only 3 iCLIP libraries ( https://www.encodeproject.org/encore-matrix/?type=Experiment&status=released&internal_tags=ENCORE ). We chose eCLIP to keep the experimental procedure more consistent in case of different methods introducing different biases. In a future version, we will explore using different datasets from multiple sources. It appears that the processed peaks are downloaded from ENCODE, but the methods used by ENCODE to identify these peaks are not described, and statistics such as p-values, false discovery rates and enrichment relative to background are not provided. Quality controls are also not provided, so it is not possible to know if the experiment worked. Methods used by ENCODE to identify peaks from eCLIP data are described here: https://www.encodeproject.org/eclip/ while the detailed description of data processing pipeline can be downloaded from here: https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf . This pipeline ensures that only high-quality peaks are identified. As processed RBP data is downloaded from ENCODE this resource does not add much to what is already available on the ENCODE website. A resource that processed the raw read data from other data resources, such as GEO, would be more valuable. There are over 2,000 eCLIP samples and over 6,000 CLIP samples in GEO. We agree that a resource that processed the raw read data from other data resources, such as GEO, would be more valuable, we will consider adding other data resources in the future updates of the webserver. The addition of our app to what is already available on the ENCODE website is advanced filtering of binding sites based on the genome position. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Pan X. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.143817.r224199 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v1#referee-response-224199 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 18 Dec 2023 Xiaoyong Pan , Shanghai Jiao Tong University, Shanghai, Shanghai, China Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.143817.r224199 ​​​​​In the paper, the author claim they download narrowPeak metadata from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type=bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true ，and the link summary is provided in the file https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt . In the ENCODE dataset, the majority of RNA-binding proteins (RBPs) have biological replicate(s) or technical replicate(s), ... Continue reading READ ALL ​​​​​In the paper, the author claim they download narrowPeak metadata from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type=bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true ，and the link summary is provided in the file https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt . In the ENCODE dataset, the majority of RNA-binding proteins (RBPs) have biological replicate(s) or technical replicate(s), with each replicate having an associated narrowPeak file. Additionally, there is another merged peak file containing reproducible peaks as determined by entropy-ordered peaks between two replicates. However, it is observed that only one file per RBP from K562 or HepG2, which is both the merged peak file. For eCLIP experiment on K562 against QKI, I just find ENCFF190XSX that is from replicate 1. A careful examination of the data is recommended to ensure accuracy and completeness. After narrowPeak download, the author filter the peak by length, excluding ones shorter than 20 and longer than 100 nucleotides. It's important to note that must short (rarely more than 4–6-nucleotide-long) sequence elements within RNA targets that are recognized and bound by RNA-binding proteins (Gerstberger, S et al. (2014 1 ). In my perspective, employing a filter based on fold change and p-value, in accordance with the eCLIP-seq Processing Pipeline of ENCODE ( https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf) is powerful. If this job is for the benefit of biologists, why not use transcripts as a reference? Because RBP binds to transcripts. And it's too simplistic for systems biologists, the author can refer to the POSTAR3 data. Is the rationale for developing the new software tool clearly explained? Yes Is the description of the software tool technically sound? Yes Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Partly Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? Partly References 1. Gerstberger S, Hafner M, Tuschl T: A census of human RNA-binding proteins. Nat Rev Genet . 2014; 15 (12): 829-45 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: The authors need solve some issues before published I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Pan X. Reviewer Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.143817.r224199 ) The direct URL for this report is: https://f1000research.com/articles/12-755/v1#referee-response-224199 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 12 Aug 2024 Panagiotis Alexiou , Department of Applied Biomedical science, University of Malta, Msida, Malta 12 Aug 2024 Author Response Reviewer Comment: ​​​​​In the paper, the author claim they download narrowPeak metadata from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type=bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true ，and the link summary is provided in the file https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt . In the ENCODE dataset, the majority of ... Continue reading Reviewer Comment: ​​​​​In the paper, the author claim they download narrowPeak metadata from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type=bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true ，and the link summary is provided in the file https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt . In the ENCODE dataset, the majority of RNA-binding proteins (RBPs) have biological replicate(s) or technical replicate(s), with each replicate having an associated narrowPeak file. Additionally, there is another merged peak file containing reproducible peaks as determined by entropy-ordered peaks between two replicates. However, it is observed that only one file per RBP from K562 or HepG2, which is both the merged peak file. For eCLIP experiment on K562 against QKI, I just find ENCFF190XSX that is from replicate 1. A careful examination of the data is recommended to ensure accuracy and completeness. Author Response: We would like to thank the reviewer for the insightful finding. We have carefully examined the downloaded metadata and adjusted the processing pipeline to ensure the merged peak file is used for every RBP. In the methods, section “Pipeline for reproducible data download and annotation”, we have added the parameter “files.analyses.status=released” that is ensuring all available files are downloaded. Updated data have been uploaded to the RBP-Tar webserver and the manuscript has been updated with the current number of binding sites and size of files. We have provided new figures with up-to-date views of the web server. Reviewer Comment: After narrowPeak download, the author filter the peak by length, excluding ones shorter than 20 and longer than 100 nucleotides. It's important to note that must short (rarely more than 4–6-nucleotide-long) sequence elements within RNA targets that are recognized and bound by RNA-binding proteins (Gerstberger, S et al. (2014 1 ). In my perspective, employing a filter based on fold change and p-value, in accordance with the eCLIP-seq Processing Pipeline of ENCODE ( https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf) is powerful. Author Response: We appreciate the reviewer's perspective on filtering criteria. Our decision to filter based on length aimed to exclude potential artifacts and prioritize biologically relevant binding sites. While fold change and p-value are valuable parameters, our focus was on ensuring the inclusion of robust binding sites within the specified length range. We will consider incorporating additional filtering parameters in future iterations leading to a new version of the web server. Reviewer Comment: If this job is for the benefit of biologists, why not use transcripts as a reference? Because RBP binds to transcripts. And it's too simplistic for systems biologists, the author can refer to the POSTAR3 data. Author Response: Our choice to focus on genomic coordinates was driven by the goal of providing a comprehensive resource for accessing RBP binding sites across the genome. While transcripts offer valuable context, our approach allows for flexibility in analyzing binding sites within different genomic regions and across multiple transcripts. However, we recognize the importance of incorporating transcript-level information and will explore integrating such data in future updates of the webserver to enhance the utility of our tool for systems biologists. Reviewer Comment: ​​​​​In the paper, the author claim they download narrowPeak metadata from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type=bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true ，and the link summary is provided in the file https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt . In the ENCODE dataset, the majority of RNA-binding proteins (RBPs) have biological replicate(s) or technical replicate(s), with each replicate having an associated narrowPeak file. Additionally, there is another merged peak file containing reproducible peaks as determined by entropy-ordered peaks between two replicates. However, it is observed that only one file per RBP from K562 or HepG2, which is both the merged peak file. For eCLIP experiment on K562 against QKI, I just find ENCFF190XSX that is from replicate 1. A careful examination of the data is recommended to ensure accuracy and completeness. Author Response: We would like to thank the reviewer for the insightful finding. We have carefully examined the downloaded metadata and adjusted the processing pipeline to ensure the merged peak file is used for every RBP. In the methods, section “Pipeline for reproducible data download and annotation”, we have added the parameter “files.analyses.status=released” that is ensuring all available files are downloaded. Updated data have been uploaded to the RBP-Tar webserver and the manuscript has been updated with the current number of binding sites and size of files. We have provided new figures with up-to-date views of the web server. Reviewer Comment: After narrowPeak download, the author filter the peak by length, excluding ones shorter than 20 and longer than 100 nucleotides. It's important to note that must short (rarely more than 4–6-nucleotide-long) sequence elements within RNA targets that are recognized and bound by RNA-binding proteins (Gerstberger, S et al. (2014 1 ). In my perspective, employing a filter based on fold change and p-value, in accordance with the eCLIP-seq Processing Pipeline of ENCODE ( https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf) is powerful. Author Response: We appreciate the reviewer's perspective on filtering criteria. Our decision to filter based on length aimed to exclude potential artifacts and prioritize biologically relevant binding sites. While fold change and p-value are valuable parameters, our focus was on ensuring the inclusion of robust binding sites within the specified length range. We will consider incorporating additional filtering parameters in future iterations leading to a new version of the web server. Reviewer Comment: If this job is for the benefit of biologists, why not use transcripts as a reference? Because RBP binds to transcripts. And it's too simplistic for systems biologists, the author can refer to the POSTAR3 data. Author Response: Our choice to focus on genomic coordinates was driven by the goal of providing a comprehensive resource for accessing RBP binding sites across the genome. While transcripts offer valuable context, our approach allows for flexibility in analyzing binding sites within different genomic regions and across multiple transcripts. However, we recognize the importance of incorporating transcript-level information and will explore integrating such data in future updates of the webserver to enhance the utility of our tool for systems biologists. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 12 Aug 2024 Panagiotis Alexiou , Department of Applied Biomedical science, University of Malta, Msida, Malta 12 Aug 2024 Author Response Reviewer Comment: ​​​​​In the paper, the author claim they download narrowPeak metadata from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type=bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true ，and the link summary is provided in the file https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt . In the ENCODE dataset, the majority of ... Continue reading Reviewer Comment: ​​​​​In the paper, the author claim they download narrowPeak metadata from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type=bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true ，and the link summary is provided in the file https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt . In the ENCODE dataset, the majority of RNA-binding proteins (RBPs) have biological replicate(s) or technical replicate(s), with each replicate having an associated narrowPeak file. Additionally, there is another merged peak file containing reproducible peaks as determined by entropy-ordered peaks between two replicates. However, it is observed that only one file per RBP from K562 or HepG2, which is both the merged peak file. For eCLIP experiment on K562 against QKI, I just find ENCFF190XSX that is from replicate 1. A careful examination of the data is recommended to ensure accuracy and completeness. Author Response: We would like to thank the reviewer for the insightful finding. We have carefully examined the downloaded metadata and adjusted the processing pipeline to ensure the merged peak file is used for every RBP. In the methods, section “Pipeline for reproducible data download and annotation”, we have added the parameter “files.analyses.status=released” that is ensuring all available files are downloaded. Updated data have been uploaded to the RBP-Tar webserver and the manuscript has been updated with the current number of binding sites and size of files. We have provided new figures with up-to-date views of the web server. Reviewer Comment: After narrowPeak download, the author filter the peak by length, excluding ones shorter than 20 and longer than 100 nucleotides. It's important to note that must short (rarely more than 4–6-nucleotide-long) sequence elements within RNA targets that are recognized and bound by RNA-binding proteins (Gerstberger, S et al. (2014 1 ). In my perspective, employing a filter based on fold change and p-value, in accordance with the eCLIP-seq Processing Pipeline of ENCODE ( https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf) is powerful. Author Response: We appreciate the reviewer's perspective on filtering criteria. Our decision to filter based on length aimed to exclude potential artifacts and prioritize biologically relevant binding sites. While fold change and p-value are valuable parameters, our focus was on ensuring the inclusion of robust binding sites within the specified length range. We will consider incorporating additional filtering parameters in future iterations leading to a new version of the web server. Reviewer Comment: If this job is for the benefit of biologists, why not use transcripts as a reference? Because RBP binds to transcripts. And it's too simplistic for systems biologists, the author can refer to the POSTAR3 data. Author Response: Our choice to focus on genomic coordinates was driven by the goal of providing a comprehensive resource for accessing RBP binding sites across the genome. While transcripts offer valuable context, our approach allows for flexibility in analyzing binding sites within different genomic regions and across multiple transcripts. However, we recognize the importance of incorporating transcript-level information and will explore integrating such data in future updates of the webserver to enhance the utility of our tool for systems biologists. Reviewer Comment: ​​​​​In the paper, the author claim they download narrowPeak metadata from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type=bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true ，and the link summary is provided in the file https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt . In the ENCODE dataset, the majority of RNA-binding proteins (RBPs) have biological replicate(s) or technical replicate(s), with each replicate having an associated narrowPeak file. Additionally, there is another merged peak file containing reproducible peaks as determined by entropy-ordered peaks between two replicates. However, it is observed that only one file per RBP from K562 or HepG2, which is both the merged peak file. For eCLIP experiment on K562 against QKI, I just find ENCFF190XSX that is from replicate 1. A careful examination of the data is recommended to ensure accuracy and completeness. Author Response: We would like to thank the reviewer for the insightful finding. We have carefully examined the downloaded metadata and adjusted the processing pipeline to ensure the merged peak file is used for every RBP. In the methods, section “Pipeline for reproducible data download and annotation”, we have added the parameter “files.analyses.status=released” that is ensuring all available files are downloaded. Updated data have been uploaded to the RBP-Tar webserver and the manuscript has been updated with the current number of binding sites and size of files. We have provided new figures with up-to-date views of the web server. Reviewer Comment: After narrowPeak download, the author filter the peak by length, excluding ones shorter than 20 and longer than 100 nucleotides. It's important to note that must short (rarely more than 4–6-nucleotide-long) sequence elements within RNA targets that are recognized and bound by RNA-binding proteins (Gerstberger, S et al. (2014 1 ). In my perspective, employing a filter based on fold change and p-value, in accordance with the eCLIP-seq Processing Pipeline of ENCODE ( https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf) is powerful. Author Response: We appreciate the reviewer's perspective on filtering criteria. Our decision to filter based on length aimed to exclude potential artifacts and prioritize biologically relevant binding sites. While fold change and p-value are valuable parameters, our focus was on ensuring the inclusion of robust binding sites within the specified length range. We will consider incorporating additional filtering parameters in future iterations leading to a new version of the web server. Reviewer Comment: If this job is for the benefit of biologists, why not use transcripts as a reference? Because RBP binds to transcripts. And it's too simplistic for systems biologists, the author can refer to the POSTAR3 data. Author Response: Our choice to focus on genomic coordinates was driven by the goal of providing a comprehensive resource for accessing RBP binding sites across the genome. While transcripts offer valuable context, our approach allows for flexibility in analyzing binding sites within different genomic regions and across multiple transcripts. However, we recognize the importance of incorporating transcript-level information and will explore integrating such data in future updates of the webserver to enhance the utility of our tool for systems biologists. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 27 Jun 2023 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 4 5 6 Version 3 (revision) 25 Nov 24 read read read read Version 2 (revision) 12 Aug 24 read read Version 1 27 Jun 23 read read Xiaoyong Pan , Shanghai Jiao Tong University, Shanghai, China Clifford A Meyer , Harvard T.H. Chan School of Public Health, Dana-Farber Cancer Institute, Boston, USA Michiel Stock , Ghent University, Ghent, Belgium Eric Van Nostrand , Baylor College of Medicine, Houston, USA M. J. Nishanth , St Joseph’s University, Bengaluru, India Zhi-Ping Liu , Shandong University, Jinan, China Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Liu Z. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 16 Jan 2025 | for Version 3 Zhi-Ping Liu , Shandong University, Jinan, Shandong, China 0 Views copyright © 2025 Liu Z. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions In this paper, the authors present the development of RBP-Tar, a searchable database and web server dedicated to experimental RNA-binding protein (RBP) binding sites. RBP-Tar currently focuses on eCLIP data for 167 RBPs mapped on the human genome, though its scope has the potential to be expanded to include a broader range of CLIP data to enhance its utility. To address the current limitation of focusing solely on eCLIP data, the authors suggest exploring the inclusion of other CLIP data types in future updates. Additionally, to clarify the purpose and content of this paper, the authors recommend refining the title and abstract to more accurately reflect the scope and contributions of their work. Furthermore, to provide context for their work, the authors need include a discussion of existing databases similar to RBP-Tar. This section should summarize the features and specificity of RBP-Tar compared to these existing resources. If possible, a comparison of the overlapping information with these databases would be beneficial to highlight the unique aspects of RBP-Tar. For the web server component of RBP-Tar, the authors need consider incorporating submission and download options for original data and query results. These features would enhance the usability and accessibility of the server, making it a more comprehensive resource for researchers studying RNA-binding proteins. Is the rationale for developing the new software tool clearly explained? Yes Is the description of the software tool technically sound? Yes Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Yes Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Bioinformatics, Systems Biology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Liu ZP. Peer Review Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.175053.r354325) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-755/v3#referee-response-354325 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Nishanth M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 16 Jan 2025 | for Version 3 M. J. Nishanth , St Joseph’s University, Bengaluru, India 0 Views copyright © 2025 Nishanth M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors have developed RBP-Tar, a database and tool that can be used to identify the known target motifs of RBPs on human genes or chromosomal loci. This would be a useful tool for scientific community to identify RBP target motifs. Following are the technical queries/suggestions for the authors: 1. The authors state that the target motifs 100 bases are excluded from the result-list. Why are the motifs < 20 bases excluded? The rationale for this parameter needs to be given. 2. It may be beneficial to add an 'evidence' column in the result/output table. This column could have the reference of the primary study/experiment which forms the evidence for the particular target site being displayed in the result table. This would be helpful for the users if further validation of the target motifs is needed. 3. The authors could consider adding a summary of the existing software tools in the realm of RBP target motif identification and related bioinformatic analyses. They could elaborate on the utility of RBP-Tar in the context of the existing software tools, which would give a broader perspective of the usefulness of RBP-Tar. A few of the existing relevant tools that could be discussed: RBP Map (https://rbpmap.technion.ac.il/), Transite (https://transite.mit.edu/), oRNAment (https://rnabiology.ircm.qc.ca/oRNAment/), and ATtRACT (https://attract.cnic.es/). 4. The authors need to detail the statistical tests and analyses on which the p-value calculations are based. Is the rationale for developing the new software tool clearly explained? Partly Is the description of the software tool technically sound? Yes Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Yes Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Yes Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Molecular biology, gene regulation I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Nishanth MJ. Peer Review Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.175053.r354315) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-755/v3#referee-response-354315 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Van Nostrand E. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 10 Jan 2025 | for Version 3 Eric Van Nostrand , Baylor College of Medicine, Houston, TX, USA 0 Views copyright © 2025 Van Nostrand E. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This article by Gresova et al build a searchable web tool for the ENCODE eCLIP data that profiles RNA binding protein interactions. Since this is a named review, I can specifically comment - as one other reviewer notes, some of the filtering choices here are done without really justifying why they are appropriate - i.e., why are peaks shorter than 20 or longer than 100nt excluded? That's something that should either be justified with analysis showing that it improves signal-to-noise, or not done. (In particular, the CLIP per peak caller used in ENCODE tends to err on the side of calling short peaks, so I highly suspect filtering peaks shorter than 20 is removing a significant amount of real signal) Similarly, we reported the fold-enrichment versus input because we found that to often be more informative than p-value (which is often more a function of transcript abundance rather than binding signal), but that is not reported here for an undescribed reason. Since the entire website is based off of the ENCODE eCLIP data, it seems appropriate to cite that manuscript (Van Nostrand EL, et al., 2020 - PMID 32728246 [Ref-1]) rather than the broader ENCODE overview Luo et al publication. If the idea is to make it extremely user-friendly, it seems like having an ability to copy-paste a UCSC browser-style region (e.g. "chr1:xxxx-yyyy") would make it simpler to use Is the rationale for developing the new software tool clearly explained? Partly Is the description of the software tool technically sound? Yes Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Yes Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Yes Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes References 1. Van Nostrand EL, Freese P, Pratt GA, Wang X, et al.: A large-scale binding and functional map of human RNA-binding proteins. Nature . 2020; 583 (7818): 711-719 PubMed Abstract | Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise eCLIP, RNA binding protein studies I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Van Nostrand E. Peer Review Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.175053.r349169) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-755/v3#referee-response-349169 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Stock M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 09 Jan 2025 | for Version 3 Michiel Stock , Ghent University, Ghent, Belgium 0 Views copyright © 2025 Stock M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This article presents RBP-tar, a small database with a web interface that enables users to access RNA-binding proteins in humans. Users can select regions on different chromosomes and view a list of all binding proteins. Additionally, there are various filter options, such as filtering by protein name for self-binding. Users can also directly download a CSV file containing the entire database, which I always appreciate. The database is designed to facilitate the development of machine learning models. The short article appears to be well explained. However, I find one aspect lacking: the comparison and relationship with similar databases, such as RBP2GO or EuRBPDB. This should be addressed in a designated section. I would also like some information on how this will be maintained. Will more RBPs be added? Furthermore, I would appreciate some additional clarification regarding what the p-values refer to. minor: - "p values" => "p-values" (clarify what the p-values are for). - what is exactly the " [-log10(p-value)] p-value of the binding site"? Is the rationale for developing the new software tool clearly explained? Partly Is the description of the software tool technically sound? Yes Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Yes Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Yes Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Bioinformatics and machine learning. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Stock M. Peer Review Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.175053.r349176) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-755/v3#referee-response-349176 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Meyer C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 05 Sep 2024 | for Version 2 Clifford A Meyer , Harvard T.H. Chan School of Public Health, Dana-Farber Cancer Institute, Boston, USA 0 Views copyright © 2024 Meyer C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The revision is not satisfactory as most of the reviewers' suggestions for improving the website were not implemented. We hope that these will be implemented in future versions. Competing Interests No competing interests were disclosed. Reviewer Expertise Epigenetics, Chromatin analysis, Gene regulation, Single cell I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 25 Nov 2024 Panagiotis Alexiou, Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic Thank you for the continued feedback on our manuscript and webserver resource. We appreciate the reviewer’s commitment to ensuring that the resource becomes more robust and user-friendly. In response to the earlier suggestions, we have implemented the following improvements in our webserver, as outlined below: Inclusion of p-values: We have added a p-value column to our data, providing an additional layer of statistical context to aid users in evaluating the significance of RNA binding protein binding sites. Filtering and sorting functionality by p-value: To enhance usability, we have introduced the functionality to filter and sort binding site data based on p-values. This improvement allows users to more easily interpret and prioritize results according to their significance. We recognize that many of the enhancements suggested in previous rounds, such as expanding the dataset scope and incorporating broader quality control metrics, require a significant overhaul and are part of our longer-term development roadmap. Our current updates reflect initial, impactful steps toward addressing reviewer concerns, and we remain committed to further expanding the features and datasets in future versions. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Meyer CA. Peer Review Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.169056.r313335) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-755/v2#referee-response-313335 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Pan X. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 23 Aug 2024 | for Version 2 Xiaoyong Pan , Shanghai Jiao Tong University, Shanghai, Shanghai, China 0 Views copyright © 2024 Pan X. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors addressed my comments. Competing Interests No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Pan X. Peer Review Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.169056.r313334) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-755/v2#referee-response-313334 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2023 Meyer C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 18 Dec 2023 | for Version 1 Clifford A Meyer , Harvard T.H. Chan School of Public Health, Dana-Farber Cancer Institute, Boston, USA 0 Views copyright © 2023 Meyer C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This paper describes a database of RNA binding protein binding sites based on 2 ENCODE cell lines. The website allows uses to search for data by querying a gene or genomic interval. The scope of the database is very limited. It is not clear why the data is restricted to eCLIP data and not CLIP data in general. Although the authors make the argument that eCLIP data is of good quality, quality will vary from sample to sample and there are likely to be high quality CLIP data sets as well as low quality eCLIP ones. It appears that the processed peaks are downloaded from ENCODE, but the methods used by ENCODE to identify these peaks are not described, and statistics such as p-values, false discovery rates and enrichment relative to background are not provided. Quality controls are also not provided, so it is not possible to know if the experiment worked. As processed RBP data is downloaded from ENCODE this resource does not add much to what is already available on the ENCODE website. A resource that processed the raw read data from other data resources, such as GEO, would be more valuable. There are over 2,000 eCLIP samples and over 6,000 CLIP samples in GEO. The search features are useful, although it is hard to interpret the results. Some ranking of the results from most significant to least is needed. It would also be helpful to enable filtering based on some binding sites statistics. Overall, the resource is limited in terms of the data included and the website features. It would be helpful to include quality control metrics to let users know which samples are more informative. Is the rationale for developing the new software tool clearly explained? Yes Is the description of the software tool technically sound? Yes Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? No Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Epigenetics, Chromatin analysis, Gene regulation, Single cell I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 12 Jul 2024 Panagiotis Alexiou, Department of Applied Biomedical science, University of Malta, Msida, Malta This paper describes a database of RNA binding protein binding sites based on 2 ENCODE cell lines. The website allows uses to search for data by querying a gene or genomic interval. The scope of the database is very limited. It is not clear why the data is restricted to eCLIP data and not CLIP data in general. Although the authors make the argument that eCLIP data is of good quality, quality will vary from sample to sample and there are likely to be high quality CLIP data sets as well as low quality eCLIP ones. We agree that the scope of the database is limited at this point and we aim to widen it in the future updates of the app. ENCODE/ENCORE has a comprehensive eCLIP experimental list, and only 3 iCLIP libraries ( https://www.encodeproject.org/encore-matrix/?type=Experiment&status=released&internal_tags=ENCORE ). We chose eCLIP to keep the experimental procedure more consistent in case of different methods introducing different biases. In a future version, we will explore using different datasets from multiple sources. It appears that the processed peaks are downloaded from ENCODE, but the methods used by ENCODE to identify these peaks are not described, and statistics such as p-values, false discovery rates and enrichment relative to background are not provided. Quality controls are also not provided, so it is not possible to know if the experiment worked. Methods used by ENCODE to identify peaks from eCLIP data are described here: https://www.encodeproject.org/eclip/ while the detailed description of data processing pipeline can be downloaded from here: https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf . This pipeline ensures that only high-quality peaks are identified. As processed RBP data is downloaded from ENCODE this resource does not add much to what is already available on the ENCODE website. A resource that processed the raw read data from other data resources, such as GEO, would be more valuable. There are over 2,000 eCLIP samples and over 6,000 CLIP samples in GEO. We agree that a resource that processed the raw read data from other data resources, such as GEO, would be more valuable, we will consider adding other data resources in the future updates of the webserver. The addition of our app to what is already available on the ENCODE website is advanced filtering of binding sites based on the genome position. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Meyer CA. Peer Review Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . F1000Research 2024, 12 :755 ( https://doi.org/10.5256/f1000research.143817.r224195) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-755/v1#referee-response-224195 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2023 Pan X. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 18 Dec 2023 | for Version 1 Xiaoyong Pan , Shanghai Jiao Tong University, Shanghai, Shanghai, China 0 Views copyright © 2023 Pan X. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions ​​​​​In the paper, the author claim they download narrowPeak metadata from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type=bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true ，and the link summary is provided in the file https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt . In the ENCODE dataset, the majority of RNA-binding proteins (RBPs) have biological replicate(s) or technical replicate(s), with each replicate having an associated narrowPeak file. Additionally, there is another merged peak file containing reproducible peaks as determined by entropy-ordered peaks between two replicates. However, it is observed that only one file per RBP from K562 or HepG2, which is both the merged peak file. For eCLIP experiment on K562 against QKI, I just find ENCFF190XSX that is from replicate 1. A careful examination of the data is recommended to ensure accuracy and completeness. After narrowPeak download, the author filter the peak by length, excluding ones shorter than 20 and longer than 100 nucleotides. It's important to note that must short (rarely more than 4–6-nucleotide-long) sequence elements within RNA targets that are recognized and bound by RNA-binding proteins (Gerstberger, S et al. (2014 1 ). In my perspective, employing a filter based on fold change and p-value, in accordance with the eCLIP-seq Processing Pipeline of ENCODE ( https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf) is powerful. If this job is for the benefit of biologists, why not use transcripts as a reference? Because RBP binds to transcripts. And it's too simplistic for systems biologists, the author can refer to the POSTAR3 data. Is the rationale for developing the new software tool clearly explained? Yes Is the description of the software tool technically sound? Yes Are sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly Is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Partly Are the conclusions about the tool and its performance adequately supported by the findings presented in the article? Partly References 1. Gerstberger S, Hafner M, Tuschl T: A census of human RNA-binding proteins. Nat Rev Genet . 2014; 15 (12): 829-45 PubMed Abstract | Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise The authors need solve some issues before published I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 12 Aug 2024 Panagiotis Alexiou, Department of Applied Biomedical science, University of Malta, Msida, Malta Reviewer Comment: ​​​​​In the paper, the author claim they download narrowPeak metadata from https://www.encodeproject.org/metadata/?status=released&internal_tags=ENCORE&assay_title=eCLIP&biosample_ontology.term_name=K562&biosample_ontology.term_name=HepG2&files.file_type=bed+narrowPeak&type=Experiment&files.analyses.status=released&files.preferred_default=true ，and the link summary is provided in the file https://github.com/ML-Bioinfo-CEITEC/rbp_encode_eclip/blob/main/csv/coord_links.txt . In the ENCODE dataset, the majority of RNA-binding proteins (RBPs) have biological replicate(s) or technical replicate(s), with each replicate having an associated narrowPeak file. Additionally, there is another merged peak file containing reproducible peaks as determined by entropy-ordered peaks between two replicates. However, it is observed that only one file per RBP from K562 or HepG2, which is both the merged peak file. For eCLIP experiment on K562 against QKI, I just find ENCFF190XSX that is from replicate 1. A careful examination of the data is recommended to ensure accuracy and completeness. Author Response: We would like to thank the reviewer for the insightful finding. We have carefully examined the downloaded metadata and adjusted the processing pipeline to ensure the merged peak file is used for every RBP. In the methods, section “Pipeline for reproducible data download and annotation”, we have added the parameter “files.analyses.status=released” that is ensuring all available files are downloaded. Updated data have been uploaded to the RBP-Tar webserver and the manuscript has been updated with the current number of binding sites and size of files. We have provided new figures with up-to-date views of the web server. Reviewer Comment: After narrowPeak download, the author filter the peak by length, excluding ones shorter than 20 and longer than 100 nucleotides. It's important to note that must short (rarely more than 4–6-nucleotide-long) sequence elements within RNA targets that are recognized and bound by RNA-binding proteins (Gerstberger, S et al. (2014 1 ). In my perspective, employing a filter based on fold change and p-value, in accordance with the eCLIP-seq Processing Pipeline of ENCODE ( https://www.encodeproject.org/documents/739ca190-8d43-4a68-90ce-1a0ddfffc6fd/@@download/attachment/eCLIP_analysisSOP_v2.2.pdf) is powerful. Author Response: We appreciate the reviewer's perspective on filtering criteria. Our decision to filter based on length aimed to exclude potential artifacts and prioritize biologically relevant binding sites. While fold change and p-value are valuable parameters, our focus was on ensuring the inclusion of robust binding sites within the specified length range. We will consider incorporating additional filtering parameters in future iterations leading to a new version of the web server. Reviewer Comment: If this job is for the benefit of biologists, why not use transcripts as a reference? Because RBP binds to transcripts. And it's too simplistic for systems biologists, the author can refer to the POSTAR3 data. Author Response: Our choice to focus on genomic coordinates was driven by the goal of providing a comprehensive resource for accessing RBP binding sites across the genome. While transcripts offer valuable context, our approach allows for flexibility in analyzing binding sites within different genomic regions and across multiple transcripts. However, we recognize the importance of incorporating transcript-level information and will explore integrating such data in future updates of the webserver to enhance the utility of our tool for systems biologists. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Pan X. Peer Review Report For: RBP-Tar – a searchable database for experimental RBP binding sites [version 3; peer review: 2 approved, 4 approved with reservations] . 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