circRNAs have emerged as a focal point of scientific inquiry, garnering widespread recognition for their unique allure within the scientific community. Particularly captivating is their enigmatic nature, which has spurred a fervent curiosity among researchers, who eagerly anticipate delving deeper into this realm, aspiring to uncover novel insights.
However, a prominent challenge facing current circRNA research lies in the scarcity of referenceable information, leaving investigators with a dearth of clear direction and objectives in advancing their studies. In light of this, the present work endeavors to facilitate researchers by recommending dozens of circRNA databases, with the aim of enhancing understanding of circRNA intricacies and catalyzing further progress in this field.
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Bioinformatics 101: circRNA Sequencing Data Analysis
http://www.circbase.org/
One resource of notable significance in the study of circRNAs is circBase, accessible via http://www.circbase.org/. CircBase serves as a repository of circRNA information spanning multiple species, including human (hg19), mouse (mm9), Caenorhabditis elegans (ce6), Drosophila melanogaster (dm3), zebrafish (latCha1), and lamprey. Its functionalities encompass the aggregation of circular RNA data from diverse species, with predictions derived from ribosomal RNA-depleted libraries utilizing the find_circ software.
Key features of circBase include:
1. Sequence-based search capabilities.
2. Database exploration facilitated through identifiers, gene descriptions, genomic coordinates, and similar criteria.
3. Utilization of a table browser for streamlined retrieval of specific datasets, akin to UCSC functionalities.
4. Versatile data export functionalities, allowing for the extraction of tables in various formats.
5. Provision for exporting FASTA files containing genomic sequences associated with circRNAs.
These attributes collectively render circBase a pivotal resource for researchers seeking comprehensive circRNA datasets and analysis tools to advance their investigations.
CircNet, accessible at http://circnet.mbc.nctu.edu.tw/, represents a specialized database meticulously curated from transcriptomic data derived from 464 samples of human origin. Its construction involved systematic analysis and identification processes, culminating in a resource comprising several pivotal components:
1. Identification of novel circRNAs: CircNet provides a catalog of circRNAs derived from comprehensive transcriptomic profiling, expanding the landscape of known circular RNA transcripts.
2. Integration of circRNA-miRNA-mRNA interaction networks: It offers an integrated perspective on the intricate interplay among circRNAs, microRNAs, and messenger RNAs, thereby facilitating deeper insights into regulatory networks governing gene expression.
3. Expression profiling of circRNA subtypes: CircNet furnishes data on the expression levels of circRNA subtypes across diverse cellular contexts, enabling researchers to discern patterns of circRNA abundance and regulation.
4. Genomic annotation of circRNA subtypes: The database includes detailed genomic annotations for circRNA subtypes, contributing to the elucidation of their genomic origins and functional characteristics.
5. Sequences of circRNA subtypes: CircNet grants access to the sequences of circRNA subtypes, facilitating detailed sequence-based analyses and investigations into their structural and functional properties.
Through its comprehensive array of features, CircNet serves as an invaluable resource for researchers investigating the intricate complexities of circRNA biology within the realm of human physiology and pathology.
CircInteractome, accessible at https://circinteractome.nia.nih.gov/, boasts a comprehensive species repertoire, encompassing various organisms such as humans, fruit flies, among others, with a primary focus on human species.
This database offers a notable feature of amalgamating existing knowledge by predicting binding sites of known RNA-binding proteins, along with the binding sites of circRNAs from CircBase, as previously highlighted. Furthermore, it adeptly integrates the prediction of potential binding sites between miRNAs and circRNAs. This feature aligns well with the approach outlined in the 36 Stratagems, facilitating ease of navigation for novices.
Functionally, CircInteractome extends beyond miRNA predictions to foresee potential downstream protein binding events. It facilitates various operations including circRNA molecular retrieval, PCR primer design, and RNA interference sequence design, thus rendering it highly user-friendly, particularly for beginners.
CIRCpedia, accessible at http://www.picb.ac.cn/rnomics/circpedia/, features an extensive taxonomic coverage spanning six species, including Homo sapiens, Mus musculus, Drosophila melanogaster, and Danio rerio, among others. It aggregates transcriptomic data from over 180 samples, identifying a staggering total of 262,782 circular RNAs.
Functionally, CIRCpedia offers versatile search capabilities based on species, cell lines, gene names, or genomic locations, leveraging its repository of circular RNA IDs. Upon query, the database provides detailed information, including the source gene of the circular RNA ID, corresponding linear transcripts, expression levels, exon start and end positions, cell lines, and conservation status. Additionally, it facilitates visual exploration of circular RNA expression across various tissues or cell lines through heatmap or scatterplot representations.
Through its comprehensive data retrieval and visualization functionalities, CIRCpedia emerges as a valuable resource for researchers seeking insights into the expression patterns and regulatory roles of circular RNAs across diverse biological contexts.
cRNADb, accessible at http://reprod.njmu.edu.cn/cgi-bin/circrnadb/circRNADb.php, stands as the pioneering database compiling circular RNAs encoded by the human genome. Illustrated with hsa_circ_07894 as an example, it elucidates the comprehensive details within individual circular RNA records.
Each entry comprises two main sections: basic information and detailed information. The basic information section encompasses the gene's ID number, genomic sequence, strand specificity, gene name, tissue and cell origin data, among others. Conversely, the detailed information section provides insights into the circular RNA's exon sequence and information, RNA splicing sequence length, circular RNA sequence details, IRES and ORF correspondence details, fundamental characteristics of predicted peptides, associated disease information, and pertinent references.
Through its meticulous organization and provision of detailed insights, cRNADb serves as a foundational resource for researchers delving into the intricate landscape of human circular RNA biology, facilitating comprehensive investigations into their genomic characteristics, functional attributes, and potential implications in disease contexts.
DeepBase, hosted at http://rna.sysu.edu.cn/deepBase/, embodies a database initiative led by Sun Yat-sen University, focusing on the annotation and identification of diverse RNA species using next-generation sequencing data. This repository is instrumental in unraveling the expression patterns of various RNA entities, including circRNAs, microRNAs (miRNAs), and piwi-interacting RNAs (piRNAs), across a spectrum of biological contexts.
Operationally, DeepBase provides a versatile platform empowering users to delve into the expression profiles, evolutionary conservation, functional annotations, and molecular interactions of circRNAs, long non-coding RNAs (lncRNAs), microRNAs, and messenger RNAs (mRNAs). Furthermore, the database facilitates seamless data retrieval, offering expression profiles spanning different species and tissue types. Noteworthy is DeepBase's emphasis on exploring competing endogenous RNA (ceRNA) molecular networks, elucidating the intricate regulatory dynamics governing gene expression.
With its comprehensive array of features, DeepBase emerges as an indispensable resource for researchers embarking on investigations into the regulatory milieu of RNA molecules across diverse species and biological contexts. Its contribution facilitates the advancement of our comprehension of gene expression regulation and molecular interactions.
Cirbank, accessible via http://www.circbank.cn/help.html, specializes in curating circular RNA (circRNA) data pertaining specifically to the human species sourced from the circBase database. This curation process involves meticulous organization of information, leveraging sequence data for the assessment of protein-coding potential and the prediction of miRNA interactions. Subsequently, these analyses are amalgamated into an online database, providing users with a platform for convenient data retrieval and exploration.
The Cirbank database offers three primary search modalities: swift and straightforward searches, searches based on circRNA information, and searches based on miRNA information. Users can initiate circRNA queries directly from the Cirbank homepage, harnessing the database's capabilities to analyze circRNA protein-coding potential, retrieve miRNA-related circRNA information, discern miRNA-circRNA interactions, and access downloadable datasets encompassing circRNA annotations, sequences, conservation, miRNA-circRNA interactions, circRNA modifications, and circRNA protein-coding potential.
By offering these comprehensive functionalities, Cirbank emerges as a pivotal resource facilitating in-depth investigations into circRNA biology and its intricate interactions. Through its contributions, Cirbank significantly furthers our comprehension of regulatory RNA networks in human biology.
The circRNA Disease database, accessible at http://cgga.org.cn:9091/circRNADisease/, is a culmination of research efforts from Capital Medical University, published in Cell Death and Disease in 2018. This repository is primarily constructed through literature retrieval of all relevant studies concerning circRNA-disease associations, with data collection extending up to November 2017. It comprises analyses from 354 studies, resulting in the identification of 330 circRNAs associated with 48 human diseases.
The database offers essential functionalities such as browsing, downloading, and submission options. It supports searches based on disease names, gene names, and circRNA identifiers, providing clear and concise presentation of results. Overall, the circRNA Disease database serves as an indispensable resource for researchers, offering comprehensive insights into circRNA-disease associations, and thereby contributing significantly to the advancement of our understanding of circRNA biology in human health and pathology.
circR2Disease, accessible at http://bioinfo.snnu.edu.cn/CircR2Disease/, encompasses data from human, mouse, and rat species. This database serves as a repository for 661 circular RNAs associated with 100 diseases, aggregating a total of 739 circRNA-disease associations. The records within this database are meticulously curated from the literature, providing comprehensive information such as disease names, expression trends of circular RNAs in afflicted individuals, and PubMed IDs of relevant literature.
9. Primarily designed for investigating the relationships between circular RNAs and diseases, circR2Disease facilitates the retrieval of such associations. Additionally, it offers the capability to construct interaction networks between circular RNAs and diseases, providing insights into the regulatory mechanisms underlying disease pathogenesis.
10. By providing access to curated literature-derived data and facilitating the exploration of circular RNA-disease associations, circR2Disease stands as a valuable tool for researchers delving into the intricate interplay between circular RNAs and disease states across multiple species.
MiOncoCirc, available at https://mioncocirc.github.io/, focuses on human species. Published in Cell in 2019, this platform stands as the first to integrate data concerning circRNAs with clinical symptoms and disease associations. Drawing from over 2000 samples, it encompasses a diverse array of circRNAs, spanning primary tumors, metastatic tumors, and rare neoplasms. The website is meticulously designed, offering downloadable data and search functionalities. The wealth of data available on MiOncoCirc presents a valuable resource for researchers exploring the intricate relationships between circRNAs and oncological phenomena.
Cir2traits, accessible at http://gyanxet-beta.com/circdb/, caters to human, mouse, and nematode species. This database is dedicated to compiling circRNAs associated with human diseases, encompassing not only tumors but also non-neoplastic conditions such as myocardial diseases, Alzheimer's disease, and vascular development disorders. Additionally, Cir2traits predicts the interactions between miRNAs and human protein-coding genes, lncRNAs, and circRNAs, constructing interaction networks. Furthermore, it conducts Gene Ontology (GO) analyses on these networks. Additionally, Cir2traits facilitates the mapping of disease-associated SNPs to circRNA loci. This multifaceted approach positions Cir2traits as a valuable tool for elucidating the intricate relationships between circRNAs and disease states across various species.
LncRNA Disease 2.0, accessible at http://www.rnanut.net/lncrnadisease/, caters to Homo sapiens, Mus musculus, Rattus norvegicus, and Gallus species. This database currently houses 19,166 entries of lncRNA information, 823 entries of circRNA information, and catalogs 529 disease entities. It serves as a repository for reported and experimentally validated associations between lncRNAs, circRNAs, and diseases. Additionally, it elucidates regulatory relationships among ncRNAs, mRNAs, and miRNAs. Furthermore, LncRNA Disease 2.0 facilitates the mapping of disease names to disease ontology and medical subject headings, providing a confidence score for each lncRNA-disease association. This comprehensive approach positions LncRNA Disease 2.0 as an invaluable resource for exploring the intricate landscape of lncRNA and circRNA involvement in disease pathogenesis across multiple species.
The Cancer-Specific Circular RNA Database (CSCD), accessible at http://gb.whu.edu.cn/CSCD/, focuses on curating circRNAs specific to tumor entities. Employing bioinformatics methodologies, it analyzes circRNA expression profiles across 87 tumor samples, identifying circRNAs expressed exclusively in cancer patients.
Functionally, users can navigate the database homepage to filter results based on sample characteristics, gene sources, and cellular localization. Each row of the search results represents a circRNA, providing details such as the gene source name, corresponding sample name, software used for analysis, and expression levels. The database offers detailed insights into gene structure visualization, chromosome positions, transcript details, circRNA chromosome positions, and splice events.
For circRNAs, comprehensive information includes visualization of structural features such as miRNA binding sites, protein binding sites, and open reading frame (ORF) regions. Additionally, the database predicts miRNA binding sites using TargetScan software and identifies RNA binding proteins based on HITS_CLIP sequencing data. Moreover, it assesses ORF regions to analyze the coding potential of circRNAs.
Through its detailed annotations and visualization tools, the CSCD provides researchers with a valuable resource for exploring the complex landscape of cancer-specific circRNAs, facilitating deeper insights into their potential roles in tumorigenesis and cancer progression.
CircFunBase, available at http://bis.zju.edu.cn/CircFunBaseBlast/, encompasses Homo sapiens, Mus musculus, Rattus norvegicus, chicken, monkey, pig, cattle, rabbit, and dozens of plant species.
Functionally, it facilitates rapid retrieval of circular RNA (circRNA) names and functional descriptions. Drawing from experimental foundations based on quantitative real-time polymerase chain reaction (qRT-PCR), it additionally provides insights into the expression modulation of circRNAs across numerous diseases, indicating whether they are upregulated or downregulated. Furthermore, CircFunBase offers sequence similarity searches via BLAST.
This database, published in 2019, represents a relatively recent addition to the field, boasting fast browsing speeds and offering a valuable resource for researchers seeking to explore the multifaceted roles of circRNAs across species and disease contexts.
CircAtlas, available at http://circatlas.biols.ac.cn/, consolidates data from six vertebrate species, encompassing humans, macaques, mice, rats, pigs, and chickens, derived from 19 distinct normal tissues.
Functionally, CircAtlas employs four robust detection algorithms—CIRI2, find_circ, CIRCexplorer2, and DCC—to discern circRNAs within each species. Leveraging the CIRI-full/CIRI-vis pipeline, it reconstructs the full-length sequences of identified circRNAs. Furthermore, it scrutinizes these full-length circRNAs for internal ribosome entry sites (IRESs) and open reading frames (ORFs) to assess their coding potential. The conservation status of circRNAs is evaluated using a multiple conservative score (MCS) approach, estimating their preservation across species, tissues, and individuals.
By amalgamating insights into co-expression networks, circRNA-miRNA interactions, and RNA-binding protein (RBP) binding sites, CircAtlas offers comprehensive annotations for circRNAs. Additionally, it predicts the putative functions of these circRNAs through the utilization of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Moreover, CircAtlas integrates data from Circad, CircR2Disease, and CircRNADisease databases to assess the implications of circRNAs in diverse disease contexts.
With its multifaceted features and integrated methodology, CircAtlas stands as an invaluable tool for researchers delving into the myriad roles of circRNAs in both physiological processes and pathological conditions across vertebrate species.
At BIOINF (Center of Clinical Laboratory Science, Jiangsu Cancer Hospital), accessible via http://www.bioinf.com.cn/, the focus lies on circRNA-related bioinformatics services catering to both human and mouse species.
Functionalities include:
1. Designing primers for circRNA.
2. Annotating the exonic and intronic components of circular RNA.
3. Graphically annotating the functional positions of circular RNA sequences within their parent genes.
4. Retrieving circular RNA from circBase.
5. Acquiring the splicing sequences and genomic sequences of circular RNA.
6. Assisting in the design of back-to-back primers for circular RNA.
7. Aiding in the design of primers spanning splice sites for circular RNA.
8. Assessing primer specificity through experimental validation.
9. Graphically depicting the positions of primers within circular RNA sequences.
10. Converting sequences into reverse complementary, reverse, and complementary sequences.
These services provide valuable support for researchers engaged in circRNA studies, facilitating primer design and sequence analysis for comprehensive investigations into circRNA biology and function.
circlncRNAnet, available at http://app.cgu.edu.tw/circlnc/, caters primarily to human species and offers a diverse array of functionalities.
These functionalities include access to chip data based on The Cancer Genome Atlas (TCGA) across up to 20 different tumor types. Users have the capability to filter genes based on criteria such as "LogFC" and "P-value". Furthermore, the database allows for the retrieval of expression information for specific genes, enabling the creation of heatmaps, scatter plots illustrating co-expression of relevant genes, Gene Ontology (GO) annotations, Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations, and interaction data represented via Circos plots. Additionally, the platform facilitates survival curve analysis.
Moreover, circlncRNAnet offers users the opportunity to upload their own chip data, thereby enabling the generation of customized analysis graphics tailored to their specific datasets.
By providing these multifaceted functionalities, circlncRNAnet serves as a comprehensive tool for researchers engaged in the exploration of lncRNA-related mechanisms in cancer biology, allowing for in-depth analysis and visualization of chip data for a range of tumor types.
The Tissue-specific CircRNA Database (TSCD), accessible via http://gb.whu.edu.cn/TSCD/, caters to both human and mouse species.
Functionally, circRNAs have been demonstrated to exhibit tissue specificity. TSCD offers a comprehensive overview of tissue-specific circRNAs in major human and mouse tissues, serving as a repository for novel biomarkers of organ development and disease progression.
This database curates transcriptomic sequencing data from various tissues of humans and mice sourced from public repositories such as ENCODE and GEO. Subsequently, circRNAs are identified within these datasets using tools like find_circ, CIRI, and circRNA_finder.
By providing a global perspective on tissue-specific circRNAs and identifying potential markers for organogenesis and disease progression, TSCD contributes significantly to our understanding of the regulatory roles of circRNAs in both physiological and pathological contexts across species.
TRCirc, available at http://www.licpathway.net/TRCirc/view/index, is focused on the human species.
Functionally, it houses an extensive collection of 92,375 circRNAs and 161 transcription factors (TFs) across more than 100 cell types. This repository encompasses 690 unified TF binding sites (TFBSs), along with 36 H3K27ac, 54 RNA-seq, and 61 450k datasets. Users can efficiently search and explore TFBSs associated with circRNAs, alongside other pertinent information, targeting specific TFs, cell lines, or circRNAs of interest. Moreover, our tool facilitates the seamless download of TF-circRNA interaction data and other relevant information across four classes of regulatory regions. TRCirc serves as a valuable resource for unraveling the transcriptional regulatory mechanisms of circRNAs.
circRNADb, accessible at http://reprod.njmu.edu.cn/circrnadb, caters to the human species.
Functionally, circRNADb 1.0 serves as a comprehensive database of human circular RNA molecules. It is freely available for non-commercial use. The latest version of circRNADb encompasses 32,914 annotated exonic circRNAs, constituting a valuable resource for large-scale circRNA studies, particularly in the context of human circRNAs. Each entry includes information on genomic location, RNA editing status, corresponding genomic sequences, internal ribosome entry site (IRES) elements, predicted open reading frames (ORFs), and relevant references. The website features a user-friendly interface, designed with clarity in mind. In the "Advance Retrieval" section, users can search based on various criteria such as gene name (gene symbol), PubMed ID, and cell or tissue type, catering to diverse query needs.
exoRBase, available at www.exoRBase.org, focuses on the human species.
Functionally, exoRBase aggregates a comprehensive collection of 58,330 circRNAs, 15,501 lncRNAs, and 18,333 mRNAs derived from 92 serum exosome RNA-seq samples. Leveraging RNA-seq data analysis from human blood exosomes, the authors additionally analyze tissue-specific RNA expression characteristics obtained from the GTEx project. This enables an exploration of the tissue origins of the respective RNA molecules. The database facilitates rapid access to information on circRNAs, lincRNAs, and mRNAs derived from human blood exosomes. The database comprises samples from various health conditions, including 32 healthy controls, 6 cases of coronary heart disease (CHD), 12 cases of colorectal cancer (CRC), 21 cases of hepatocellular carcinoma (HCC), 14 cases of pancreatic adenocarcinoma (PAAD), and 2 cases of breast cancer. Multiple search pathways are provided, allowing users to search for circRNAs and linear lncRNAs or mRNAs separately. Furthermore, targeted searches can be conducted based on specimen type, gene type, tissue expression specificity, and other criteria.
MiOncoCirc, developed by the University of Michigan, presents a compilation of circular RNA (circRNA) data derived from clinical cancer samples.
This database allows for the interrogation of the expression patterns of specific circRNAs across various clinical cancer samples. MiOncoCirc stands as a pioneering and extensive clinical circRNA resource centered on cancer. Crucially, our database is primarily constructed from clinical cancer samples (2000+), spanning a diverse array of disease sites, unlike other resources that have extracted features from cancer cell lines. The transcriptional processes occurring in petri dishes, along with the resultant circRNA formation, undoubtedly differ significantly from the natural tumor microenvironment. This distinction enables MiOncoCirc to better represent the authentic circRNA landscape associated with cancer. Moreover, MiOncoCirc embodies a rich resource encompassing primary tumors, metastatic tumors, and exceptionally rare cancer types. Researchers interested in mutations and copy numbers can also query MiOncoCirc, as our samples are collected from previously published genomic studies.
circRNABase, accessible at http://starbase.sysu.edu.cn/starbase2/mirCircRNA.php, serves as a comprehensive repository integrating published circRNA and CLIP-Seq data.
The website catalogues miRNA-circRNA interactions that overlap with CLIP-Seq data, providing a platform for the analysis of miRNA-circRNA interactions. This functionality facilitates users in identifying potential microRNA targets.