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Closing the circle : current state and perspectives of circular RNA databases

Marieke Vromman (UGent) , Jo Vandesompele (UGent) and Pieter-Jan Volders (UGent)
(2021) BRIEFINGS IN BIOINFORMATICS. 22(1). p.288-297
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Abstract
Circular RNAs (circRNAs) are covalently closed RNA molecules that have been linked to various diseases, including cancer. However, a precise function and working mechanism are lacking for the larger majority. Following many different experimental and computational approaches to identify circRNAs, multiple circRNA databases were developed as well. Unfortunately, there are several major issues with the current circRNA databases, which substantially hamper progression in the field. First, as the overlap in content is limited, a true reference set of circRNAs is lacking. This results from the low abundance and highly specific expression of circRNAs, and varying sequencing methods, data-analysis pipelines, and circRNA detection tools. A second major issue is the use of ambiguous nomenclature. Thus, redundant or even conflicting names for circRNAs across different databases contribute to the reproducibility crisis. Third, circRNA databases, in essence, rely on the position of the circRNA back-splice junction, whereas alternative splicing could result in circRNAs with different length and sequence. To uniquely identify a circRNA molecule, the full circular sequence is required. Fourth, circRNA databases annotate circRNAs' microRNA binding and protein-coding potential, but these annotations are generally based on presumed circRNA sequences. Finally, several databases are not regularly updated, contain incomplete data or suffer from connectivity issues. In this review, we present a comprehensive overview of the current circRNA databases and their content, features, and usability. In addition to discussing the current issues regarding circRNA databases, we come with important suggestions to streamline further research in this growing field.
Keywords
Molecular Biology, Information Systems, circRNA, circRNA databases

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MLA
Vromman, Marieke, et al. “Closing the Circle : Current State and Perspectives of Circular RNA Databases.” BRIEFINGS IN BIOINFORMATICS, vol. 22, no. 1, 2021, pp. 288–97, doi:10.1093/bib/bbz175.
APA
Vromman, M., Vandesompele, J., & Volders, P.-J. (2021). Closing the circle : current state and perspectives of circular RNA databases. BRIEFINGS IN BIOINFORMATICS, 22(1), 288–297. https://doi.org/10.1093/bib/bbz175
Chicago author-date
Vromman, Marieke, Jo Vandesompele, and Pieter-Jan Volders. 2021. “Closing the Circle : Current State and Perspectives of Circular RNA Databases.” BRIEFINGS IN BIOINFORMATICS 22 (1): 288–97. https://doi.org/10.1093/bib/bbz175.
Chicago author-date (all authors)
Vromman, Marieke, Jo Vandesompele, and Pieter-Jan Volders. 2021. “Closing the Circle : Current State and Perspectives of Circular RNA Databases.” BRIEFINGS IN BIOINFORMATICS 22 (1): 288–297. doi:10.1093/bib/bbz175.
Vancouver
1.
Vromman M, Vandesompele J, Volders P-J. Closing the circle : current state and perspectives of circular RNA databases. BRIEFINGS IN BIOINFORMATICS. 2021;22(1):288–97.
IEEE
[1]
M. Vromman, J. Vandesompele, and P.-J. Volders, “Closing the circle : current state and perspectives of circular RNA databases,” BRIEFINGS IN BIOINFORMATICS, vol. 22, no. 1, pp. 288–297, 2021.
@article{8654354,
  abstract     = {{Circular RNAs (circRNAs) are covalently closed RNA molecules that have been linked to various diseases, including cancer. However, a precise function and working mechanism are lacking for the larger majority. Following many different experimental and computational approaches to identify circRNAs, multiple circRNA databases were developed as well. Unfortunately, there are several major issues with the current circRNA databases, which substantially hamper progression in the field. First, as the overlap in content is limited, a true reference set of circRNAs is lacking. This results from the low abundance and highly specific expression of circRNAs, and varying sequencing methods, data-analysis pipelines, and circRNA detection tools. A second major issue is the use of ambiguous nomenclature. Thus, redundant or even conflicting names for circRNAs across different databases contribute to the reproducibility crisis. Third, circRNA databases, in essence, rely on the position of the circRNA back-splice junction, whereas alternative splicing could result in circRNAs with different length and sequence. To uniquely identify a circRNA molecule, the full circular sequence is required. Fourth, circRNA databases annotate circRNAs' microRNA binding and protein-coding potential, but these annotations are generally based on presumed circRNA sequences. Finally, several databases are not regularly updated, contain incomplete data or suffer from connectivity issues. In this review, we present a comprehensive overview of the current circRNA databases and their content, features, and usability. In addition to discussing the current issues regarding circRNA databases, we come with important suggestions to streamline further research in this growing field.}},
  author       = {{Vromman, Marieke and Vandesompele, Jo and Volders, Pieter-Jan}},
  issn         = {{1467-5463}},
  journal      = {{BRIEFINGS IN BIOINFORMATICS}},
  keywords     = {{Molecular Biology,Information Systems,circRNA,circRNA databases}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{288--297}},
  title        = {{Closing the circle : current state and perspectives of circular RNA databases}},
  url          = {{http://dx.doi.org/10.1093/bib/bbz175}},
  volume       = {{22}},
  year         = {{2021}},
}

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