Charting a Future for Sequencing RNA and Its Modifications A New Era for Biology and Medicine (2024) / Chapter Skim
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4 Standards and Databases for RNA Modifications
4 Standards and Databases for RNA Modifications
Pages 110-128
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From page 110... ...
There are no universal guidelines for submission of raw sequencing and mapping data generated from direct RNA-sequencing technologies to journals and repositories, and the nomenclature for RNA modifications is not yet uniform. As a result, storage methods for RNA sequences and their modification information are not streamlined.
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From page 111... ...
Broadly, standards needed for RNA modification and sequence analysis can be categorized as physical, data, and database standards. There are also standards that could be applied to biochemical methods and biological reagents.
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From page 112... ...
In the technology development phase, it is important to develop standards for the raw data generated by instruments to help researchers work collectively on solving the challenges of extracting signals from complex data. Data standards are also critical when projects are in data collection phases to enable researchers to collect data generated from disparate contexts and conditions, allowing more holistic perspectives to uncover new biology of RNA modifications.
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From page 113... ...
Once established, these approaches can then be disseminated and serve as benchmarks for interlab tests, such as those conducted by the Association of Biomolecular Resource Facilities Research Groups.2 Physical Standards Two categories of physical standards are necessary when characterizing RNA modifications: (1) standards for modified nucleosides and (2)
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From page 114... ...
The second category of physical standards desired for defining all the RNA modifications and their sequence context is a single RNA sequence or collection of RNA sequences with modifications present at known locations and in measured stoichiometries. Moreover, such standards enable instruments to define the analytical performance of current and future technologies, such as basecalling accuracy, reproducibility, and signal-to-noise requirements for optimal performance.
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. Standards for Raw Data, Nomenclature, and Common Ontologies Multiple considerations come into play when reviewing the state of data standards in the RNA modification field.
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These standards support a variety of data streams from emerging and novel technologies in genomics, and they play a crucial role in global collaborations and data governance strategies. Database standards encompass the following aspects of database management: • Data modeling: Database standards offer guidelines for creating data models that accurately represent biology of RNA processing pathways as they occur in living systems and their relationships with other biological pathways.
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From page 117... ...
THE CURRENT STATE OF DATABASES RNA modification databases are critical resources that provide valuable information on the chemical structure of modified RNAs, the location of modifications within RNA molecules, and the enzymes responsible for catalyzing the modification-related reactions. Some databases also include information on the functional implications of the modification, such as its effect on RNA stability, translation efficiency, or protein binding.
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From page 118... ...
PIANO A web server that identifies the site and function of 2020 human computation pseudouridine modifications, the most abundant RNA modification of uridine. m7GHub V2.0 Focuses on N7-methylguanosine (m7G)
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From page 119... ...
Comparative analyses using the information in RNA modification databases help identify conserved modifications across species and can lead to the discovery of species-specific modifications, aiding the understanding of the intricate regulatory mechanisms involving RNA modifications. RNA Biotypes in a Database Biotype classification is a scheme for cataloging types of RNA, such as mRNA, microRNA, and long noncoding RNA.
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Given the paucity of commercially available modified RNA nucleosides and the fact that most are not available in a form compatible with existing solid-phase synthesis schemes, there is a need to prioritize making physical standards for RNA modifications available, ensuring that all interested parties have access through a commercial or nonprofit resource. Furthermore, efforts to create appropriate phosphoramidites or nucleotide triphosphate versions of these standards would accelerate their incorporation into oligonucleotides or RNA sequences generated via chemical synthesis or enzymatic synthesis, respectively.
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From page 121... ...
Data Standards Defining the data quality that provides solid evidence for the presence of RNA modifications remains a significant challenge. Ensuring that the raw data generated by any RNA sequencing technology is available to other interested parties via acceptable portals would improve experimental rigor and reproducibility and enable new technology developments, such as improved basecalling or modification mapping algorithms, to be applied to previously published datasets.
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To meet these challenges, database standards need to adapt to emerging and future trends in biomedicine, artificial intelligence, and machine learning, in order to shape the future of data management for storing, distributing, and visualizing RNA modification datasets. CONCLUSIONS Conclusion 4-1: Although synthetic or biological routes exist for generating several modified nucleoside and RNA standards, few commercial or nonprofit sources of these physical standards are available to researchers.
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From page 123... ...
● Database standards: ○ Collaborate with key public, private, and international groups to define standards necessary for developing and managing RNA modification databases and resources. o Establish an agreed-upon model for RNA modification data resources with guidelines for data inclusion, sharing, and accessibility.
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2023. "RM2Target: A comprehensive database for targets of writers, erasers and readers of RNA modifications." Nucleic Acids Research 51 (D1)
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2011. "The RNA Modification Database, RNAMDB: 2011 update." Nucleic Acids Research 39 (suppl_1)
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2023. "tModBase: Deciphering the landscape of tRNA modifications and their dynamic changes from epitranscriptome data." Nucleic Acids Research 51 (D1)
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2023. "RMDisease V2.0: An updated database of genetic variants that affect RNA modifications with disease and trait implication." Nucleic Acids Research 51 (D1)
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2023. "RMBase v3.0: Decode the landscape, mechanisms and functions of RNA modifications." Nucleic Acids Research 52 (D1)
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