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Toward Sequencing and Mapping of RNA Modifications

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RNA plays critical roles in nearly all biological processes, but current methods for sequencing RNA are significantly limited. This is partially because RNA molecules are chemically modified within the cell to enable their proper function, and currently, the available sequencing technologies can only detect a small number of these modifications. This limits our understanding of different molecular processes and leaves a gap in our knowledge related to human diseases and disorders. This committee will assess the scientific and technological breakthroughs, workforce, and infrastructure needs to sequence, and ultimately understand the roles RNA modifications play in biological processes and disease.

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Description

The National Academies of Sciences, Engineering, and Medicine will convene an ad hoc committee to conduct a study on direct sequencing of modifications of RNA (referred to as epitranscriptome) from humans and model organisms. As part of this study, the committee will develop a roadmap for achieving direct sequencing of modifications of RNA. The National Academies’ committee will examine:

  • Scientific needs for sequencing of modifications of RNA.
  • Current RNA sequencing methodologies and technologies and their current limitations, documenting which RNA bases and modifications can be sequenced and whether the RNA is sequenced directly or indirectly.
  • Current RNA and RNome* databases, including the types of RNA included, the organisms from which the RNA sequences were obtained, and limitations of the databases.
  • Challenges associated with current methodologies and technologies for sequencing RNA and its modifications for scientific, clinical, and public health analyses.
  • Scientific and technological hurdles including computational and analytic technologies, that need to be overcome to achieve direct sequencing of RNA modifications.
  • Computational and analytic technologies needed to analyze modified RNA.
  • Data ecosystem for supporting sequencing and analysis of RNA modifications.
  • Policy, workforce, and infrastructure needs to support sequencing and analysis of RNA modifications.
  • Potential for existing and new technologies to discover previously-unrecognized RNA modifications.

The National Academies will produce a consensus report that focuses on defining the science and technology roadmap and actionable recommendations toward achievement of direct sequencing of RNA modifications. During the study, the committee will hold a series of coordinated activities (e.g., workshops, meeting of experts, ideation challenges) to provide platforms for creative collaboration among experts from multiple scientific disciplines and organizations. Individual products summarizing key outcomes from these activities may be produced as interim products of the consensus study.
* The RNome refers to all of the RNA species in a cell at a given time (Arora, 2018).

Contributors

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Steven Moss

Staff Officer

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Conflict of Interest Disclosure

The conflict of interest policy of the National Academies of Sciences, Engineering, and Medicine (http://www.nationalacademies.org/coi) prohibits the appointment of an individual to a committee authoring a Consensus Study Report if the individual has a conflict of interest that is relevant to the task to be performed. An exception to this prohibition is permitted if the National Academies determines that the conflict is unavoidable and the conflict is publicly disclosed. A determination of a conflict of interest for an individual is not an assessment of that individual’s actual behavior or character or ability to act objectively despite the conflicting interest.

Dr. Adams has a conflict of interest in relation to his service on the Committee on Mapping and Sequencing Chemical Modifications of RNA because he is an employee of Thermo Fisher Scientific, a company which develops nucleic acid-related tools and technologies.

The National Academies has concluded that for this committee to accomplish the tasks for which it was established, its membership must include at least one person who has current experience developing tools and technologies for industry or the private sector, particularly in the rapidly change field of RNA chemical modification. As described in his biographical summary, Dr. Adams, in his current role at Thermo Fisher Scientific, is responsible for the development of new tools and technologies for oligonucleotide analysis. These tools include the ability to mix, separate, and analyze different oligonucleotides. An understanding of these techniques and the approach that industry is taking to developing different tools and technologies, will be critical to completing the study.

The National Academies has determined that the experience and expertise of Dr. Adams is needed for the committee to accomplish the task for which it has been established. The National Academies could not find another available individual with the equivalent experience and expertise who does not have a conflict of interest. Therefore, the National Academies has concluded that the conflict is unavoidable.

The National Academies believes that Dr. Adams can serve effectively as a member of the committee, and the committee can produce an objective report, taking into account the composition of the committee, the work to be performed, and the procedures to be followed in completing the study.

Sponsors

National Institutes of Health

Warren Alpert Foundation

Staff

Trisha Tucholski

Lead

Jessica De Mouy

Kathryn Asalone

Nam Vu

Kavita Berger

Lyly Luhachack

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