Quantifying RNA modifications by mass spectrometry: a novel source of biomarkers in oncology

Amalric, Amandine; Bastide, Amandine; Attina, Aurore; Choquet, Armelle; Vialaret, Jérôme; Lehmann, Sylvain; David, Alexandre; Hirtz, Christophe

doi:10.1080/10408363.2021.1958743

Cited by 20 publications

(16 citation statements)

References 85 publications

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“…Epitranscriptomics may represent a novel source for biomarkers. Some studies correlate the level of a given nucleoside with disease onset or progression (reviewed in ref ( 9 )). Nevertheless, analysis of multiple epitranscriptomics marks has never been employed for diagnosis purpose.…”

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confidence: 99%

“…epitranscriptomics) emerged as a novel layer of gene expression regulation in healthy tissues (e.g., brain), as well as in several pathologies such as neurodegenerative diseases 7 and cancer. 8,9 In particular, we and others associated several chemical marks with cancer evolution, adaptation, as well as the response to conventional therapy. 8,10,11 Building on these observations, we reasoned that several epitranscriptomics marks may vary along cancer progression and even play a role in this process.…”

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confidence: 99%

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Multivariate Analysis of RNA Chemistry Marks Uncovers Epitranscriptomics-Based Biomarker Signature for Adult Diffuse Glioma Diagnostics

et al. 2022

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One of the main challenges in cancer management relates to the discovery of reliable biomarkers, which could guide decision-making and predict treatment outcome. In particular, the rise and democratization of high-throughput molecular profiling technologies bolstered the discovery of “biomarker signatures” that could maximize the prediction performance. Such an approach was largely employed from diverse OMICs data (i.e., genomics, transcriptomics, proteomics, metabolomics) but not from epitranscriptomics, which encompasses more than 100 biochemical modifications driving the post-transcriptional fate of RNA: stability, splicing, storage, and translation. We and others have studied chemical marks in isolation and associated them with cancer evolution, adaptation, as well as the response to conventional therapy. In this study, we have designed a unique pipeline combining multiplex analysis of the epitranscriptomic landscape by high-performance liquid chromatography coupled to tandem mass spectrometry with statistical multivariate analysis and machine learning approaches in order to identify biomarker signatures that could guide precision medicine and improve disease diagnosis. We applied this approach to analyze a cohort of adult diffuse glioma patients and demonstrate the existence of an “epitranscriptomics-based signature” that permits glioma grades to be discriminated and predicted with unmet accuracy. This study demonstrates that epitranscriptomics (co)evolves along cancer progression and opens new prospects in the field of omics molecular profiling and personalized medicine.

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confidence: 99%

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confidence: 99%

Multivariate Analysis of RNA Chemistry Marks Uncovers Epitranscriptomics-Based Biomarker Signature for Adult Diffuse Glioma Diagnostics

et al. 2022

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“…Through -omics methodology, MS can provide these data via high throughput technologies for larger RNAs as well as heterogeneous biological samples (cell lysates, etc.) [ 112 , 113 , 114 ]. Additionally, advances have been made in native MS to provide tertiary contact information as well as the stability of certain folded RNAs [ 115 , 116 , 117 , 118 ].…”

Section: Experiments That Can Help Validate MD Simulation Resultsmentioning

confidence: 99%

Challenges with Simulating Modified RNA: Insights into Role and Reciprocity of Experimental and Computational Approaches

D'Esposito

Myers

Chen

et al. 2022

Genes

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RNA is critical to a broad spectrum of biological and viral processes. This functional diversity is a result of their dynamic nature; the variety of three-dimensional structures that they can fold into; and a host of post-transcriptional chemical modifications. While there are many experimental techniques to study the structural dynamics of biomolecules, molecular dynamics simulations (MDS) play a significant role in complementing experimental data and providing mechanistic insights. The accuracy of the results obtained from MDS is determined by the underlying physical models i.e., the force-fields, that steer the simulations. Though RNA force-fields have received a lot of attention in the last decade, they still lag compared to their protein counterparts. The chemical diversity imparted by the RNA modifications adds another layer of complexity to an already challenging problem. Insight into the effect of RNA modifications upon RNA folding and dynamics is lacking due to the insufficiency or absence of relevant experimental data. This review provides an overview of the state of MDS of modified RNA, focusing on the challenges in parameterization of RNA modifications as well as insights into relevant reference experiments necessary for their calibration.

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“…Over the years, therapeutic strategies based on post-transcriptional RNA modifications have received growing interest. For instance, modified messenger RNA were reported as potential treatment for infectious disease and some RNA modifications were reported as cancer biomarkers for diagnostic purposes …”

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confidence: 99%

“…For instance, modified messenger RNA were reported as potential treatment for infectious disease 8 and some RNA modifications were reported as cancer biomarkers for diagnostic purposes. 9 Nowadays, more than 150 post-transcriptional modifications are described in the literature and referenced in the Modomics database 10 for all types of RNA. The variety of modifications goes from simple chemical groups such as methylations, which are the most naturally abundant, to more complex modifications such as total rearrangements of the nucleic bases.…”

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confidence: 99%

Nucleos’ID: A New Search Engine Enabling the Untargeted Identification of RNA Post-transcriptional Modifications from Tandem Mass Spectrometry Analyses of Nucleosides

et al. 2023

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As RNA post-transcriptional modifications are of growing interest, several methods were developed for their characterization. One of them established for their identification, at the nucleosidic level, is the hyphenation of separation methods, such as liquid chromatography or capillary electrophoresis, to tandem mass spectrometry. However, to our knowledge, no software is yet available for the untargeted identification of RNA post-transcriptional modifications from MS/MS data-dependent acquisitions. Thus, very long and tedious manual data interpretations are required. To meet the need of easier and faster data interpretation, a new user-friendly search engine, called Nucleos'ID, was developed for CE-MS/ MS and LC−MS/MS users. Performances of this new software were evaluated on CE-MS/MS data from nucleoside analyses of already well-described Saccharomyces cerevisiae transfer RNA and Bos taurus total tRNA extract. All samples showed great true positive, true negative, and false discovery rates considering the database size containing all modified and unmodified nucleosides referenced in the literature. The true positive and true negative rates obtained were above 0.94, while the false discovery rates were between 0.09 and 0.17. To increase the level of sample complexity, untargeted identification of several RNA modifications from Pseudomonas aeruginosa 70S ribosome was achieved by the Nucleos'ID search following CE-MS/MS analysis.

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Quantifying RNA modifications by mass spectrometry: a novel source of biomarkers in oncology

Cited by 20 publications

References 85 publications

Multivariate Analysis of RNA Chemistry Marks Uncovers Epitranscriptomics-Based Biomarker Signature for Adult Diffuse Glioma Diagnostics

Multivariate Analysis of RNA Chemistry Marks Uncovers Epitranscriptomics-Based Biomarker Signature for Adult Diffuse Glioma Diagnostics

Challenges with Simulating Modified RNA: Insights into Role and Reciprocity of Experimental and Computational Approaches

Nucleos’ID: A New Search Engine Enabling the Untargeted Identification of RNA Post-transcriptional Modifications from Tandem Mass Spectrometry Analyses of Nucleosides

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