Epitranscriptome analysis of NAD-capped RNA by spike-in-based normalization and prediction of chronological age
© 2023 The Authors..
Nicotinamide adenine dinucleotide (NAD) can be used as an initiating nucleotide in RNA transcription to produce NAD-capped RNA (NAD-RNA). RNA modification by NAD that links metabolite with expressed transcript is a poorly studied epitranscriptomic modification. Current NAD-RNA profiling methods involve multi-steps of chemo-enzymatic labeling and affinity-based enrichment, thus presenting a critical analytical challenge to remove unwanted variations, particularly batch effects. Here, we propose a computational framework, enONE, to remove unwanted variations. We demonstrate that designed spike-in RNA, together with modular normalization procedures and evaluation metrics, can mitigate technical noise, empowering quantitative and comparative assessment of NAD-RNA across different datasets. Using enONE and a human aging cohort, we reveal age-associated features of NAD-capping and further develop an accurate RNA-based aging clock that combines signatures from both transcriptome and NAD-modified epitranscriptome. enONE facilitates the discovery of NAD-RNA responsive to physiological changes, laying an important foundation for functional investigations into this modification.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
iScience - 26(2023), 12 vom: 15. Dez., Seite 108558 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Dean [VerfasserIn] |
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| Links: |
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| Themen: |
Computational bioinformatics |
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| Anmerkungen: |
Date Revised 14.12.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.isci.2023.108558 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM365849464 |
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| 520 | |a Nicotinamide adenine dinucleotide (NAD) can be used as an initiating nucleotide in RNA transcription to produce NAD-capped RNA (NAD-RNA). RNA modification by NAD that links metabolite with expressed transcript is a poorly studied epitranscriptomic modification. Current NAD-RNA profiling methods involve multi-steps of chemo-enzymatic labeling and affinity-based enrichment, thus presenting a critical analytical challenge to remove unwanted variations, particularly batch effects. Here, we propose a computational framework, enONE, to remove unwanted variations. We demonstrate that designed spike-in RNA, together with modular normalization procedures and evaluation metrics, can mitigate technical noise, empowering quantitative and comparative assessment of NAD-RNA across different datasets. Using enONE and a human aging cohort, we reveal age-associated features of NAD-capping and further develop an accurate RNA-based aging clock that combines signatures from both transcriptome and NAD-modified epitranscriptome. enONE facilitates the discovery of NAD-RNA responsive to physiological changes, laying an important foundation for functional investigations into this modification | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Computational bioinformatics | |
| 650 | 4 | |a Methodology in biological sciences | |
| 650 | 4 | |a Sequence analysis | |
| 650 | 4 | |a Transcriptomics | |
| 700 | 1 | |a Ge, Shuwen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yandong |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Miaomiao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xueting |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Guojing |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Sili |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Niu, Kongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Lefeng |e verfasserin |4 aut | |
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