Evidence map›Paper›PMID 33846332›Full record

ArticleNature communications2021

Learning cis-regulatory principles of ADAR-based RNA editing from CRISPR-mediated mutagenesis.

Xin Liu, Tao Sun, Anna Shcherbina, Qin Li, Inga Jarmoskaite, Kalli Kappel, Gokul Ramaswami, Rhiju Das, Anshul Kundaje, Jin Billy Li

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. ADAR-GPT: A continually fine-tuned language model for predicting A-to-I RNA editing sites.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. RNA editing: Expanding the potential of RNA therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Review
  12. UncoveringmBio · 2022
    Article
  13. Review
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Xin Liu *Department of Genetics, Stanford University, Stanford, CA, USA.ORCID 0000-0002-9622-672X
Tao Sun *Department of Genetics, Stanford University, Stanford, CA, USA.
Anna Shcherbina *Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
Qin LiDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID 0000-0002-8948-2717
Inga JarmoskaiteDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID 0000-0001-5847-5867
Kalli KappelBiophysics Program, Stanford University, Stanford, CA, USA.ORCID 0000-0002-2129-199X
Gokul RamaswamiDepartment of Genetics, Stanford University, Stanford, CA, USA.
Rhiju DasDepartment of Biochemistry, Stanford University, Stanford, CA, USA.ORCID 0000-0001-7497-0972
Anshul KundajeDepartment of Genetics, Stanford University, Stanford, CA, USA. akundaje@stanford.edu.ORCID 0000-0003-3084-2287
Jin Billy LiDepartment of Genetics, Stanford University, Stanford, CA, USA. jin.billy.li@stanford.edu.ORCID 0000-0003-0713-1399
Stanford University · USStanford Medicine · US

Funding

Profiling and Dissecting the Dynamic Regulation of RNA EditingR01GM102484 · NIGMS · STANFORD UNIVERSITY · PI LI, JIN BILLY · 2013 to 2021
$3.1M
Deep learning frameworks for regulatory genomics.DP2GM123485 · NIGMS · STANFORD UNIVERSITY · PI KUNDAJE, ANSHUL · 2016 to 2016
$2.4M
Systematic approaches to deciphering cis regulation of A-to-I RNA editingR01GM124215 · NIGMS · STANFORD UNIVERSITY · PI LI, JIN BILLY · 2017 to 2020
$1.7M
NIGMS NIH HHS DP2 GM123485NIGMS NIH HHS R01 GM102484NIGMS NIH HHS R01 GM124215
6 · The paper itself

Abstract

Adenosine-to-inosine (A-to-I) RNA editing catalyzed by ADAR enzymes occurs in double-stranded RNAs. Despite a compelling need towards predictive understanding of natural and engineered editing events, how the RNA sequence and structure determine the editing efficiency and specificity (i.e., cis-regulation) is poorly understood. We apply a CRISPR/Cas9-mediated saturation mutagenesis approach to generate libraries of mutations near three natural editing substrates at their endogenous genomic loci. We use machine learning to integrate diverse RNA sequence and structure features to model editing levels measured by deep sequencing. We confirm known features and identify new features important for RNA editing. Training and testing XGBoost algorithm within the same substrate yield models that explain 68 to 86 percent of substrate-specific variation in editing levels. However, the models do not generalize across substrates, suggesting complex and context-dependent regulation patterns. Our integrative approach can be applied to larger scale experiments towards deciphering the RNA editing code.

Indexed as

Adenosine DeaminaseAlgorithmsBase SequenceClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9HEK293 CellsHumansMachine LearningModels, GeneticMutagenesisMutationNucleic Acid ConformationRegulatory Sequences, Nucleic AcidRNARNA EditingSubstrate SpecificityAdenosine DeaminaseCRISPR-Associated Protein 9RNA

Identifiers

PMID33846332
PMCPMC8041805
OpenAlexW3156328581

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.