Evidence map›Paper›PMID 38116123›Full record

ArticleCell genomics2023

Single-cell methylation analysis of brain tissue prioritizes mutations that alter transcription.

Jonathan Flint, Matthew G Heffel, Zeyuan Chen, Joel Mefford, Emilie Marcus, Patrick B Chen, Jason Ernst, Chongyuan Luo

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 24% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Epigenomic insights into common human disease pathology.Cellular and molecular life sciences : CMLS · 2024
    Review
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

8 authors at 3 institutions in 1 country.

Jonathan FlintDepartment of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: jflint@mednet.ucla.edu.
Matthew G HeffelDepartment of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Zeyuan ChenDepartment of Computer Science, Samueli School of Engineering, University of California Los Angeles, Los Angeles, CA, USA.
Joel MeffordDepartment of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Emilie MarcusDepartment of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Patrick B ChenDepartment of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
Jason ErnstDepartment of Computer Science, Samueli School of Engineering, University of California Los Angeles, Los Angeles, CA, USA; Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Chongyuan LuoDepartment of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
University of California, Los Angeles · USSamueli Institute · USNeurobehavioral Systems · US

Funding

Training Grant in Neurobehavioral GeneticsT32NS048004 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, OPHOFF, ROEL A · 2004 to 2025
$5.8M
Spatiotemporal epigenomic and chromosomal architectural cell atlas of developing human brainsU01MH130995 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Chongyuan Luo, Mercedes Paredes · 2022 to 2026
$4.4M
SINGLE-CELL MULTI-OMIC APPROACHES TO MECHANISTICALLY CHARACTERIZE PSYCHIATRIC DISORDER RISK LOCI IN THE HUMAN BRAINR01MH125252 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUO, CHONGYUAN · 2021 to 2025
$3.7M
Developing a Pathway from Genetic Locus to Gene for Complex Traits in RodentsR01MH115979 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FLINT, JONATHAN · 2018 to 2022
$3.5M
Deciphering the Relationship between Substance Use and Psychiatric Disorders from Whole Genome Sequencing DataDP1DA044371 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ERNST, JASON · 2017 to 2021
$2.3M
NIDA NIH HHS DP1 DA044371NIMH NIH HHS R01 MH115979NIMH NIH HHS R01 MH125252NIMH NIH HHS U01 MH130995NINDS NIH HHS T32 NS048004
6 · The paper itself

Abstract

Relating genetic variants to behavior remains a fundamental challenge. To assess the utility of DNA methylation marks in discovering causative variants, we examined their relationship to genetic variation by generating single-nucleus methylomes from the hippocampus of eight inbred mouse strains. At CpG sequence densities under 40 CpG/Kb, cells compensate for loss of methylated sites by methylating additional sites to maintain methylation levels. At higher CpG sequence densities, the exact location of a methylated site becomes more important, suggesting that variants affecting methylation will have a greater effect when occurring in higher CpG densities than in lower. We found this to be true for a variant's effect on transcript abundance, indicating that candidate variants can be prioritized based on CpG sequence density. Our findings imply that DNA methylation influences the likelihood that mutations occur at specific sites in the genome, supporting the view that the distribution of mutations is not random.

Indexed as

hippocampusinbred mouse strainsmethylationvariant function

Identifiers

PMID38116123
PMCPMC10726494
OpenAlexW4389298516

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.