Evidence map›Paper›PMID 37404460›Full record

ArticleFrontiers in neuroscience2023

Hierarchical deconvolution for extensive cell type resolution in the human brain using DNA methylation.

Ze Zhang, John K Wiencke, Karl T Kelsey, Devin C Koestler, Annette M Molinaro, Steven C Pike, Prasoona Karra, Brock C Christensen, Lucas A Salas

Abstract read
In one paragraph

Article in Frontiers in neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

17 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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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

9 authors.

Ze ZhangDepartment of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, United States.
John K WienckeDepartment of Neurological Surgery, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, United States.
Karl T KelseyDepartment of Epidemiology, Department of Pathology and Laboratory Medicine, Brown University School of Public Health, Providence, RI, United States.
Devin C KoestlerDepartment of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, KS, United States.
Annette M MolinaroDepartment of Neurological Surgery, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, United States.
Steven C PikeDepartment of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, United States.
Prasoona KarraDepartment of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, United States.
Brock C ChristensenDepartment of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, United States.
Lucas A SalasDepartment of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, United States.

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Fred W Kolling IV · 1985 to 2026
$91.3M
Mentoring CoreP20GM103418 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI John A Stanford · 2012 to 2026
$63.0M
Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Susan M Chang · 2002 to 2026
$57.4M
Transgenic & Gene-Targeting Shared ResourceP30CA168524 · NCI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI ROY A. JENSEN · 2012 to 2026
$40.1M
Relation Between In-utero Vitamin D and Immune Function in Early Childhood P20GM104416 · NIGMS · DARTMOUTH COLLEGE · PI KARAGAS, MARGARET RITA · 2013 to 2022
$23.7M
Using Integrated Omics to Identify Dysfunctional Genetic Mechanisms Influencing Schizophrenia and Sleep DisturbancesP20GM130423 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Kalyani Pyaram, Steven Allan Soper · 2019 to 2026
$21.5M
Immune epigenetic biomarkers of survival in glioma epidemiologyR01CA207360 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WIENCKE, JOHN K. · 2017 to 2021
$3.8M
DNA-based Immune Phenotyping in HNSCC for Biomarkers of Response to ImmunotherapyR01CA253976 · NCI · BROWN UNIVERSITY · PI CHRISTENSEN, BROCK C, KELSEY, KARL TIMOTHY · 2021 to 2025
$3.3M
(PQ3) Immune epigenetic biomarkers of bladder cancer outcomesR01CA216265 · NCI · DARTMOUTH COLLEGE · PI CHRISTENSEN, BROCK CLARKE · 2017 to 2021
$2.9M
Metabolic health phenotype, accelerated aging and obesity-related cancer risk and mortalityK00CA264400 · NCI · DARTMOUTH COLLEGE · PI KARRA, PRASOONA · 2022 to 2024
$300k
NCI NIH HHS K00 CA264400NCI NIH HHS P30 CA023108NCI NIH HHS P30 CA168524NCI NIH HHS P50 CA097257NCI NIH HHS R01 CA207360NCI NIH HHS R01 CA216265NCI NIH HHS R01 CA253976NIGMS NIH HHS P20 GM103418NIGMS NIH HHS P20 GM104416NIGMS NIH HHS P20 GM130423
6 · The paper itself

Abstract

Introduction: The human brain comprises heterogeneous cell types whose composition can be altered with physiological and pathological conditions. New approaches to discern the diversity and distribution of brain cells associated with neurological conditions would significantly advance the study of brain-related pathophysiology and neuroscience. Unlike single-nuclei approaches, DNA methylation-based deconvolution does not require special sample handling or processing, is cost-effective, and easily scales to large study designs. Existing DNA methylation-based methods for brain cell deconvolution are limited in the number of cell types deconvolved. Methods: Using DNA methylation profiles of the top cell-type-specific differentially methylated CpGs, we employed a hierarchical modeling approach to deconvolve GABAergic neurons, glutamatergic neurons, astrocytes, microglial cells, oligodendrocytes, endothelial cells, and stromal cells. Results: We demonstrate the utility of our method by applying it to data on normal tissues from various brain regions and in aging and diseased tissues, including Alzheimer's disease, autism, Huntington's disease, epilepsy, and schizophrenia. Discussion: We expect that the ability to determine the cellular composition in the brain using only DNA from bulk samples will accelerate understanding brain cell type composition and cell-type-specific epigenetic states in normal and diseased brain tissues.

Indexed as

brain deconvolutionbrain heterogeneitydeconvolutionDNA methylationepigenetics

Identifiers

PMID37404460
PMCPMC10315586

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Registered trials

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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.