Evidence map›Paper›PMID 41094691›Full record

ArticleGenome medicine2025

Epigenetic profiles of tissue informative CpGs inform ALS disease status and progression.

Christa Caggiano, Marco Morselli, Xiaoyu Qian, Barbara Celona, Michael J Thompson, Shivangi Wani, Anela Tosevska, Kodi Taraszka, Galen Heuer, Shyuan T Ngo and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–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

3 citing papers in PubMed.

  1. Article
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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

26 authors.

Christa Caggiano *Department of Neurology, UCLA, Los Angeles, CA, USA. christa@ucla.edu.
Marco Morselli *Department of Molecular, Cell, and Developmental Biology, UCLA, Los Angeles, CA, USA.
Xiaoyu QianInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Barbara CelonaCardiovascular Research Institute, UCSF, San Francisco, CA, USA.
Michael J ThompsonDepartment of Neurology, UCLA, Los Angeles, CA, USA.
Shivangi WaniInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Anela TosevskaDepartment of Molecular, Cell, and Developmental Biology, UCLA, Los Angeles, CA, USA.
Kodi TaraszkaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Galen HeuerComputational and Systems Biology Interdepartmental Program, UCLA, Los Angeles, California, USA.
Shyuan T NgoAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia.
Frederick J SteynSchool of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
Peter J NestorQueensland Brain Institute, University of Queensland, Brisbane, Australia.
Leanne WallaceInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Pamela McCombeDepartment of Neurology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Susan HeggieDepartment of Neurology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Kathryn ThorpeDepartment of Neurology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Caitlin McElligottMater Public Hospital, Brisbane, Australia.
Gemyka EnglishInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Anjali HendersInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Robert HendersonDepartment of Neurology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Catherine Lomen-HoerthDepartment of Neurology, UCSF, San Francisco, California, USA.
Naomi R WrayInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Allan F McRaeInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Matteo PellegriniDepartment of Molecular, Cell, and Developmental Biology, UCLA, Los Angeles, CA, USA.
Fleur C Garton *Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Noah Zaitlen *Department of Neurology, UCLA, Los Angeles, CA, USA. nzaitlen@ucla.edu.

Funding

A Comprehensive Protocol for Tissue of Origin Prediction in Circulating Cell-Free DNAF31NS122538 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CAGGIANO, CHRISTA · 2021 to 2022
$76k
NINDS NIH HHS F31 NS122538
6 · The paper itself

Abstract

backgroundCell-free DNA (cfDNA), derived from dying cells, has demonstrated utility across multiple clinical applications. However, its potential in neurodegenerative diseases remains underexplored, with most existing cfDNA technologies tailored to specific disease contexts like cancer or non-invasive prenatal screening.

methodsTo address this gap, we developed a novel approach to characterize epigenetic cfDNA profiles by identifying key regions of DNA methylation that reveal the tissues origins undergoing apoptosis or necrosis. We evaluated this method in the largest cfDNA study of amyotrophic lateral sclerosis (ALS) and other neurological diseases (OND) to date, encompassing two independent cohorts (n = 192) from Australia (UQ N

resultsOur approach accurately distinguished ALS patients from controls (UQ AUC = 0.82, UCSF AUC = 0.99) and from individuals with other neurological diseases (AUC = 0.91). It also identified an asymptomatic carrier of a pathogenic C9orf72 variant, and strongly correlated with ALS disease progression measures (Pearson's R = 0.66, p = 3.71 × 10⁻⁹).

conclusionsWe identified DNA methylation signals from multiple tissue types in ALS cfDNA, highlighting diverse tissue involvement in ALS pathology. These findings promote epigenetic cfDNA analysis as a powerful tool for advancing our understanding of neurodegenerative disease.

Indexed as

Amyotrophic Lateral SclerosisCpG IslandsDNA MethylationEpigenesis, GeneticAdultAgedC9orf72 ProteinCell-Free Nucleic AcidsDisease ProgressionFemaleHumansMaleMiddle AgedOrgan SpecificityC9orf72 ProteinC9orf72 protein, humanCell-Free Nucleic AcidsCell-free DNAEpigeneticsNeurodegeneration

Identifiers

PMID41094691
PMCPMC12529837

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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.