Evidence map›Paper›PMID 41040299›Full record

ArticlebioRxiv : the preprint server for biology2025

From Correlation to Causation: Cell-Type-Specific Gene Regulatory Networks in Alzheimer's Disease.

Danni Liu, Zhongli Jiang, Hyunjin Kim, Anke M Tukker, Ashish Dalvi, Junkai Xie, Yan Li, Chongli Yuan, Aaron B Bowman, Dabao Zhang and 1 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Danni LiuDepartment of Epidemiology and Biostatistics, University of California, Irvine, CA, 92617.ORCID 0000-0002-2863-0288
Zhongli JiangDepartment of Epidemiology and Biostatistics, University of California, Irvine, CA, 92617.
Hyunjin KimSchool of Health Sciences, Purdue University, West Lafayette, IN, 47907.
Anke M TukkerSchool of Health Sciences, Purdue University, West Lafayette, IN, 47907.
Ashish DalviCenter for Complex Biological Systems, University of California, Irvine, CA, 92617.
Junkai XieDavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47906.
Yan LiDepartment of Epidemiology and Biostatistics, University of California, Irvine, CA, 92617.
Chongli YuanDavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47906.
Aaron B BowmanSchool of Health Sciences, Purdue University, West Lafayette, IN, 47907.
Dabao ZhangDepartment of Epidemiology and Biostatistics, University of California, Irvine, CA, 92617.
Min ZhangDepartment of Epidemiology and Biostatistics, University of California, Irvine, CA, 92617.

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Modeling functional genomics of susceptibility to the persistent effects of environmental toxins in an elderly rural Indiana neurodegenerative cohortR01AG080917 · NIA · PURDUE UNIVERSITY · PI Aaron B Bowman, Chongli Yuan · 2022 to 2026
$4.1M
Modeling Homeostasis of Human Blood MetabolitesR01GM131491 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAFTERY, DANIEL, ZHANG, DABAO · 2020 to 2023
$2.2M
Human stem cell derived forebrain model to study persistent neurotoxic effects of trans-placental developmental exposures to environmental pollutantsK99ES036290 · NIEHS · PURDUE UNIVERSITY · PI TUKKER, ANKE MARIJE · 2024 to 2025
$251k
NCI NIH HHS P30 CA062203NIA NIH HHS R01 AG080917NIEHS NIH HHS K99 ES036290NIGMS NIH HHS R01 GM131491
6 · The paper itself

Abstract

introductionAlzheimer's disease (AD) involves complex regulatory disruptions across multiple brain cell types, yet a comprehensive understanding of the intracellular causal mechanisms remains unclear.

methodsWe presented an integrative analysis framework using single-nucleus transcriptomic with matched subject-level genotype data from 272 human AD in the Religious Orders Study and the Rush Memory and Aging Project (ROSMAP) study, and constructed causality-based, cell-type-specific gene regulatory networks (GRNs).

resultsOur method identifies regulatory genes from both transcription factors (TFs) and non-TFs, thereby capturing a complete and accurate causal regulatory map across different brain cell types. This work revealed both established and novel regulations, pathways, and cell-type-unique hub genes in AD. Beyond constructing transcriptome-wide GRNs, we quantitatively assessed hub genes and distinguished those with regulatory or responsive roles. DISCUSSION: Our study provides a comprehensive mapping of cell-type-specific causal GRNs in AD, providing a powerful resource for dynamic pathway exploration, hypothesis generation, and functional interpretation.

Indexed as

Alzheimer’s diseasecausalitycell-type-specificgene regulatory network

Identifiers

PMID41040299
PMCPMC12485798

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.