Evidence map›Paper›PMID 38043319›Full record

SynthesisEnvironment international2024

Systematic transcriptome-wide meta-analysis across endocrine disrupting chemicals reveals shared and unique liver pathways, gene networks, and disease associations.

Zacary Zamora, Susanna Wang, Yen-Wei Chen, Graciel Diamante, Xia Yang

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Environment international, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

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

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Integrating network analysis and machine learning to elucidate chemical-induced pancreatic toxicity in zebrafish embryos.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Article
  6. Article
  7. 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

5 authors.

Zacary ZamoraMolecular Toxicology Interdepartmental Program, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Integrative Biology and Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Susanna WangDepartment of Integrative Biology and Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Yen-Wei ChenMolecular Toxicology Interdepartmental Program, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Integrative Biology and Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Graciel DiamanteDepartment of Integrative Biology and Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. Electronic address: gdiam001@ucla.edu.
Xia YangMolecular Toxicology Interdepartmental Program, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Integrative Biology and Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. Electronic address: xyang123@ucla.edu.

Funding

Systems Genetics Dissection of Non-alcoholic SteatohepatitisR01DK117850 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Aldons Jake Lusis · 2019 to 2026
$4.6M
Training in Molecular ToxicologyT32ES015457 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ALLARD, PATRICK, HANKINSON, OLIVER NMN · 2008 to 2025
$4.0M
NIDDK NIH HHS R01 DK117850NIEHS NIH HHS T32 ES015457
6 · The paper itself

Abstract

Cardiometabolic disorders (CMD) are a growing public health problem across the world. Among the known cardiometabolic risk factors are compounds that induce endocrine and metabolic dysfunctions, such as endocrine disrupting chemicals (EDCs). To date, how EDCs influence molecular programs and cardiometabolic risks has yet to be fully elucidated, especially considering the complexity contributed by species-, chemical-, and dose-specific effects. Moreover, different experimental and analytical methodologies employed by different studies pose challenges when comparing findings across studies. To explore the molecular mechanisms of EDCs in a systematic manner, we established a data-driven computational approach to meta-analyze 30 human, mouse, and rat liver transcriptomic datasets for 4 EDCs, namely bisphenol A (BPA), bis(2-ethylhexyl) phthalate (DEHP), tributyltin (TBT), and perfluorooctanoic acid (PFOA). Our computational pipeline uniformly re-analyzed pre-processed quality-controlled microarray data and raw RNAseq data, derived differentially expressed genes (DEGs) and biological pathways, modeled gene regulatory networks and regulators, and determined CMD associations based on gene overlap analysis. Our approach revealed that DEHP and PFOA shared stable transcriptomic signatures that are enriched for genes associated with CMDs, suggesting similar mechanisms of action such as perturbations of peroxisome proliferator-activated receptor gamma (PPARγ) signaling and liver gene network regulators VNN1 and ACOT2. In contrast, TBT exhibited highly divergent gene signatures, pathways, network regulators, and disease associations from the other EDCs. In addition, we found that the rat, mouse, and human BPA studies showed highly variable transcriptomic patterns, providing molecular support for the variability in BPA responses. Our work offers insights into the commonality and differences in the molecular mechanisms of various EDCs and establishes a streamlined data-driven workflow to compare molecular mechanisms of environmental substances to elucidate the underlying connections between chemical exposure and disease risks.

Indexed as

Cardiovascular DiseasesDiethylhexyl PhthalateEndocrine DisruptorsPhenolsAnimalsBenzhydryl CompoundsBisphenol A CompoundsGene Expression ProfilingGene Regulatory NetworksHumansLiverMiceRatsTranscriptomeBenzhydryl Compoundsbisphenol ABisphenol A CompoundsDiethylhexyl PhthalateEndocrine DisruptorsPhenolsCardiometabolic diseaseEndocrine disrupting chemicalsLiverMeta-analysisNetwork analysisTranscriptome

Identifiers

PMID38043319
PMCPMC11216742

What OpenQuestion holds

Textmetadata
LicenceTDM
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.