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Persistent gene expression and DNA methylation alterations linked to carcinogenic effects of dichloroacetic acid [RNA-seq]

GSE242661 Mus musculus (mouse) DNA methylation 78 samples Submitted 2024/04/29 Platform GPL17021
At a glance

DNA methylation · mouse · 78 samples

What it is
DNA methylationChemical marks on DNA that help switch genes on or off.
Organism
Mus musculus (mouse)
Samples
78 samples: 78 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Persistent gene expression and DNA methylation alterations linked to carcinogenic effects of dichloroacetic acidFrontiers in oncology · 2024
Summary (written by the submitters)
Mechanistic understanding of transient exposures that lead to adverse health outcomes will enhance our ability to recognize biological signatures of disease. Here, we measured the transcriptomic and epigenomic alterations due to exposure to the metabolic reprogramming agent, dichloroacetic acid (DCA). Previously, we showed that exposure to DCA increased liver cancer in B6C3F1 mice after continuous or early life exposures similarly over background level.
Read the full summary ↓
Measures from these studies did not support direct cytotoxic, mitogenic, or genotoxic modes-of-action of tumorigenesis. Using archived formalin-fixed liver samples, we utilized modern methodologies to measure gene expression and DNA methylation levels to link to previously generated phenotypic measures. Gene expression was measured by targeted RNA sequencing (TempO-seq 1500+ toxicity panel: 2754 total genes) in liver samples collected from 10-, 32-, 57-, and 78-week old mice exposed to deionized water (controls), DCA continuously at 3.5g/L in drinking water (“Direct” group), or DCA at 3.5g/L for 10-, 32-, or 57-weeks followed by control water (“Stop” groups). Genome-scaled alterations in DNA methylation were measured by Reduced Representation Bisulfite Sequencing (RRBS) at 78-weeks. Transcriptomic changes were most robust with concurrent or adjacent timepoints after exposure stoppage. DNA methylation alterations followed a similar pattern, measuring 2720 and 567 differentially methylated regions (DMRs) in 78-week Direct and 10-week “Stop” DCA exposure groups, respectively. Gene pathway analysis indicated cellular effects linked to increased oxidative metabolism, a primary mechanism of action for DCA, closer to exposure windows especially early in life. Conversely, many gene signatures and pathways reversed patterns later in life and reflected more pro-tumorigenic patterns for both current and prior DCA exposures. DNA methylation patterns linked to early gene pathway perturbations, suggesting persistence in the epigenome and possible regulatory effects. In total, results suggested that liver metabolic reprogramming effects of DCA interact with normal age mechanisms to increase tumor burden with both continuous and prior DCA exposure in the B6C3F1 rodent model.
Published in
Persistent gene expression and DNA methylation alterations linked to carcinogenic effects of dichloroacetic acid
Carswell G, Chamberlin J, Bennett BD et al. · Frontiers in oncology 2024 · PMID 38764585 · doi:10.3389/fonc.2024.1389634
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE242661_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: Look for beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1013984 and SRA study SRP459128. Searching any of these in the dataset finder brings you back here.

Study design
78 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 78 sample titles: 78 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 38 more — browse all 78 samples with per-sample file links →

Datasets on a similar topic

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