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A multiomic analysis of Waldenström macroglobulinemia defines distinct disease subtypes

GSE296167 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 26 samples Submitted 2025/05/02 Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 26 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Topic
Waldenström macroglobulinaemiaThis series is part of our curated briefing on it.
Samples
26 samples: 6 conditions, mostly with about 6 replicates eachGroups 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
A multiomic analysis of Waldenström macroglobulinemia defines distinct disease subtypesBlood · 2025
Summary (written by the submitters)
We carried out a single-cell (sc) multiomic analysis on a series of MYD88 mutated Waldenström macroglobulinemia (WM) cases and identified two distinct subtypes of disease, memory B-cell-like (MBC-like) and plasma cell-like (PC-like), based on their expression of key lineage defining genes. Biologically, the subtypes are characterized by their variable capacity to differentiate fully towards a plasma cell (PC) and exhibit unique transcriptomic, chromatin accessibility, and genomic profiles.
Read the full summary ↓
The MBC-like subtype is unable to differentiate beyond the memory B-cell (MBC) stage, upregulates key MBC genes, and is characterized by upregulated BCR and AKT/mTOR signaling. In contrast, the PC-like subtype can partially differentiate towards a PC, upregulates key PC genes, has enhanced NF-kB signaling, and has an upregulated unfolded protein response. Pseudotime trajectory analysis of combined scRNA-sequencing and scATAC-sequencing supports the variable differentiation capacity of each subtype and implicate key transcription factors SPI1, SPIB, BCL11A, and XBP1 in these features. The existence and generalizability of the two disease subtypes were validated further using hierarchical clustering of bulk RNA-seq data from a secondary set of cases. The biological significance of the subtypes was further established using whole genome sequencing, where it was shown that CXCR4, NIK, and ARID1A mutations occur predominantly in the MBC-like subtype and 6q deletions in the PC-like subtype. We conclude that the variable differentiation blockade seen in WM manifests itself clinically as two disease subtypes with distinct epigenetic, mutational, transcriptional, and clinical features with potential implications for WM treatment strategies.
Published in
A multiomic analysis of Waldenström macroglobulinemia defines distinct disease subtypes
Gagler DC, Ghamlouch H, Zhang D et al. · Blood 2025 · PMID 40332467 · doi:10.1182/blood.2024028164
This dataset
Open GSE296167 in finder → Find more human ChIP / ATAC / CUT&Tag datasets → Waldenström macroglobulinaemia landscape →
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.

Series matrix ↓
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 GSE296167_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
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.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1258074 and SRA study SRP582767. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40332467) ↗
Study design
6 conditions, mostly with about 6 replicates each
sorted B-cells, scATAC-seq from individual pa… ×6 sorted B-cells, scRNA-seq from individual pat… ×6 sorted B-cells, scATAC-seq from individual pa… ×5 sorted B-cells, scRNA-seq from individual pat… ×4 sorted B-cells, scATAC-seq from individual pa… ×2 sorted B-cells, scRNA-seq from individual pat… ×2 sorted B-cells, scRNA-seq from individiual pa… ×1

Supports a between-group comparison across 25 samples.

How we read this: 6 replicated groups read from 26 sample titles; they account for 25 of them. 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
More Waldenström macroglobulinaemia datasets

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