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Multimodal single cell analyses reveal mechanisms of perianal fistula in diverse Crohn’s disease [scRNA-seq]

GSE260842 Homo sapiens (human) Single-cell RNA-seq 34 samples Submitted 2024/05/16 Platform GPL24676
At a glance

Single-cell RNA-seq · human · 34 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism
Homo sapiens (human)
Samples
34 samples: 34 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
Multimodal single-cell analyses reveal mechanisms of perianal fistula in diverse patients with Crohn's diseaseMed (New York, N.Y.) · 2024
Summary (written by the submitters)
Crohn’s disease (CD) is a chronic inflammatory condition that can affect any part of the gastrointestinal tract. African ancestry (AA) populations have been substantially under-represented in genome-wide association studies (GWAS) of CD and inflammatory bowel disease (IBD), reflecting in part the lower prevalence of CD in AA compared to European ancestry (EA) populations.
Read the full summary ↓
Importantly, CD complicated by perianal fistulae has been found to be more prevalent and severe in African-ancestry patients. Perianal fistulae arise from the distal rectal mucosa and can course to a cutaneous surface, resulting in highly morbid complications. Monoclonal antibodies against anti-TNF are the mainstay of treatment, but recurrence and secondary loss-of-response is common. In severe, uncontrolled cases, complete proctectomy is required. The intestine is unique among adult tissues in that under homeostasis, residential macrophages are continually replenished from recruited blood monocytes. In EA cohorts, we established that chronic monocyte cultures stimulated with NOD2 agonists result in aberrant myeloid-stromal differentiation stratified by risk allele carrier status. NOD2 risk alleles are not associated with perianal fistulae; African-American patients with CD do not carry them (except via recent European ancestry admixture). There is no direct association between known CD GWAS risk loci and the risk of developing perianal fistula. Here, we present direct ex-vivo, single cell multiomic analyses of colorectal tissues and perianal fistulous tracts in AA and EA cases to define mechanisms of perianal fistula development. We implicate myeloid-stromal crosstalk and define cell subtypes using single cell RNA (scRNASeq), ATAC sequencing, and chronic, unstimulated monocyte cultures. Transcription factor motifs and ATAC signals co-localized with fine-mapped GWAS loci provide insight to cell-specific and transcriptional network regulation.
Published in
Multimodal single-cell analyses reveal mechanisms of perianal fistula in diverse patients with Crohn's disease
Levantovsky RM, Tastad C, Zhang J et al. · Med (New York, N.Y.) 2024 · PMID 38663404 · doi:10.1016/j.medj.2024.03.021
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 GSE260842_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1083604 and SRA study SRP493276. Searching any of these in the dataset finder brings you back here.

Study design
34 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 34 sample titles: 34 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
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