Foundry120 atlas

← IBD spatial transcriptomics

Single-cell single-molecule spatial transcriptomics using CosMx on colectomy specimens collected during Pouch surgery in IBD patients.

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Dataset overview

Participants 8
Samples 8
Reuse readiness 7.1/10 evidence-backed score

Histopathologic Evaluation and Single-Cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients with Inflammatory Bowel Disease.

Olivas AD, Ngai PCM, Schahrer E, Olortegui KS, Cursio JF, Akiyama S, Chang EB, Shen L, et al. · bioRxiv : the preprint server for biology · 2025

Abstract

<h4>Background and aims</h4>Total abdominal colectomy (TAC) with a staged ileal pouch-anal anastomosis (IPAA) is a common surgical treatment for ulcerative colitis (UC). However, a significant percentage of patients experience pouch failure, leading to morbidity. This retrospective case-control study identified histopathological features of the TAC specimen associated with pouch failure and investigated the molecular mechanisms of this susceptibility using single-cell spatial transcriptomics.<h4>Methods</h4>We analyzed a cohort of 417 patients who underwent IPAA between 2000-2010 at the University of Chicago Medical Center for up to 18 years. Histological examination of TAC specimens focused on disease activity, depth of inflammation, and specific features, including granulomas and deep ulcers. A subset of patients was profiled using single-cell spatial transcriptomics to map gene expression and immune cell interactions in relation to the risk of pouch failure.<h4>Results</h4>The 18-year pouch failure risk was 23%, with post-procedure diagnosis of CD as a major risk factor (HR = 4.3, 95% CI: 2.3-8.1) as well as high-risk histologic features, including deep chronic inflammation (HR = 21, 95% CI: 11-41) and severe disease activity (HR = 14, 95% CI: 5.7-32) in TAC specimens. Spatial transcriptomics showed immune infiltration of T and myeloid cells, reduced myocyte-glial interactions, and cytokine signaling pathways such as IL-10, IL-1β, and type I/II interferons, associated with an increased risk of pouch failure.<h4>Conclusion</h4>Histological features and spatial molecular profiling are predictive of IPAA failure. These findings support the use of histologic evaluation and targeted molecular analysis of the TAC specimen to identify high-risk patients and improve IPAA outcomes.

doi:10.1101/2025.01.27.635092 ↗ PMID 39974918 ↗ PMC11838289 ↗

Study facts

Organism
Homo sapiens
Platform
NanoString CosMx Spatial Molecular Imager
Age group
adult
Disease groups
Ulcerative colitis
Anatomical sites
Left colon, failure, Left colon, non-failure

Data availability

  • Raw counts
  • Processed matrix
  • Analysis code

File types CSVTXT

Strengths & limitations for reuse

Strengths

  • Raw counts are advertised
  • Processed matrices are advertised
  • Analysis code is available
  • Participant counts are documented

Limitations

  • Not documented: spatial coordinates are advertised
Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

FieldValueEvidence
assay.number_of_cells_or_spots 352531
After quality control analysis, 352,531 cells were profiled

Section Single-cell spatial transcriptomics results, offset 18100
assay.panel_size 994 inferred
a 1K Human Universal Panel (974 genes) and a 20-gene custom panel

Section Sample Processing, offset —
assay.platform NanoString CosMx Spatial Molecular Imager
Samples were processed on the CosMx instrument

Section Sample Processing, offset 11200
assay.resolution cellular
single-cell resolution of gene expression across entire tissue sections (CosMx)

Section Introduction, offset 4000
assay.segmentation_method CellPose
Cells were segmented using CellPose

Section Data processing and analysis, offset 12700
assay.sequencing_based False inferred
spatial transcriptomics that enable single-molecule RNA detection and single-cell resolution

Section Introduction, offset 4000
assay.whole_transcriptome False
using a 1K Human Universal Panel (974 genes) and a 20-gene custom panel

Section Sample Processing, offset 11200

Cohort

FieldValueEvidence
cohort.age_group adult from source
GEO age characteristics: 46; 35; 18; 46; 36; 44; 31; 31

Section GEO family SOFT, offset —
cohort.disease_activity_metadata_available True
"severity_score": "severely active"

Section samples.characteristics, offset —
cohort.study_design longitudinal
This study followed a longitudinal University of Chicago cohort for up to 18 years.

Section Discussion, offset —
cohort.total_participants 8
"n_samples": 8

Section geo_record_summary, offset —
cohort.treatment_response_metadata_available True
"pouch outcome": "failure"

Section geo_family_soft, offset 8500
cohort.ulcerative_colitis_participants 8
The samples were matched for activity, diagnosis of TAC specimen (all UC)

Section Single-cell Resolution Spatial Transcriptomics, offset 6880

Data_Assets

FieldValueEvidence
data_assets.analysis_code True
Bioinformatic code is published on GitHub

Section Data, analytic methods, and study materials availability, offset 22000
data_assets.file_manifest True
index.html

Section geo_document, offset —
data_assets.open_access True
Public on Feb 26 2025

Section geo_family_soft, offset —
data_assets.participant_metadata True
GSE283625_metadata.csv.gz

Section repository files, offset —
data_assets.processed_matrix True inferred
GSE283625_counts.csv.gz

Section geo_document, offset —
data_assets.raw_counts True
GSE283625_RAW.tar.gz

Section geo_document, offset —
data_assets.sample_metadata True
GSE283625_metadata.csv.gz

Section geo_document, offset —

Specimens

FieldValueEvidence
specimens.anatomical_sites ['Left colon, failure', 'Left colon, non-failure'] from source
GEO sample source names: Left colon, failure; Left colon, non-failure

Section GEO family SOFT, offset —
specimens.inflamed_status_available True
"severity_score": "severely active"

Section geo_family_soft, offset 8500
specimens.number_of_samples 8 computed
8 GSM records parsed from GEO family SOFT

Section GEO family SOFT, offset —
specimens.number_of_tissue_sections 8
Four histologically matched cross-sections from failure (F1–4) and four non-failure (NF1–4) cases were profiled using CosMx.

Section Single-cell Resolution Spatial Transcriptomics, offset 14750
specimens.preservation_method FFPE
Spatial transcriptomics was conducted on 8 FFPE colon samples

Section Sample Processing, offset 11200
specimens.specimen_type resection
we profiled TAC specimens from four pouch failure patients and four non-failure patients

Section Single-cell Resolution Spatial Transcriptomics, offset 6880