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Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy

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Dataset overview

Participants None
Samples None
Reuse readiness 4.3/10 evidence-backed score

Single-Cell Analysis of Crohn's Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy.

Martin JC, Chang C, Boschetti G, Ungaro R, Giri M, Grout JA, Gettler K, Chuang LS, et al. · Cell · 2019

Abstract

Clinical benefits of cytokine blockade in ileal Crohn's disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in four independent iCD cohorts (n = 441), and its presence at diagnosis correlated with failure to achieve durable corticosteroid-free remission upon anti-TNF therapy. These results emphasize the limitations of current diagnostic assays and the potential for single-cell mapping tools to identify novel biomarkers of treatment response and tailored therapeutic opportunities.

doi:10.1016/j.cell.2019.08.008 ↗ PMID 31474370 ↗ PMC7060942 ↗

Study facts

Organism
Homo sapiens
Platform
Illumina HiSeq 2000
Age group
paediatric
Disease groups
—
Anatomical sites
ileum

Data availability

  • Processed matrix

File types CSV

Strengths & limitations for reuse

Strengths

  • Processed matrices are advertised

Limitations

  • Not documented: raw counts are advertised
  • Not documented: cell metadata are advertised
  • Not documented: participant counts are documented
Extraction evidence & provenance

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

Assay

FieldValueEvidence
assay.library_chemistry TruSeq RNA Sample preparation
library preparation were performed using TruSeq RNA Sample preparation (Illumina)

Section samples, offset —
assay.platform Illumina HiSeq 2000
Illumina HiSeq 2000

Section samples, offset —
assay.reference_genome Gencode v23
Gencode v23 as the reference genome

Section samples, offset —

Cohort

FieldValueEvidence
cohort.age_group paediatric from source
GEO age characteristics: 6.6; A1a; 8.0; A1a; 9.2; A1a; 9.5; A1a; 10.4; A1b; 10.7; A1b; 11.8; A1b; 12.6; A1b; 12.8; A1b; 13.6; A1b; 13.8; A1b; 14.2; A1b; 14.3; A1b; 14.8; A1b; 14.8; A1b; 14.8; A1b; 15.4; A1b; 15.8; A1b; 15.8; A1b; 15.9; A1b; 16.9; A1b; 6.2; A1a; 6.3; A1a; 6.5; A1a; 7.2; A1a; 7.3; A1a; 7.6; A1a; 7.7; A1a; 7.9

Section GEO family SOFT, offset —
cohort.disease_activity_metadata_available True
"inflammation": "Histologically involved"

Section samples, offset —

Data_Assets

FieldValueEvidence
data_assets.open_access True
Public on Aug 21 2019

Section series.series_status, offset —
data_assets.participant_metadata True
"characteristics": {"gender": "Male", "tissue": "Ileal biopsy", "agedxyrs": "6.6", "location": "2", "diagnosis": "CD", "paris age": "A1a"}

Section samples, offset —
data_assets.processed_matrix True
GSE134881_RISKfpkmAll.csv.gz

Section series.series_supplementary_file, offset —

Processing

FieldValueEvidence
processing.normalization_method transcripts per million
with transcripts per million as the output

Section samples, offset —

Specimens

FieldValueEvidence
specimens.anatomical_sites ['ileum']
Ileal biopsy

Section samples, offset —
specimens.inflamed_status_available True
"inflammation": "Histologically involved"

Section samples, offset —
specimens.specimen_type biopsy
Ileal biopsy, J10352

Section samples, offset —