Comparative proteomics analysis of the mouse mini-gut organoid: insights into markers of gluten challenge from celiac disease intestinal biopsies.

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Such models of the intestinal epithelium can provide significant knowledge for the study of celiac disease and provide an additional context for the nature of markers observed from patient biopsy data.\nMethods: Using LC-MS/MS, the proteomes of the crypt and enterocyte-like states of a mouse mini-gut organoid model were measured. The data were further compared with published biopsy data by comparing the changes induced by gluten challenge after a gluten-free diet.\nResults and discussion: These analyses identified 4,850 protein groups and revealed how 400 putative biomarkers of dietary challenge were differentially expressed in the organoid model. In addition to the extensive changes within the differentiated cells, the data reiterated the disruption of the crypt-villus axis after gluten challenge. The mass spectrometry data are available via ProteomeXchange with the identifier PXD025690.", "claims": [{"id": "claim-method", "statement": "Statistical analyses were carried out for the medians of the technical replicates for the imputed data using the reproducibility-optimized test statistic (ROTS) (Elo et al., 2009).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39263374", "locator": "sections[6] \"2.4 LC–MS/MS data processing and statistical analysis\" paragraph 3", "quote": "Statistical analyses were carried out for the medians of the technical replicates for the imputed data using the reproducibility-optimized test statistic (ROTS) (Elo et al., 2009)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ebi.ac.uk/pride/archive/projects/PXD025690.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39263374", "locator": "sections[17] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ebi.ac.uk/pride/archive/projects/PXD025690."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ROTS analysis showed that crypt-like or undifferentiated intestinal markers were predominantly upregulated after gluten challenge, whereas differentiated enterocyte markers were predominantly downregulated.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39263374", "locator": "sections[12] \"3.2 Comparison with putative CD markers\" paragraph 2", "quote": "Overall, the comparison reiterated how the markers detected in the biopsies presented an increased abundance of proteins reflecting the undifferentiated, ENRC-like state and a decrease in proteins associated with the differentiated, ENRI-like state."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "ROTS analysis showed that crypt-like or undifferentiated intestinal markers were predominantly upregulated after gluten challenge, whereas differentiated enterocyte markers were predominantly downregulated.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39263374"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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