P084 Ileal gene expression changes are associated with colonic disease activity in patients with ulcerative colitis
Bibliographic record
Abstract
ulcerative colitis (UC) is a chronic, relapsing disorder characterised by inflammation limited to the colon and rectum. From a pathophysiologic point of view, there is no explanation for the spatial restriction of inflammation, and studies on the involvement of ileal changes in patients with UC are scarce. Here we therefore aimed to investigate gene expression profiles of the unaffected ileum of UC patients, and compare these to non-IBD controls to see whether these factors contribute to disease perpetuation. Biopsies were collected from normal terminal ileum of 16 patients with UC (50% male, median [interquartile range, IQR] age 49.5 [29.4–66.7] years, median [IQR] disease duration 11 [7–15.5] years, Montreal disease extent 1 E1/8 E2/7 E3); and 14 controls (42.9% male, age 56.7 [45.7–60.6] years) who underwent endoscopy for polyp screening. Patients with backwash ileitis were excluded. Disease activity for UC was based on endoscopic findings, with active disease defined as Mayo endoscopic subscore ≥2. Next-generation single-end sequencing was performed using the Illumina HiSeq 4000 NGS platform. One sample was removed from analysis due to suboptimal read counts. Differential expression analysis was performed using DESeq. One-fourth of UC patients had active colonic disease at the time the biopsy was taken. Comparative analyses of gene expression levels between active UC patients and controls identified seven genes with significant different expression (false discovery rate (FDR) ≤0.1 and fold change (FC) ≥2). The top signals were seen for MUC4 which was significantly upregulated (FC=3.89, FDR = 0.01), and FAM21B which was significantly downregulated (FC = 0.06, FDR = 0.05) in ileum of active UC compared with controls. All other significant genes were upregulated (CEACAM20, CASP10, LRG1, PDZK1IP1, and GRAMD2). Pathway analysis showed association with antiviral innate immunity and apoptosis signalling. When comparing ileal samples from inactive UC patients with controls, however, we did not observe any differentially expressed genes after adjustment for multiple testing. Also among UC patients, no differentially expressed genes were seen for those with active colonic disease vs. those without. Our study showed that—while no overt inflammation is generally seen in ileum of UC patients—subtle ileal gene expression changes do occur in patients depending on disease activity of the colon. The identified genes are involved in a range of UC-associated biological processes, including barrier function, cell trafficking, apoptosis, angiogenesis, and immune signalling. Whether ileal changes in these processes should be seen as a driving factor in UC or secondary epiphenomenon remains to be confirmed with functional studies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".