A161 MUCOSAL TRANSCRIPTOMICS IN NON-INFLAMED ILEUM OF CROHN’S DISEASE PATIENTS SHOWS DIFFERENTIALLY EXPRESSED GENE PROFILE COMPARED TO ILEUM OF HEALTHY CONTROLS
Bibliographic record
Abstract
Abstract Background The terminal ileum is the most susceptible location to develop Crohn’s disease (CD) and therefore is a valuable tissue to investigate biological mechanisms underlying chronic inflammation. Gene expression is highly affected by the level of inflammation, however, data on ileal transcriptomic profile in the absence of active inflammation is limited. Aims To investigate the ileal mucosal transcriptomic profile of CD patients in endoscopic and histologic remission compared to healthy controls (HC). Methods Ileal biopsies were collected during colonoscopy from patients with CD and HC. Biopsies were classified as non-inflamed based on endoscopic appearance and histologic criteria. Endo-histologic remission (EHR) was defined as simple endoscopic score < 3 and absence of active histologic inflammation. We included CD patients with EHR and HC for the analysis of this study. CD phenotype was divided into isolated colonic CD (cCD) that included Montreal L2 and ileal predominant CD (iCD) that included Montreal L1 and L3. Total RNA was extracted from samples, sequenced using a HiSeq 2500 instrument (Illumina, San Diego, CA, USA) and differential expression analysis was performed in EdgeR. Genes that were differentially expressed at the average of 2-fold-change (FC) in mean expression and False Discovery Rate (FDR) < 0.05 were considered significant. Results Ileal samples from 14 CD patients in EHR and 29 HC were included in the analysis. CD patients were significantly younger (median age 28.5 years, interquartile range (IQR)=24–40) compared with HC (median age 56 years, IQR=51–64). There were no differences in gender distribution (42.9% males in CD and 55.2% males in HC). We found 101 differentially expressed genes in CD patients compared to HC (99 genes were up-regulated and two were down-regulated). Dual oxidase 2 (DUOX2) and complement C6 were respectively the most significant up-regulated (logFC=4.45, FDR=1.3e-8) and down-regulated (logFC=-2.73, FDR=0.0006) genes in non-inflamed ileum CD group when compared with HC. In a subgroup analysis comparing ileal samples of CD patients with cCD (n=8) versus iCD phenotype (n=6), no differentially expressed genes were identified. Conclusions The mucosal transcriptomic profile of patients with inactive endoscopic and histologic ileal CD shows significant differentially expressed gene profile compared to ileal mucosa of HC. The clinical relevance of these findings should be further investigated. Funding Agencies IBD Genetics Consortium
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| 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".