A155 MOLECULAR LANDSCAPE OF ULCERATIVE COLITIS AND CROHN’S DISEASE IS CONSERVED
Bibliographic record
Abstract
While disease-specific differences between IBD phenotypes are important, it is also of interest to see the conserved elements that reflect the response to injury shared by the phenotypes. To map the elements conserved between Ulcerative Colitis (UC) and ileal Crohn’s Disease (CD) we used microarrays to study the molecular landscape of 63 UC biopsies compared to 16 control colon biopsies, and 37 ileal CD biopsies compared to 7 control ileal biopsies. These comparisons were expressed as “molecular landscapes” using volcano plots of molecular association strength via p-value (x-axis) versus fold change (y-axis). The landscape of UC (Fig 1) was compared to that of ileal CD (Fig 2) for all 13709 interquartile-range filtered probe sets. We labeled transcripts of interest, including TNFalpha, calprotectin (S100A8 and S100A9), TNFalpha-inducible transcripts, inflammasome associated transcripts, IFNG-inducible transcripts, transcripts representing the response to injury (increased in UC and CD), and transcripts decreased in injured tissue (conserved epithelial genes associated with parenchymal function and metabolism). There was striking conservation between the molecular landscape of the two disease processes. In both UC and CD, TNF-alpha was interestingly only mildly increased in UC (Fold change= 1.2, P=NS) and CD (Fold change=2.4, P=0.02) compared to controls; however calprotectin (S100A8 and S100A9) was strongly induced in both UC (P=0.0006) and ileal CD (P=0.0001) but the fold change increase in CD was higher than that induced in UC (14x vs 4x). TNFalpha-inducible and inflammasome-associated transcripts were highly conserved across both UC and ileal CD. As expected, expression of inflammasome transcript NOD2 was only associated with CD (Fold change=2.7, P=0.003), but not in UC (P=NS). Epithelial transcripts were variably downregulated in both diseases, indicating the stereotyped dedifferentiation of the parenchyma. Analyses of specific differences between UC and ileal CD and of the most significantly up- and downregulated signals are currently being undertaken. We conclude that although one might expect UC and ileal CD would have different inflammatory profiles as they present with markedly different phenotypes and in different epithelia, the large-scale molecular changes are strikingly conserved. Calprotectin expression was high in UC and CD in keeping with its current use a fecal biomarker in both diseases. None
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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 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".