Microarray Analysis of Crohnʼs Disease and Correlation With Traditional Clinical and Histologic Features
Bibliographic record
Abstract
Introduction: As a T cell-mediated disease of the gastrointestinal epithelium, Crohn's disease (CD) is likely to share pathogenic elements with other T cell-mediated inflammatory diseases. Recently we showed that ulcerative colitis (UC) manifested large-scale molecular disturbances that correlated with endoscopic and histologic features(IBD 20: 2353, 2014). We hypothesized that ileal CD would manifest similar disturbance. Methods: We studied 27 patients in 31 biopsies with ileal CD, characterizing the clinical, endoscopic and histological features and defined the mRNA phenotype using microarray analysis of ileal biopsies. We measured the expression of pathogenesis-based transcript sets (PBTs) previously published for ulcerative colitis representing effector T cells, macrophages, IFNG effects, and parenchymal injury-repair response and dedifferentiation (table 1). The molecular features were then correlated with conventional assessments including clinical features (modified Harvey Bradshaw index(HBI), simple endoscopic score for CD(SES-CD), c-reactive protein, albumin) and histologic features (lamina propria neutrophilic and lymphoplasmacytic infiltrate, crypt abscess, ulcers present and crypt architectural distortion). Results: CD ileal biopsies arranged by injury-repair score (IRRAT) manifested coordinate transcript changes with IFNG-induced transcripts (GRIT), macrophage transcripts (QCMAT), and injury-repair transcripts increasing while parenchymal transcripts (PT) decreased (figure 1). Lymphoplasmacytic infiltrate was significantly correlated with IRRAT (P=0.005) and negatively correlated with parenchymal transcript expression (P=0.01). Neutrophilic lamina propria infiltrate (p=0.03) and number of ulcers (p=0.03) also correlated with IRRAT. No significant correlation was seen between the molecular features and the HBI (P=0.5), SES-CD(P=0.8) or CRP (0.2).Figure 1Table 1: Pathogenesis-based transcript sets (PBTs)Conclusion: The molecular phenotype of CD manifests a large-scale coordinate disturbance similar to that in UC and other T cell-mediated diseases, reflecting changes in inflammatory cells and parenchymal elements and correlating with histologic assessment, especially the lymphoplasmacytic and neutrophilic lamina propria infiltrate, but not with the clinical and endoscopic features. This raises further questions about our clinical and endoscopic assessments of CD. Novel molecular systems for quantitating and staging the disease elements in the tissues in CD may add a significant new dimension to patient management beyond our current standards.
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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 | 0.001 |
| 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".