A Prospectively Created Living Organoid Biobank of Crohn’s Disease Patients Enables Integrative Therapeutics
Bibliographic record
Abstract
Abstract Adult stem cells from various organs can be propagated as epithelial organoids that not only retain their tissue identity, but also their genetic and epigenetic disease-driving traits. We report the establishment of Crohn’s Disease (CD) patient-derived organoid cultures (PDOs) using biopsied tissues from colons of 50 consecutive subjects representing all clinical subtypes (Montreal Classification B1–B3 and perianal disease). Organoids were also generated from healthy subjects. The spectrum of phenotypic and genotypic changes within the “living biobank” agrees well with many observations reported in CD tissues. Gene expression analyses show that despite the heterogeneity of clinical subtypes, there are two major molecular subtypes, each with unique phenotypic features: immune-deficient infectious-CD [IDICD] and senescence-induced fibrostenotic-CD [SIFCD]. CD-PDOs are amenable to high-throughput drug screens allowing for the detection of phenotype reversal. As examples, defective barrier integrity in B1-PDOs was restored with pre-/pro-biotics, impaired microbial clearance in IDICD was reversed using agonists for nuclear receptors, and SIFCD was rectified using senolytics and - morphics. Phenotyped-genotyped CD-PDOs may fill the gap between basic biology and patient trials by enabling pre-clinical Phase ‘0’ human trials for personalized and integrative therapeutics.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".