Rewiring of Transcription Factor Binding: Another Piece of the Intricate Puzzle of IBD Pathogenesis
Bibliographic record
Abstract
Whatever stimuli come from the global environment (the exposome), being they exogenous like microbial, dietary, and chemical ones, or endogenous, like genetic, metabolic, biochemical, and physical ones, the body reacts by setting in motion an intricate cascade of cellular, molecular, and signaling events that culminate with gene regulation (activation or suppression) and the transcription-mediated production of bioactive molecules. These events occur both in physiological as well as pathological conditions, and represent fundamental steps that maintain health or mediate disease. Each of these steps is multifactorial, complex, and biologically indispensable, but this commentary will discuss primarily the regulation of gene expression and the consequences for inflammatory bowel disease (IBD). The pathogenesis of IBD is highly complex on its own and is currently believed to result from the integration of environmental, genomic, microbial, and immune factors. As a chronic inflammatory condition, it is easy to envision that a multitude of genes are deregulated in IBD at both the systemic and intestinal level, but it is still unclear which are the primary or secondary drivers of this modulation, and which ones actually mediate disease. However, regardless of the primary or secondary nature of the gene modulation process, the basic steps and components involved in this process are basically the same. Unfortunately, the investigation of these steps has been relatively limited in IBD, particularly in regard to upstream events, as the vast majority of studies have been focused on downstream events and how to block the resulting pro-inflammatory products for justifiable therapeutic purposes. This focused but skewed approach to IBD has left large gaps in our understanding of the molecular underpinnings of ulcerative colitis (UC) and Crohn’s disease (CD), and particularly the factors that regulate and control gene expression.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.004 |
| Scholarly communication | 0.003 | 0.005 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.005 | 0.009 |
| Insufficient payload (model declined to judge) | 0.003 | 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".