Bibliographic record
Abstract
The accurate control of when and where genes are expressed is central to our understanding of development and disease. Elucidating the mechanisms that control this complex, multifaceted process is a major endeavor at the forefront of genetics and genome biology. The acute phase response (APR) is an evolutionarily conserved systemic response to inflammation that triggers rapid gene expression changes in the liver and other tissues. Genes induced during the APR are regulated via unique mechanisms that facilitate their rapid expression upon stimulation while maintaining their silencing under basal conditions. To dissect the mechanisms controlling APR gene expression, I employ a combination of epigenetic profiling, comparative genomics, and chromatin conformation capture to characterize the cis-regulation of a representative APR gene, PLAU. I investigate how PLAU is dysregulated in Quebec platelet disorder, a bleeding disorder in which a single tandem-duplication of PLAU causes its ectopic >100-fold overexpression in platelets and megakaryocytes. I demonstrate that the silencing of PLAU is normally facilitated by local 3-dimensional (3D) chromatin architecture which isolates it from the activity of nearby tissue-specific enhancers, while disruption of this architecture in QPD results in ectopic activation of PLAU by a conserved megakaryocyte enhancer. Employing a similar multi-omics approach, I investigate genome-wide transcriptional and epigenetic changes during the APR in the context of 3D chromatin architecture in the mouse liver. I demonstrate that enhancer-gene pairs within the same chromatin loop are more likely to show concordant changes in gene expression than equidistant genes in different domains, together illustrating a paradigm in which 3D chromatin architecture coordinates both the activation and silencing of acute-phase gene expression.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".