Bibliographic record
Abstract
Abstract G-quadruplexes and i -motifs are non-canonical secondary structures of DNA that act as conformational switches in controlling genomic events. Within the genome, G- and C-rich sequences with the potential to fold into G-quadruplexes and i -motifs are overrepresented in important regulatory domains, including, but not limited to, the promoter regions of oncogenes. We previously have shown that some promoter sequences can adopt coexisting duplex, G-quadruplex, i -motif, and coiled conformations; moreover, their distribution can be modelled as a dynamic equilibrium in which the fractional population of each conformation is determined by the sequence and local conditions. On that basis, we proposed a hypothesis in which the level of expression of a gene with G- and C-rich sequences in the promoter is regulated thermodynamically by fine-tuning the duplex-to-G-quadruplex ratio, with the G-quadruplex modulating RNA polymerase activity. Any deviation from the evolutionarily tuned, gene-specific distribution of conformers, such as might result from mutations in the promoter or a change in cellular conditions, may lead to under- or overexpression of the gene and pathological consequences. We now expand on this hypothesis in the context of supporting evidence from molecular and cellular studies and from biophysico-chemical investigations of oligomeric DNA. Thermodynamic control of transcription implies that G-quadruplex and i -motif structures in the genome form as thermodynamically stable conformers in competition with the duplex conformation. That is in addition to their recognized formation as kinetically trapped, metastable states within domains of single-stranded DNA, such as a transcription bubble or R-loop, that are opened in a prior cellular event.
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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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".