Exploring Nucleobase Modifications in Oligonucleotide Analogues for Use as Environmentally Responsive Fluorophores and Beyond
Bibliographic record
Abstract
Over the past two decades, it has become abundantly clear that nucleic acid biochemistry, especially with respect to RNA, is more convoluted and complex than previously appreciated. Indeed, the application and exploitation of nucleic acids beyond their predestined role as the medium for storage and transmission of genetic information to the treatment and study of diseases has been achieved. In other areas of endeavor, utilization of nucleic acids as a probe molecule requires that they possess a reporter group. The reporter group of choice is often a luminophore because fluorescence spectroscopy has emerged as an indispensable tool to probe the structural and functional properties of modified nucleic acids. The scope of this review spans research done in the Hudson lab at The University of Western Ontario and is focused on modified pyrimidine nucleobases and their applications as environmentally sensitive fluorophores, base discriminating fluorophores, and in service of antisense applications as well as tantalizing new results as G-quadruplex destabilizing agents. While this review is a focused personal account, particularly influential work of colleagues in the chemistry community will be highlighted. The intention is not to make a comprehensive review, citations to the existing excellent reviews are given, any omission of the wonderful and impactful work being done by others globally is not intentional. Thus, this review will briefly introduce the context of our work, summarize what has been accomplished and finish with the prospects of future developments.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".