Bibliographic record
Abstract
The vast majority of deoxyribozyme-based sensors are designed using modified RNA-cleaving deoxyribozymes and detect analytes that act as allosteric regulators of their catalytic activity. These sensors are susceptible to background signals due to catalytic activity in the absence of target or contaminant molecules that cleave the RNA substrate, mimicking the deoxyribozyme reaction. In this manuscript, we introduce a novel system that avoids these problems by using the analyte as the substrate for a deoxyribozyme catalyzed self-phosphorylation reaction. This reaction creates a modified deoxyribozyme product that can be circularized and subjected to massive signal amplification by rolling circle amplification, leading to a sensor system with high sensitivity and low background, which can be coupled to numerous reporter systems. As an example of the potential of this system, we used the self-phosphorylating deoxyribozyme Dk2 to detect as little as 25 nM GTP even in the presence of 1 mM ATP, a potential contaminant. To demonstrate the adaptive properties of this system, we appended another DNA sequence to Dk2, which, once amplified by RCA, codes for a fluorescence generating deoxyribozyme. This two-deoxyribozyme system was able to report the presence of GTP from 4 μM to 1 mM, with specificity over other NTP molecules. Using this model system, we were able to show that small molecule modifying deoxyribozymes can be converted to analyte sensors by coupling their catalytic activity to signal amplification and reporting.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".