Mapping PARP-1 Auto-ADP-ribosylation Sites by Liquid Chromatography–Tandem Mass Spectrometry
Bibliographic record
Abstract
We demonstrate a novel method for the identification of poly(ADP-ribose) polymerase-1 (PARP-1) autopoly(ADP-ribosyl)ation sites that is suited to collision induced dissociation (CID) tandem mass spectrometry. By employing phosphodiesterase to remove the majority of the poly(ADP-ribose) (pADPr) modification, we reduce the complexity of tandem mass spectrometric analysis of pADPr-modified tryptic peptides. The simplified ribose-5'-phosphate form of the peptides produce tandem mass spectra by CID that are readily interpreted and enable effective localization of the exact sites of PARP-1-catalyzed poly(ADP-ribosyl)ation. In conjunction with a phosphopeptide-like enrichment strategy that captures the ribose-5'-phosphate peptides, we identified eight novel sites of PARP-1 automodification, confirmed the localization of two sites previously reported, and provided evidence for two additional targeted peptides with ambiguous modification site assignments. Given the simplicity of the approach, the method is readily applicable to analysis of complex samples.
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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 | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".