Identification of the sequence determinants of protein N-terminal acetylation through a decision tree approach
Bibliographic record
Abstract
N-terminal acetylation is one of the most common protein modifications in eukaryotes and occurs co-translationally when the N-terminus of the nascent polypeptide is still attached to the ribosome. This modification has been shown to be involved in a wide range of biological phenomena such as protein half-life regulation, protein-protein and protein-membrane interactions, and protein subcellular localization. Thus, accurately predicting which proteins receive an acetyl group based on their protein sequence is expected to facilitate the functional study of this modification. As the occurrence of N-terminal acetylation strongly depends on the context of protein sequences, attempts to understand the sequence determinants of N-terminal acetylation were conducted initially by simply examining the N-terminal sequences of many acetylated and unacetylated proteins and more recently by machine learning approaches. However, a complete understanding of the sequence determinants of this modification remains to be elucidated. We obtained curated N-terminally acetylated and unacetylated sequences from the UniProt database and employed a decision tree algorithm to identify the sequence determinants of N-terminal acetylation for proteins whose initiator methionine (iMet) residues have been removed. The results suggested that the main determinants of N-terminal acetylation are contained within the first five residues following iMet and that the first and second positions are the most important discriminator for the occurrence of this phenomenon. The results also indicated the existence of position-specific preferred and inhibitory residues that determine the occurrence of N-terminal acetylation. The developed predictor software, termed NT-AcPredictor, accurately predicted the N-terminal acetylation, with an overall performance comparable or superior to those of preceding predictors incorporating machine learning algorithms. Our machine learning approach based on a decision tree algorithm successfully provided several sequence determinants of N-terminal acetylation for proteins lacking iMet, some of which have not previously been described. Although these sequence determinants remain insufficient to comprehensively predict the occurrence of this modification, indicating that further work on this topic is still required, the developed predictor, NT-AcPredictor, can be used to predict N-terminal acetylation with an accuracy of more than 80%.
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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| 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".