Identifying putative substrates of Calpain-15 in neurodevelopment
Bibliographic record
Abstract
Calpain 15 (CAPN15) is an intracellular cysteine protease belonging to the non-classical small optic lobe (SOL) family of calpains, which has an important role in developmental processes. Loss of Capn15 in mice leads to developmental eye anomalies and volumetric changes in the brain. Human individuals with biallelic variants in CAPN15 have developmental delay, neurodevelopmental disorders, as well as congenital malformations, including eye anomalies. However, the substrates of Capn15 are still unidentified. Here, using Capn15 KO P2 mice of both sexes, we have used RNA sequencing (RNA-SEQ), proteomics, and N-terminomics/terminal amino isotopic labelling of substrates (TAILS), to examine putative substrates of Capn15. There were few changes in the transcriptome profile, and we could not verify a protein change in one selected mRNA between Capn15-/- and WT mice, although a putative transcription factor linked to these changes, Pax2, did show a significant increase after the loss of Capn15. TAILS revealed a preference for cleavage at basic residues, and while no hits showed a significant change in cleavage, some were more abundant when Capn15 was removed. These included Doublecortin and Tubb3, and the Doublecortin predicted cleavage was at a lysine residue. Cleavages at lysine residues were enriched in peptides that were lost or reduced when Capn15 was removed, but not in cleavages that were unchanged when Capn15 was removed.
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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 | 0.000 |
| 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".