SuperResNET – single-molecule network analysis detects changes to clathrin structure induced by small-molecule inhibitors
Bibliographic record
Abstract
SuperResNET is a network analysis pipeline for the analysis of point cloud data generated by single-molecule localization microscopy (SMLM). Here, we applied SuperResNET network analysis of SMLM direct stochastic optical reconstruction microscopy (dSTORM) data to determine how the clathrin endocytosis inhibitors pitstop 2, dynasore and latrunculin A (LatA) alter the morphology of clathrin-coated pits. SuperResNET analysis of HeLa and Cos7 cells identified three classes of clathrin structures: small oligomers (class I), pits and vesicles (class II), and larger clusters corresponding to fused pits or clathrin plaques (class III). Pitstop 2 and dynasore treatment induced distinct homogeneous populations of class II structures in HeLa cells, suggesting that they arrest endocytosis at different stages. Inhibition of endocytosis was not via actin depolymerization, as the actin-depolymerizing agent LatA induced large, heterogeneous clathrin structures. Ternary analysis of SuperResNET shape features presented a distinct more planar profile for blobs from pitstop 2-treated cells, which aligned with clathrin pits identified with high-resolution minimal photon fluxes (MINFLUX) microscopy, whereas control structures resembled MINFLUX clathrin vesicles. SuperResNET analysis therefore showed that pitstop 2 arrests clathrin pit maturation at early stages of pit formation, representing an approach to detect the effect of small molecules on target structures in situ in the cell from SMLM datasets.
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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 | 0.002 |
| 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".