Potential of dissimilarity measure-based computation of protein thermal stability data for determining protein interactions
Bibliographic record
Abstract
Determining the interacting proteins in multiprotein complexes can be technically challenging. An emerging biochemical approach to this end is based on the 'thermal proximity co-aggregation' (TPCA) phenomenon. Accordingly, when two or more proteins interact to form a complex, they tend to co-aggregate when subjected to heat-induced denaturation and thus exhibit similar melting curves. Here, we explore the potential of leveraging TPCA for determining protein interactions. We demonstrate that dissimilarity measure-based information retrieval applied to melting curves tends to rank a protein-of-interest's interactors higher than its non-interactors, as shown in the context of pull-down assay results. Consequently, such rankings can reduce the number of confirmatory biochemical experiments needed to find bona fide protein-protein interactions. In general, rankings based on dissimilarity measures generated through metric learning further reduce the required number of experiments compared to those based on standard dissimilarity measures such as Euclidean distance. When a protein mixture's melting curves are obtained in two conditions, we propose a scoring function that uses melting curve data to inform how likely a protein pair is to interact in one condition but not another. We show that ranking protein pairs by their scores is an effective approach for determining condition-specific protein-protein interactions. By contrast, clustering melting curve data generally does not inform about the interacting proteins in multiprotein complexes. In conclusion, we report improved methods for dissimilarity measure-based computation of melting curves data that can greatly enhance the determination of interacting proteins in multiprotein complexes.
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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 | 0.002 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.000 | 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) | 0.001 | 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".