MAGPIE: A Machine Learning Approach to Decipher Protein–Protein Interactions in Human Plasma
Bibliographic record
Abstract
Immunoprecipitation coupled to tandem mass spectrometry (IP-MS/MS) methods are often used to identify protein-protein interactions (PPIs). While these approaches are prone to false positive identifications through contamination and antibody nonspecific binding, their results can be filtered using negative controls and computational modeling. However, such filtering does not effectively detect false-positive interactions when IP-MS/MS is performed on human plasma samples. Therein, proteins cannot be overexpressed or inhibited, and existing modeling algorithms are not adapted for execution without such controls. Hence, we introduce MAGPIE, a novel machine learning-based approach for identifying PPIs in human plasma using IP-MS/MS, which leverages negative controls that include antibodies targeting proteins not expected to be present in human plasma. A set of negative controls used for false positive interaction modeling is first constructed. MAGPIE then assesses the reliability of PPIs detected in IP-MS/MS experiments using antibodies that target known plasma proteins. When applied to five IP-MS/MS experiments as a proof of concept, our algorithm identified 68 PPIs with an FDR of 20.77%. MAGPIE significantly outperformed a state-of-the-art PPI discovery tool and identified known and predicted PPIs. Our approach provides an unprecedented ability to detect human plasma PPIs, which enables a better understanding of biological processes in plasma.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.003 |
| 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".