Emerging proteomic technologies for elucidating context‐dependent cellular signaling events: A big challenge of tiny proportions
Bibliographic record
Abstract
Aberrant cell signaling events either drive or compensate for nearly all pathologies. A thorough description and quantification of maladaptive signaling flux in disease is a critical step in drug development, and complex proteomic approaches can provide valuable mechanistic insights. Traditional proteomics-based signaling analyses rely heavily on in vitro cellular monoculture. The characterization of these simplified systems generates a rich understanding of the basic components and complex interactions of many signaling networks, but they cannot capture the full complexity of the microenvironments in which pathologies are ultimately made manifest. Unfortunately, techniques that can directly interrogate signaling in situ often yield mass-limited starting materials that are incompatible with traditional proteomics workflows. This review provides an overview of established and emerging techniques that are applicable to context-dependent proteomics. Analytical approaches are illustrated through recent proteomics-based studies in which selective sample acquisition strategies preserve context-dependent information, and where the challenge of minimal starting material is met by optimized sensitivity and coverage. This review is organized into three major technological themes: (i) LC methods in line with MS; (ii) antibody-based approaches; (iii) MS imaging with a discussion of data integration and systems modeling. Finally, we conclude with future perspectives and implications of context-dependent proteomics.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".