bioRxivJClub
Temporal Phosphoproteomic Network Reconstruction of Condition-Dependent EGFR Signaling Routes Through Unmeasured Proteins
bioRxiv · · Preprint · Open access
Lee, Lee
Abstract ↗AI summary
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TS-BFS-BS reconstructs temporally continuous EGFR signaling routes through unmeasured bridge proteins from EGF time-course phosphoproteomics, retaining 94–99% of endpoints after removing measured hubs CBL and SRC.
- Why it matters: Phosphoproteomic time courses miss proteins with no detectable phosphorylation changes, leaving gaps that prevent linking fast signaling dynamics into coherent pathways.
- What they did: The method uses temporal ordering from time-resolved phosphoproteomics to steer a beam-pruned breadth-first search over STRING v12.5 priors, producing routes that can traverse unmeasured bridge proteins.
- The result: Correct temporal order yields endpoint overlap with Jaccard indices of 0.23–0.33 when orders are incorrect, and iterative refinement is supported by recovering CBL and SRC as bridges and excluding PTPN11 under SHP2 inhibition (0.25–0.35) until washout.
The findingWhy it mattersWhat they didThe result
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