PPI-Caliper puts a false-discovery-rate guarantee on protein language model interaction predictions, until the data shift
- PPI-Caliper is a model-agnostic wrapper that applies conformal calibration to pick protein interactions at a user-set false discovery rate, using held-out labels and no retraining.
- Across five species and two protein-language-model predictors, each with two versions of human training data, the empirical error rate stayed at or below target when calibration data matched the test data.
- Under distribution shift, thresholds carried over from another setting turned conservative when predictions improved but could fail to control errors when performance dropped.
For target discovery the benchmark AUC was never the real question; it is how many of the top-ranked interactions you can afford to chase before the follow-up assays dry up. An explicit FDR dial answers that, and the honest shift result matters most: calibrating on a well-studied organism then applying to a poorly annotated one is exactly where it can break. Try it on an in-house interactome with orthogonal validation before trusting it.
Error-Controlled Discovery of Protein Interactions via Conformal Calibration ↗