aiqbench analysis
CaliPPer introduces a post-hoc framework that significantly enhances the reliability of binding prediction models by quantifying generalizability across diverse immune-receptor domains and chemical scaffolds. By pairing sample-to-domain distance metrics with Bayesian recalibration, this tool effectively bridges the gap between computational outputs and experimental validation, directly addressing the critical issue of unpredictable performance on new datasets.
CaliPPer: quantifying, predicting and improving AI model performance for binding prediction
arXiv:2606.07258v1 Announce Type: cross Abstract: Binding prediction models accelerate therapeutic antibody and TCR discovery, but their performance on new datasets is unpredictable, often leading to low discovery rates. Density-ratio methods (PAPE, M-CBPE) provide label-free performance estimation for binary classification, but their assumptions and aggregate-only outputs limit binding prediction on neoepitopes, antigen variants and chemical scaffolds. Here we present CaliPPer (Calibration and Prediction of Performance), a post-hoc framework pairing a multi-chain Sample-to-Domain Distance (S2DD) with distance-aware Bayesian recalibration, operating at three resolutions: generalisability score, aggregate performance prediction, and per-sample confidence. Across ten models, eight architectures and two immune-receptor domains, CaliPPer attains distance--performance correlations $|r|=0.80\text{--}0.92$, predicts AUROC/AP/F1 with mean absolute errors $0.008\text{--}0.070$, and improves AUROC by up to $+0.20$ on unseen epitopes/variants. Applied retrospectively to five published TCR, BCR, MHC--peptide and small-molecule studies, CaliPPer raises true discovery rates in all five (e.g.\ $0/5 \to 3/5$ confirmed neoantigens), providing a triage layer between computational prediction and experimental validation.
Abstract:Binding prediction models accelerate therapeutic antibody and TCR discovery, but their performance on new datasets is unpredictable, often leading to low discovery rates. Density-ratio methods (PAPE, M-CBPE) provide label-free performance estimation for binary classification, but their assumptions and aggregate-only outputs limit binding prediction on neoepitopes, antigen variants and chemical scaffolds. Here we present CaliPPer (Calibration and Prediction of Performance), a post-hoc framework pairing a multi-chain Sample-to-Domain Distance (S2DD) with distance-aware Bayesian recalibration, operating at three resolutions: generalisability score, aggregate performance prediction, and per-sample confidence. Across ten models, eight architectures and two immune-receptor domains, CaliPPer attains distance--performance correlations $|r|=0.80\text{--}0.92$, predicts AUROC/AP/F1 with mean absolute errors $0.008\text{--}0.070$, and improves AUROC by up to $+0.20$ on unseen epitopes/variants. Applied retrospectively to five published TCR, BCR, MHC--peptide and small-molecule studies, CaliPPer raises true discovery rates in all five (e.g.\ $0/5 \to 3/5$ confirmed neoantigens), providing a triage layer between computational prediction and experimental validation.
Computational Engineering, Finance, and Science (cs.CE); Artificial Intelligence (cs.AI); Machine Learning (cs.LG); Quantitative Methods (q-bio.QM)
arXiv:2606.07258 [cs.CE]
(or arXiv:2606.07258v1 [cs.CE] for this version)
https://doi.org/10.48550/arXiv.2606.07258 Focus to learn more arXiv-issued DOI via DataCite
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Full text under the publisher's open licence · 254 words
