← 研踪 PaperTrailarXiv:2611.01512 · v1
Abstention Spends Its Budget on Local Label Variance More Than on Novelty: Auditing Conformal Calibration and Selective Prediction under Molecular Scaffold Shift
首次提交 2026-11-01 11:44
版本更新 2026-11-01 11:44
雷达观测 2026-11-04 23:43
摘要
Selective prediction with split conformal calibration promises a post-hoc fix for molecular property prediction: abstain on the least reliable compounds, ideally out-of-distribution chemistry, and the retained set becomes trustworthy without retraining. We audit this recipe for a gradient-boosted fingerprint model on lipophilicity (regression) and BBBP (classification) under a Bemis-Murcko scaffold split, holding the fitted model and evaluation molecules fixed while varying only the calibration fold (18 replicates). (i) On lipophilicity, coverage depends on calibration provenance: calibrating on held-out training-scaffold molecules falls below nominal (PICP 0.841 at a 0.90 target), while novel-scaffold calibration recovers it (0.904); on BBBP, coverage stays above nominal in every regime. (ii) For split conformalized quantile regression (CQR) the conformal correction is a constant, so conformalization does not change what is abstained on. (iii) The abstention score (CQR width; effectively ensemble variance on BBBP) tracks local label variance more than chemical novelty: controlling for local label variance largely explains away the novelty association (partial Spearman 0.067 and 0.047). (iv) At a fixed assay budget, gating on interval width or ensemble variance never improves hit precision over ranking by point prediction, at the pre-specified operating point or across 20 exploratory settings; a plain novelty gate shows small, uncorrected gains at the smallest budgets. (v) In an exploratory analysis, exact conformal selection exceeds its false discovery rate target under training-scaffold calibration (0.303 at q=0.2) and is consistent with it under novel-scaffold calibration, contributing a data-driven batch size rather than a better ranking. Conformalization earns its keep through guarantees whose validity hinges on calibration provenance, not by choosing what to abstain on.
作者备注：12 pages, 4 figures, 6 tables
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v1 · 2026-11-01 11:44 · 最新观测版本
Abstention Spends Its Budget on Local Label Variance More Than on Novelty: Auditing Conformal Calibration and Selective Prediction under Molecular Scaffold Shift
Selective prediction with split conformal calibration promises a post-hoc fix for molecular property prediction: abstain on the least reliable compounds, ideally out-of-distribution chemistry, and the retained set becomes trustworthy without retraining. We audit this recipe for a gradient-boosted fingerprint model on lipophilicity (regression) and BBBP (classification) under a Bemis-Murcko scaffold split, holding the fitted model and evaluation molecules fixed while varying only the calibration fold (18 replicates). (i) On lipophilicity, coverage depends on calibration provenance: calibrating on held-out training-scaffold molecules falls below nominal (PICP 0.841 at a 0.90 target), while novel-scaffold calibration recovers it (0.904); on BBBP, coverage stays above nominal in every regime. (ii) For split conformalized quantile regression (CQR) the conformal correction is a constant, so conformalization does not change what is abstained on. (iii) The abstention score (CQR width; effectively ensemble variance on BBBP) tracks local label variance more than chemical novelty: controlling for local label variance largely explains away the novelty association (partial Spearman 0.067 and 0.047). (iv) At a fixed assay budget, gating on interval width or ensemble variance never improves hit precision over ranking by point prediction, at the pre-specified operating point or across 20 exploratory settings; a plain novelty gate shows small, uncorrected gains at the smallest budgets. (v) In an exploratory analysis, exact conformal selection exceeds its false discovery rate target under training-scaffold calibration (0.303 at q=0.2) and is consistent with it under novel-scaffold calibration, contributing a data-driven batch size rather than a better ranking. Conformalization earns its keep through guarantees whose validity hinges on calibration provenance, not by choosing what to abstain on.
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