TY  - JOUR
T1  - Interpretable Pharmacoinformatics Beyond Descriptor Importance: A Validation Framework for Mechanistically Grounded, Uncertainty-Aware, and Decision-Relevant Molecular Explanations
A1  - Kenji Tanaka
A1  - Yui Kobayashi
A1  - Takeshi Nakamura
JF  - International Journal of Pharmaceutical Research and Allied Sciences
JO  - Int J Pharm Res Allied Sci
SN  - 2277-3657
Y1  - 2024
VL  - 13
IS  - 1
DO  - 10.51847/yrdoe1CDev
SP  - 128
EP  - 137
N2  - Feature importance has become a common language for explaining quantitative structure–activity relationship and molecular machine-learning models, yet an attribution is only one kind of interpretive claim. A descriptor, atom, bond, fragment, or learned concept can receive high importance without establishing that the explanation is stable across model specifications, faithful to the model’s actual decision process, representative of global behaviour, mechanistically causal, or useful for a medicinal-chemistry decision. This critical review examines evidence from 2017–2024 on molecular explainability, QSAR validation, counterfactuals, graph explanations, uncertainty, activity cliffs, representation dependence, and interpretable model design. The evidence supports a central distinction between prediction performance and explanation validity, and shows that chemical plausibility cannot substitute for tests of faithfulness, stability, applicability, and scope. We propose an interpretability claim ladder in which descriptor attribution, model-behaviour explanation, mechanistic hypothesis, and decision-relevant interpretation are progressively stronger claims with progressively stronger validation requirements. The ladder is not an empirically validated scoring system; it is an evidence-bounded synthesis for preventing inferential escalation. Pharmacoinformatics becomes more interpretable not when more importance maps are produced, but when each explanation is matched to its explanatory object, molecular representation, chemical-space support, validation design, uncertainty, and intended decision.
UR  - https://ijpras.com/article/interpretable-pharmacoinformatics-beyond-descriptor-importance-a-validation-framework-for-mechanist-kt2hbzkzvkj3zre
ER  -