Method Profile

NephroTox AI: Confidence-Aware Kidney Toxicity Classification

A molecular-descriptor classifier evaluated on an independently sourced set, with performance reported before and after confidence filtering.

KidneyComputational Models
Macao Polytechnic University buildings with the university name visible on the facade.
Macao Polytechnic University, photographed in January 2023. (LN9267, CC BY-SA 4.0)

Research Applications

Early-stage ranking of candidate compounds for possible drug-associated kidney toxicity while identifying predictions that the model treats as uncertain.

Model & Design

Random-forest classifier using RDKit two-dimensional descriptors; tree-to-tree variation defines four confidence tiers.

Experimental Format

Ten internal data partitions for model development and a separate DIRIL external set; compare full-set performance with a retained high/medium-confidence subset.

Model Components

  • Component

    Source labels

    Description

    Three curated datasets with structure deduplication and label reconciliation; 1,829 development compounds and 247 retained external compounds.

  • Component

    Inputs and outputs

    Description

    Two-dimensional molecular descriptors, binary nephrotoxicity classification, probability and confidence tier; no injury-subtype prediction.

Measurements & Endpoints

  • External ROC AUC
  • Coverage after confidence filtering
  • False-positive and false-negative distribution by confidence tier

Analysis

Report external AUC and coverage together. SHAP feature attribution is a statistical explanation of predictions, not direct evidence of a renal-injury mechanism.

Published Evidence

  • Study Design

    Source-separated external comparison followed by confidence-filtered analysis.

    Study Sample

    1,829 development compounds; 247 external compounds; about 54 external compounds retained at high or medium confidence.

    Comparison

    DIRIL external nephrotoxicity labels; full external set versus the selected confidence subset.

    Finding

    Full external AUC 0.727; retained-subset AUC 0.902 at 21.7% coverage. Low/very-low tiers contained 88.3% of false negatives and 94.5% of false positives.

    Interpretation & Limits
    • Filtered AUC does not apply to all external compounds.
    • Binary labels do not identify renal-injury subtypes.
    • New DrugBank positives were not prospectively validated in renal-cell experiments.

Sources

  1. Liu J, Guo J, Tong HHY, Li S. NephroTox AI: an explainable machine learning framework with uncertainty quantification for drug-induced nephrotoxicity prediction. Journal of Cheminformatics. Article in Press, 2026. DOI: 10.1186/s13321-026-01299-y. ↗