# Improving Counterfactual Truthfulness for Molecular Property Prediction through Uncertainty Quantification

arXiv: https://arxiv.org/abs/2504.02606 · HTML: https://mlsanity.com/paper/2504.02606/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 36 of its 52 references that are in the map.
- First posted on arXiv 3 Apr 2025.

## Builds on (most cited first, 30 of 36)

- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [How Powerful are Graph Neural Networks?](https://mlsanity.com/paper/1810.00826/) (2018)
- [Simple and Scalable Predictive Uncertainty Estimation using Deep Ensembles](https://mlsanity.com/paper/1612.01474/) (2016)
- [Towards A Rigorous Science of Interpretable Machine Learning](https://mlsanity.com/paper/1702.08608/) (2017)
- [Explanation in Artificial Intelligence: Insights from the Social Sciences](https://mlsanity.com/paper/1706.07269/) (2017)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [How Attentive are Graph Attention Networks?](https://mlsanity.com/paper/2105.14491/) (2021)
- [A Review of Uncertainty Quantification in Deep Learning: Techniques, Applications and Challenges](https://mlsanity.com/paper/2011.06225/) (2020)
- [A Survey of Uncertainty in Deep Neural Networks](https://mlsanity.com/paper/2107.03342/) (2021)
- [A Simple Baseline for Bayesian Uncertainty in Deep Learning](https://mlsanity.com/paper/1902.02476/) (2019)
- [Stein Variational Gradient Descent: A General Purpose Bayesian Inference Algorithm](https://mlsanity.com/paper/1608.04471/) (2016)
- [Counterfactual Explanations and Algorithmic Recourses for Machine Learning: A Review](https://mlsanity.com/paper/2010.10596/) (2020)
- [Bayesian Neural Networks: An Introduction and Survey](https://mlsanity.com/paper/2006.12024/) (2020)
- [Explainable Artificial Intelligence (XAI) 2.0: A Manifesto of Open Challenges and Interdisciplinary Research Directions](https://mlsanity.com/paper/2310.19775/) (2023)
- [On the Pitfalls of Heteroscedastic Uncertainty Estimation with Probabilistic Neural Networks](https://mlsanity.com/paper/2203.09168/) (2022)
- [CF-GNNExplainer: Counterfactual Explanations for Graph Neural Networks](https://mlsanity.com/paper/2102.03322/) (2021)
- [Repulsive Deep Ensembles are Bayesian](https://mlsanity.com/paper/2106.11642/) (2021)
- [Getting a CLUE: A Method for Explaining Uncertainty Estimates](https://mlsanity.com/paper/2006.06848/) (2020)
- [Learning and Evaluating Graph Neural Network Explanations based on Counterfactual and Factual Reasoning](https://mlsanity.com/paper/2202.08816/) (2022)
- [Robust Counterfactual Explanations on Graph Neural Networks](https://mlsanity.com/paper/2107.04086/) (2021)
- [Uncertainty Quantification Using Neural Networks for Molecular Property Prediction](https://mlsanity.com/paper/2005.10036/) (2020)
- [The Intriguing Relation Between Counterfactual Explanations and Adversarial Examples](https://mlsanity.com/paper/2009.05487/) (2020)
- [Generating Interpretable Counterfactual Explanations By Implicit Minimisation of Epistemic and Aleatoric Uncertainties](https://mlsanity.com/paper/2103.08951/) (2021)
- [Metrics for Graph Comparison: A Practitioner's Guide](https://mlsanity.com/paper/1904.07414/) (2019)
- [MEG: Generating Molecular Counterfactual Explanations for Deep Graph Networks](https://mlsanity.com/paper/2104.08060/) (2021)
- [A Survey on Graph Counterfactual Explanations: Definitions, Methods, Evaluation, and Research Challenges](https://mlsanity.com/paper/2210.12089/) (2022)
- [Calibrated Uncertainty for Molecular Property Prediction using Ensembles of Message Passing Neural Networks](https://mlsanity.com/paper/2107.06068/) (2021)
- [Diverse, Global and Amortised Counterfactual Explanations for Uncertainty Estimates](https://mlsanity.com/paper/2112.02646/) (2021)
- [Optimal Training of Mean Variance Estimation Neural Networks](https://mlsanity.com/paper/2302.08875/) (2023)
- [Uncertainty Estimation and Out-of-Distribution Detection for Counterfactual Explanations: Pitfalls and Solutions](https://mlsanity.com/paper/2107.09734/) (2021)

## Built on by (most cited first, 1 of 1)

- [Molecular Machine Learning in Chemical Process Design](https://mlsanity.com/paper/2508.20527/) (2025)

## Abstract (arXiv)

Explainable AI (xAI) interventions aim to improve interpretability for complex black-box models, not only to improve user trust but also as a means to extract scientific insights from high-performing predictive systems. In molecular property prediction, counterfactual explanations offer a way to understand predictive behavior by highlighting which minimal perturbations in the input molecular structure cause the greatest deviation in the predicted property. However, such explanations only allow for meaningful scientific insights if they reflect the distribution of the true underlying property -- a feature we define as counterfactual truthfulness. To increase this truthfulness, we propose the integration of uncertainty estimation techniques to filter counterfactual candidates with high predicted uncertainty. Through computational experiments with synthetic and real-world datasets, we demonstrate that traditional uncertainty estimation methods, such as ensembles and mean-variance estimation, can already substantially reduce the average prediction error and increase counterfactual truthfulness, especially for out-of-distribution settings. Our results highlight the importance and potential impact of incorporating uncertainty estimation into explainability methods, especially considering the relatively high effectiveness of low-effort interventions like model ensembles.