# A Semi-supervised Molecular Learning Framework for Activity Cliff Estimation

arXiv: https://arxiv.org/abs/2601.04507 · HTML: https://mlsanity.com/paper/2601.04507/

## Key facts

- Cited by 3 papers in the map (data through 14 Oct 2026).
- Builds on 27 of its 60 references that are in the map.
- First posted on arXiv 8 Jan 2026.

## Builds on (most cited first, 27 of 27)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Graph Attention Networks](https://mlsanity.com/paper/1710.10903/) (2017)
- [How Powerful are Graph Neural Networks?](https://mlsanity.com/paper/1810.00826/) (2018)
- [Neural Message Passing for Quantum Chemistry](https://mlsanity.com/paper/1704.01212/) (2017)
- [Fast Graph Representation Learning with PyTorch Geometric](https://mlsanity.com/paper/1903.02428/) (2019)
- [FixMatch: Simplifying Semi-Supervised Learning with Consistency and Confidence](https://mlsanity.com/paper/2001.07685/) (2020)
- [The Many Faces of Robustness: A Critical Analysis of Out-of-Distribution Generalization](https://mlsanity.com/paper/2006.16241/) (2020)
- [Self-training with Noisy Student improves ImageNet classification](https://mlsanity.com/paper/1911.04252/) (2019)
- [Temporal Ensembling for Semi-Supervised Learning](https://mlsanity.com/paper/1610.02242/) (2016)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [Graph Contrastive Learning with Adaptive Augmentation](https://mlsanity.com/paper/2010.14945/) (2020)
- [Pseudo-Labeling and Confirmation Bias in Deep Semi-Supervised Learning](https://mlsanity.com/paper/1908.02983/) (2019)
- [In Defense of Pseudo-Labeling: An Uncertainty-Aware Pseudo-label Selection Framework for Semi-Supervised Learning](https://mlsanity.com/paper/2101.06329/) (2021)
- [Label Propagation for Deep Semi-supervised Learning](https://mlsanity.com/paper/1904.04717/) (2019)
- [ChemRL-GEM: Geometry Enhanced Molecular Representation Learning for Property Prediction](https://mlsanity.com/paper/2106.06130/) (2021)
- [When Does Self-Supervision Help Graph Convolutional Networks?](https://mlsanity.com/paper/2006.09136/) (2020)
- [Accurate Learning of Graph Representations with Graph Multiset Pooling](https://mlsanity.com/paper/2102.11533/) (2021)
- [Semi-Supervised Learning with Generative Adversarial Networks](https://mlsanity.com/paper/1606.01583/) (2016)
- [MoCL: Data-driven Molecular Fingerprint via Knowledge-aware Contrastive Learning from Molecular Graph](https://mlsanity.com/paper/2106.04509/) (2021)
- [Does GNN Pretraining Help Molecular Representation?](https://mlsanity.com/paper/2207.06010/) (2022)
- [Molformer: Motif-based Transformer on 3D Heterogeneous Molecular Graphs](https://mlsanity.com/paper/2110.01191/) (2021)
- [Infinite Variational Autoencoder for Semi-Supervised Learning](https://mlsanity.com/paper/1611.07800/) (2016)
- [Quantitative Evaluation of Explainable Graph Neural Networks for Molecular Property Prediction](https://mlsanity.com/paper/2107.04119/) (2021)

## Built on by (most cited first, 3 of 3)

- [MolEvolve: LLM-Guided Evolutionary Search for Interpretable Molecular Optimization](https://mlsanity.com/paper/2603.24382/) (2026)
- [SurfDesign: Effective Protein Design on Molecular Surfaces](https://mlsanity.com/paper/2606.07567/) (2026)
- [Deciphering Fingerprints of 3D Molecular Surfaces for Accurate Epitope Prediction](https://mlsanity.com/paper/2606.23830/) (2026)

## Abstract (arXiv)

Machine learning (ML) enables accurate and fast molecular property predictions, which are of interest in drug discovery and material design. Their success is based on the principle of similarity at its heart, assuming that similar molecules exhibit close properties. However, activity cliffs challenge this principle, and their presence leads to a sharp decline in the performance of existing ML algorithms, particularly graph-based methods. To overcome this obstacle under a low-data scenario, we propose a novel semi-supervised learning (SSL) method dubbed SemiMol, which employs predictions on numerous unannotated data as pseudo-signals for subsequent training. Specifically, we introduce an additional instructor model to evaluate the accuracy and trustworthiness of proxy labels because existing pseudo-labeling approaches require probabilistic outputs to reveal the model's confidence and fail to be applied in regression tasks. Moreover, we design a self-adaptive curriculum learning algorithm to progressively move the target model toward hard samples at a controllable pace. Extensive experiments on 30 activity cliff datasets demonstrate that SemiMol significantly enhances graph-based ML architectures and outpasses state-of-the-art pretraining and SSL baselines.