# Improving Self-supervised Molecular Representation Learning using Persistent Homology

arXiv: https://arxiv.org/abs/2311.17327 · HTML: https://mlsanity.com/paper/2311.17327/

## Key facts

- Cited by 6 papers in the map (data through 14 Oct 2026).
- Builds on 43 of its 70 references that are in the map.
- First posted on arXiv 29 Nov 2023.

## Builds on (most cited first, 30 of 43)

- [A Simple Framework for Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2002.05709/) (2020)
- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Representation Learning with Contrastive Predictive Coding](https://mlsanity.com/paper/1807.03748/) (2018)
- [Inductive Representation Learning on Large Graphs](https://mlsanity.com/paper/1706.02216/) (2017)
- [XGBoost: A Scalable Tree Boosting System](https://mlsanity.com/paper/1603.02754/) (2016)
- [How Powerful are Graph Neural Networks?](https://mlsanity.com/paper/1810.00826/) (2018)
- [Unsupervised Learning of Visual Features by Contrasting Cluster Assignments](https://mlsanity.com/paper/2006.09882/) (2020)
- [Unsupervised Feature Learning via Non-Parametric Instance-level Discrimination](https://mlsanity.com/paper/1805.01978/) (2018)
- [Graph Contrastive Learning with Augmentations](https://mlsanity.com/paper/2010.13902/) (2020)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [Strategies for Pre-training Graph Neural Networks](https://mlsanity.com/paper/1905.12265/) (2019)
- [TUDataset: A collection of benchmark datasets for learning with graphs](https://mlsanity.com/paper/2007.08663/) (2020)
- [GraphMAE: Self-Supervised Masked Graph Autoencoders](https://mlsanity.com/paper/2205.10803/) (2022)
- [InfoGraph: Unsupervised and Semi-supervised Graph-Level Representation Learning via Mutual Information Maximization](https://mlsanity.com/paper/1908.01000/) (2019)
- [With a Little Help from My Friends: Nearest-Neighbor Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2104.14548/) (2021)
- [GPT-GNN: Generative Pre-Training of Graph Neural Networks](https://mlsanity.com/paper/2006.15437/) (2020)
- [Graph Contrastive Learning Automated](https://mlsanity.com/paper/2106.07594/) (2021)
- [Pre-training Molecular Graph Representation with 3D Geometry](https://mlsanity.com/paper/2110.07728/) (2021)
- [Persistence Images: A Stable Vector Representation of Persistent Homology](https://mlsanity.com/paper/1507.06217/) (2015)
- [Adversarial Graph Augmentation to Improve Graph Contrastive Learning](https://mlsanity.com/paper/2106.05819/) (2021)
- [Self-Supervised Learning of Graph Neural Networks: A Unified Review](https://mlsanity.com/paper/2102.10757/) (2021)
- [SimGRACE: A Simple Framework for Graph Contrastive Learning without Data Augmentation](https://mlsanity.com/paper/2202.03104/) (2022)
- [On Feature Decorrelation in Self-Supervised Learning](https://mlsanity.com/paper/2105.00470/) (2021)
- [Motif-based Graph Self-Supervised Learning for Molecular Property Prediction](https://mlsanity.com/paper/2110.00987/) (2021)
- [3D Infomax improves GNNs for Molecular Property Prediction](https://mlsanity.com/paper/2110.04126/) (2021)
- [DiffCSE: Difference-based Contrastive Learning for Sentence Embeddings](https://mlsanity.com/paper/2204.10298/) (2022)
- [A roadmap for the computation of persistent homology](https://mlsanity.com/paper/1506.08903/) (2015)
- [Self-supervised Graph-level Representation Learning with Local and Global Structure](https://mlsanity.com/paper/2106.04113/) (2021)
- [Contrastive Adapters for Foundation Model Group Robustness](https://mlsanity.com/paper/2207.07180/) (2022)
- [Does GNN Pretraining Help Molecular Representation?](https://mlsanity.com/paper/2207.06010/) (2022)

## Built on by (most cited first, 6 of 6)

- [Classic GNNs are Strong Baselines: Reassessing GNNs for Node Classification](https://mlsanity.com/paper/2406.08993/) (2024)
- [Can Classic GNNs Be Strong Baselines for Graph-level Tasks? Simple Architectures Meet Excellence](https://mlsanity.com/paper/2502.09263/) (2025)
- [MOL-Mamba: Enhancing Molecular Representation with Structural & Electronic Insights](https://mlsanity.com/paper/2412.16483/) (2024)
- [Topology-Aware CLIP Few-Shot Learning](https://mlsanity.com/paper/2505.01694/) (2025)
- [Scalar Function Topology Divergence: Comparing Topology of 3D Objects](https://mlsanity.com/paper/2407.08364/) (2024)
- [Multi-level Self-supervised Pretraining on Compositional Hierarchical Graph for Molecular Property Prediction](https://mlsanity.com/paper/2605.16088/) (2026)

## Abstract (arXiv)

Self-supervised learning (SSL) has great potential for molecular representation learning given the complexity of molecular graphs, the large amounts of unlabelled data available, the considerable cost of obtaining labels experimentally, and the hence often only small training datasets. The importance of the topic is reflected in the variety of paradigms and architectures that have been investigated recently. Yet the differences in performance seem often minor and are barely understood to date. In this paper, we study SSL based on persistent homology (PH), a mathematical tool for modeling topological features of data that persist across multiple scales. It has several unique features which particularly suit SSL, naturally offering: different views of the data, stability in terms of distance preservation, and the opportunity to flexibly incorporate domain knowledge. We (1) investigate an autoencoder, which shows the general representational power of PH, and (2) propose a contrastive loss that complements existing approaches. We rigorously evaluate our approach for molecular property prediction and demonstrate its particular features in improving the embedding space: after SSL, the representations are better and offer considerably more predictive power than the baselines over different probing tasks; our loss increases baseline performance, sometimes largely; and we often obtain substantial improvements over very small datasets, a common scenario in practice.