Does GNN Pretraining Help Molecular Representation?
Not on the map. Why?
Abstract (arXiv)
Extracting informative representations of molecules using Graph neural networks (GNNs) is crucial in AI-driven drug discovery. Recently, the graph research community has been trying to replicate the success of self-supervised pretraining in natural language processing, with several successes claimed. However, we find the benefit brought by self-supervised pretraining on small molecular data can be negligible in many cases. We conduct thorough ablation studies on the key components of GNN pretraining, including pretraining objectives, data splitting methods, input features, pretraining dataset scales, and GNN architectures, to see how they affect the accuracy of the downstream tasks. Our first important finding is, self-supervised graph pretraining do not always have statistically significant advantages over non-pretraining methods in many settings. Secondly, although noticeable improvement can be observed with additional supervised pretraining, the improvement may diminish with richer features or more balanced data splits. Thirdly, hyper-parameters could have larger impacts on accuracy of downstream tasks than the choice of pretraining tasks, especially when the scales of downstream tasks are small. Finally, we provide our conjectures where the complexity of some pretraining methods on small molecules might be insufficient, followed by empirical evidences on different pretraining datasets.
Key facts. Cited by 59 papers in the map (data through 7 Oct 2026). Builds on 26 of its 43 references that are in the map. First posted on arXiv 13 Jul 2022.
Builds on
26 of 43 references.
References · 26
- 2018BERT: Pre-training of Deep Bidirectional Transformers for Language Understandingcited by 40,204
- 2020Language Models are Few-Shot Learnerscited by 32,199
- 2019Exploring the Limits of Transfer Learning with a Unified Text-to-Text Transformercited by 14,491
- 2020A Simple Framework for Contrastive Learning of Visual Representationscited by 11,979
- 2017Graph Attention Networkscited by 8,854
- 2019Momentum Contrast for Unsupervised Visual Representation Learningcited by 7,482
- 2017Model-Agnostic Meta-Learning for Fast Adaptation of Deep Networkscited by 4,861
- 2018How Powerful are Graph Neural Networks?cited by 4,355
- 2021Finetuned Language Models Are Zero-Shot Learnerscited by 3,747
- 2020Graph Contrastive Learning with Augmentationscited by 1,203
- 2017MoleculeNet: A Benchmark for Molecular Machine Learningcited by 1,037
- 2019Strategies for Pre-training Graph Neural Networkscited by 964
14 more
- 2020Contrastive Multi-View Representation Learning on Graphscited by 651
- 2020Graph Contrastive Learning with Adaptive Augmentationcited by 519
- 2017Representation Learning on Graphs: Methods and Applicationscited by 456
- 2021Do Transformers Really Perform Bad for Graph Representation?cited by 318
- 2020GPT-GNN: Generative Pre-Training of Graph Neural Networkscited by 302
- 2020Towards Deeper Graph Neural Networkscited by 296
- 2021Pre-training Molecular Graph Representation with 3D Geometrycited by 248
- 2022Structure-Aware Transformer for Graph Representation Learningcited by 191
- 2022Pure Transformers are Powerful Graph Learnerscited by 188
- 2021Self-Supervised Learning of Graph Neural Networks: A Unified Reviewcited by 184
- 2022SimGRACE: A Simple Framework for Graph Contrastive Learning without Data Augmentationcited by 171
- 2020When Does Self-Supervision Help Graph Convolutional Networks?cited by 121
- 2021MoCL: Data-driven Molecular Fingerprint via Knowledge-aware Contrastive Learning from Molecular Graphcited by 65
- 2019Alchemy: A Quantum Chemistry Dataset for Benchmarking AI Modelscited by 36
Built on by
Citing papers per year: 2022: 3; 2023: 21; 2024: 19; 2025: 9; 2026: 7.
59 papers.
Sort:
By area:
- 2023GIMLET: A Unified Graph-Text Model for Instruction-Based Molecule Zero-Shot Learningcited by 70
- 2023Enhancing Activity Prediction Models in Drug Discovery with the Ability to Understand Human Languagecited by 44
- 2023Towards Foundational Models for Molecular Learning on Large-Scale Multi-Task Datasetscited by 37
- 2023Fast Graph Condensation with Structure-based Neural Tangent Kernelcited by 36
- 2022A Systematic Survey of Chemical Pre-trained Modelscited by 34
- 2023Graph-Aware Language Model Pre-Training on a Large Graph Corpus Can Help Multiple Graph Applicationscited by 33
- 2023Graph Positional and Structural Encodercited by 31
- 2023Automated 3D Pre-Training for Molecular Property Predictioncited by 24
- 2023Data-Centric Learning from Unlabeled Graphs with Diffusion Modelcited by 19
- 2024FedSSP: Federated Graph Learning with Spectral Knowledge and Personalized Preferencecited by 16
- 2023Search to Fine-tune Pre-trained Graph Neural Networks for Graph-level Taskscited by 13
- 2024Towards Neural Scaling Laws on Graphscited by 13
38 more
- 2022MolCPT: Molecule Continuous Prompt Tuning to Generalize Molecular Representation Learningcited by 12
- 2024Tensor-view Topological Graph Neural Networkcited by 12
- 2022Transfer learning for chemically accurate interatomic neural network potentialscited by 11
- 2023Identifying Semantic Component for Robust Molecular Property Predictioncited by 10
- 2025CEGA: A Cost-Effective Approach for Graph-Based Model Extraction and Acquisitioncited by 9
- 2023Instructor-inspired Machine Learning for Robust Molecular Property Predictioncited by 8
- 2024Learning Molecular Representation in a Cellcited by 8
- 2024MAGE: Model-Level Graph Neural Networks Explanations via Motif-based Graph Generationcited by 7
- 2024When is an Embedding Model More Promising than Another?cited by 7
- 2024Molecular Topological Profile (MOLTOP) -- Simple and Strong Baseline for Molecular Graph Classificationcited by 7
- 2023Knowledge-augmented Graph Machine Learning for Drug Discovery: A Surveycited by 6
- 2023Multi-channel learning for integrating structural hierarchies into context-dependent molecular representationcited by 6
- 2023Improving Self-supervised Molecular Representation Learning using Persistent Homologycited by 6
- 2024Towards Graph Foundation Models: A Study on the Generalization of Positional and Structural Encodingscited by 4
- 2023Learning to Group Auxiliary Datasets for Moleculecited by 3
- 2024Unifying Invariance and Spuriousity for Graph Out-of-Distribution via Probability of Necessity and Sufficiencycited by 3
- 2025Omni-Mol: Multitask Molecular Model for Any-to-any Modalitiescited by 3
- 2025GraphBridge: Towards Arbitrary Transfer Learning in GNNscited by 3
- 2025Safeguarding Graph Neural Networks against Topology Inference Attackscited by 3
- 2026A Semi-supervised Molecular Learning Framework for Activity Cliff Estimationcited by 3
- 2023Enhancing Molecular Property Prediction via Mixture of Collaborative Expertscited by 2
- 2024Graph Learning with Distributional Edge Layoutscited by 2
- 2024Transfer Learning for Molecular Property Predictions from Small Data Setscited by 2
- 2024Unifying Invariant and Variant Features for Graph Out-of-Distribution via Probability of Necessity and Sufficiencycited by 2
- 2024DELTA: Dual Consistency Delving with Topological Uncertainty for Active Graph Domain Adaptationcited by 2
- 2025Beyond Atoms: Enhancing Molecular Pretrained Representations with 3D Space Modelingcited by 2
- 2024Enhancing Molecular Property Prediction with Auxiliary Learning and Task-Specific Adaptationcited by 1
- 2024Heterogeneous Graph Neural Network on Semantic Treecited by 1
- 2024Towards Graph Prompt Learning: A Survey and Beyondcited by 1
- 2024SiMilarity-Enhanced Homophily for Multi-View Heterophilous Graph Clusteringcited by 1
- 2025Heterogeneous Graph Prompt Learning via Adaptive Weight Pruningcited by 1
- 2026PCEvo: Path-Consistent Molecular Representation via Virtual Evolutionarycited by 1
- 2023Implicit Geometry and Interaction Embeddings Improve Few-Shot Molecular Property Predictioncited by 0
- 2023On Data Imbalance in Molecular Property Prediction with Pre-trainingcited by 0
- 20233D Denoisers are Good 2D Teachers: Molecular Pretraining via Denoising and Cross-Modal Distillationcited by 0
- 2023Current Methods for Drug Property Prediction in the Real Worldcited by 0
- 2023On the Equivalence of Graph Convolution and Mixupcited by 0
- 2024A Strong Baseline for Molecular Few-Shot Learningcited by 0
50 most cited of 59 All 59 (JSON)
- 2026Rethinking Message Passing as Retrieval for Text-Attributed Graph Learning27 Aug 2026
- 2026Mol-JEPA: A multimodal Joint Embedding Predictive Architecture for Molecules23 Aug 2026
- 2026Rethinking Generalization in Graph Neural Networks: A Structural Complexity Perspective13 May 2026
- 2026Approximate Subgraph Matching with Neural Graph Representations and Reinforcement Learning18 Mar 2026
- 2026PCEvo: Path-Consistent Molecular Representation via Virtual Evolutionary27 Jan 2026
- 2026A Semi-supervised Molecular Learning Framework for Activity Cliff Estimation8 Jan 2026
- 2026Beyond Homophily: Community Search on Heterophilic Graphs5 Jan 2026
- 2025Safeguarding Graph Neural Networks against Topology Inference Attacks5 Sep 2025
- 2025A Graph Laplacian Eigenvector-based Pre-training Method for Graph Neural Networks2 Sep 2025
- 2025Heterogeneous Graph Prompt Learning via Adaptive Weight Pruning12 Jul 2025
- 2025CEGA: A Cost-Effective Approach for Graph-Based Model Extraction and Acquisition21 Jun 2025
- 2025Towards Multimodal Graph Large Language Model11 Jun 2025
38 more
- 2025Pretraining a Foundation Model for Small-Molecule Natural Products22 Mar 2025
- 2025Beyond Atoms: Enhancing Molecular Pretrained Representations with 3D Space Modeling13 Mar 2025
- 2025GraphBridge: Towards Arbitrary Transfer Learning in GNNs26 Feb 2025
- 2025Omni-Mol: Multitask Molecular Model for Any-to-any Modalities3 Feb 2025
- 2024Towards Graph Foundation Models: A Study on the Generalization of Positional and Structural Encodings10 Dec 2024
- 2024FedSSP: Federated Graph Learning with Spectral Knowledge and Personalized Preference26 Oct 2024
- 2024SiMilarity-Enhanced Homophily for Multi-View Heterophilous Graph Clustering4 Oct 2024
- 2024DELTA: Dual Consistency Delving with Topological Uncertainty for Active Graph Domain Adaptation13 Sep 2024
- 2024Towards Graph Prompt Learning: A Survey and Beyond26 Aug 2024
- 2024Unifying Invariant and Variant Features for Graph Out-of-Distribution via Probability of Necessity and Sufficiency21 Jul 2024
- 2024Molecular Topological Profile (MOLTOP) -- Simple and Strong Baseline for Molecular Graph Classification16 Jul 2024
- 2024Geometric Self-Supervised Pretraining on 3D Protein Structures using Subgraphs20 Jun 2024
- 2024Learning Molecular Representation in a Cell17 Jun 2024
- 2024When is an Embedding Model More Promising than Another?11 Jun 2024
- 2024MAGE: Model-Level Graph Neural Networks Explanations via Motif-based Graph Generation21 May 2024
- 2024Transfer Learning for Molecular Property Predictions from Small Data Sets20 Apr 2024
- 2024A Strong Baseline for Molecular Few-Shot Learning2 Apr 2024
- 2024Graph Learning with Distributional Edge Layouts26 Feb 2024
- 2024Heterogeneous Graph Neural Network on Semantic Tree21 Feb 2024
- 2024Unifying Invariance and Spuriousity for Graph Out-of-Distribution via Probability of Necessity and Sufficiency14 Feb 2024
- 2024Towards Neural Scaling Laws on Graphs3 Feb 2024
- 2024Enhancing Molecular Property Prediction with Auxiliary Learning and Task-Specific Adaptation29 Jan 2024
- 2024Tensor-view Topological Graph Neural Network22 Jan 2024
- 2023Enhancing Molecular Property Prediction via Mixture of Collaborative Experts6 Dec 2023
- 2023Improving Self-supervised Molecular Representation Learning using Persistent Homology29 Nov 2023
- 2023Identifying Semantic Component for Robust Molecular Property Prediction8 Nov 2023
- 2023Multi-channel learning for integrating structural hierarchies into context-dependent molecular representation5 Nov 2023
- 2023Fast Graph Condensation with Structure-based Neural Tangent Kernel17 Oct 2023
- 2023Towards Foundational Models for Molecular Learning on Large-Scale Multi-Task Datasets6 Oct 2023
- 2023On the Equivalence of Graph Convolution and Mixup29 Sep 2023
- 20233D Denoisers are Good 2D Teachers: Molecular Pretraining via Denoising and Cross-Modal Distillation8 Sep 2023
- 2023On Data Imbalance in Molecular Property Prediction with Pre-training17 Aug 2023
- 2023Search to Fine-tune Pre-trained Graph Neural Networks for Graph-level Tasks14 Aug 2023
- 2023Current Methods for Drug Property Prediction in the Real World25 Jul 2023
- 2023Graph Positional and Structural Encoder14 Jul 2023
- 2023Learning to Group Auxiliary Datasets for Molecule8 Jul 2023
- 2023Automated 3D Pre-Training for Molecular Property Prediction13 Jun 2023
- 2023Graph-Aware Language Model Pre-Training on a Large Graph Corpus Can Help Multiple Graph Applications5 Jun 2023
50 newest of 59 All 59 (JSON)
- 2023GIMLET: A Unified Graph-Text Model for Instruction-Based Molecule Zero-Shot Learningcited by 70
- 2023Enhancing Activity Prediction Models in Drug Discovery with the Ability to Understand Human Languagecited by 44
- 2023Towards Foundational Models for Molecular Learning on Large-Scale Multi-Task Datasetscited by 37
- 2023Fast Graph Condensation with Structure-based Neural Tangent Kernelcited by 36
- 2022A Systematic Survey of Chemical Pre-trained Modelscited by 34
- 2023Graph-Aware Language Model Pre-Training on a Large Graph Corpus Can Help Multiple Graph Applicationscited by 33
- 2023Graph Positional and Structural Encodercited by 31
- 2023Automated 3D Pre-Training for Molecular Property Predictioncited by 24
- 2024FedSSP: Federated Graph Learning with Spectral Knowledge and Personalized Preferencecited by 16
- 2023Search to Fine-tune Pre-trained Graph Neural Networks for Graph-level Taskscited by 13
- 2024Towards Neural Scaling Laws on Graphscited by 13
- 2022MolCPT: Molecule Continuous Prompt Tuning to Generalize Molecular Representation Learningcited by 12
12 most cited of 56 All 56 (JSON)
- 2026Mol-JEPA: A multimodal Joint Embedding Predictive Architecture for Molecules23 Aug 2026
- 2026Rethinking Generalization in Graph Neural Networks: A Structural Complexity Perspective13 May 2026
- 2026Approximate Subgraph Matching with Neural Graph Representations and Reinforcement Learning18 Mar 2026
- 2026PCEvo: Path-Consistent Molecular Representation via Virtual Evolutionary27 Jan 2026
- 2026A Semi-supervised Molecular Learning Framework for Activity Cliff Estimation8 Jan 2026
- 2026Beyond Homophily: Community Search on Heterophilic Graphs5 Jan 2026
- 2025Safeguarding Graph Neural Networks against Topology Inference Attacks5 Sep 2025
- 2025A Graph Laplacian Eigenvector-based Pre-training Method for Graph Neural Networks2 Sep 2025
- 2025Heterogeneous Graph Prompt Learning via Adaptive Weight Pruning12 Jul 2025
- 2025CEGA: A Cost-Effective Approach for Graph-Based Model Extraction and Acquisition21 Jun 2025
- 2025Towards Multimodal Graph Large Language Model11 Jun 2025
- 2025Pretraining a Foundation Model for Small-Molecule Natural Products22 Mar 2025
12 newest of 56 All 56 (JSON)