KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction
Abstract
Designing accurate deep learning models for molecular property prediction plays an increasingly essential role in drug and material discovery. Recently, due to the scarcity of labeled molecules, self-supervised learning methods for learning generalizable and transferable representations of molecular graphs have attracted lots of attention. In this paper, we argue that there exist two major issues hindering current self-supervised learning methods from obtaining desired performance on molecular property prediction, that is, the ill-defined pre-training tasks and the limited model capacity. To this end, we introduce Knowledge-guided Pre-training of Graph Transformer (KPGT), a novel self-supervised learning framework for molecular graph representation learning, to alleviate the aforementioned issues and improve the performance on the downstream molecular property prediction tasks. More specifically, we first introduce a high-capacity model, named Line Graph Transformer (LiGhT), which emphasizes the importance of chemical bonds and is mainly designed to model the structural information of molecular graphs. Then, a knowledge-guided pre-training strategy is proposed to exploit the additional knowledge of molecules to guide the model to capture the abundant structural and semantic information from large-scale unlabeled molecular graphs. Extensive computational tests demonstrated that KPGT can offer superior performance over current state-of-the-art methods on several molecular property prediction tasks.
Benchmark Results
Tested on 5 datasets
Tables show presented results in global context (best 3 papers + GCN + MLP).
MoleculeNet
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | HIMP | 0.8740
±0.0050 | |
| 2 | GINE w/ VN | 0.8720
±0.0030 | |
| 3 | NaiveGINe+ K=3 w/ VN | 0.8700
±0.0040 | |
| 9 | KPGT | 0.8480
±0.0130 | This paper |
| 13 | Contextpred+Sup | 0.8400
±0.0230 | This paper |
| 14 | GCN | 0.8400
±0.0040 | |
| 15 | GROVER | 0.8380
±0.0170 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| 25 | Masking+Sup | 0.8280
±0.0130 | This paper |
| 31 | JOAO | 0.8230
±0.0220 | prev best: GraphMAE: Self-Supervised Masked Graph Autoencoders (KDD 2022) |
| 35 | EdgePred | 0.8180
±0.0250 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 37 | Infomax | 0.8160
±0.0210 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| 46 | ContextPred | 0.8060
±0.0120 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 47 | GraphCL | 0.8050
±0.0170 | prev best: Omni-Granular Ego-Semantic Propagation for Self-Supervised Graph Representation Learning (ICML 2022) |
| 48 | 3D Infomax | 0.8050
±0.0320 | This paper |
| 61 | GraphMVP | 0.7990
±0.0180 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 66 | masking | 0.7980
±0.0250 | This paper |
| 71 | GraphLoG | 0.7960
±0.0250 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | ProtoMol | 0.9140
±0.0030 | |
| 2 | MMSG | 0.9080
±0.0050 | |
| 3 | MemGNN | 0.9070 | |
| 36 | KPGT | 0.8680
±0.0110 | This paper |
| 43 | GIN | 0.8646
±0.0081 | |
| 100 | JOAO | 0.8340
±0.0330 | prev best: GraphMAE: Self-Supervised Masked Graph Autoencoders (KDD 2022) |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | MAGPrompt+ | 0.9432
±0.0238 | |
| 2 | CamS-LLaMA | 0.9420 | |
| 3 | SE(3)-I MPPH | 0.9400
±0.0210 | |
| 32 | KPGT | 0.9080
±0.0100 | This paper |
| 34 | GIN | 0.8875
±0.0049 | |
| 36 | GraphCL | 0.8870
±0.0190 | prev best: GraphMAE: Self-Supervised Masked Graph Autoencoders (KDD 2022) |
| 37 | GROVER | 0.8870
±0.0060 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| 39 | JOAO | 0.8790
±0.0200 | prev best: Omni-Granular Ego-Semantic Propagation for Self-Supervised Graph Representation Learning (ICML 2022) |
| 40 | ContextPred | 0.8770
±0.0260 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 41 | 3D Infomax | 0.8770
±0.0140 | This paper |
| 43 | Contextpred+Sup | 0.8750
±0.0110 | This paper |
| 44 | EdgePred | 0.8730
±0.0160 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 47 | masking | 0.8640
±0.0280 | This paper |
| 49 | GraphMVP | 0.8600
±0.0340 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 50 | Masking+Sup | 0.8590
±0.0200 | This paper |
| 54 | GraphLoG | 0.8460
±0.0080 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 55 | Infomax | 0.8400
±0.0260 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | KA-GAT | 0.8470
±0.0020 | |
| 2 | KA-GCN | 0.8420
±0.0010 | |
| 3 | GraphKAN | 0.8370
±0.0010 | |
| 49 | KPGT | 0.6490
±0.0090 | This paper |
| 52 | GROVER | 0.6380
±0.0050 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| 66 | GIN | 0.6403
±0.0104 | |
| 68 | JOAO | 0.6400
±0.0100 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 70 | GraphMVP | 0.6390
±0.0120 best reported | best at pub: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 103 | ContextPred | 0.6090
±0.0130 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) Improvement within reported uncertainty; not highlighted. |
| 108 | Contextpred+Sup | 0.6200
±0.0090 | This paper |
| 114 | GraphCL | 0.6183
±0.0060 best reported | best at pub: Omni-Granular Ego-Semantic Propagation for Self-Supervised Graph Representation Learning (ICML 2022) best today: Pre-training Graph Neural Networks on Molecules by Using Subgraph-Conditioned Graph Information Bottleneck (AAAI 2024) Difference within reported uncertainty; not counted as underperformance. |
| 120 | Infomax | 0.6160
±0.0240 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) Improvement within reported uncertainty; not highlighted. |
| 123 | GraphLoG | 0.6150
±0.0130 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) Improvement within reported uncertainty; not highlighted. |
| 138 | Masking+Sup | 0.6110
±0.0030 | This paper |
| 155 | 3D Infomax | 0.6060
±0.0078 best reported | best today: A Generalist Cross-Domain Molecular Learning Framework for Structure-Based Drug Discovery (2025) Difference within reported uncertainty; not counted as underperformance. |
| 170 | EdgePred | 0.6030
±0.0250 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) Improvement within reported uncertainty; not highlighted. |
| 221 | masking | 0.5730
±0.0120 | prev best: MoCL: Data-driven Molecular Fingerprint via Knowledge-aware Contrastive Learning from Molecular Graph (KDD 2021) Improvement within reported uncertainty; not highlighted. |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | GeomGCL | 0.7630 | |
| 2 | LiGhT DeepGPT | 0.7570
±0.0110 | |
| 3 | CoMPT | 0.7550 | |
| 6 | KPGT | 0.7460
±0.0020 | This paper |
| 14 | GCN | 0.7350
±0.0020 | |
| 18 | Contextpred+Sup | 0.7240
±0.0150 | This paper |
| 25 | 3D Infomax | 0.7160
±0.0130 | This paper |
| 26 | Masking+Sup | 0.7150
±0.0070 | This paper |
| 28 | ContextPred | 0.7140
±0.0180 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 30 | EdgePred | 0.7120
±0.0110 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 31 | JOAO | 0.7110
±0.0140 | prev best: Omni-Granular Ego-Semantic Propagation for Self-Supervised Graph Representation Learning (ICML 2022) |
| 34 | GROVER | 0.7080
±0.0150 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| 42 | GraphCL | 0.6960
±0.0230 | prev best: Omni-Granular Ego-Semantic Propagation for Self-Supervised Graph Representation Learning (ICML 2022) |
| 49 | Infomax | 0.6900
±0.0120 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| 50 | GraphMVP | 0.6890
±0.0100 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 64 | GraphLoG | 0.6770
±0.0190 | prev best: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) |
| 83 | masking | 0.6630
±0.0180 | This paper |
