Does GNN Pretraining Help Molecular Representation?
Abstract
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.
Benchmark Results
Tested on 6 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 | |
| 14 | GCN | 0.8400
±0.0040 | |
| 34 | Masking Node + Supervised | 0.8193
±0.0179 | This paper |
| 36 | Context Prediction + Supervised | 0.8171
±0.0179 | This paper |
| 40 | Supervised | 0.8113
±0.0239 | This paper |
| 73 | Node Prediction | 0.7957
±0.0203 | This paper |
| 84 | Motif Prediction | 0.7922
±0.0238 | This paper |
| 86 | No pretrain | 0.7920
±0.0199 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| 90 | Context Prediction | 0.7905
±0.0251 | This paper |
| 107 | Contrastive learning | 0.7845
±0.0244 | This paper |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | ProtoMol | 0.9140
±0.0030 | |
| 2 | MMSG | 0.9080
±0.0050 | |
| 3 | MemGNN | 0.9070 | |
| 11 | Context Prediction + Supervised | 0.8872
±0.0168 | This paper |
| 22 | No pretrain | 0.8743
±0.0163 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| 23 | Node Prediction | 0.8732
±0.0167 | This paper |
| 27 | Motif Prediction | 0.8716
±0.0166 | This paper |
| 32 | Context Prediction | 0.8698
±0.0126 | This paper |
| 33 | Supervised | 0.8691
±0.0186 | This paper |
| 34 | Masking Node + Supervised | 0.8690
±0.0204 | This paper |
| 40 | Contrastive learning | 0.8667
±0.0240 | This paper |
| 43 | GIN | 0.8646
±0.0081 |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | MAGPrompt+ | 0.9432
±0.0238 | |
| 2 | CamS-LLaMA | 0.9420 | |
| 3 | SE(3)-I MPPH | 0.9400
±0.0210 | |
| 5 | Masking Node + Supervised | 0.9343
±0.0250 | This paper |
| 11 | Context Prediction | 0.9268
±0.0119 | This paper |
| 12 | Motif Prediction | 0.9263
±0.0119 | This paper |
| 15 | Contrastive learning | 0.9231
±0.0158 | This paper |
| 16 | Context Prediction + Supervised | 0.9227
±0.0157 | This paper |
| 17 | Node Prediction | 0.9224
±0.0276 | This paper |
| 18 | No pretrain | 0.9223
±0.0307 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| 23 | Supervised | 0.9165
±0.0211 | This paper |
| 34 | GIN | 0.8875
±0.0049 |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | SE(3)-I MPPH | 0.9930
±0.0040 | |
| 2 | KA-GCN | 0.9920
±0.0050 | |
| 3 | KA-GAT | 0.9910
±0.0050 | |
| 19 | GCN | 0.9130
±0.0170 | |
| 28 | No pretrain | 0.8970
±0.0093 | 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 | |
| 44 | Supervised | 0.6534
±0.0017 | This paper |
| 47 | Context Prediction + Supervised | 0.6519
±0.0017 | This paper |
| 48 | Node Prediction | 0.6508
±0.0012 | This paper |
| 60 | Contrastive learning | 0.6439
±0.0063 | This paper |
| 64 | Masking Node + Supervised | 0.6406
±0.0028 | This paper |
| 65 | Motif Prediction | 0.6405
±0.0023 | This paper |
| 66 | GIN | 0.6403
±0.0104 | |
| 88 | Context Prediction | 0.6284
±0.0046 | This paper |
| 101 | No pretrain | 0.6230
±0.0114 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | GeomGCL | 0.7630 | |
| 2 | LiGhT DeepGPT | 0.7570
±0.0110 | |
| 3 | CoMPT | 0.7550 | |
| 14 | GCN | 0.7350
±0.0020 | |
| 20 | Context Prediction + Supervised | 0.7219
±0.0079 | This paper |
| 23 | Masking Node + Supervised | 0.7166
±0.0073 | This paper |
| 24 | Supervised | 0.7164
±0.0046 | This paper |
| 39 | Context Prediction | 0.7018
±0.0044 | This paper |
| 41 | Node Prediction | 0.6977
±0.0013 | This paper |
| 46 | No pretrain | 0.6913
±0.0055 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| 48 | Motif Prediction | 0.6909
±0.0007 | This paper |
| 55 | Contrastive learning | 0.6837
±0.0080 | This paper |
